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Innate Immunity: Phagocytes and Antigen Presentation

The immune system Immune system The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs is equipped with a varied repertoire of defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual's subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms against pathogens. Functionally, the immune system Immune system The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs is differentiated into the innate and adaptive components. Innate immunity, the 1st protective layer of defense, is a system that recognizes threatening microbes, distinguishes self-tissues from pathogens, and subsequently eliminates the foreign invaders. The response is nonspecific and uses different layers of protection: barriers such as the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, pattern recognition receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (PRRs) as well as circulating proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (e.g., complement) that relay signals of a threat, and immune cells that help eliminate the microbe. Pathogen-associated molecular patterns Pathogen-Associated Molecular Patterns Sepsis and Septic Shock ( PAMPs PAMPs Sepsis and Septic Shock) in microorganisms and damage-associated molecular patterns Damage-Associated Molecular Patterns Sepsis and Septic Shock (DAMPs) from injured tissues are identified, and the appropriate cells are recruited. Involved cells include phagocytes and accessory cells. The offending pathogens are engulfed by phagocytes for destruction. In antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells (the most potent of which is the dendritic cell), parts of the pathogen material or peptides are transported to the cell surface. Through a unique antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-loading mechanism specific to MHC I or II, the processed antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides are then presented to the appropriate T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions, leading to T-cell activation. This interaction links innate immunity with adaptive immunity.

Last updated: 25 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Components of the Innate Immune System

Professional Phagocytes

Overview

Immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs

The immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs provides defense (immunity) against invading pathogens ranging from viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology to parasites, and components are interconnected by blood and the lymphatic circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment.

There are 2 lines of defense Lines of Defense Inflammation (that overlap):

Innate immunity (which is nonspecific)
Adaptive immunity (based on specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination recognition):
- Cell-mediated immunity Cell-mediated immunity Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Squamous Cell Carcinoma (SCC): adaptive response in the cells/tissues involving the T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions
- Humoral immunity: adaptive response in the fluids (humoral) involving B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions and immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions

Innate versus adaptive immunity

**Table: Innate versus adaptive immunity**
	Innate immunity	Adaptive immunity
Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics	Germline encoded	Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics rearrangements involved in lymphocyte development
Immune response	Nonspecific	Highly specific
Timing of response	Immediate (minutes to hours)	Develops over a longer period of time
Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment response	None	Responds quickly upon recognition of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination with memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment response
Recognition of pathogen	Pattern recognition receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (PRRs) such as TLRs recognize pathogen-associated molecular patterns Pathogen-Associated Molecular Patterns Sepsis and Septic Shock ( PAMPs PAMPs Sepsis and Septic Shock)	Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment cells (T and B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions) Activated B cells Activated B cells Humoral Adaptive Immunity
Components	Anatomical barriers (e.g., skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions) Chemical and biologic barriers (e.g., gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD), vaginal flora) Cells (e.g., granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology) Secreted proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis: Enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes (e.g., lysozyme) Other PRRs (e.g., antimicrobial peptides Antimicrobial peptides Innate Immunity: Barriers, Complement, and Cytokines ( AMPs AMPs Innate Immunity: Barriers, Complement, and Cytokines) Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response* Complement* system	Cell-mediated immunity Cell-mediated immunity Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Squamous Cell Carcinoma (SCC): T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions Humoral immunity: B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions, immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions

*Mediators with roles in adaptive immunity

Components of the Innate Immune System

Innate immune response Innate Immune Response Immunity to pathogens is divided into innate and adaptive immune responses. The innate immune response is the 1st line of defense against a variety of pathogens, including bacteria, fungi, viruses, and parasites. In essentially the same form, the innate type of immunity is present in all multicellular organisms. Innate Immunity: Barriers, Complement, and Cytokines

