Type II hypersensitivity, also known as antibody-mediated cytotoxicCytotoxicParvovirus B19 hypersensitivity, is caused by immunoglobulin G (IgGIgGThe major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b.Hypersensitivity Pneumonitis) and IgMIgMA class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin.Immunoglobulins: Types and FunctionsantibodiesAntibodiesImmunoglobulins (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 directed against antigens on cells or extracellular materials. The reaction leads to cytotoxicCytotoxicParvovirus B19 processes involving antibodiesAntibodiesImmunoglobulins (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 and the complement systemComplement systemSerum 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. Interference with the normal cellular operation generating either stimulatory or inhibitory dysfunction is another mechanism that occurs. The inciting antigenAntigenSubstances that are recognized by the immune system and induce an immune reaction.Vaccination can be intrinsic or part of the host cell. Extrinsic antigens such as blood products or medications can provoke a similar reaction. For diagnosis, laboratory tests and invasive procedures are utilized, depending on the system affected. Management of resulting disease ranges from supportive care to antibiotics, immunosuppressive medications, and surgery.
A “hyper” or exaggerated response to what should be considered harmless environmental antigens
Types I, II, and III are immediate reactions occurring within 24 hours.
Type IV reaction develops over several days.
Type II hypersensitivity reaction
Hypersensitivity reaction mediated by immunoglobulin M (IgMIgMA class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin.Immunoglobulins: Types and Functions) and IgGIgGThe major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b.Hypersensitivity PneumonitisantibodiesAntibodiesImmunoglobulins (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 (Ab) that bindBINDHyperbilirubinemia of the Newborn to:
Intrinsic antigens on cell surfaces (e.g., RBCsRBCsErythrocytes, 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) or extracellular materials (e.g., basement membraneBasement membraneA darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers.Thin Basement Membrane Nephropathy (TBMN))
Extrinsic antigens (e.g., blood products, drugs)
Antibody (AB)-antigen complex leads to processes resulting in cell lysis, tissue damage, and/or dysfunction.
Activation of the complement systemComplement systemSerum 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
The following mechanisms are triggered by the binding of Ab-antigen complexes:
Complements: large, distinct proteinsProteinsLinear 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 involved in a sequentialSequentialComputed Tomography (CT) enzyme cascade for host defense
Complement numbers (C1-4) do not indicate the order of activation; they reflect the order of discovery.
Pathways from C1 are mobilized by Ab-antigen complexes → C3 → cleaved to C3a and C3b → C3b cleaves C5 to C5a and C5b
C3a, C4a,and C5a:
Mediators of inflammationInflammationInflammation 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 = anaphylatoxinsAnaphylatoxinsSerum peptides derived from certain cleaved complement proteins during complement activation. They induce smooth muscle contraction; mast cell histamine release; platelet aggregation; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.Innate Immunity: Barriers, Complement, and Cytokines
Mast cellMast cellGranulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor.Angioedema and basophil degranulation
C5a also causes neutrophil chemotaxisChemotaxisThe movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.Leukocyte Adhesion Deficiency Type 1.
C5b and C6, C7, C8, C9:
Membrane attack complex (MAC)
Attaches to cell membraneCell MembraneA cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane and creates ion-permeable channelsChannelsThe Cell: Cell Membrane causing osmotic changes and cell lysis
C3b:
An opsonin (tags antigens for eliminationEliminationThe initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy by phagocytes = opsonization) mediating phagocytosisPhagocytosisThe engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes).Innate Immunity: Phagocytes and Antigen Presentation of target cells
Examples: transfusion reaction, autoimmune hemolytic anemiaAutoimmune Hemolytic AnemiaAutoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self RBCs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia
Antibody-dependent cell-mediated cytotoxicityAntibody-Dependent Cell-Mediated CytotoxicityThe phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface immunoglobulin G whose Fc portion is intact. The effector cell is a ‘killer’ cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Humoral Adaptive Immunity (ADCCADCCThe phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface immunoglobulin G whose Fc portion is intact. The effector cell is a ‘killer’ cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Humoral Adaptive Immunity)
AntibodiesAntibodiesImmunoglobulins (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, or opsonins, bindBINDHyperbilirubinemia of the Newborn their antigen-binding fragment (FabFabUnivalent antigen-binding fragments composed of one entire immunoglobulin light chain and the amino terminal end of one of the immunoglobulin heavy chains from the hinge region, linked to each other by disulfide bonds. Fab contains the immunoglobulin variable regions, which are part of the antigen-binding site, and the first immunoglobulin constant regions. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme papain.Immunoglobulins: Types and Functions) sites to antigensand tag them for phagocytosisPhagocytosisThe engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes).Innate Immunity: Phagocytes and Antigen Presentation.
