Immune System

Abstract

The immune system comprises an interacting assemblage of cells and soluble molecules, whose primary function is to kill the invading microorganisms that may cause damage to the body. Two interdependent kinds of immune systems are present in most vertebrates, which together trigger one or more different killing mechanisms according to whether the microbes live within or outside the cells of the body. An innate system, mediated by receptors that recognise uniquely microbial structures, responds rapidly to the threat of invading organisms. This underlies an adaptive system, mediated by antigen receptors on lymphocytes, which produces a more sustained and comprehensive response. Only the adaptive system, found exclusively in vertebrates, retains a memory of exposure to each microbe and ensures that the system is mobilised more rapidly on a subsequent infection by the same pathogen.

Key Concepts:

  • A rapidly mobilisable form of defence (the immune system) is required to kill microbes that breach the skin and other passive defences of the body.

  • Physical injury to tissues triggers inflammation, which serves to mobilise the immune system and to repair tissue damage.

  • The innate immune system is mobilised first in response to microbes and is triggered by receptors for microbial components that are not found in the body.

  • The innate system comprises cells such as phagocytes (macrophages and neutrophils) and natural killer cells and soluble antimicrobial components such as complement.

  • The adaptive immune system is mediated by T and B lymphocytes, which are activated through the recognition of microbial components using antigen receptors.

  • The genes for antigen receptors are produced by a unique process of gene rearrangement that results in a vast repertoire of antigen receptors, each with a unique antigen specificity.

  • The repertoire of antigen receptors present in the body ensures that any invading microbe missed by the innate system can be recognised by the adaptive system.

  • The adaptive system uses many of the same killing (effector) mechanisms as the innate system, and is likely to have evolved only in vertebrates.

  • Antibodies are soluble forms of the B lymphocyte antigen receptor that are produced in large quantities during an adaptive immune response; one function of antibodies is to bind to microbes and render them more susceptible to phagocytosis.

  • Because each lymphocyte has a different receptor, the adaptive system is mobilised more gradually than the innate system; however, the response is more sustained, less easily evaded by microbes and unlike the innate system, it retains a memory of exposure to a particular microbe to ensure a more rapid response to the same microbe on subsequent exposure.

Keywords: immunity; antigen; antibody; lymphocyte; infection

Figure 1.

Overview of the acute phase of inflammation. Tissue damage causes mast cell degranulation in the tissues, either directly or via the bradykinin cascade (not shown), thereby releasing histamine and chemotactic factors. Histamine is vasoactive (causes vasodilation and increased vascular permeability) and increases the expression of adhesion molecules, enabling phagocytic neutrophils to adhere and cross into the tissue. Innate immune responses are triggered first. Neutrophils, guided by chemotactic factors, ingest microorganisms by phagocytosis. Increased vascular permeability allows components of the complement cascade to enter, which generates a variety of antimicrobial and proinflammatory substances. Meanwhile, tissue macrophages ingest any microorganisms and in so doing, release inflammatory cytokines. These also cause vasodilation, increased permeability and increased expression of adhesion molecules. Inflammatory cytokines also cause Langerhans cells (not shown) to migrate to draining lymph nodes where they activate T lymphocytes and initiate an adaptive immune response.

Figure 2.

Complement cascades are enzymatic cascades that generate a variety of antimicrobial and proinflammatory substances that help phagocytes to clear away invading microorganisms. The innate or alternative pathway can be activated directly by the cell walls of microbes, or via bound lectins such as the acute‐phase proteins generated during inflammation. The classical pathway is triggered by antibodies bound to the surface of microbes. Despite the nomenclature it is almost certain that the classical pathway has evolved recently than the innate pathways. It provides a good example of an effector mechanism that can be triggered by innate and adaptive forms of recognition. Thereafter, all pathways converge on a common, lytic pathway that culminates in the formation of a MAC.

Figure 3.

Antigen processing and presentation by APCs. Class II MHC molecules are found only on all professional APCs (dendritic cells, macrophages and B lymphocytes). As a general rule, antigens ingested from outside the APC enter this pathway and are processed into peptide fragments by enzymatic degradation in endosomal compartments. These peptides are picked up by class II MHC molecules and presented to CD4 (‘helper’) T lymphocytes. In contrast, class I MHC molecules are found on all nucleated cells in the body (including APCs). These molecules present processed peptides to CD8 CTLs, and antigens presented by this pathway usually originate from within the cell (as is the case in viral infection) and are processed in the cytosol. By this means, all cells have the capacity to be recognised and killed by CTLs should they become infected. There is evidence that dendritic cells can also load class I from antigen derived from outside the cell.

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References

Aderem A and Underhill DM (1999) Mechanisms of phagocytosis in macrophages. Annual Review of Immunology 17: 593–623.

Banchereau J , Pascual V and O'Garra A (2012) From IL‐2 to IL‐37: the expanding spectrum of anti‐inflammatory cytokines. Nature Immunology 13: 925–931.

Belkaid Y (2007) Regulatory T cells and infection: a dangerous necessity. Nature Reviews Immunology 7: 875–888.

Berger AC and Roche PA (2009) MHC class II transport at a glance. Journal of Cell Science 122: 1–4.

Braff MH and Gallo RL (2006) Antimicrobial peptides: an essential component of the skin defensive barrier. Current Topics in Microbiology and Immunology 306: 91–110.