Barriers:
- 1st line of defense (mechanical, chemical, and biologic)
- Define and line body surfaces
- Secrete substances to remove and reduce pathogens
Microbe detection: The innate system uses the following to recognize the pathogen:
- Pattern recognition receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (PRRs): proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that distinguish self from foreign material, recognizing components specific to microbes:
  - Pathogen-associated molecular patterns Pathogen-Associated Molecular Patterns Sepsis and Septic Shock ( PAMPs PAMPs Sepsis and Septic Shock): structures conserved among microbial species
  - Damage-associated molecular patterns Damage-Associated Molecular Patterns Sepsis and Septic Shock (DAMPs), or alarmins: endogenous molecules released from damaged cells
- According to the location of the interactions of the PRR and PAMPs PAMPs Sepsis and Septic Shock, PRRs can be cell-associated (transmembrane or intracellular receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors):
  - TLRs
  - Retinoic acid–inducible gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (RIG) I–like receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( RLRs RLRs Innate Immunity: Barriers, Complement, and Cytokines)
  - NOD-like receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( NLRs NLRs Innate Immunity: Barriers, Complement, and Cytokines)
  - C-type lectin receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( CLRs CLRs Innate Immunity: Barriers, Complement, and Cytokines)
- When the interaction occurs in body fluids (bloodstream and interstitial fluids), PRRs are secreted and circulating:
  - AMPs AMPs Innate Immunity: Barriers, Complement, and Cytokines
  - Collectins Collectins A class of c-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short n-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region. Innate Immunity: Barriers, Complement, and Cytokines
  - Lectins Lectins Proteins that share the common characteristic of binding to carbohydrates. Some antibodies and carbohydrate-metabolizing proteins (enzymes) also bind to carbohydrates, however they are not considered lectins. Plant lectins are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (hemagglutinins). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition. Innate Immunity: Barriers, Complement, and Cytokines
  - Pentraxins Pentraxins Innate Immunity: Barriers, Complement, and Cytokines
  - Antimicrobial oligosaccharides Antimicrobial oligosaccharides Innate Immunity: Barriers, Complement, and Cytokines
A breach in the barriers triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) several processes → inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation:
- Occurs in response to infection or injury
- Results in the cardinal signs ( swelling Swelling Inflammation, redness Redness Inflammation, heat Heat Inflammation, and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways)
- Once the pathogen is identified via PRRs, proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are secreted:
  - Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response (functions include recruitment Recruitment Skeletal Muscle Contraction, cell-to-cell communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence, and antiviral Antiviral Antivirals for Hepatitis B, antibacterial Antibacterial Penicillins, and antifungal Antifungal Azoles actions)
  - Chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity (cell migration)
  - Complement system Complement system Serum glycoproteins participating in the host defense mechanism of complement activation that creates the complement membrane attack complex. Included are glycoproteins in the various pathways of complement activation (classical complement pathway; alternative complement pathway; and lectin complement pathway). Innate Immunity: Barriers, Complement, and Cytokines (complements (assists in) eliminating the microbes)
  - Some PRRs (e.g., AMPs AMPs Innate Immunity: Barriers, Complement, and Cytokines) are also involved in pathogen elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy.
Cellular response: Various cells (e.g., phagocytes) are recruited and participate in microbial killing.
The immune response is terminated when there is no longer a need ( homeostasis Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Cell Injury and Death).

Cells of the innate immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs

Many subsets of cells (that are involved in the innate response) develop from hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis (HSCs) in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow (a primary lymphoid organ):
- HSCs → common myeloid progenitor → giving rise to:
  - Granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology: professional phagocytes (neutrophils, monocytes/macrophages), eosinophils, basophils, mast cells
  - Megakaryocytes → platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
- HSCs → common lymphoid progenitor → giving rise to lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology (which generally undergo activation and proliferation in the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs) such as:
  - B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions and T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions (adaptive immunity)
  - Natural killer (NK) cells (mostly innate immune response Innate Immune Response Immunity to pathogens is divided into innate and adaptive immune responses. The innate immune response is the 1st line of defense against a variety of pathogens, including bacteria, fungi, viruses, and parasites. In essentially the same form, the innate type of immunity is present in all multicellular organisms. Innate Immunity: Barriers, Complement, and Cytokines)
  - NK– T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions (bridge innate and adaptive immunity)
Individually, the cells have varying functions and targets in the immune response.
Among the crucial roles are:
- Phagocytosis: Microbes or damaged particles are engulfed and digested.
- Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor: performed by dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions, macrophages, and B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions, facilitating antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination recognition by adaptive immunity

Stem cells differentiate into 2 pathways:
Myeloid pathways produce erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, and cells of the innate immune response Innate Immune Response Immunity to pathogens is divided into innate and adaptive immune responses. The innate immune response is the 1st line of defense against a variety of pathogens, including bacteria, fungi, viruses, and parasites. In essentially the same form, the innate type of immunity is present in all multicellular organisms. Innate Immunity: Barriers, Complement, and Cytokines. Lymphoid pathways produce the cells of adaptive response and natural killer cells Natural killer cells A specialized subset of T-lymphocytes that exhibit features of innate immunity similar to that of natural killer cells. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D antigen. Lymphocytes: Histology.
Image by Lecturio.

