overcome the block on vesicle fusion. TH2 and TH17 subsets produce cytokines that are specialized for promoting responses against parasites or extracellular bacteria and fungi, respectively. CD4 T cells, and their specialized subsets, play a pervasive role in adaptive immunity, and we will be returning to them many times in this book, including in Chapters 8, 9, 11 and 12.
1-22 Inherited and acquired defects in the immune system result in increased susceptibility to infection.
We tend to take for granted the ability of our immune systems to free our bodies of infection and prevent its recurrence. In some people, however, parts of the immune system fail. In the most severe of these immunodeficiency diseases, adaptive immunity is completely absent, and death occurs in infancy from overwhelming infection unless heroic measures are taken. Other less catastrophic failures lead to recurrent infections with particular types of pathogens, depending on the particular deficiency. Much has been learned about the functions of the different components of the human immune system through the study of these immunodeficiencies, many of which are caused by inherited genetic defects. Because understanding the features of immunodeficiencies requires a detailed knowledge of normal immune mechanisms, we have postponed discussion of most of these diseases until Chapter 13, where they can be considered together.
More than 30 years ago, a devastating form of immunodeficiency appeared, the acquired immune deficiency syndrome, or AIDS, which is caused by an infectious agent, the human immunodeficiency viruses HIV-1 and HIV-2. This disease destroys T cells, dendritic cells, and macrophages bearing CD4, leading to infections caused by intracellular bacteria and other pathogens
Fig. 1.34 Mechanism of host defense against intracellular infection by mycobacteria. mycobacteria are engulfed by macrophages but resist being destroyed by preventing the intracellular vesicles in which they reside from fusing with lysosomes containing bactericidal agents. thus the bacteria are protected from being killed. In resting macrophages, mycobacteria persist and replicate in these vesicles. When the phagocyte is recognized and activated by a tH1 cell, however, the phagocytic vesicles fuse with lysosomes, and the bacteria can be killed. macrophage activation is controlled by tH1 cells, both to avoid tissue damage and to save energy. the light micrographs (bottom row) show resting (left) and activated (right) macrophages infected with mycobacteria. the cells have been stained with an acid-fast red dye to reveal mycobacteria. these are prominent as red-staining rods in the resting macrophages but have been eliminated from the activated macrophages. Photographs courtesy of g. Kaplan.
Fig. 1.35 Immune responses can be beneficial or harmful, depending on the nature of the antigen. Beneficial responses are shown in white, harmful responses in red shaded boxes. Where the response is beneficial, its absence is harmful.
normally controlled by such cells. These infections are the major cause of death from this increasingly prevalent immunodeficiency disease, which is discussed fully in Chapter 13 together with the inherited immunodeficiencies.
1-23 Understanding adaptive immune responses is important for the control of allergies, autoimmune disease, and the rejection of transplanted organs.