Immunity: Humoral and Cellular

Abstract

The immune system evolved to recognise and combat infectious pathogens. The ability to discriminate between normal self and nonself is a critical property of the immune system which enables it to eradicate pathogens without causing autoimmune disease and harming the host. The first line of defence, the older ‘innate’ immune system of cells (granulocytes, monocytes–macrophages, natural killer and other innate lymphoid cells) and soluble mediators (cytokines, chemokines and complement factors), provides a rapid, short‐lived response to a broad range of generic pathogen‐associated molecules. Innate immunity primes the second line of defence, the ‘adaptive’ immune system, first present in jawed vertebrates, comprising lymphocytes (T cells and antibody‐producing B cells) with highly specific antigen receptors and antigenic memory. Dendritic cells are a type of innate immune cell that links innate and adaptive immunity by their ability to present antigens to T cells. The spatial framework of the immune system with its mobile and fixed elements is described herein.

Key Concepts

  • The immune system is designed to recognise, react to and eradicate ‘nonself’, in particular infectious pathogens.
  • The immune system comprises fixed and mobile elements.
  • The elements of the immune system sequentially mediate innate immunity, providing a rapid, broad defence and adaptive immunity, providing highly specific, long‐lasting defences.
  • The exquisite specificity and diversity of adaptive immunity is based on postgenetic, somatic hypermutation‐ and recombination‐based polymorphism of the receptors for antigens on T and B cells, and of the major histocompatibility complex (MHC) molecules that bind antigenic peptides recognised by T‐cell receptors.
  • Nonspecific costimulation via surface‐interacting molecules or soluble cytokines and chemokines shapes the differentiation of T and B cells in the adaptive immune response.
  • Immune responses are highly context‐dependent, being influenced by the local immune and nonimmune environment, and the epigenetic regulation of immune genes.

Keywords: innate; adaptive; antigen; MHC; T cell; B cell; antibody; cytokine; chemokine

Figure 1. Interactions between the antigen‐presenting cell (APC) and the T cell. Antigen peptide (Ag) processed by the APC is presented on the major histocompatibility complex (MHC) molecule to the cognate T‐cell receptor (TCR). This contact is stabilised by intercellular adhesion molecule (ICAM) 1–leucocyte functional antigen (LFA)‐1, LFA‐3–CD2 and MHC–CD4 or MHC–CD8 interactions. In addition to stimulation via the highly specific MHC–Ag–TCR interaction, nonspecific costimulation occurs via B7–CD28. This is essential for proper activation of the responding T cell, without which it may become subsequently unresponsive (anergic). Cytokines secreted by the APC direct T‐cell differentiation. Upregulation of CD40 ligand (CD40L) on the T cell further stimulates the APC to present antigen and secrete cytokines. T‐cell proliferation is limited by the upregulation of CTLA‐4, which inhibits costimulation mediated by CD28. PD‐1 and its ligands are members of the CD28/CTLA‐4 family of T‐cell regulators that have a general effect to negatively regulate T‐cell responses.
Figure 2. Structure of an IgG antibody molecule. Reproduced from Lucas AH (2003) © Wiley.
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References

Allen SJ, Crown SE and Handel TM (2007) Chemokine: receptor structure, interactions, and antagonism. Annual Review of Immunology 25: 787–820.

Bandala‐Sanchez E, Zhang Y, Reinwald S, et al. (2013) T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec‐10. Nature Immunology 14: 741–748.

Bosch X and Ramos‐Casals M (2014) Granulocytes: neutrophils, basophils, eosinophils. In: Rose N and Mackay I (eds) The Autoimmune Diseases, pp. 201–215, 5th edn, Chapter 14. Amsterdam: Elsevier Inc.

Gordon S and Taylor PR (2005) Monocyte and macrophage heterogeneity. Nature Reviews Immunology 5: 953–964.

Griffith JW, Sokol CL and Luster AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annual Review of Immunology 32: 659–702.

Holers VM (2014) Complement and its receptors: new insights into human disease. Annual Review of Immunology 32: 433–459.

Iwasaki A and Medzhitov R (2015) Control of adaptive immunity by the innate immune system. Nature Immunology 16: 343–353.

Litman GW, Rast JP and Fugmann SD (2010) The origins of vertebrate adaptive immunity. Nature Reviews Immunology 10: 543–553.

Lucas AH (2003) Antibody function. eLS. Chichester: John Wiley & Sons Ltd. http://www.els.net. DOI: 10.1038/npg.els.0000907.

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

Oppenheim JJ (2014) Cytokines, their receptors and signals. In: Rose N and Mackay I (eds) The Autoimmune Diseases, pp. 229–241, 5th edn, Chapter 16. Amsterdam: Elsevier Inc.

Sakaguchi S, Yamaguchi T, Nomura T and Ono M (2008) Regulatory T cells and immune tolerance. Cell 133: 775–789.

Sarma JV and Ward PA (2011) The complement system. Cell and Tissue Research 343: 227–235.

Schmitt EG and Williams CB (2013) Generation and function of induced regulatory T cells. Frontiers in Immunology 4 (152): 1–13.

Schmitt N and Ueno H (2015) Regulation of human helper T cell subset differentiation by cytokines. Current Opinion in Immunology 34: 130–136.

Schroeder HW and Cavacini L (2010) Structure and function of immunoglobulins. Journal of Allergy and Clinical Immunology 125: S41–S52.

Smith‐Garvin JE, Koretzky GA and Jordan MS (2009) T cell activation. Annual Review of Immunology 27: 591–619.

Steinman R and Banchereau J (2007) Taking dendritic cells into medicine. Nature 449: 419–426.

Vivier E, Tomasello E, Baratin M, et al. (2008) Functions of natural killer cells. Nature Immunology 9: 503–510.

Wynn TA (2015) Type 2 cytokines: mechanisms and therapeutic strategies. Nature Reviews Immunology 15: 271–282.

Yamane H and Paul WE (2013) Early signaling events that underlie fate decisions of naive CD4 T cells toward distinct T‐helper cell subsets. Immunology Reviews 252: 12–23.

Further Reading

Delves PJ, Martin SJ, Burton DR and Roitt IM (eds) (2011) Part 1: fundamentals of Immunology. Roitt's Essential Immunology, 12th edn, pp. 3–78. Chichester and Oxford: Wiley‐Blackwell.

Dinarello CA (2007) Historical review of cytokines. European Journal of Immunology 37 (Suppl 1): S34–S45.

Fitzgerald KA, O'Neill LAJ, Gearing AJH and Callard RE (2001) The Cytokine Factsbook, 2nd edn. London: Academic Press.

Kono H and Rock KL (2008) How dying cells alert the immune system to danger. Nature Reviews Immunology 8: 279–289.

Macauley MS, Crocker PR and Paulson JC (2014) Siglec‐mediated regulation of immune cell function in disease. Nature Reviews Immunology 14: 653–666.

Mosmann TR and Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7: 145–173.

Murphy KM, Travers P and Walport M (eds) (2008) Janeway's Immunobiology, 7th edn. London: Garland Science Publishing.

Rose N and Mackay I (2014) The Autoimmune Diseases, 5th edn. Amsterdam: Elsevier Inc.

Spits H, Artis D, Colonna M, et al. (2013) Innate lymphoid cells ‐ a proposal for uniform nomenclature. Nature Reviews Immunology 13: 145–149.

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Harrison, Leonard C(Apr 2016) Immunity: Humoral and Cellular. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001236.pub3]