Professional Phagocytes

Phagocytes “eat” the foreign material, and help detect, clear, and repair damaged tissue, recognizing pathogens via PRRs or opsonization (by complement or immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions).

Neutrophils

Description:
- 1st cells to be recruited into sites of infection
- Chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity secreted by immune or epithelial cells (at the sites) to attract neutrophils:
  - N-formyl bacterial oligopeptide
  - Complement-derived C5a
  - Leukotriene B4 Leukotriene B4 The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). Eicosanoids (secreted by numerous immune cells)
  - IL-8
Microbicidal functions:
- Phagocytosis and production of reactive oxygen species Reactive oxygen species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include singlet oxygen; superoxides; peroxides; hydroxyl radical; and hypochlorous acid. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to nucleic acids; proteins; and lipids. Nonalcoholic Fatty Liver Disease ( respiratory burst Respiratory burst A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent often die as a result of recurrent bacterial infections. Leukocyte Adhesion Deficiency Type 1) that are cytotoxic Cytotoxic Parvovirus B19 to bacterial pathogens
- Neutrophil cytoplasmic granule proteases Proteases Proteins and Peptides: neutrophil elastase Elastase A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25, 000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. Proteins and Peptides and cathepsin G
- Production of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response such as tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF))
- Use of extracellular strands of chromatin Chromatin The material of chromosomes. It is a complex of dna; histones; and nonhistone proteins found within the nucleus of a cell. DNA Types and Structure laced with antimicrobial proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (neutrophil extracellular traps (NETs)) that catch and kill pathogens

Neutrophil-granulocyte-cells-of-the-innate-immune-system — Neutrophil:
Granulocyte with multilobed nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and fine faintly pink granules
Image: “ Granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology can be distinguished by the number of lobes in their nuclei and the staining properties of their granules.” by Parker N et al AL Amyloidosis. License: CC BY 4.0, cropped by Lecturio.

Mechanism of neutrophil extracellular traps (nets) — Neutrophil:
Granulocyte with multilobed nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and fine faintly pink granules
Image: “ Granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology can be distinguished by the number of lobes in their nuclei and the staining properties of their granules.” by Parker N et al AL Amyloidosis. License: CC BY 4.0, cropped by Lecturio.

Monocytes/macrophages

Description: Monocytes develop in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow and enter the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment.
- Some remain as monocytes, picking up and bringing antigens to the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy.
- When monocytes migrate out of the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and go to tissues, monocytes differentiate into macrophages.
- Macrophages are found in:
  - Lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow, perivascular connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology, and serous cavities
  - In other tissues: lung ( alveolar macrophages Alveolar macrophages Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells. Acute Respiratory Distress Syndrome (ARDS)), liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy ( Kupffer cells Kupffer cells Specialized phagocytic cells of the mononuclear phagocyte system found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells. Benign Liver Tumors), bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types ( osteoclasts Osteoclasts A large multinuclear cell associated with the bone resorption. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. Bones: Development and Ossification), CNS ( microglia Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Nervous System: Histology cells), and synovium (type A lining cells)
- Also differentiate into dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions during inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
Functions:
- Respond briskly to pathogens, facilitated by high density of surface PRRs
- Use NO to kill pathogens, and also produce large amounts of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response
- Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor to lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology (stimulating the adaptive immune response Adaptive immune response Immune responses against pathogens are divided into the innate and adaptive immune response systems. The adaptive immune response, also called the acquired immune system, consists of 2 main mechanisms: the humoral- and cellular-mediated immune responses. Adaptive Immune Response)
- Play a role in iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements homeostasis Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Cell Injury and Death