If antigen-Ab complexes are too large to be phagocytosed, Fc-receptor–bearing effector cellsEffector cellsCells have been activated by a matching antigenAdaptive Immune Response, mainly natural killer (NK) cells,are recruited.
NK cellsNK cellsA 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: HistologybindBINDHyperbilirubinemia of the Newborn to FcFcCrystallizable fragments composed of the carboxy-terminal halves of both immunoglobulin heavy chains linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (complement fixation, binding to the cell membrane via fc receptors, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme papain.Immunoglobulins: Types and FunctionsreceptorReceptorReceptors 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 Ab→ release toxic granules into cells → perforinPerforinA 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 and granzymesGranzymesA 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 boreholes in membrane → cell lysis
Examples: transplant rejection, immune reaction against neoplasm
Antibody-mediated cellular dysfunction
Non-cytotoxic; cell function impaired without cell injuryCell injuryThe cell undergoes a variety of changes in response to injury, which may or may not lead to cell death. Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Cell Injury and Death or inflammationInflammationInflammation 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
AutoantibodiesAutoantibodiesAntibodies that react with self-antigens (autoantigens) of the organism that produced them.Blotting TechniquesbindBINDHyperbilirubinemia of the Newborn to cell-surface receptorsReceptorsReceptors 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.Receptorsto produce an abnormal activation/blockade of the signaling process.
Examples:
Myasthenia gravisMyasthenia GravisMyasthenia 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 (Ab causes blockade of acetylcholineAcetylcholineA neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Receptors and Neurotransmitters of the CNSreceptorReceptorReceptors 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)
Graves’ diseaseGraves’ diseaseA common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy).Thyrotoxicosis and Hyperthyroidism (Ab causes stimulation of thyroidThyroidThe thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck.Thyroid Gland: Anatomy stimulating hormone (TSH) receptorReceptorReceptors 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)
Pernicious anemiaPernicious anemiaA megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor.Megaloblastic Anemia (Ab against intrinsic factorIntrinsic factorA glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to vitamin B12 deficiency and anemia, pernicious.Gastritis)
Type II hypersensitivity can result from the following conditions:
Transfusion reactionsTransfusion reactionsTransfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions (ABO or blood group incompatibility)
Blood group ABlood group ABlood Group Systems or O recipient would react with a type AB or B donor (due to the presence of anti-B antibodiesAntibodiesImmunoglobulins (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)
Blood group BBlood group BBlood Group Systems or O recipient would react with type A or AB donor (due to the presence of anti-A antibodiesAntibodiesImmunoglobulins (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)
Symptoms: feverFeverFever 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, itching, urticariaUrticariaUrticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation.Urticaria (Hives); serious reaction results in respiratory distress and hypotensionHypotensionHypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
Transfusion reactions induced by type II hypersensitivity reactions. This diagram shows blood type groups and their corresponding antibodies and antigens.
Image by Lecturio.
Autoimmune hemolytic anemiaAutoimmune Hemolytic AnemiaAutoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self RBCs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia (against RBCsRBCsErythrocytes, 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)
Manifested by weakness, shortness of breathShortness of breathDyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary).Dyspnea, pallor from anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types to jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, icterusIcterusA clinical manifestation of hyperbilirubinemia, characterized by the yellowish staining of the skin, mucous membranes, and sclera. Clinical jaundice usually is a sign of liver dysfunction.Jaundice, dark urine from hemolysis
Pernicious anemiaPernicious anemiaA megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor.Megaloblastic Anemia (against intrinsic factorIntrinsic factorA glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to vitamin B12 deficiency and anemia, pernicious.Gastritis)
Ab prevents absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of vitamin B12, causing B12 deficiency anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types.
B12 deficiency can lead to general symptoms of anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, glossitis, paresthesiasParesthesiasSubjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.Posterior Cord Syndrome, gaitGaitManner or style of walking.Neurological Examination problems.
Hemolytic disease of the fetusHemolytic disease of the fetusHemolytic disease of the fetus and newborn (HDFN), also known as erythroblastosis fetalis, is caused by maternal IgG antibody destruction of the fetal RBCs. Rhesus (Rh) blood group incompatibility (frequently triggered by D antigen) and ABO incompatibility are common causes. Hemolytic Disease of the Fetus and Newborn and newbornNewbornAn infant during the first 28 days after birth.Physical Examination of the Newborn (against RBCsRBCsErythrocytes, 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; RhD incompatibility)
First pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care: Rhesus-negative woman conceives a rhesus-positive fetus.
