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Interferons

Interferon (IFN) is a cytokine with antiviral Antiviral Antivirals for Hepatitis B properties (it interferes with 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 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). Type I IFNs have been extensively studied; these 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 bind BIND Hyperbilirubinemia of the Newborn to cell-surface 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 when triggered by a viral infection. After stimulation, pathways are activated to produce 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., ribonuclease) that inhibit viral replication. An antiviral Antiviral Antivirals for Hepatitis B state is created in both infected and uninfected cells. Type I IFN also has antitumor properties. The antiviral Antiviral Antivirals for Hepatitis B activity of type II IFN (IFN-ɣ) is not as potent as that of type I, but IFN- ɣ is crucial in macrophage activation Macrophage activation The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (maf) and the macrophage migration-inhibitory factor (mmif), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. IL-12 Receptor Deficiency. The recently discovered IFN-ƛ is noted to have activity against intestinal 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. With a wide range of biologic effects, interferons are used in therapy for malignancies, 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 other immune-related conditions (e.g., multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor).

Last updated: 21 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Interferons are a group of 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 belonging to a class of signaling molecules Signaling molecules Second Messengers known as 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 and are released by a variety of cells during the inflammatory response.

General functions

  • Antiviral Antiviral Antivirals for Hepatitis B 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 (so named because they were found to interfere with viral replication) 
  • Important immunoregulatory 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 affecting cell growth, differentiation, 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 transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription, and translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation
Interferons

Interferons:
Interferons are 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 that are released by cells infected with a 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, 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, and other immune cells. To limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation the infection, responses of cells to interferon include inhibition of protein synthesis Synthesis Polymerase Chain Reaction (PCR), activation of immune cells, and induction of 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.

Image: “Interferons” by OpenStax. License: CC BY 4.0

Types of Interferons

Type I interferons

  • Primarily includes interferon (IFN)-α and IFN-β
  • Most extensively studied
  • Produced by almost all cells, such as fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis, 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, and plasmacytoid dendritic cells Plasmacytoid dendritic cells Innate Immunity: Phagocytes and Antigen Presentation (triggered by viral stimulation of 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)
  • Functions:
    • Prevent viral replication inside cells (creating an antiviral Antiviral Antivirals for Hepatitis B state in both infected and uninfected cells)
    • Increases expression of class I MHC Class I MHC Genetic loci in the vertebrate major histocompatibility complex which encode polymorphic characteristics not related to immune responsiveness or complement activity, e.g., B loci (chicken), dla (dog), gpla (guinea pig), h-2 (mouse), rt-1 (rat), hla-a, -b, and -c class I genes of man. Adaptive Cell-mediated Immunity molecules on virus-infected cells
    • Possesses antitumor responses
    • Induces inhibition of angiogenesis Angiogenesis Bartonella
    • Regulates cell survival and 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

Type II interferon

  • Also known as IFN-γ 
  • Produced by T lymphocytes T lymphocytes 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, natural killer (NK) cells, and macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation
  • IL-12 and IL-2 trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation 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 IFN-γ from 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.
  • Functions:
    • ​​Up-regulates class I and II MHC molecules and promotes the differentiation of naive 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 into 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
    • Important role in macrophage activation Macrophage activation The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (maf) and the macrophage migration-inhibitory factor (mmif), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. IL-12 Receptor Deficiency (↑ phagocytosis Phagocytosis The 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, ↑ microbial killing) and 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
    • Antiviral Antiviral Antivirals for Hepatitis B activity is not as potent as that for type I IFN.
Type iv hypersensitivity_dendritic cells are releasing il-12-lpr

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-γ, which activates macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation 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 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation 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.

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Type III interferon

  • More recently discovered
  • Also known as IFN-ƛ
  • Functions:
    • Mucosal immunity
    • Defense against intestinal 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 (e.g., rotavirus Rotavirus A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. Seven species (rotaviruses A through G) are recognized. Rotavirus, norovirus Norovirus Norovirus is a nonenveloped, single-stranded, positive-sense RNA virus belonging to the Caliciviridae family. Norovirus infections are transmitted via the fecal-oral route or by aerosols from vomiting. The virus is one of the most common causes of nonbacterial gastroenteritis epidemic worldwide. Symptoms include watery and nonbloody diarrhea, nausea, vomiting, and low-grade fever. Norovirus)

Description of types of interferons

Table: Characteristics of types of interferons
Other designation Chromosomal location Cell of origin
IFN-ɑ Intron-A 9p22 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
IFN-β IFN-b2 9p21 Fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis
IFN-ɣ Macrophage activating factor: immune-interferon 12q14 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, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, NK cells NK 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, 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
IFN-ƛ IL-28A, IL-28B, IL-29, IFNA14 19q13.13 Epithelial cells