Crotty S (2011) Follicular helper CD4 T cells (TFH). Annual Review of Immunology 29: 621–663.

Danilova N (2006) The evolution of immune mechanisms, Journal of Experimental Zoology. Part B: Molecular and Developmental Evolution 306: 496–520.

Dunkelberger JR and Song WC (2010) Complement and its role in innate and adaptive immune responses. Cell Research 20: 34–50.

Flutter B and Gao B (2004) MHC class I antigen presentation – recently trimmed and well presented. Cellular and Molecular Immunology 1: 22–30.

Hart AL , Ng SC , Mann E et al. (2010) Homing of immune cells: role in homeostasis and intestinal inflammation. Inflammatory Bowel Diseases 16: 1969–1977.

Hinz A and Tampe R (2012) ABC transporters and immunity: mechanism of self‐defense. Biochemistry 51: 4981–4989.

Jabeen R and Kaplan MH (2012) The symphony of the ninth: the development and function of Th9 cells. Current Opinion in Immunology 24: 303–307.

Jerud ES , Bricard G and Porcelli SA (2006) CD1d‐restricted natural killer T cells: roles in tumor immunosurveillance and tolerance. Transfusion Medicine and Hemotherapy 33: 18–36.

Kawai T and Akira S (2010) The role of pattern‐recognition receptors in innate immunity: update on toll‐like receptors. Nature Immunology 11: 373–384.

Kemper C and Atkinson JP (2007) T‐cell regulation: with complements from innate immunity. Nature Reviews Immunology 7: 9–18.

Kracker S and Durandy A (2011) Insights into the B cell specific process of immunoglobulin class switch recombination. Immunology Letters 138: 97–103.

McGeachy MJ and McSorley SJ (2012) Microbial‐induced Th17: superhero or supervillain? Journal of Immunology 189: 3285–3291.

Mucida D and Cheroutre H (2010) The many face‐lifts of CD4 T helper cells. Advances in Immunology 107: 139–152.

Murphy WJ , Parham P and Miller JS (2012) NK cells – from bench to clinic. Biology of Blood and Marrow Transplantation 18: S2–S7.

Murray PJ and Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nature Reviews Immunology 11: 723–737.

Neefjes J , Jongsma ML , Paul P and Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nature Reviews Immunology 11: 823–836.

O'Shea JJ and Paul WE (2010) Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327: 1098–1102.

Pepper M and Jenkins MK (2011) Origins of CD4(+) effector and central memory T cells. Nature Immunology 12: 467–471.

Sallusto F and Lanzavecchia A (2009) Heterogeneity of CD4+ memory T cells: functional modules for tailored immunity. European Journal of Immunology 39: 2076–2082.

Sallusto F , Lanzavecchia A , Araki K and Ahmed R (2010) From vaccines to memory and back. Immunity 33: 451–463.

Sallusto F and Mackay CR (2004) Chemoattractants and their receptors in homeostasis and inflammation. Current Opinion in Immunology 16: 724–731.

Sato K , Ohtsuka K , Watanabe H , Asakura H and Abo T (1993) Detailed characterization of gamma delta T cells within the organs in mice: classification into three groups. Immunology 80: 380–387.

Savina A and Amigorena S (2007) Phagocytosis and antigen presentation in dendritic cells. Immunological Reviews 219: 143–156.

Schatz DG and Ji Y (2011) Recombination centres and the orchestration of V(D)J recombination. Nature Reviews Immunology 11: 251–263.

Shlomchik MJ and Weisel F (2012) Germinal center selection and the development of memory B and plasma cells. Immunological Reviews 247: 52–63.

Theoharides TC , Alysandratos KD , Angelidou A et al. (2012) Mast cells and inflammation. Biochimica et Biophysica Acta 1822: 21–33.

Yoshida T , Mei H , Dorner T et al. (2010) Memory B and memory plasma cells. Immunological Reviews 237: 117–139.

Zhang N and Bevan MJ (2011) CD8(+) T cells: foot soldiers of the immune system. Immunity 35: 161–168.

Further Reading

Aly HA (2012) Cancer therapy and vaccination. Journal of Immunological Methods 382: 1–23.

Bailey M , Christoforidou Z and Lewis M (2013) Evolution of immune systems: specificity and autoreactivity. Autoimmunity Reviews 12(6): 643–647.

Burton DR , Poignard P , Stanfield RL and Wilson IA (2012) Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science 337: 183–186.

Conti AA (2010) The parallel evolution of immunology and pharmacology. International Journal of Immunopathology and Pharmacology 23: 655–657.

Kotwal GJ (1997) Microorganisms and their interaction with the immune system. Journal of Leukocyte Biology 62: 415–429.

Laird DJ , De Tomaso AW , Cooper MD and Weissman IL (2000) 50 million years of chordate evolution: seeking the origins of adaptive immunity. Proceedings of the National Academy of Sciences of the USA 97: 6924–6926.

Nabel GJ (2013) Designing tomorrow's vaccines. New England Journal of Medicine 368: 551–560.

Pulendran B and Ahmed R (2011) Immunological mechanisms of vaccination. Nature Immunology 12: 509–517.

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How to Cite close
Davies, D Huw(Sep 2013) Immune System. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000898.pub3]