The depletion of CD4 T cells in people with HIV/AIDS causes ineffective TH1 responses that can lead to the dissemination of microbes that are normally cleared by macrophages. This is the case with the opportunist fungal pathogen Pneumocystis jirovecii (see also Chapter 13). The lungs of healthy people are kept clear of P. jirovecii by phagocytosis and intracellular killing by alveolar macrophages. Pneumonia caused by P. jirovecii is, however, a frequent cause of death in people with AIDS. In the absence of CD4 T cells, phagocytosis of P. jirovecii and intracellular killing by lung macrophages are impaired, and the
Granuloma multi-nucleated giant cell epithelioid cell T cells mycobacteria IFN-˜Partial removal of live M. tuberculosis TH1
Fig. 11.13 Granulomas form when an intracellular pathogen or its constituents cannot be completely eliminated. When mycobacteria (red) resist the effects of macrophage activation, a characteristic localized inflammatory response called a granuloma develops. This consists of a central core of infected macrophages. The core may include multinucleate giant cells, which are fused macrophages, surrounded by large macrophages often called epithelioid cells, but in granulomas caused by mycobacteria the core usually becomes necrotic. Mycobacteria can persist in the cells of the granuloma. The central core is surrounded by T cells, many of which are CD4-positive. The exact mechanisms by which this balance is achieved, and how it breaks down, are unknown. Granulomas, as seen in the bottom panel, also form in the lungs and elsewhere in a disease known as sarcoidosis, which may be caused by inapparent mycobacterial infection. Photograph courtesy of J. Orrell.
Panel a: the whipworm Trichuris trichiura is a helminth parasite that lives partly embedded in intestinal epithelial cells. This scanning electron micrograph of mouse colon shows the head of the parasite buried in an epithelial cell and its posterior lying free in the lumen. Panel b: a cross-section of crypts from the colon of a mouse infected with T. trichiura shows the markedly increased production of mucus by goblet cells in the intestinal epithelium. The mucus is seen as large droplets in vesicles inside the goblet cells and stains dark blue with periodic acid–Schiff reagent. Magnification ×400.
pathogen colonizes the surface of the lung epithelium and invades lung tissue. The requirement for CD4 T cells seems to be due, at least in part, to a requirement for the macrophage-activating cytokines IFN-γ and TNF-α produced by TH1 cells.
11-9 TH2 cells coordinate type 2 responses to expel intestinal helminths and repair tissue injury.