Outline of immunology

Immunology
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The following outline is provided as an overview of and topical guide to immunology:

Immunology is the study of all aspects of the immune system in all organisms.^[1] It deals with the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo.

Essence of immunology[]

Immunology

• Branch of Biomedical science
• Immune system
• Immunity

Branches of immunology[]

• Classical immunology
• Clinical immunology
• Computational immunology
• Diagnostic immunology
• Evolutionary immunology
• Systems immunology
• Immunomics
• Immunoproteomics
• Immunophysics
• Immunochemistry
• Ecoimmunology
• Immunopathology
• Nutritional immunology
• Psychoneuroimmunology
• Reproductive immunology
• Immunotoxicology
• Palaeoimmunology

• Testicular immunology - Testes
• Immunodermatology - Skin
• Intravascular immunology - Blood
• Osteoimmunology - Bone
• Mucosal immunology - Mucosal surfaces

• Respiratory tract antimicrobial defense system - Respiratory tract

• Neuroimmunology - Neuroimmune system in the Central nervous system
• - Ocular immune system in the Eye
• Cancer immunology/Immunooncology - Tumors

History of immunology[]

History of immunology

• Timeline of immunology

General immunological concepts[]

• Immunity:

• Immunity against:

• Pathogens
  • Pathogenic bacteria
  • Viruses
  • Fungi
  • Protozoa
• Parasites
• Tumors
• Allergens
• Self-proteins

• Autoimmunity
• Alloimmunity
• Cross-reactivity

• Tolerance

• Central tolerance
• Peripheral tolerance
• Clonal anergy
• Clonal deletion
• Tolerance in pregnancy
• Immunodeficiency

• Antigen

• Antigenicity
• Immunogen
• Superantigen
• Allergen
• Hapten
• Epitope

• Linear
• Conformational
• Mimotope

• Tumor antigen
• Antigen-antibody interaction

• Immunogenetics

• Affinity maturation

• Somatic hypermutation
• Clonal selection

• V(D)J recombination

• Artemis complex
• Recombination-activating gene

• RAG1
• RAG2

• Recombination signal sequences

• Junctional diversity
• Immunoglobulin class switching
• Allelic exclusion
• Polyclonal response

• Phagocytosis

• Opsonin

• Intrinsic immunity
• Leukocyte extravasation
• Cross-presentation
• Immune repertoire
• Original antigenic sin
• Antigen presentation
• Immunological synapse
• Co-stimulation

Components of the immune system[]

Immune system

  Adaptive immune system[]

Adaptive immune system

• Humoral immunity

• Antibodies

• Kinds of antibodies

• Monoclonal antibodies
• Polyclonal antibodies
• Autoantibody
• Microantibody
• Neutralizing antibody

• Classification

• Allotype
• Isotype
• Idiotype

• Functions

• Antibody opsonization
• Neutralisation

• Regions

• Paratope
• Complementarity-determining region (CDRs)
• Hypervariable region
• Framework region
• Fab Region
• Fc Region

• Polyclonal B cell response

• Cell-mediated immunity

  Innate immune system[]

Innate immune system

• Complement system

• Classical complement pathway
• Mannan-binding lectin pathway
• Alternate complement pathway
• Complement membrane attack complex

• Surface barriers – Physical or chemical barriers that prevent infection (i.e. skin, tears, mucus, saliva, Gastric acid, etc.)