Labor: During labor, fetal RBCsRBCsErythrocytes, 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 leak into the mother.
Postpartum: Fetal RBCsRBCsErythrocytes, 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 survive long enough to elicit an IgGIgGThe major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b.Hypersensitivity Pneumonitis response.
Second pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care: Maternal anti-D antibodiesAntibodiesImmunoglobulins (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 cross the placentaPlacentaA highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones).Placenta, Umbilical Cord, and Amniotic Cavity and attack fetal RBCsRBCsErythrocytes, 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 of the second rhesus-positive fetus.
Newborns may present with self-limitingSelf-LimitingMeningitis in Childrenhemolytic anemiaHemolytic AnemiaHemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia to hydropsHydropsCholecystitis fetalis (severe anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, skinSkinThe 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 FunctionsedemaEdemaEdema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, ascitesAscitesAscites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection).Ascites, pulmonary/pericardial effusionPericardial effusionFluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade.Pericardial Effusion and Cardiac Tamponade).
Autoimmune thrombocytopenic purpura
Phagocytes destroy sensitized plateletsPlateletsPlatelets 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 in the blood.
Acute rheumatic feverRheumatic feverAcute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis. Acute rheumatic fever usually occurs 2-4 weeks after an untreated infection and affects the heart, skin, joints, and nervous system. Rheumatic Fever
AntibodiesAntibodiesImmunoglobulins (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 against the cell wallCell wallThe outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents.Cell Types: Eukaryotic versus Prokaryotic of StreptococcusStreptococcusStreptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci.Streptococcus also react with the myocardiumMyocardiumThe muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow.Heart: Anatomy.
Goodpasture syndromeGoodpasture SyndromeGoodpasture 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
AntibodiesAntibodiesImmunoglobulins (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 attack antigens in the basement membraneBasement membraneA darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers.Thin Basement Membrane Nephropathy (TBMN) of alveoliAlveoliSmall polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place.Acute Respiratory Distress Syndrome (ARDS) (pulmonary hemorrhage) and kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy (nephritis).
Initially presents with systemic complaints, followed by renal (hematuriaHematuriaPresence of blood in the urine.Renal Cell Carcinoma) and pulmonary symptoms (dyspneaDyspneaDyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, hemoptysisHemoptysisHemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis, cough)
Graves’ diseaseGraves’ diseaseA common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy).Thyrotoxicosis and Hyperthyroidism
TSH-receptor antibodiesAntibodiesImmunoglobulins (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 stimulate the thyroidThyroidThe thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck.Thyroid Gland: Anatomy gland to produce free T4T4The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism.Thyroid Hormones and T3T3A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3.Thyroid Hormones without TSH.
GoiterGoiterA goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter, exophthalmos on exam with symptoms such as heatHeatInflammation intolerance, anxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder, tremors, palpitationsPalpitationsEbstein’s Anomaly, weight lossWeight lossDecrease in existing body weight.Bariatric Surgery.
Myasthenia gravisMyasthenia GravisMyasthenia 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
AntibodiesAntibodiesImmunoglobulins (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 inhibit the binding of acetylcholineAcetylcholineA neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Receptors and Neurotransmitters of the CNS to the nicotinic acetylcholineAcetylcholineA neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Receptors and Neurotransmitters of the CNSreceptorReceptorReceptors 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.
AntibodiesAntibodiesImmunoglobulins (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 also activate complement-mediated receptorReceptorReceptors 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 destruction.
Fluctuating muscle weakness, worse at the end of the day or after exercise (ptosisPtosisCranial Nerve Palsies, diplopiaDiplopiaA visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe.Myasthenia Gravis, fatigable chewing, limb weakness)
Respiratory muscle weaknessRespiratory muscle weaknessRespiratory Acidosis leads to respiratory failureRespiratory failureRespiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure (myasthenia crisis).
Mechanism of Graves’ disease (left) and Myasthenia gravis (right), both caused by type II hypersensitivity mechanism.
Diagnosis and management vary depending on the manifestations, organ system involved, and severity of impairment produced by the reaction.
