Resting macrophages have few or no MHC class II molecules on their surface and do not express B7. The expression of both MHC class II molecules and B7 is induced by the ingestion of microorganisms and recognition of their microbe-associated molecular patterns (MAMPs). Macrophages, like dendritic cells, have a variety of pattern recognition receptors that recognize microbial surface components (see Chapter 3). Receptors such as Dectin-1, scavenger receptors, and complement receptors take up microorganisms into phagosomes, where they are degraded to produce peptides for presentation, while recognition of pathogen components via TLRs triggers intracellular signaling that contributes to the expression of MHC class II molecules and B7. However, unlike conventional dendritic cells, tissue-resident macrophages are generally nonmigratory; they do not traffic to T-cell zones of lymphoid tissues when activated by pathogens. It is thus likely that increased expression of MHC class II molecules and co-stimulatory molecules by activated macrophages is more important for locally amplifying T-cell responses already initiated by dendritic cells. This appears to be important for the maintenance and functioning of effector or memory T cells that enter a site of infection.
In addition to residing in tissues, macrophages are found in lymphoid organs (see Fig. 9.13). They are present in many areas of the lymph node, including the marginal sinus, where the afferent lymph enters the lymphoid tissue, and in the medullary cords, where the efferent lymph collects before flowing into the blood. However, they are largely sequestered from T-cell zones and are inefficient activators of naive T cells. Rather, their main function in lymphoid tissues appears to be the ingestion of microbes and particulate antigens to prevent them from entering the blood. They are also important scavengers of apoptotic lymphocytes.
Macrophages in other sites also continuously scavenge dead or dying cells, which are rich sources of self antigens, so it is particularly important that they should not activate naive T cells. The Kupffer cells of the liver sinusoids and the macrophages of the splenic red pulp, in particular, remove large numbers of dying cells from the blood daily. Kupffer cells express little MHC class II and no TLR-4, the receptor that signals the presence of bacterial LPS. Thus, although they generate large amounts of self peptides in their endosomes, these macrophages are not likely to elicit an immune response.
9-13 B cells are highly efficient at presenting antigens that bind to their surface immunoglobulin.
B cells are uniquely adapted to bind specific soluble molecules through their membrane-bound antigenic receptor, or B-cell receptor (BCR), the antigen-binding component of which is membrane-associated IgM, which is highly efficient at internalizing the bound molecules by receptor-mediated endocytosis. If the antigen contains a protein component, the B cell will process the internalized protein to peptide fragments and then display the fragments as peptide:MHC class II complexes. Through this mechanism B cells are able to take up and present even low concentrations of specific antigen to T cells. B cells also constitutively express high levels of MHC class II molecules, and so high levels of specific peptide:MHC class II complexes appear on the B-cell surface (Fig. 9.18). As we will see in Chapter 10, this pathway of antigen presentation allows the B cell to specifically interact with a CD4 T cell that has been previously activated by the same antigen as a mechanism to receive signals from the T cell to drive the B cell's differentiation into an antibody-producing cell.