Development of monocyte — Monocyte development starts from hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis (HSCs) and progresses through stages to the colony-forming unit granulocyte-macrophage (CFU-GM):
The 1st monocyte precursor is the monoblast Monoblast White Myeloid Cells: Histology, which has a round or oval nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles.
The promonocyte Promonocyte White Myeloid Cells: Histology follows and has a convoluted nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles.
The monocyte arises with an indented nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and is released from the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow to become a macrophage in the tissues.
Image by Lecturio. License: CC BY-NC-SA 4.0

Dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions

Description:
- Most potent antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells
- Name derived from presence of dendritic (branching) extensions
- Arise from bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
- Link innate and adaptive immunity by antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity, which attract T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions and B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions when a pathogen is detected.
Types of dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions:
- Myeloid dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions:
  - Also called conventional dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions
  - Can be interstitial dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions (in blood and interstices of lung, heart, kidney) or Langerhans dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions
- Plasmacytoid dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions:
  - Lymphoid lineage
  - Plasmacytoid dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions primarily reside in and recirculate through lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs.
  - Inefficient antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells but massively produce type I interferon ( IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons) when viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease occur
Functions (vary with maturation):
- Phagocytosis of microbes, molecules from damaged tissue, self-antigens, tumors
- Subsequent steps lead to maturation (expression of MHC II and costimulatory molecules, PRRs, with up-regulation Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (gene expression regulation), mRNAs, and proteins. Pharmacokinetics and Pharmacodynamics of cytokine receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors)
- Become more antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-specific with maturity and participate in the adaptive immune response Adaptive immune response Immune responses against pathogens are divided into the innate and adaptive immune response systems. The adaptive immune response, also called the acquired immune system, consists of 2 main mechanisms: the humoral- and cellular-mediated immune responses. Adaptive Immune Response
- Once mature, dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions present antigens to T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions, which then proliferate.
- Positive feedback: effector T lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology secrete IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons‒ɣ → make the dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions produce ↑ IL-12 and ↑ microbicidal activity of macrophages

Dendritic cells releasing il-12 — Dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology IL-12, which activates CD4 Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions cells. These Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions cells produce IL-2, stimulating production of more Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions T-cell subsets. Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions cells also release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons-γ, which activates macrophages and activates fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis to cause angiogenesis Angiogenesis Bartonella and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans. If these macrophages are persistently stimulated by pathogens, such as Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium and Schistosoma Schistosoma Schistosomiasis is an infection caused by Schistosoma, a trematode. Schistosomiasis occurs in developing countries with poor sanitation. Freshwater snails are the intermediate host and are transmitted to humans through skin contact with contaminated fresh water. The clinical presentation occurs as a result of the host’s immune response to antigens from the eggs. Schistosoma/Schistosomiasis, granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis are formed.
Image by Lecturio.

Dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions versus follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma

It is important to note that follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma are completely unrelated to dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions in lineage and function.

Follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma:

Concentrated in the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs where B-cell activation occurs
Trap antigens on their surfaces that are then bound by the B-cell receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors of B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions (B-cell activation)

Table: Differences between dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions and follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma
	Dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions	Follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma
Origin	Derived from hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis	Derived from mesenchymal stem cells
Sites	Present throughout the body	Present only in germinal centers of secondary lymphoid tissues
MHC class and costimulatory molecules	Possess MHC II and costimulatory (e.g., B7) molecules	Lack MHC II and costimulatory molecules
Functions	Activate helper T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions Initially phagocytic	Do not activate helper T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions Specialized in presenting antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination to B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions Never phagocytic

Phagocytosis

Attachment Attachment The binding of virus particles to virus receptors on the host cell surface, facilitating virus entry into the cell. Virology is either via recognition of the PRR or mediated by opsonins ( proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that bind BIND Hyperbilirubinemia of the Newborn/tag pathogens and make them palatable for phagocytes).
- Engulfment of the pathogen in a vesicle Vesicle Primary Skin Lesions follows.
- The phagocyte forms a pseudopod that wraps around the pathogen, and this becomes a pinched-off membrane vesicle Vesicle Primary Skin Lesions called a phagosome.
- A phagolysosome Phagolysosome Chédiak-Higashi Syndrome is formed as the phagosome fuses with a lysosome.
- In the compartment, the pathogen is eliminated by different microbial killing mechanisms.
When the pathogen is destroyed, the phagocyte undergoes apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage (e.g., seen in pus) or the waste is eliminated by exocytosis Exocytosis Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. The Cell: Cell Membrane.
In antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells, parts of the pathogen material or peptides are transported to the cell surface for antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor.

