Chapter 14 : Toll-Like Receptors and Control of Adaptive Immunity

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This chapter focuses on how pattern recognition is used by the innate immune system to distinguish self from nonself and how this discrimination is translated into induction of adaptive immunity. The past few years have seen significant advances in our understanding of how adaptive immune responses are controlled by the initial innate recognition of microbial infection. In particular, the identification of the Toll-like receptor (TLR) family as the critical receptor family involved in the recognition of infectious nonself has enabled researchers to examine the mechanisms by which adaptive responses are controlled by the innate immune system. Before discussing the specific mechanisms by which TLRs control adaptive immunity, the chapter talks about the general mechanisms by which self/nonself discrimination is regulated within the adaptive immune system. The second half of the chapter focuses on how TLRs control some of these mechanisms and link microbial recognition to self and nonself discrimination by the adaptive immune system. Upon activation, lymphocytes undergo a period of rapid proliferation. The innate immune system keeps the infection in check long enough for lymphocytes to expand and eventually eliminate the microbial challenge. Immature B cells that have receptors capable of recognizing membrane-bound selfantigens receive signals leading to apoptosis of the self-reactive B lymphocyte. IgG2 antibodies are effective at eliminating a variety of intracellular and extracellular pathogens because they can fix complement and direct the lysis of infected cells in a process called antibody-dependent cellular cytotoxicity.

Citation: Barton G, Pasare C, Medzhitov R. 2004. Toll-Like Receptors and Control of Adaptive Immunity, p 271-285. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch14
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Image of FIGURE 1

Control of DC maturation by TLRs. Microbial infection is recognized by immature DCs in the tissues when TLRs are activated. Signals initiated by TLRs lead to DC maturation, which includes migration to secondary lymphoid organs, upregulation of MHC and costimulatory molecules, and production of cytokines.

Citation: Barton G, Pasare C, Medzhitov R. 2004. Toll-Like Receptors and Control of Adaptive Immunity, p 271-285. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch14
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Image of FIGURE 2

Control of T regulatory cell function by TLRs. Treg cells suppress activation of naive T cells and prevent responses to self-antigens. During an infection, TLR ligation on DCs leads to upregulation of MHC and costimulatory molecules as well as production of cytokines such as IL-6. IL-6 provides signals to effector T cells (Te) that render them resistant to the effects of Treg cells, allowing T-cell activation to proceed.

Citation: Barton G, Pasare C, Medzhitov R. 2004. Toll-Like Receptors and Control of Adaptive Immunity, p 271-285. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch14
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Image of FIGURE 3

Innate immune recognition controls induction of differential immune responses. Microbes that engage TLRs induce a characteristic adaptive immune response leading to Th1 T-cell differentiation and the production of IgG2 antibodies. Large multicellular pathogens, such as worms, induce Th2 T-cell differentiation and the production of IgE antibodies. How innate recognition of worms is achieved and how this recognition leads to induction of Th2 differentiation remain unclear.

Citation: Barton G, Pasare C, Medzhitov R. 2004. Toll-Like Receptors and Control of Adaptive Immunity, p 271-285. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch14
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