Transfusion reactionsTransfusion reactionsTransfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions
Diagnosis: clinical; Coombs test
Management: cessation of transfusion, repeat of blood typing and crossmatchingCrossmatchingTesting erythrocytes to determine presence or absence of blood-group antigens, testing of serum to determine the presence or absence of antibodies to these antigens, and selecting biocompatible blood by crossmatching samples from the donor against samples from the recipient. Crossmatching is performed prior to transfusion.Transfusion Reactions and supportive care (disseminated intravascular coagulationDisseminated intravascular coagulationDisseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation (DICDICDisseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation) work-up depending on severity of reaction)
Autoimmune hemolytic anemiaAutoimmune Hemolytic AnemiaAutoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self RBCs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia
Diagnosis: hemolysis work-up; Coombs test
Management (first-line): glucocorticoidsGlucocorticoidsGlucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs.Glucocorticoids; treat the underlying condition
Refractory cases may require immunosuppressive drugsImmunosuppressive drugsAgents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging.Organ Transplantation, splenectomySplenectomySurgical procedure involving either partial or entire removal of the spleen.Rupture of the Spleen.
Pernicious anemiaPernicious anemiaA megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor.Megaloblastic Anemia
Diagnosis: CBC, B12, folateFolateFolate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 level with confirmatory tests if with borderline levels
Management: B12 supplementation
Hemolytic disease of the fetusHemolytic disease of the fetusHemolytic disease of the fetus and newborn (HDFN), also known as erythroblastosis fetalis, is caused by maternal IgG antibody destruction of the fetal RBCs. Rhesus (Rh) blood group incompatibility (frequently triggered by D antigen) and ABO incompatibility are common causes. Hemolytic Disease of the Fetus and Newborn and newbornNewbornAn infant during the first 28 days after birth.Physical Examination of the Newborn
Diagnosis: pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care history, maternal antibodiesAntibodiesImmunoglobulins (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, ultrasound, fetal lab tests
Prevention:anti-RhD at 28 weeks’ gestation and within 72 hours of birth
Autoimmune thrombocytopenic purpura
Diagnosis: clinical with CBC, peripheral smear, HIVHIVAnti-HIV Drugs, hepatitis CHepatitis CHepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC).Hepatitis C Virus, and other tests based on history
Goal of management: prevent clinically important bleeding
If with bleeding, management may include: platelet transfusion, intravenous immunoglobulin (IVIGIVIGDermatomyositis), glucocorticoidsGlucocorticoidsGlucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs.Glucocorticoids
Acute rheumatic feverRheumatic feverAcute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis. Acute rheumatic fever usually occurs 2-4 weeks after an untreated infection and affects the heart, skin, joints, and nervous system. Rheumatic Fever
Management: antibiotics for StreptococcusStreptococcusStreptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci.Streptococcus and supportive care
Goodpasture syndromeGoodpasture SyndromeGoodpasture 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
Diagnosis: clinical along with labs (antineutrophil cytoplasmic antibodiesAntibodiesImmunoglobulins (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 (ANCAANCAGroup of systemic vasculitis with a strong association with anca. The disorders are characterized by necrotizing inflammation of small and medium size vessels, with little or no immune-complex deposits in vessel walls.Rapidly Progressive Glomerulonephritis), anti-glomerular basement membraneBasement membraneA darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers.Thin Basement Membrane Nephropathy (TBMN) (anti-GBM) Ab), renal biopsyRenal BiopsyAntineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
Management: plasmapheresisPlasmapheresisProcedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use.Stevens-Johnson Syndrome and immunosuppressive therapy
Graves’ diseaseGraves’ diseaseA common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy).Thyrotoxicosis and Hyperthyroidism
Diagnosis: TSH-receptor Ab confirms diagnosis; thyroid function testsThyroid Function TestsBlood tests used to evaluate the functioning of the thyroid gland.Ion Channel Myopathy
Management: symptom control (beta-blockersBeta-blockersDrugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Class 2 Antiarrhythmic Drugs (Beta Blockers)) and reduction of thyroidThyroidThe thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck.Thyroid Gland: Anatomy hormone synthesisSynthesisPolymerase Chain Reaction (PCR) (antithyroid drugs, radioiodine, or thyroidectomyThyroidectomySurgical removal of the thyroid gland.Goiter)
Myasthenia gravisMyasthenia GravisMyasthenia 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
Diagnosis: single-fiber electromyographyElectromyographyRecording of the changes in electric potential of muscle by means of surface or needle electrodes.Becker Muscular Dystrophy (most sensitive) and immunologic studies
Management: pyridostigminePyridostigmineA cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.Cholinomimetic Drugs, immunotherapies, and thymectomyThymectomySurgical removal of the thymus gland.Myasthenia Gravis