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The innate immune system 

The innate immune system

Chapter:
The innate immune system
Author(s):

Paul Bowness

DOI:
10.1093/med/9780199204854.003.050101

August 28, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

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date: 24 April 2017

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and lack of plasticity, ‘learning’, or memory, and they involve various different cell types, cell-associated receptors, and soluble factors.

Cellular components—these are mainly derived from myeloid precursors in the bone marrow and include monocytes, macrophages, dendritic cells, and granulocytes (neutrophils, eosinophils, and basophils). Two small populations of lymphoid cells—NK and NKT cells—are also included because they lack the clonally rearranged receptors of B and T lymphocytes.

Receptors—the innate immune system uses a relatively small repertoire of germline-encoded largely non-rearranging receptors, including (1) Pattern recognition receptors (PRR)—these recognize invariant molecular signatures, usually microbial in origin, known as pathogen associated molecular patterns (PAMPs), Toll-like receptors and mannose receptors (2) Natural killer (NK) family of receptors—these largely have specificity for self or altered self molecules, e.g. recognizing conserved features of human leucocyte antigen (HLA) class molecules; can be either stimulatory or inhibitory. (3) Other pattern recognition receptors (PRRs).

Soluble mediators—these include (1) complement (see Chapter 5.1.2); (2) defensins—typically small microbicidal proteins, with other actions to stimulate both innate and adaptive immune responses; and (3) cytokines—frequently act over relatively short distances by binding to cell-surface receptors and initiating signalling via intracellular second messengers; play major roles in stimulating immune cell differentiation and proliferation.

Clinical features of dysregulation of the innate immune system—(1) hypofunction—can result in uncontrolled infections, e.g. in chronic granulomatous disease; (2) excess activity—can result in autoinflammatory disease, e.g. periodic fever syndromes; (3) dysfunction—may contribute to common conditions of multifactorial aetiology, e.g. Crohn’s disease.

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