Chapter 8T Cell-Mediated Immunity

Once they have completed their development in thethymus,T cells enter the bloodstreamand are carried by the circulation. On reaching a peripheral lymphoid organ they leavethe blood again to migrate through the lymphoid tissue, returning to the bloodstream torecirculate between blood and peripheral lymphoid tissue until they encounter theirspecificantigen. Mature recirculating T cells that have not yet encountered theirantigens are known asnaive T cells. To participate in anadaptive immune response, a naive T cell must first encounter antigen, and then be induced toproliferate and differentiate into cells capable of contributing to the removal of theantigen. We will term such cellsarmed effector T cells because they act very rapidly when they encounter their specificantigen on other cells. The cells on which armed effector T cells act will be referredto as theirtarget cells.

In this chapter, we will see how naiveT cells are activated to producearmed effector T cells the first time they encounter their specificantigen in the form of a peptide:MHCcomplex on the surface of an activatedantigen-presenting cell(APC). The most important antigen-presenting cells are the highlyspecialized dendritic cells, whose onlyknown function is to ingest and present antigen. Tissue dendritic cells ingest antigenat sites of infection and are activated as part of the innateimmune response. Thisinduces their migration to local lymphoid tissue and their maturation into cells thatare highly effective at presenting antigen to recirculating T cells. These maturedendritic cells are distinguished by surface molecules, known asco-stimulatorymolecules, that synergize with antigen in the activation of naive T cells.Macrophages, which we described inChapter 2 as phagocytic cells thatprovide a first line of defense against infection, can also be activated to expressco-stimulatory and MHC class II molecules. This enables them to act asantigen-presenting cells, although they are less powerful than dendritic cells atactivating naive T cells. B cells can also serve as antigen-presenting cells in somecircumstances. Once a T-cell response has been initiated, macrophages and B cells thathave taken up specific antigen also become targets for armed effector T cells.Dendritic cells, macrophages, and B cells are often known as professional antigen-presentingcells.

EffectorT cells, as we learned in Chapter5, fall into three functional classes that detect peptide antigens derived fromdifferent types of pathogen. Peptides from intracellular pathogens that multiply in thecytoplasm are carried to the cell surface by MHC class I molecules and presented toCD8 T cells. These differentiate intocytotoxic T cells that kill infectedtarget cells. Peptide antigens from pathogensmultiplying in intracellular vesicles, and those derived from ingested extracellularbacteria and toxins, are carried to the cell surface by MHC class II molecules andpresented toCD4 T cells. These can differentiate into two types of effector T cell,calledT_H1 andT_H2. Pathogens thataccumulate in large numbers inside macrophage and dendritic cell vesicles tend tostimulate the differentiation ofT_H1 cells, whereas extracellular antigenstend to stimulate the production ofT_H2 cells. T_H1 cells activatethe microbicidal properties of macrophages, and induce B cells to makeIgG antibodiesthat are very effective at opsonizing extracellular pathogens for uptake by phagocyticcells. T_H2 cells initiate the humoralimmune response by activating naiveantigen-specific B cells to produceIgM antibodies. These T_H2 cells cansubsequently stimulate the production of differentisotypes, includingIgA andIgE, aswell as neutralizing and/or weakly opsonizing subtypes of IgG.Fig. 8.1 shows the involvement of the different effector T cellsin the immune responses to different classes of pathogens.

Figure 8.1

The role of effector T cells in cell-mediated and humoral immuneresponses to representative pathogens. Cell-mediated immune responses involve the destruction of infected cells bycytotoxic T cells, or the destruction of intracellular pathogens bymacrophages(more...)

The activation of naiveT cells in response toantigen, and their subsequentproliferation and differentiation, constitutes aprimary immune response. At the same time as providingarmed effector T cells, this response generatesimmunological memory, which gives protection fromsubsequent challenge by the same pathogen. The generation of memory T cells, long-livedcells that give an accelerated response to antigen, is much less well understood thanthe generation of effector T cells and will be dealt with in Chapter 10. Memory T cells differ in several ways from naive Tcells, but like naive T cells they are quiescent and require activation byantigen-presenting cells with co-stimulatory activity in order to regenerate effector Tcells.

Armed effectorT cells differ in many ways from their naive precursors, and these changesequip them to respond quickly and efficiently when they encounter specificantigen ontarget cells. In the last two sections of this chapter we will describe the specializedmechanisms of T cell-mediated cytotoxicity and of macrophage activation byarmed effector T cells, the major components of cell-mediated immunity. We will leave the activation of B cells by helper Tcells until Chapter 9, where the humoral,orantibody-mediated,immune response is discussed.

Contents

• The production of armed effector T cells
• General properties of armed effector T cells
• T cell-mediated cytotoxicity
• Macrophage activation by armed CD4 T_H1 cells
• Summary to Chapter 8
• General references
• Section references

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