Accessory Cells

Eosinophils

Description:
- Recognized by their prominent eosinophilic cytoplasmic granules
- Located primarily in the lamina propria Lamina propria Whipple’s Disease of the GI tract
Functions:
- Released extracellular traps contain eosinophil granules (that secrete their contents, including the cytotoxic Cytotoxic Parvovirus B19 major basic protein) when stimulated
- Have cytotoxic Cytotoxic Parvovirus B19 effect against helminths Helminths Commonly known as parasitic worms, this group includes the acanthocephala; nematoda; and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. Anthelmintic Drugs and other parasites
- Also have extensive antibacterial Antibacterial Penicillins and antiviral Antiviral Antivirals for Hepatitis B activity
- Mediate eosinophilic GI diseases

Basophils

Description:
- Circulating leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology; not found in tissues
- Express high-affinity receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors for IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
Functions:
- With IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, basophils participate in immediate hypersensitivity types of allergic immune response
- Provide resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing against helminths Helminths Commonly known as parasitic worms, this group includes the acanthocephala; nematoda; and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. Anthelmintic Drugs
- Activities are mediated by histamine, cathelicidin, and other mediators
- Produce IL-4 and IL-13, which promote Th2 Th2 A subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins il-4; il-5; il-6; and il-10. These cytokines influence b-cell development and antibody production as well as augmenting humoral responses. T cells: Types and Functions response

Eosinophil and basophil
Both are granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology, with eosinophils possessing a bilobed nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and dark pink granules and basophils having a bilobed or trilobed nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles, and dark blue granules.
Image: “ Granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology can be distinguished by the number of lobes in their nuclei and the staining properties of their granules.” by Parker N et al AL Amyloidosis. License: CC BY 4.0, cropped by Lecturio.

Mast cells

Description:
- Morphologically similar to basophils
- Found in large numbers in interstitial tissues
- Express:
  - TLRs 1, 2, 4, and 6 (for the complement anaphylatoxin C5a)
  - Receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors for mannose-binding lectin (MBL)
Functions:
- Participate in allergic responses and have antimicrobial and antiprotozoan functions
- Release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology upon activation:
  - TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)-ɑ
  - IL-8
  - Inflammatory mediators (heparin, histamine, platelet-activating factor, leukotrienes Leukotrienes A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. Eicosanoids)
  - Proteases Proteases Proteins and Peptides (e.g., tryptase Tryptase A family of neutral serine proteases with trypsin-like activity. Tryptases are primarily found in the secretory granules of mast cells and are released during mast cell degranulation. Exocrine Pancreatic Cancer, chymase)
  - Antimicrobial peptides Antimicrobial peptides Innate Immunity: Barriers, Complement, and Cytokines such as cathelicidin and defensins Defensins Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Innate Immunity: Barriers, Complement, and Cytokines

Natural killer cells Natural killer cells A specialized subset of T-lymphocytes that exhibit features of innate immunity similar to that of natural killer cells. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D antigen. Lymphocytes: Histology

Description:
- Lymphoid cells that do not express T- or B-cell receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
- Express a number of activating and inhibitory receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
- Have granules with perforins and granzymes Granzymes A family of serine endopeptidases found in the secretory granules of leukocytes such as cytotoxic T-lymphocytes and natural killer cells. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells. Lymphocytes: Histology
- Become senescent with age and obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
Functions:
- Activating receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors are key to the “killer function” in viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and malignant tumors, effecting pathogen death through:
  - Fas– Fas ligand Fas ligand A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-lymphocytes and natural killer cells. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the fas receptor and triggering apoptosis. Tumor Necrosis Factor (TNF) caspase pathway
  - Granzyme/ perforin Perforin A calcium-dependent pore-forming protein synthesized in cytolytic lymphocytes and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell. Lymphocytes: Histology pathway
- Avoid attacking host cells through recognition of MHC I molecules expressed in all healthy host cells
NK– T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions: have both T-cell and NK-cell surface markers and functions

Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology

Description: circulating small cell fragments (bud off from megakaryocytes)
Functions:
- Express PRRs
- Produce cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response
- Recruit leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology to sites of injury or inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
- Megakaryocytes secrete IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons-α and IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons-β

Antigen Presentation

Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells (such as dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions and macrophages) detect, process, and present the antigens to T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions, allowing adaptive immunity to recognize and mount a response every time the pathogen is encountered (immunologic memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment).

