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Adaptive immune system

Last updated: December 22, 2020

Summary

Adaptive (acquired) immunity is a part of the immune system that provides an antigen-specific response following exposure to a microbial pathogen or foreign substance (e.g., antigen). The adaptive immune system primarily involves B cells, T cells, and circulating antibodies, all of which mount a targeted immune response to a particular antigen/invading pathogen. An important component of adaptive immunity is immunologic memory, a mechanism by which the immune system forms memory B cells and memory T cells. These cells are able to trigger a more rapid and extensive response following subsequent antigen exposure. Adaptive immunity can be conferred via vaccination, which induces immunity through selective exposure to antigens that have been rendered innocuous. Autoimmunity is a disorder of the adaptive immune system and is characterized by immune responses to the body's own tissue. Immunodeficiency conditions, in which a compromised immune system leaves the body highly susceptible to infections, can be either congenital (see the article on congenital immunodeficiency disorders for more information) or acquired (e.g., HIV infection, iatrogenic immunosuppression).

T cells (T lymphocytes)

Overview [1][2][3]

T-cell receptors (TCRs)

The cells of the acquired immune system (B cells, T cells) are activated upon antigen recognition.

T-cell development [4]

T cells originate from lymphoid progenitor cells in the bone marrow and mature in the thymus.

Defective negative T-cell selection can cause autoimmune disorders (e.g., type 1 autoimmune polyendocrine syndrome).

“Life is ACHe without AIRE”: Autoimmune regulator protein (AIRE) dysfunction can lead to Adrenal insufficiency, chronic mucocutaneous Candidiasis, and Hypoparathyroidism.

T-cell activation

Overview

Mechanism

  1. Antigen presentation
  2. Costimulatory signal: mediates survival and proliferation of T cells
  3. Effect

T cell effects

  1. T cells (CD8+): direct cell lysis or induction of apoptosis via perforin and proteases
  2. Th1 cell (CD4+): cell‑mediated response
  3. Th2 cell (CD4+): cell‑mediated response

T cell subtypes

Overview of T cell subtypes
Cell type Important surface markers Function Stimulate/activate Clinical significance

Cytotoxic T cells (killer T cells)

T-helper cells (Th cells) Th1 cells
Th2 cells
Th17 cells
  • Regulate tissue inflammation (both proinflammatory and antiinflammatory effects)
  • Fight extracellular pathogens
T follicular helper cells (TFH cells)
  • Support B cell activation and maturation in lymphoid follicles
  • Autoimmune diseases
Regulatory T cells (Treg, suppressor T cells)
  • Stimulate or suppress CD4+ and CD8+T effector cells
  • sIPEX syndrome

Surface markers

Surface protein expression determines the specific function of T cell subtypes.

Differentiation of T helper cell subtypes
Cell type Surface marker Stimulated by Cytokines produced Inhibited by
Th1 cell
Th2 cell
  • CRTH2
  • CCR4
  • CCR3
Th17 cell
  • CCR6+
  • CCR4+
TFH cell
Treg cell


CD8 proteins on the surface of cytotoxic T cells interact with MHC I receptors, while CD4 proteins on the surface of T-helper cells interact with MHC II receptors.

Rule of 8: MHC I x CD 8 = 8. MHC II x CD 4 = 8.References:[4][5][6][7][8][9]

B cells (B lymphocytes)

Overview [1][2][3][10]

“Mr. Epstein, you have to be 21 to Be in this Barr!”: The Epstein-Barr virus uses the CD21 receptor to invade B cells.

B-cell receptors (BCRs)

B cell activation

B cell activation and class switching require an initial signal, as well as a costimulatory signal. Activated B cells migrate to germinal centers of secondary lymphoid organs.

Affinity maturation

  • Definition: : A process in which B cells interact with Th cells within the germinal center ; of secondary lymphoid tissue in order to secrete immunoglobulins with higher affinity for specific antigens.
  • Mechanisms
    • Somatic hypermutation: point mutations that create random alterations in the variable region of the antibody gene
    • Clonal selection: B cells that possess antibodies with higher affinity for the antigen have a survival advantage through a positive selection that allows them to proliferate and predominate within the follicle.

Isotype switching (class switching)

Within the germinal centers of lymph nodes, activated B cells change the antibody isotype in response to specific cytokines that are released by Th cells. IgM, the primary antibody on B cells before getting activated, is switched to IgA, IgE, or IgG. IgM is also secreted by plasma cells (stimulated by IL-6).

Immunoglobulins

Overview

Immunoglobulins (antibodies) have two functional parts: the Fc region and the Fab region. The two enzymes papain and pepsin can be used to identify the different functional parts.

  • Fc region
    • Contains the constant region
    • Formed by heavy (H) chains
    • Determines the antibody isotype (e.g., IgA, IgG, IgM)
    • Binds complement (IgG, IgM)
    • Binds various immunological cells, such as macrophages, to stimulate phagocytic or cytotoxic activity
    • Contains the carboxy terminal
    • Has many carbohydrate side chains
  • Fab region
    • Contains the variable/hypervariable region
    • Formed bylight (L) chains and heavy chains (H)
    • Recognizes and binds to antigens via epitope
    • Determines the idiotype, which is specific for one antigen only

Fc Complement, Constant, Carboxy terminal, Carbohydrate side chains
FabAntigen binding

Immunoglobulin properties

Immunoglobulin types

Type Structure Characteristics Examples and clinical relevance
IgM Pentamer
  • Largest antibody , located on the surface of B cells as a monomer and circulating as pentamer (with J chain)
  • Formed early (evidence of recent infection)
  • Activates complement
IgG Monomer
IgA Monomer or dimer
  • Monomer in circulation and dimer when secreted
  • Most abundant immunoglobulin in the body but has a low serum concentration
  • Found especially on mucosal surfaces and in bodily fluids
  • Prevents binding of pathogens to host cells
  • Secretory component protects IgA from proteases (e.g., in the gastrointestinal tract)
IgE Monomer
IgD Monomer
  • Function is incompletely understood

To memorize the timing of IgM formation, think of IgM as forming iMmediately!

