Immune System

D Huw Davies, University of California, Irvine, California, USA

Published online: December 2008

DOI: 10.1002/9780470015902.a0000898.pub2

Full Article on Wiley Online Library

The immune system comprises an interacting assemblage of cells and soluble molecules whose primary function is to kill invading microorganisms that may cause damage to the body. Two interdependent kinds of immune system 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 which recognize 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 the system is mobilized more rapidly upon a subsequent infection by the same pathogen.

Key concepts

A rapidly mobilizable 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 mobilize the immune system and to repair tissue damage.
The innate immune system is moblized 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, 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 recognized 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 functionof antibodies is to bind to microbes and render them more susceptible to phagocytosis.
Because each lymphocyte has a different receptor, the adaptive system is mobilized 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 upon subsequent exposure.

Keywords: immunity; antigen; antibody; lymphocyte; infection

Further Reading
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	Beverley PC (2008) Primer: making sense of T-cell memory. Nature Clinical Practice. Rheumatology 4: 43–49.
	Burton DR and Woof JM (1992) Human antibody effector function. Advances in Immunology 51: 1–84.
	Germain RN (2008) A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm. Immunology 123: 20–27.
	Kagi D, Ledermann B, Burki K, Zinkernagel RM and Hengartner H (1996) Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Annual Review of Immunology 14: 207–232.
	Kinoshita T (1991) Biology of complement: the overture. Immunology Today 12: 291–295.
	Matsushita M (1996) The lectin pathway of the complement system. Microbiology and Immunology 40: 887–893.
	McHeyzer-Williams LJ, Malherbe LP and McHeyzer-Williams MG (2006) Helper T cell-regulated B cell immunity. Current Topics in Microbiology and Immunology 311: 59–83.
	Sakaguchi S, Wing K and Miyara M (2007). Regulatory T cells: a brief history and perspective. European Journal of Immunology 37(suppl. 1): S116–S123.
	Stuart LM and Ezekowitz RA (2008) Phagocytosis and comparative innate immunity: learning on the fly. Nature Reviews. Immunology 8(2): 131–141.
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	Uematsu S and Akira S (2008) Toll-like receptors (TLRs) and their ligands. Handbook of Experimental Pharmacology 183: 1–20.
	Walzer T, Dalod M, Robbins SH, Zitvogel L and Vivier E (2005) Natural-killer cells and dendritic cells: “l'union fait la force”. Blood 106(7): 2252–2258.

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	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 pro-inflammatory 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 membrane attack complex.
	Figure 3. Antigen processing and presentation by antigen-presenting cells (APCs). Class II major histocompatibility complex (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 (cytotoxic) T lymphocytes (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 recognized 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.

Immune System

Key concepts

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