Major histocompatibility complex (MHC)

Proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis found in antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting (and other) cells that are encoded by the HLA genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, located on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 6
Principal function: present the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination to adaptive immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs ( T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions)
Represents the interaction between the innate (e.g., antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells) and adaptive immunity ( T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions)
MHC classified as:
- MHC I:
  - Found on all nucleated cells
  - When a cell has an intracellular pathogen (e.g., virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology), MHC brings endogenous antigens to the surface, presenting them to CD8+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
  - Structure: 1 short and 1 long chain (ɑ chain with 3 domains: ɑ1, ɑ2, ɑ3), associated with the β₂-microglobulin
- MHC II:
  - Found only on certain immune cells (APCs)
  - Present exogenous antigens (e.g., bacterial proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis) to CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions
  - Structure: 2 ɑ and 2 β chains of equal length

Structure of mhc i and mhc ii — Structures of MHC I and MHC II:
MHC I has 1 short and 1 long chain (ɑ chain with 3 domains: ɑ₁, ɑ₂, and ɑ₃), associated with the β₂-microglobulin. MHC II has 2 ɑ and 2 β chains. The peptide antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination goes to the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding cleft.
MHC: major histocompatibility complex
Image by Lecturio.

Routes of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

MHC I:
- Proteasomes degrade proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (within the cell) into peptides.
- Peptide fragments are transported (via transporter associated with antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination processing) to the ER.
- In the ER, aminopeptidases Aminopeptidases A subclass of exopeptidases that act on the free n terminus end of a polypeptide liberating a single amino acid residue. Proteins and Peptides further trim the peptides.
- Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides are then loaded onto the MHC I molecules → to the Golgi apparatus for posttranslational modification
- Then the complexes are transported to the cell surface, where they are presented to CD8+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
MHC II:
- Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells take up extracellular antigens and are engulfed within phagosomes.
- Phagosomes fuse with lysosomes Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes membrane fusion. The Cell: Organelles (containing proteolytic enzymes Proteolytic enzymes Proteins and Peptides that cleave the phagocytosed proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis into small peptides).
- In the ER:
  - Newly synthesized MHC II molecules have the invariant chain, which binds the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding cleft.
  - With the site occluded, other ER-resident peptides cannot bind BIND Hyperbilirubinemia of the Newborn the cleft.
  - From the ER, the invariant chain directs the MHC II complex to the acidified endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus (where antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides are).
  - In the endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus, the invariant chain is released → peptides are loaded onto MHC II complexes (chaperoned by HLA- DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus)
  - Peptide-loaded MHC II complexes are transported to the cell surface, allowing antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor to CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.

Routes of antigen presentation — Routes of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor by MHC class I and II molecules:
In class I antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor (left), proteasomes degrade endogenous antigens or proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (within the cell) into peptides. Peptide fragments are transported (via transporter associated with antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination processing (TAP)) to the ER, where they are further trimmed by aminopeptidases Aminopeptidases A subclass of exopeptidases that act on the free n terminus end of a polypeptide liberating a single amino acid residue. Proteins and Peptides and loaded onto the MHC class I molecule. MHC class I–loaded complexes go to the Golgi apparatus for posttranslational modification. Then the complexes are transported to the cell surface, where they are presented to CD8+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions. IN class II antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor (right), extracellular/exogenous antigens are taken up within phagosomes by antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells. The phagosomes then fuse with proteolytic enzyme-filled lysosomes Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes membrane fusion. The Cell: Organelles. This results in the breakdown of phagocytosed proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis into small peptides. Meanwhile, in the endoplasmic reticulum Endoplasmic reticulum A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced. The Cell: Organelles (ER), new MHC class II molecules are synthesized. These molecules have the invariant chain (pink structure in the right image, marked Ii), which binds the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding cleft. With the cleft occluded (by the invariant chain), ER-resident peptides cannot bind BIND Hyperbilirubinemia of the Newborn. The invariant chain directs the MHC II complex to the acidified endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus (where antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides are) as it exits from the ER. When MHC II complexes are delivered to the endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus, the invariant chain is released, allowing loading of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides (chaperoned by a protein, HLA- DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus) onto the MHC class II molecules. Once loaded, the formed antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptide-MHC class II complexes are brought to the cell surface, ready to present the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination to CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
Ii: MHC class II–associated invariant chain
MIIC: MHC class II compartment
Image by Lecturio.