• Antimicrobial peptides
• Defensins
• Lysozyme

• Inflammation

• Inflammatory reflex
• Inflammasome
• Granuloma
• Acute-phase proteins

• Amyloid

• Positive

• Negative

Organs of the immune system[]

Lymphatic system

  Primary lymphoid organs[]

Primary lymphoid organs

• Thymus - Site of T cell maturation
• Bone marrow - Site of haematopoiesis and B cell maturation

  Secondary lymphoid organs[]

Secondary lymphoid organs

• Spleen
  • White pulp
  • Red pulp
  • Marginal zone
• Lymph nodes
• Mucosa-associated lymphoid tissue

• Gut-associated lymphoid tissue
• Bronchus-associated lymphoid tissue

Cells of the immune system[]

White blood cells

  Myeloid cells[]

Main articles: Myeloid cells and Phagocytes

See also: Sentinel cell

• Granulocytes
  • Neutrophils
  • Eosinophils
  • Basophils
  • Mast cells
• Monocytes
• Macrophages

• Histiocytes (Tissue resident macrophages)

• Adipose tissue macrophages
• Kupffer cell - Liver
• Alveolar macrophage (Dust cell) - Lung
• Langerhans cell - Skin
• - Dermis
• Microglia - CNS
• - Meninges
• Hofbauer cell - Placenta
• Osteoclasts - Bone
• - Bone marrow
• - Spleen
• - Spleen
• - Splenic red pulp
• Tingible body macrophage (White pulp macrophage) - Splenic white pulp

• Giant cells

• Foreign-body giant cell
• Langhans giant cell
• Touton giant cells

• Epithelioid cells
• Bone marrow-derived macrophages - Generated in vitro

• Dendritic Cells

• Conventional Dendritic Cells
• Plasmacytoid dendritic cells

  Lymphoid cells[]

Lymphoid cells

• B cells
  • Plasma B cells
  • Memory B cells
  • B-1 cells
  • (the conventional B cells most texts refer to)
  • Marginal-zone B cells
  • Follicular B cells
• T cells
  • Naive T cells
  • Helper T cells - Commonly termed CD4+ T cells
    • Th1 cells
    • Th2 cells
    • Th3 cells
    • Th17 cells
    • T_FH cells - Follicular helper T cells
  • Cytotoxic T cells - Commonly termed CD8+ T cells
  • Memory T cells
  • Regulatory T cells
  • Natural Killer T cells (NKT cells)
  • γδ T cells
  • Mucosal associated invariant T cells
• Innate lymphoid cells (ILC)
  • Group 1 ILC
    • Natural killer cells (NK cells)
  • Group 2 ILC
    • Nuocyte
  • Group 3 ILC
    • (LTi cells)

  Others[]

(Non-hematopoietic cells with immune functions)

• Stromal cells

• Lymph node stromal cells
• Follicular dendritic cells

• Epithelial cells
• Pericytes
• Microfold cells (M cells)

  Hematopoiesis[]

Main articles: Hematopoiesis and Hematopoietic stem cell

See also: Leukopoiesis, Extramedullary hematopoiesis, and Cellular differentiation

• Lymphopoiesis

• Lymphoblast
• Prolymphocyte

• Thymocyte

• Large pre-B cell

• Myelopoiesis

• Common myeloid progenitor (CFU-GEMM)

• Granulocyte-macrophage progenitor (CFU-GM)

• Granulopoiesis

• Myeloblast (CFU-G)
• Promyelocyte
• Myelocyte
• Metamyelocyte
• Band cell

• Monocytopoiesis

• Monoblast (CFU-M)

• CFU-DL - Dendritic cell / Langerhans cell precursor

• Promonocyte

• CFU-Baso (Basophil precursor)
• CFU-Eos (Eosinophil precursor)
• Megakaryocyte-erythroid progenitor cell (MEP)

• Megakaryocytopoiesis

• CFU-Meg
• Megakaryoblast
• Promegakaryocyte
• Megakaryocyte
• Thrombopoiesis

• Thrombocyte (Platelets)

• Erythropoiesis

• Proerythroblast
• Normoblast
• Reticulocyte

• CFU-Mast

Molecules of the immune system[]

Immune receptors[]

   Antigen receptors[]

• B cells

• Antigen receptor - B cell receptor (BCR)
• Subunits- Immunoglobulin heavy chain / Immunoglobulin light chain
• Co-receptors

• Stimulatory

• CD21
• CD19
• CD81

• Inhibitory

• CD22

• Accessory molecule (CD79)