Immunologic memory

Memory cells are a large pool of antigen-specific lymphocytes that can respond faster and more efficiently than naive lymphocytes when re-exposed to the antigen! These cells form the basis for the immunologic response to vaccinations!

Autoimmunity

Autoantibodies

Name Target of the autoantibody Possible detection in
Antinuclear antibodies (ANA) Nuclear antigens
Antineutrophil cytoplasmic antibodies (ANCA) Cytoplasmic antigens
Thyroid peroxidase antibodies (TPO Ab) Thyroid peroxidase
TSH receptor antibodies TSH receptor
Transglutaminase antibodies Tissue transglutaminase in the bowel
ACh receptor antibodies Acetylcholine receptor
Anti-glomerular basement membrane antibodies Type IV collagen on glomerular basement membrane
Anti-β2 glycoprotein antibodies Glycoprotein
Anticardiolipin antibodies Cardiolipin
Rheumatoid factor IgM against Fc region of IgG
Anti-CCP antibody Citrullinated peptides
Lupus anticoagulant Cell membrane phospholipids
Anticentromere antibodies Centromeres
Anti-desmoglein antibodies Desmosomes
Anti-glutamic acid decarboxylase antibodies Islet cell cytoplasm
Anti-hemidesmosome antibodies Hemidesmosomes
Anti-synthetase antibodies (anti-Jo-1 antibodies) tRNA synthetase
Anti-SRP antibodies Signal recognition particle
Anti-Mi-2 antibodies (anti-helicase antibodies) Helicase
Anti-mitochondrial antibodies Liver cells mitochondria
Anti-intrinsic factor antibodies Parietal cells
Anti-phospholipase A2 receptor antibodies Phospholipase A2 receptor
Anti-Scl-70 DNA topoisomerase I
Anti-smooth muscle antibodies Smooth muscle
Anti-SSA; Anti-SSB (anti-Ro, anti-La) Intracellular autoantigens
Anti-presynaptic calcium channel antibodies Voltage-gated calcium channel

p-ANCA

Neutrophil myeloperoxidase
c-ANCA Neutrophil proteinase
Anti-histone antibodies Histones
Anti-dsDNA Double-stranded DNA
Anti-Smith antibodies Nonhistone nuclear proteins
Anti-U1 RNP antibodies Ribonucleoprotein

Immune deficiency

Cause Disease example

Increased susceptibility to:

Antibody deficiency

Defective cellular immunity

References

  1. Kurosaki et al.. Memory B cells. Nature Reviews Immunology. 2015; 15 : p.149–159. doi: 10.1038/nri3802 . | Open in Read by QxMD
  2. Zanetti. Immunological Memory. eLS. undefined . doi: 10.1002/9780470015902.a0000951.pub3 . | Open in Read by QxMD
  3. Ademokun, Dunn-Walters. Immune Responses: Primary and Secondary. eLS. 2010 . doi: 10.1002/9780470015902.a0000947.pub2  . | Open in Read by QxMD
  4. Doan T, Melvold R, Viselli S, Waltenbaugh C. Immunology. Lippincott Williams & Wilkins ; 2012
  5. Levinson W. Review of Medical Microbiology and Immunology. Lange ; 2012
  6. Gartner LP. Textbook of Histology. Elsevier ; 2017
  7. Murphy KM. Janeway's Immunobiology. Garland Science ; 2011
  8. Murphy K, Weaver C. Janeway's Immunobiology. Garland Science ; 2016
  9. Janeway CA, Travers P, Walport M et al.. Immunobiology: The Immune System in Health and Disease. Garland Science ; 2001
  10. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P . Molecular Biology of the Cell. Garland Science ; 2002
  11. Suga M, Yamasaki H, Nakagawa K, Kohrogi H, Ando M. Mechanisms accounting for granulomatous responses in hypersensitivity pneumonitis. Sarcoidosis Vasc Diffuse Lung Dis. 1997; 14 (2): p.131-8.
  12. Identification of CD4+ TH1, TH2, and TH17 Populations in Human PBMC. https://technical.sanguinebio.com/identification-of-cd4-th1-th2-and-th17-populations-in-human-pbmc/. Updated: December 12, 2012. Accessed: November 14, 2018.
  13. Baumjohann D, Ansel KM. Identification of T follicular helper (Tfh) cells by flow cytometry. Protocol Exchange. 2013 . doi: 10.1038/protex.2013.060 . | Open in Read by QxMD
  14. Mahnke et al.. The who's who of T‐cell differentiation: Human memory T‐cell subsets. European Journal of Immunology. 2013; 43 (11): p.2797-2809. doi: 10.1002/eji.201343751 . | Open in Read by QxMD
  15. CHORZELSKI TP, BEUTNER EH, SULEJ J, et al. IgA anti-endomysium antibody. A new immunological marker of dermatitis herpetiformis and coeliac disease. Br J Dermatol. 1984; 111 (4): p.395-402. doi: 10.1111/j.1365-2133.1984.tb06601.x . | Open in Read by QxMD