Antigen-presenting cell and t cell interaction — Routes of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor by MHC class I and II molecules:
In class I antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor (left), proteasomes degrade endogenous antigens or proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (within the cell) into peptides. Peptide fragments are transported (via transporter associated with antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination processing (TAP)) to the ER, where they are further trimmed by aminopeptidases Aminopeptidases A subclass of exopeptidases that act on the free n terminus end of a polypeptide liberating a single amino acid residue. Proteins and Peptides and loaded onto the MHC class I molecule. MHC class I–loaded complexes go to the Golgi apparatus for posttranslational modification. Then the complexes are transported to the cell surface, where they are presented to CD8+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions. IN class II antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor (right), extracellular/exogenous antigens are taken up within phagosomes by antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells. The phagosomes then fuse with proteolytic enzyme-filled lysosomes Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes membrane fusion. The Cell: Organelles. This results in the breakdown of phagocytosed proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis into small peptides. Meanwhile, in the endoplasmic reticulum Endoplasmic reticulum A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced. The Cell: Organelles (ER), new MHC class II molecules are synthesized. These molecules have the invariant chain (pink structure in the right image, marked Ii), which binds the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding cleft. With the cleft occluded (by the invariant chain), ER-resident peptides cannot bind BIND Hyperbilirubinemia of the Newborn. The invariant chain directs the MHC II complex to the acidified endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus (where antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides are) as it exits from the ER. When MHC II complexes are delivered to the endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus, the invariant chain is released, allowing loading of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptides (chaperoned by a protein, HLA- DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus) onto the MHC class II molecules. Once loaded, the formed antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptide-MHC class II complexes are brought to the cell surface, ready to present the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination to CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
Ii: MHC class II–associated invariant chain
MIIC: MHC class II compartment
Image by Lecturio.

MHC I versus MHC II

**Table: MHC I versus MHC II**
	MHC I	MHC II
Loci	HLA-A HLA-A Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the a locus of multiple alleles on chromosome 6. They serve as targets for t-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts. Organ Transplantation, HLA-B HLA-B Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., hla-b27, -b7, -b8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes. Organ Transplantation, HLA-C HLA-C Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the c locus on chromosome 6. They have significantly lower immunogenicity than the hla-a and -b determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondyloarthritis, psoriasis, multiple myeloma). Organ Transplantation	HLA-DP, HLA-DQ, HLA-DR
Binding	CD8 T cell	CD4 T cell
Distribution	All nucleated cells (none on RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)	Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-presenting cells
Role	Present endogenous antigens to CD8+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions (cytolytic)	Present exogenous antigens to CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions
Structure	1 long chain 1 short chain	2 chains of equal length (2 ɑ, 2 β)
Associated protein	β₂-microglobulin	Invariant chain
Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination loading	Loading of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptide onto MHC I in ER (delivered via TAP)	Loading of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination peptide onto MHC II in the acidified phagolysosome Phagolysosome Chédiak-Higashi Syndrome after release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of invariant chain

TAP: transporter associated with antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination processing

Related diseases

The HLA region encodes several molecules that perform key functions in the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs. There is a robust association between the HLA region and several diseases.