• Ig-α (CD79A)
• Ig-β (CD79B)

• T cells

• Antigen receptor - T cell receptor (TCR)

• Subunits - TRA@ / / TRD@ / TRG@

• Co-receptors

• CD8 (CD8α / )
• CD4

• Accessory molecules

• CD3

• Subunits - one CD3γ / one CD3δ / two CD3ε

• ζ-chain (CD247, CD3ζ, TCRζ)

   Pattern recognition receptors (PRRs)[]

Pattern recognition receptor

• Membrane-bound PRRs

• Toll-like receptors (TLRs)

• C-type lectin receptors (CLRs) ^[2][3]

See also: C-type lectin

• Group 1 CLRs - Mannose receptors

• Group 2 CLRs - Asialoglycoprotein receptor family

• Dectin 1 subfamily

• DCIR subfamily

• Scavenger receptors

• Class A - Trimers

• Class B - Two transmembrane domains

• Others

• Formyl peptide receptors (FPRs)

• Cytoplasmic PRRs

• NOD-like receptors (NLRs)

• NLRA (A for acidic transactivating domain)

• CIITA

• NLRB (B for BIR, or Inhibitor of apoptosis domain)

• NAIP

• NLRC (C for CARD domain)

• NLRP (P for Pyrin domain)

• NLRX

• NLRX1

• RIG-I-like receptors (RLRs) - Intracellular sensors of viral replication by direct interaction with dsRNA

• Complement system (see complement proteins section)
• Collectins

• Peptidoglycan recognition proteins (PGRPs)^[4]

• Ficolins

   Complement receptors[]

Complement receptor

• CR1 (CD35)
• CR2 (CD21)
• CR3 - Heterodimer: CD11b / CD18
• CR4 - Heterodimer: CD11c / CD18
• CRIg (Complement receptor of the immunoglobulin family)
• Anaphylatoxin receptors

• C3a receptor
• C5a receptor (CD88)
• C5AR2

   Fc receptors[]

Fc receptor

• Fc-gamma receptors (FcγR)

• FcγRI (CD64)
• FcγRIIA (CD32A)
• FcγRIIB (CD32B)
• FcγRIIIA (CD16a)
• FcγRIIIB (CD16b)
• FcγRT (Neonatal Fc receptor)

• Fc-alpha receptors (FcαR)

• FcαRI (CD89, FCAR)
• Fcα/μR

• Fc-epsilon receptors (FcεR)

• FcεRI - Tetramer: FCER1A / FCER1B / two FCER1G
• FcεRII (CD23)

• Secreted Fc receptors

• Polymeric immunoglobulin receptor (poly-Ig)

• Fc receptor-like molecules

   Cytokine receptors[]

Cytokine receptor

• Type I cytokine receptors (Hemopoietin receptors) - Share extracellular WSXWS motif, Grouped by common receptor subunits

• Common gamma chain (γ-chain, CD132)

• IL2R - Heterotrimer: IL2RA (CD25) / IL2RB (CD122) / γ_c
• IL4R / IL13R - Heterodimer: IL4RA / (IL13RA1/IL13RA2)
• IL7R - Heterodimer: IL7RA (CD127) / γ-chain
• IL9R - Heterodimer: IL9R / γ-chain
• IL15R - Heterotrimer: IL15RA / IL2RB / γ-chain
• IL21R - Heterodimer: IL21R / γ-chain

• Common beta chain (β-chain, CD131)

• IL3R - Heterodimer: IL3RA / β-chain
• IL5R - Heterodimer: IL5RA / β-chain
• GM-CSFR (CD116) - Heterdimer: GM-CSFRA / β-chain

• Common gp130 subunit (gp130, CD130)

• IL6R - Heterodimer: IL6RA / gp130
• IL11R - Heterodimer: IL11RA / gp130
• IL27R - Heterodimer: IL27RA / gp130
• OSMR - Heterodimer: OSMR / gp130
• LIFR (CD118) - Heterodimer: LIFR / gp130

