Normal and Abnormal Immune Responses
4. Early: pathogen-associated molecular patterns (PAMPs) on microbial structures (e.g., lipopolysaccharide and peptidoglycan) stimulate toll-like receptors (TLRs) and other receptors on DCs and macrophages that make cytokines
• Lymphocytes interact with antigen-presenting cells (APCs) in lymph nodes (Fig. 4-1), the spleen, and mucosal-associated lymphoid tissue, which includes tonsils, adenoids, appendix, and Peyer patches; cytokines define the nature of the response (Table 4-1).
IFN, interferon; IL, interleukin; PAMP, pathogen-associated molecular pattern; TGF, transforming growth factor; TH, helper T cell; TNF, tumor necrosis factor; Treg/sup, regulatory or suppressive T cell.
4-1 Antigen-dependent lymphocyte activity in peripheral lymph node. Antigen carried in the lymph becomes associated with dendritic cells (DCs) to be presented to lymphocytes. The paracortex contains mainly T cells, many of which are associated with interdigitating antigen-presenting cells (DCs). After initial activation, T cells migrate to the cortex, where they interact with B cells in primary follicles, which develop into secondary follicles, with active B cell proliferation and differentiation occurring in the germinal centers. Lymphocytes leave the node through the efferent lymphatic vessel.
4. Initial activation and proliferation of naive CD8 cytotoxic T (TC) cells triggered by binding of antigenic peptides associated with class I MHC molecules on DCs for recognition of infected cells, tumor cells, and grafts
1. Rechallenge with an antigen produces a secondary specific response that is faster and stronger (anamnestic response) than primary response to the same antigen because DCs and any APCs can present antigen to T cells and because of the presence of memory B and T cells (Fig. 4-2).
4-2 Time course of primary and secondary humoral (antibody) immune responses. After initial challenge with a particular antigen, secreted antibody is detectable only after a lag period of several days and initially consists of IgM. The secondary immune response (anamnestic response) after rechallenge with the same antigen reaches a higher titer, lasts longer, and consists predominantly of IgG.
• Hypersensitivity reactions are important in the immune response to certain antigens, but they also cause pathologic changes associated with many autoimmune diseases and infections, especially viral infections (Table 4-2).
4-3 Type I hypersensitivity. IgE produced in response to initial allergen exposure binds to Fc receptors on mast cells and basophils. Rechallenge with the same allergen leads to release of histamine and other mediators, which produce various symptoms of localized atopic reaction or generalized anaphylaxis. Ag, antigen; IL-4, interleukin-4.