Cd40

Macrophage with CD40L ingested bacteria

IFN-y receptor

CD4+ effector T cell (Th1 cell)

IFN-y receptor

CD4+ effector T cell (Th1 cell)

Secretion of inflammatory cytokines

Increased expression of molecules required for T cell activation

Macrophage response

Role in cell-mediated immunity

Production of reactive oxygen species, nitric oxide, increased lysosomal enzymes

Killing of microbes in phagolysosomes (effector function of macrophages)

Secretion of cytokines (TNF, IL-1, IL-12) and chemokines

TNF, IL-1, chemokines: leukocyte recruitment (inflammation)

IL-12: Th1 differentiation, IFN-y production

Increased expression of B7 costimulators, MHC molecules

Increased T cell activation (amplification of T cell response)

FIGURE 10-7 Macrophage activation by TH1 cells. A, Macrophages are activated by CD40L-CD40 interactions and by IFN-y expressed by Th1 cells and perform several functions that kill microbes, stimulate inflammation, and enhance the antigen-presenting capacity of the cells. B, The principal molecules that mediate the functions of macrophages are listed. Macrophages are also activated during innate immune reactions and perform the same functions (see Chapter 4).

FIGURE 10-7 Macrophage activation by TH1 cells. A, Macrophages are activated by CD40L-CD40 interactions and by IFN-y expressed by Th1 cells and perform several functions that kill microbes, stimulate inflammation, and enhance the antigen-presenting capacity of the cells. B, The principal molecules that mediate the functions of macrophages are listed. Macrophages are also activated during innate immune reactions and perform the same functions (see Chapter 4).

inflammation through the secretion of cytokines, mainly TNF, IL-1, and chemokines, and short-lived lipid mediators such as prostaglandins, leukotrienes, and platelet-activating factor. The collective action of these macrophage-derived cytokines and lipid mediators is to recruit more leukocytes, which improves the ability to destroy infectious organisms. Activated macrophages amplify cell-mediated immune responses by becoming more efficient APCs because of increased levels of molecules involved in antigen processing and increased surface expression of class II MHC molecules and costimulators and by producing cytokines (such as IL-12) that stimulate T lymphocyte differentiation into effector cells.

Some tissue injury may normally accompany TH1 cell-mediated immune reactions to microbes because the microbicidal products released by activated macrophages and neutrophils are capable of injuring normal tissue and do not discriminate between microbes and host tissue. However, this tissue injury is usually limited in extent and duration, and it resolves as the infection is cleared. As mentioned earlier, delayed hypersensitivity is an example of a TH1-mediation reaction that can cause significant tissue injury (see Chapter 18).

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