• IL12 receptor beta 1 subunit (IL12RB1)

• IL12R - Heterodimer: IL12RB1 / IL12RB2
• IL23R - Heterodimer: IL23RA / IL12RB1

• Others

• EPOR (Erythropoietin receptor) - Homodimer
• G-CSFR (CD114) - Homodimer upon ligand binding
• MPL (CD110, Thrombopoietin receptor) - Homodimer upon ligand binding
• GHR (Growth hormone receptor) - Homodimer upon ligand binding
• PRLR (Prolactin receptor)

• Type II cytokine receptor - Lack WSXWS motif

• Interferon receptors

• Interferon-α/β receptor (IFNAR) - Heterodimer: IFNAR1 / IFNAR2
• Interferon-γ receptor (IFNGR) - Heterodimer: IFNGR1 / IFNGR2

• Interleukin receptors

• IL10R - Heterodimer: IL10RA / IL10RB
• IL20R - Heterodimer: IL20RA / IL20RB
• IL22R - Heterodimer: IL22RA1 / IL10RB
• IL28R - Heterodimer: IL28RA / IL10RB

• Immunoglobulin superfamily (Some members)

• CSF1
• CD117 (c-KIT)
• IL1 receptor family (IL1R)

• IL1R type 1 (CD121a)
• IL1R type 2 (CD121b)
• IL1R accessory protein (IL1RAP)
• IL1RL1 (IL33R, ST2)

• IL18R - Heterodimer: IL18R1 / IL18RAP

• IL17 family

• IL17RA
• IL17RB
• IL17RC
• IL17RD

• Tumor necrosis factor (TNF) receptor family - Trimeric cytokine receptors

• Chemokine receptors - 7-transmembrane G protein-coupled receptors

• CC chemokine receptors (CCRs)

• CXC chemokine receptors (CXCRs)

• (XCRs)

• XCR1

• (CX₃CRs)

• CX₃CR1 (Fractalkine receptor)

• TGF beta receptors - Single transmembrane pass serine/threonine kinase receptors

• TGFBR1
• TGFBR2
• TGFBR3

   Natural killer cell receptors[]

Natural killer cell receptors

• Killer activation receptors (KARs)

• (NCRs)

• receptors (NKG2s)

• Activating KIRs

• KIR2DS1

• Killer inhibitory receptors (KIRs)

• Two domains, long cytoplasmic tail

• Two domains, short cytoplasmic tail

• Three domains, long cytoplasmic tail

• Three domains, short cytoplasmic tail

   Others[]

• Leukocyte immunoglobulin-like receptors (LILRs)

• Eicosanoid receptors

Antibodies[]

Antibodies

• Immunoglobulin A (IgA)
  • IgA1
  • IgA2
• Immunoglobulin D (IgD)
• Immunoglobulin E (IgE)
• Immunoglobulin G (IgG)
  • IgG1
  • IgG2
  • IgG3
  • IgG4
• Immunoglobulin M (IgM)

Cytokines[]

Cytokine

• Chemokines

See also: Chemotaxis

• CC chemokines

• CXC chemokines

• C chemokines

• XCL1
• XCL2

• CX₃C chemokines

• CX₃CL1 (Fractalkine, Neurotactin)

• Interferons
  • Interferon type I
    • IFN-α
    • IFN-β
    • IFN-ω
  • Interferon type II
    • IFN-γ
• Interleukins

• Tumor necrosis factors

• Colony stimulating factors

• CSF1 (M-CSF)
• CSF2 (GM-CSF)
• CSF3 (G-CSF)

MHCs[]

Major histocompatibility complex

• MHC class I

• MHC class II

Complement proteins[]

• Early stage (divided by pathway)

• Classical complement pathway

• C1Q complex - C1R / C1S
• C4 - C4a
• C2

• Mannan-binding lectin pathway

• MASP1 / MASP2
• Mannan-binding lectin

• Alternative complement pathway

• Factor B
• Factor D
• Factor P (Properdin)

