Significance and Result of Antigen Presented by MHC Class II Molecules on a Macrophage

As discussed in chapter 15, macrophages routinely engulf and degrade invading microbes, rapidly clearing most organisms even before an adaptive immune response is mounted. Some microbes, however, can evade this method of destruction, enabling them to survive and actually multiply within the phagocytic cell. Th1 cells recognize macrophages that have engulfed microbes that resist such killing and then activate those macrophages by delivering cytokines that induce more potent destructive mechanisms. If the response is still not sufficient to control the infection, activated macrophages are able to fuse together, forming giant cells. These, along with other macrophages and T cells, can form granulomas that wall off the offending agent, preventing infectious microbes from escaping to infect other cells. Activated macrophages are an important aspect of the immune response against many diseases such as tuberculosis, Hansen's disease (leprosy), brucellosis, tularemia, and histoplasmosis that are caused by organisms that can survive within macrophages. ■ giant cell, p. 385 ■ granuloma, p. 385

When macrophages engulf material, they bring the substance into the cell enclosed within a membrane-bound phagosome (figure 16.19). Proteins contained within the phagosome are degraded to produce short peptides that can then be loaded into the groove of an MHC class II molecule (see figure 16.16b). If a Th1 cell recognizes a peptide: MHC class II complex displayed by a macrophage, it establishes close contact with the cell. As a result of the interaction, the Th1 cell begins synthesizing cytokines, delivering them directly to the macrophage. This activation process leads to several morphological and physiological changes in the macrophage; it enlarges, the plasma membrane becomes ruffled and irregular, and the cell increases its metabolism so that the lysosomes, each containing antimicrobial substances, increase in number. The activated macrophage also begins producing nitric oxide, a potent antimicrobial chemical, along with various compounds that can be released to destroy extracellular microorganisms. ■ phagosome, p. 385

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