FIGURE 55–3 Scheme of cellular interactions during the generation of cell-mediated and humoral immune responses (see text). The cell-mediated arm of the immune response involves the ingestion and digestion of antigen by antigen-presenting cells such as macrophages. Activated TH cells secrete IL-2, which causes proliferation and activation of cytotoxic T lymphocytes as well as TH1 and TH2 cell subsets. TH1 cells also produce IFN-γ and TNF-β, which can directly activate macrophages and NK cells. TH17 cells may be induced by IL-1, -6, -23 or TGF-β secretion by antigen-presenting cells; TH17 cells are inflammatory and secrete IL-17 and -22. The humoral response is triggered when B lymphocytes bind antigen via their surface immunoglobulin. They are then induced by TH2-derived IL-4 and IL-5 to proliferate and differentiate into memory cells and antibody-secreting plasma cells. Regulatory cytokines such as IFN-γ and IL-10 down-regulate TH2 and TH1 responses, respectively (dashed arrows).
Whereas the normally functioning immune response can suc-Hypersensitivity can be classified as antibody-mediated or cellcessfully neutralize toxins, inactivate viruses, destroy transformed mediated. Three types of hypersensitivity are antibody-mediated cells, and eliminate pathogens, inappropriate responses can lead (types I–III), while the fourth is cell-mediated (type IV). Hypersento extensive tissue damage (hypersensitivity) or reactivity against sitivity occurs in two phases: the sensitization phase and the effector self antigens (autoimmunity); conversely, impaired reactivity to phase. Sensitization occurs upon initial encounter with an antigen; appropriate targets (immunodeficiency) may occur and abrogate the effector phase involves immunologic memory and results in essential defense mechanisms. tissue pathology upon a subsequent encounter with that antigen.
–S-S––S-S– Fc receptor Fc region Opsonization Antigen-binding region Hinge region Bacteria BAEpitope Macrophage Bacterial lysis Complement activation –S-S– –S-S– Complementarity-determining region (CDR) CH1 VH CH2 CH3 VL CL FIGURE 55–4 Antibody has multiple functions. The prototypical antibody consists of two heavy (H) and two light (L) chains, each subdivided into constant (CL, CH) and variable (VL, VH) domains. The structure is held together by intraand interchain disulfide bridges. A: The complementarity-determining region (CDR) of the antigen-binding portion of the antibody engages the antigenic determinant (epitope) in a lock-and-key fashion. B: Antigen-antibody complexes activate complement to produce split complement components that cause bacterial lysis. C: The Fc portion of anti-bodies binds to Fc receptors on phagocytes (eg, macrophages, neutrophils) and facilitates uptake of bacteria (opsonization).
1.
Type I—Immediate, or type I, hypersensitivity is IgE-mediated, with symptoms usually occurring within minutes following the patient’s reencounter with antigen. Type I hypersensitivity results from cross-linking of membrane-bound IgE on blood basophils or tissue mast cells by antigen. This cross-linking causes cells to degranulate, releasing substances such as histamine, leukotrienes, and eosinophil chemotactic factor, which induce anaphylaxis, asthma, hay fever, or urticaria (hives) in affected individuals (Figure 55–5). A severe type I hypersensitivity reaction such as systemic anaphylaxis (eg, from insect envenomation, ingestion of certain foods, or drug hypersensitivity) requires immediate medical intervention.
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