**Table: HLA subtypes and associated conditions**
HLA subtype	Condition(s)	Mnemonics
A3	Hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis	HA3mochromatosis Fe3 ( iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements = hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis), A3
B8	Addison’s disease Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis Graves’ disease	Don’t B l8, Dr. Addison, or you’ll send my patient to the grave!
B27	Psoriatic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew’s disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis Inflammatory bowel disease-associated arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis ( seronegative arthropathies Seronegative Arthropathies Ankylosing Spondylitis)	PAIR
C	Psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis	“C-riasis”
DQ2/DQ8	Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease	I 8 2 much gluten Gluten Prolamins in the endosperm of seeds from the triticeae tribe which includes species of wheat; barley; and rye. Celiac Disease at Dairy Queen (DQ2/8; gluten Gluten Prolamins in the endosperm of seeds from the triticeae tribe which includes species of wheat; barley; and rye. Celiac Disease = celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease)
DR2	Multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor Hay fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever Goodpasture syndrome Goodpasture Syndrome Goodpasture syndrome, also known as anti-glomerular basement membrane (GBM) disease, is an autoimmune disease characterized by circulating antibodies directed against glomerular and alveolar basement membranes. Affected individuals present with symptoms of rapidly progressive glomerulonephritis and alveolar hemorrhage. Goodpasture Syndrome Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus)	Drive 2 multiple hay pastureS 2-3, SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
DR3	SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus type 1 Type 1 Spinal Muscular Atrophy Graves’ disease Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis Addison’s disease	2-3, SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus 3-4, sugar ( diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus) Dr. Hashimoto is odd (odd numbers 3, 5)
DR4	Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus type 1 Type 1 Spinal Muscular Atrophy Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis Addison disease	Add rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, and you’re on all 4s (joints)! 3-4, sugar ( diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus)
DR5	Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis	Dr. Hashimoto is odd (odd numbers 3, 5)
DR7	Steroid-responsive nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome	7, “pee in heaven” (nephrotic)

Clinical Relevance

Severe congenital neutropenia Congenital neutropenia Severe Congenital Neutropenia ( SCN SCN Severe congenital neutropenia (SCN) affects myelopoiesis and has many different subtypes. Scn manifests in infancy with life-threatening bacterial infections. Severe Congenital Neutropenia): condition with a deficiency of neutrophils. Severe congenital neutropenia Congenital neutropenia Severe Congenital Neutropenia manifests in infancy with life-threatening bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. Kostmann disease (SCN3) has an autosomal recessive inheritance Autosomal recessive inheritance Autosomal Recessive and Autosomal Dominant Inheritance pattern, whereas the most common subtype (SCN1) shows autosomal dominant inheritance Autosomal dominant inheritance Autosomal Recessive and Autosomal Dominant Inheritance. The most common cause is a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the ELANE gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics. The treatment proven to be effective is the administration of granulocyte colony-stimulating factor Granulocyte colony-stimulating factor A glycoprotein of mw 25 kda containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. White Myeloid Cells: Histology, which elevates the decreased neutrophil count.
Chediak-Higashi syndrome ( CHS CHS Cannabinoids): autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder that is caused by mutations affecting a lysosomal trafficking regulator Lysosomal trafficking regulator Chédiak-Higashi Syndrome protein. This protein plays a crucial role in the inability of neutrophils to kill phagocytosed microbes. NK-cell hyporesponsiveness is also noted in some cases. Individuals with CHS CHS Cannabinoids exhibit recurrent pyogenic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, easy bleeding and bruising, and neurologic manifestations.
Chronic granulomatous disease Granulomatous disease A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern. Common Variable Immunodeficiency (CVID) ( CGD CGD Chronic granulomatous disease (CGD), as the name implies, is a chronic disorder that is characterized by granuloma formation. This disorder is a consequence of defective phagocytic cells that are unable to produce bactericidal superoxide because of a defect in nicotinamide adenine dinucleotide phosphate (NADPH), the oxidase responsible for the respiratory burst in phagocytic leukocytes. Chronic Granulomatous Disease): genetic condition characterized by recurrent severe bacterial and fungal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, and granuloma formation. Defective nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes ( NADPH NADPH Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5′-phosphate (nmn) coupled by pyrophosphate linkage to the 5′-phosphate adenosine 2. Pentose Phosphate Pathway) oxidase Oxidase Neisseria (responsible for the respiratory burst Respiratory burst A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent often die as a result of recurrent bacterial infections. Leukocyte Adhesion Deficiency Type 1) in neutrophils and macrophages leads to impaired phagocytosis. Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease commonly affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment the lung, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy. A neutrophil function test, dihydrorhodamine (DHR) 123, is abnormal, and genotyping Genotyping Methods used to determine individuals’ specific alleles or snps (single nucleotide polymorphisms). Polymerase Chain Reaction (PCR) confirms the diagnosis.

References

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