Chapter 22 Immune System
Comparison of Innate Immunity and Adaptive Immunity
***Figure 22.2Overview of the Immune System. The immune system is composed of two overlapping and complementary components: the innate immune system, which is initiated by many different components against a wide array of substances, and the adaptive immune system, which involves the response of lymphocytes to a specific antigen.^^
General Structure of Lymphocytes - T-lymphocytes and B-lymphocytes differ from other immune cells because each lymphocyte has a unique receptor complex, which are composed of several different and separate proteins. There are typically about 100,000 receptor complexes per cell. A receptor complex will bind one specific antigen. The antigen receptor (which is a portion of a receptor complex) of a T-lymphocyte is referred to as the TCR (or T-cell receptor), and the antigen receptor of a B-lymphocyte is called a BCR (or B-cell receptor) (figure 22.10).
Figure 22.10T-Lymphocytes and B-Lymphocytes. The receptors of T-lymphocytes and B-lymphocytes are plasma membrane molecules. (a) Helper T-lymphocytes contain TCRs (T-cell receptors) and CD4 proteins, whereas cytotoxic T-lymphocytes contain TCRs and CD8 protein. (b) B-lymphocytes contain BCRs (B-cell receptors). Note: There are many other receptors embedded within both T-lymphocytes and B-lymphocytes. This figure depicts only the TCR, CD4, or CD8 receptors of T-lymphocytes and the BCR of B-lymphocytes.
Activation of T-Lymphocytes - Activation of Helper T-Lymphocytes - The specifics of activation of helper T-lymphocytes is shown in figure 22.16b. The first signal is direct physical contact between the MHC class II molecule of an antigen-presenting cell (APC) and the TCR of a helper T-lymphocyte. Exogenous antigen previously engulfed by an APC is presented on its surface with MHC class II molecules (as described in section 22.4c). The APC either is housed in the secondary lymphatic structure (e.g., macrophage) or migrates there from the skin (e.g., dendritic cells) to make contact with the helper T-lymphocyte. A helper T-lymphocyte binds to the APC to inspect the antigen: The specific TCR of a T-lymphocyte binds with the peptide fragment presented with an MHC class II molecule of the APC. This interaction is stabilized by the CD4 molecule of the helper T-lymphocyte binding to other regions of the MHC class II molecule. If the TCR does not recognize the presented antigen, it disengages from the APC. If it does recognize the antigen, contact between the two cells lasts several hours. The second signal takes place when other receptors of the APC (e.g., B7) interact with receptors of the helper T-lymphocyte (e.g., CD28). Ultimately, helper T-lymphocytes are induced to synthesize and release the cytokine interleukin 2 (IL-2), which occurs within about 24 hours. IL-2 acts as an autocrine hormone (see section 17.3b) to further stimulate the helper T-lymphocyte from which it was released.
Figure 22.16Activation of Lymphocytes. Activation of lymphocytes occurs in secondary lymphatic structures, usually the lymph nodes or spleen. Activation results in lymphocyte proliferation and differentiation to form a clone of identical cells that includes memory cells. Two signals (costimulation) are required to activate each type of lymphocyte: (a) cytotoxic T-lymphocyte, (b) helper T-lymphocyte, and (c) B-lymphocyte.
Effector Response of Helper T-Lymphocytes - Activated and memory helper T-lymphocytes leave the secondary lymphatic structure after several days of exposure to antigen. They migrate to the site of infection, where they continue to release the cytokines to regulate other immune cells (figure 22.17a). Although helper T-lymphocytes were named based on their function in helping activate B-lymphocytes, their contributions are much more encompassing. Helper T-lymphocytes activate cytotoxic T-lymphocytes, as described in section 22.6a, through the release of cytokines (e.g., IL-2); they also enhance formation and activity of cells of the innate immune system, including macrophages and NK cells. Thus, healthy helper T-lymphocytes play a central role in a normally functioning immune system (see Clinical View 22.9: "HIV and AIDS").
Figure 22.17Effector Response of T-Lymphocytes. The effector response of helper T-lymphocytes and cytotoxic T-lymphocytes occurs at the site of infection. (a) Helper T-lymphocytes release various cytokines, and (b) cytotoxic T-lymphocytes destroy abnormal cells through the release of the cytotoxic chemicals perforin and granzymes, which induces apoptosis.
Measure of Immunologic Memory - ***Antibody titer (concentration of antibody) in blood serum is one measure of immunologic memory. The graphs shown in figure 22.21 reflect the changes in serum antibody titer (specifically, the amount of IgM and IgG in the blood) over time in response to both the initial exposure (the antigen challenge) and subsequent exposures to an antigen. The degree of protection is indicated by levels of circulating IgG.^^
Figure 22.21Primary and Secondary (Anamnestic) Response in Humoral Immunity. Graph of the primary response that shows the level of IgM and IgG antibody produced by plasma cells on the first exposure to a given antigen. Graph of the secondary response that depicts the level of these antibodies on all subsequent exposures to the same antigen.
Nonspecific Internal Defenses: Cells
Figure 22.3Cells of the Innate Immune System. The cells of the innate immune system use multiple tactics to combat pathogens, including (a) phagocytosis (example shown is a macrophage), (b) chemical secretion that increases inflammation (example shown is a basophil), (c) chemical secretion by NK cells that destroys unhealthy cells by inducing apoptosis, and (d) chemical secretion by eosinophils that helps eliminate parasites.