Porth's Pathophysiology, 9e

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UNIT IV Infection, Inflammation, and Immunity

Innate immunity

Adaptive immunity

Characteristics

Recognition

Molecular patterns common to microbes

Specific microbial molecules

Different microbes Identical mannose receptor

Different microbes

Distinct antibodies

Receptors

Limited diversity expressed by germline genes

Great diversity expressed through recombination of somatic genes

B-cell receptor

Plasma cell

B cell

Antibody

Toll-like receptor

Mannose receptor

Cellular expression

Effector cell types express identical receptors (e.g., neutrophils express Toll-like receptors).

Each clone of lymphocytes expresses unique receptors.

Self–nonself discrimination

Yes, by recognizing molecules unique to pathogen, NK cells recognize MHC-I self-recognizing molecules.

Yes, lymphocytes use MHC-I and -II and foreign peptides (e.g., microbial peptides in recognition).

FIGURE 13.3  •  Recognition systems of innate and adaptive immunity.

gram-negative bacteria. TLR2 binds to peptidoglycan, which is an essential component of the cell wall of gram-positive bacteria. Finally, TLR5 can recognize the protein flagellin found in flagellated bacteria. In addition to their role in the immune response, TLRs have been shown to have a patho- logic role in disorders such as atherosclerosis, allergies, and certain autoimmune diseases. 21,22

inflammatory process including acute-phase proteins, lec- tins, and complement. Components of the adaptive immune response can also act as opsonins. For example, when the humoral response is activated, IgG and IgM antibodies can coat cellular particles on pathogens and bind to Fc receptors on neutrophils and macrophages, enhancing the phagocytic function of innate cells. Inflammatory Cytokines Cytokines are low molecular weight proteins that serve as sol- uble chemical messengers and which mediate the interaction between immune and tissue cells. They are part of an integrated signaling network with extensive functions in both the innate (nonspecific) and adaptive immune defenses. The cytokines involved in innate immunity include TNF- α and lymphotoxin; interferons (IFN- γ , IFN- α , IFN- β ); the interleukins IL-1, IL-6, and IL-12; and chemokines (see Table 13.2). These substances modulate innate immunity by stimulating the development of cells involved in both innate and adaptive immunity, produc- ing chemotaxis within leukocytes, stimulating acute-phase pro- tein production, and inhibiting viral replication. Once an innate immune phagocyte is activated via PRR–PAMP with a patho- gen, cytokines are released into the surrounding tissues where they exert their effect. If large numbers of cells are activated, then cytokines may be able to stimulate inflammatory processes in tissues far from the initial site of infection. Under normal circumstances, the duration of activity of cytokines is relatively short so that a prolonged immune response does not occur.

Soluble Mediators of Innate Immunity

While cells of the innate immune system communicate critical information about invading microorganisms and self–nonself recognition through cell-to-cell contact, soluble mediators are also essential for many other aspects of the innate immune response. Development of innate immune response is very much dependent upon the secretion of soluble molecules such as opsonins, cytokines, and acute-phase proteins. Opsonins Opsonins are molecules that coat negatively charged par- ticles on cell membranes and as a result enhance the recog- nition and binding of phagocytic cells to microorganisms. The process by which the cellular particles on microbes are coated is called opsonization . Once the opsonin binds to the microbe, it is able to activate the phagocyte after attachment to a PRR on the phagocytic cell. There are sev- eral opsonins important in innate immunity and the acute