Effects of Interferons

Induction

  • Strong inducers of IFN include:
    • Type I IFN:
      • 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
      • Double-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
    • Type II IFN:
      • Antigens, mitogens
      • Other interferons
      • 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 (e.g., IL-2)
      • NK 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
    • Type III IFN: 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
  • When induced (e.g., viral entry to a cell), the infected cell or an NK or a T cell produces IFN, sending signals to other cells.
  •  IFN binds to a specific cell-surface receptor Receptor 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 in the uninfected cell:
    • Type I IFN (IFN-ɑ, IFN-β): both bind BIND Hyperbilirubinemia of the Newborn to the same 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 (IFNAR1 and IFNAR2)
    • IFN-ɣ: binds to IFGNR1 and IFNGR2
    • IFN-ƛ: binds to a set of 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 (which are shared with IL-10, IL-28A, IL-28B, and IL-29)

Effects

  • After binding to the receptor Receptor 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 → JAK, STAT signaling pathways activated
  • 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 are instructed to produce 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 inhibit viral replication. 
    • Ribonuclease: degrades mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure
    • Protein kinase: inhibits protein synthesis Synthesis Polymerase Chain Reaction (PCR) (by phosphorylating eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic initiation factor 2 (eIF-2))
    • Oligo(A) synthetase: Oligo(A) activates ribonuclease.
  • When the 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 tries to infect the cell, the 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 perform their functions.
  • The cell dies from the effects (without producing progeny 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), ultimately restricting the spread of infection.
  • IFNs have overlapping biologic effects during the early phase of infection, leading to:
    • Antiviral Antiviral Antivirals for Hepatitis B activity
    • Antiproliferative activity (other 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 are also also down-regulated)
    • Immunoregulatory activity (immune cells such as macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation are activated)
  • The IFNs also have unique functions that have differing effects (e.g.,  IFN-β is used for treatment of multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor, whereas IFN-γ can exacerbate the condition).

Interferons and Diseases

Interferons as treatment

Table: Interferons as treatment
Interferon Condition(s) treated
Interferon-α
  • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C
  • Papillomavirus ( condylomata acuminata Condylomata Acuminata Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts))
  • Hairy cell leukemia Hairy cell leukemia Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias. Hairy Cell Leukemia
  • Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions’s sarcoma
  • Recurrence of melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma
  • Essential thrombocythemia Essential thrombocythemia Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm characterized by the clonal thrombocytosis linked to somatic mutations involving Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL). Patients can be asymptomatic or present with vasomotor symptoms. Essential Thrombocythemia
Interferon-β Multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
Interferon-γ
  • Chronic granulomatous disease Chronic Granulomatous Disease 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 ( 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)
  • Osteopetrosis

Evading interferons

  • 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 have developed mechanisms of evading interferons by:
    • Inhibiting IFN synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Inhibiting the effects of the antiviral Antiviral Antivirals for Hepatitis B 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
    • Blocking IFN signaling
    • Producing decoys to molecules that induce interferon signaling 
    • Encapsidating the genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics
  • Some examples include:
    • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and HIV HIV Anti-HIV Drugs block IFN synthesis Synthesis Polymerase Chain Reaction (PCR).
    • Hepatitis C Hepatitis C Hepatitis 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 reduces interferon-induced 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 production.

Clinical Relevance

  • Viral hepatitis: viral infection of the 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 that causes 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 and damage. Interferon is used as part of the treatment of 2 primary hepatitis 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: B and C. Management of acute hepatitis Acute Hepatitis Autoimmune Hepatitis is typically supportive, whereas for chronic infection, options such as interferon and oral antiviral Antiviral Antivirals for Hepatitis B agents are available. Interferon-ɑ inhibits protein synthesis Synthesis Polymerase Chain Reaction (PCR) via antiviral Antiviral Antivirals for Hepatitis B 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. The medication can cause flu-like symptoms Flu-Like Symptoms Babesia/Babesiosis and elevated 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 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.
  • Multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor ( MS MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis): chronic inflammatory autoimmune disease leading to demyelination Demyelination Multiple Sclerosis of the CNS. The clinical 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 of MS MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis varies depending on the site of lesions, but neurologic symptoms affecting vision Vision Ophthalmic Exam, motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology functions, sensation, and autonomic function are typically seen. Interferon-β is an option among disease-modifying therapies for relapsing MS MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis. Flu-like symptoms Flu-Like Symptoms Babesia/Babesiosis 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 dysfunction are adverse effects.
  • Chronic granulomatous disease Chronic Granulomatous Disease 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 ( 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 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation and macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation leads to impaired phagocytosis Phagocytosis The 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. 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. Prophylactic treatment includes IFN-ɣ. Side effects include 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 and myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus.
  • Hairy cell leukemia Hairy cell leukemia Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias. Hairy Cell Leukemia: rare, chronic B-cell leukemia characterized by the accumulation of small mature B lymphocytes B lymphocytes 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 that have hair-like projections visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis (causing fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans), and 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. Interferon-ɑ is part of the treatment regimen, as it inhibits cell growth and interferes with oncogene and surface antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination expression.

References

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