• Middle stage

• C3 - C3a / C3b / iC3b
• C5 - C5a
• C3-convertase
• C5-convertase

• Late stage

• Membrane attack complex (MAC)

• C6
• C7
• C8
• C9

• Complement pathway inhibitors

• C1-inhibitor - Classical, Lectin, Alternate
• Decay-accelerating factor (CD59) - Classical, Lectin, Alternate
• Factor I - Classical, Lectin, Alternate
• C4BP - Classical, Lectin
• Factor H - Alternate

Antimicrobial peptides[]

Antimicrobial peptides

Transcription factors[]

• NF-κB
• AP-1
• Interferon regulatory factors (IRF)
• NFAT

• T-bet - T_H1 differentiation
• GATA3 - T_H2 differentiation
• RORγT - T_H17 differentiation
• BCL6 - T_FH differentiation
• FoxP3 - T_reg differentiation

Signaling pathways[]

• JAK-STAT signaling pathway

• TGF beta signaling pathway
• TLR signalling pathway

Cell adhesion molecules (CAMs)[]

Cell adhesion molecules

• Integrins - Obligate heterodimers of one alpha and one beta subunits

• Alpha subunits

• Beta subunits

• Dimers

• Cytoadhesin receptor

• Glycoprotein IIb/IIIa - Heterodimer: ITGA2B / ITGB3

• Fibrinogen receptor

• Macrophage-1 antigen (CR3) - Heterodimer: CD11b / CD18

• Fibronectin receptor:

• Integrin alpha4beta1

• Leukocyte-adhesion receptor:

• LFA-1 - Heterodimer: CD11a / CD18
• Macrophage-1 antigen (CR3) - Heterodimer: CD11b / CD18
• Integrin alphaXbeta2 (CR4) - Heterodimer: CD11c / CD18

• Very late antigen receptor:

• VLA-4 - Heterodimer: CD49d / CD29
• Alpha-5 beta-1

• Vitronectin receptor:

• Alpha-v beta-3
• Alpha-v beta-5

• Immunoglobulin superfamily CAMs

• - Synaptic cell adhesion molecules
• NCAMs - Neural cell adhesion molecules
• Intercellular adhesion molecules (ICAMs)

• VCAM-1 (CD106)
• PECAM-1 (CD31)
• L1 family

• SIGLEC family - Sialic acid binding lectins

• Nectins

• CD2
• CD58
• Signaling lymphocytic activation molecules (SLAMs)

• Cadherins
• Selectins

• E-selectin
• L-selectin
• P-selectin

• Others

• Lymphocyte homing receptors

• CD34
• GLYCAM-1
• Addressin (MAdCAM-1)

• CD44
• Carcinoembryonic antigens

• CD24
• CD44
• CD146
• CD164

Others[]

• CD69
• Sphingosine-1-phosphate receptors

• CD80 - Expressed by APCs
• CD86 - Expressed by APCs

• CD28 - Expressed by T Cells
• CD278 (ICOS) - Homodimer, expressed by T Cells
• CTLA-4 (CD152)
• PD-1 (CD279)

Immune system disorders[]

Immune disorder

Hypersensitivity and Allergy[]

• Type 1 hypersensitivity / Allergy / Atopy

• Foreign (Allergen)

• Atopic eczema
• Allergic urticaria
• Allergic rhinitis (Hay fever)
• Allergic asthma
• Anaphylaxis
• Food allergy

• Milk allergy
• Egg allergy
• Peanut allergy
• Tree nut allergy
• Seafood allergy
• Soy allergy
• Wheat allergy
• Garlic allergy

• Penicillin allergy

• Type 2 hypersensitivity / Antibody-dependent cell-mediated cytotoxicity (ADCC)

• Foreign

• Pernicious anemia
• Hemolytic disease of the newborn

• Autoimmune

• Cytotoxic

• Autoimmune hemolytic anemia
• Idiopathic thrombocytopenic purpura
• Bullous pemphigoid
• Pemphigus vulgaris
• Rheumatic fever
• Goodpasture's syndrome

• Type 5 / Receptor mediated

• Graves' disease
• Myasthenia gravis

• Type 3 hypersensitivity / Immune complex

• Foreign

• Henoch–Schönlein purpura
• Hypersensitivity vasculitis
• Reactive arthritis
• Farmer's lung
• Post-streptococcal glomerulonephritis
• Serum sickness
• Arthus reaction

• Autoimmune

• Systemic lupus erythematosus
• Subacute bacterial endocarditis
• Rheumatoid arthritis

• Type 4 hypersensitivity (Delayed-Type Hypersensitivity)

• Foreign

• Allergic contact dermatitis
• Mantoux test

• Autoimmune

• Diabetes mellitus type 1
• Hashimoto's thyroiditis
• Guillain–Barré syndrome
• Multiple sclerosis
• Coeliac disease
• Giant-cell arteritis

• GVHD (Graft-versus-host disease)

• Transfusion-associated graft versus host disease

• Unknown/Multiple types

• Foreign

• Hypersensitivity pneumonitis
• Allergic bronchopulmonary aspergillosis
• Transplant rejection
• Latex allergy (I+IV)

• Autoimmune

• Sjögren's syndrome
• Autoimmune hepatitis
• Autoimmune polyendocrine syndrome ( / APS2)
• Autoimmune adrenalitis
• Systemic autoimmune disease

Immunodeficiency[]

Immunodeficiency

• Primary immunodeficiency
• Acquired immunodeficiency
• Complement deficiency

Cancers of the immune system[]

Myeloid diseases[]

Inflammatory diseases[]

• Sepsis
• Inflammatory bowel disease (IBD)
• Cytokine storm

Immunoproliferative immunoglobulin disorders[]

Immunoproliferative immunoglobulin disorders

Lymphatic organ disease[]

Immunologic techniques and tests[]

• Flow cytometry
• Mass cytometry
• Histology
• Adoptive cell transfer
• Experiments in immunology
• Genetically modified mouse
• Immunofluorescence
• Immunofixation
• Immunoadsorption
• MHC multimer
• Hybridoma technology

• Rabbit hybridoma
• Developmental studies hybridoma bank

Immunology and health[]

• Prevention
• Immunostimulants
• Immunotherapy

• Activation immunotherapy

• Cancer immunotherapy
• Autologous immune enhancement therapy

• Immunosuppression

• Sublingual immunotherapy
• Allergen immunotherapy
• Immunosuppressive drug

• Artificial induction of immunity
• Immunization

• Active immunotherapy
• Passive immunity

• Adoptive immunity

• Vaccination

• Vaccine-naive
• Vaccine
• Herd immunity
• Adjuvant

• Organ transplantation

• Allotransplant
• Transplant rejection

Immunologists[]

List of immunologists

Immunology lists[]

• List of autoimmune diseases
• List of immunologists
• List of viruses
• List of human clusters of differentiation
• List of vaccine ingredients
• List of allergens

References[]

External links[]

• BMC: Immunology- BioMed Central:Immunology is an open access journal publishing original peer-reviewed research articles.
• Nature Reviews Immunology (journal home)
• Janeway's Immunobiology textbook Searchable free online version at the National Center for Biotechnology Information
• Overview at Medical College of Georgia
• MUGEN NoE murine models for immunological disease
• Transplantation Immunology^{[permanent dead link]} Interesting web site made by the faculty of medicine of the University of Geneva dealing with the immunological issues linked with the transplantation of materials genetically different between donor and recipient (hematopoietical stem cells, organs or the transfusion of blood).
• Online lectures in immunology University of South Carolina
• BRT-Burleson Research Technologies Tests the effects of pharmaceuticals in the developmental stage on the immune system.