Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 4)

The Immune ResponseInnate Immunity As they have co-evolved with microbes, higher organisms have developed mechanisms for recognizing and responding to microorganisms. Many of these mechanisms, referred to together as innate immunity, are evolutionarily ancient, having been conserved from insects to humans. In general, innate immune mechanisms exploit molecular patterns found specifically in pathogenic microorganisms. These "pathogen signatures" are recognized by host molecules that either directly interfere with the pathogen or initiate a response that does so. Innate immunity serves to protect the host without prior exposure to an infectious agent—i.e., before specific or adaptive immunity has had a chance...
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Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 4) Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 4) The Immune Response Innate Immunity As they have co-evolved with microbes, higher organisms have developedmechanisms for recognizing and responding to microorganisms. Many of thesemechanisms, referred to together as innate immunity, are evolutionarily ancient,having been conserved from insects to humans. In general, innate immunemechanisms exploit molecular patterns found specifically in pathogenicmicroorganisms. These pathogen signatures are recognized by host moleculesthat either directly interfere with the pathogen or initiate a response that does so.Innate immunity serves to protect the host without prior exposure to an infectiousagent—i.e., before specific or adaptive immunity has had a chance to develop.Innate immunity also functions as a warning system that activates components ofadaptive immunity early in the course of infection. Toll-like receptors (TLRs) are instructive in illustrating how organisms aredetected and send signals to the immune system. There are at least 11 TLRs, eachspecific to different biologic classes of molecules. For example, even minusculeamounts of lipopolysaccharide (LPS), a molecule found uniquely in gram-negativebacteria, are detected by LPS-binding protein, CD14, and TLR4 (see Fig. 114-3).The interaction of LPS with these components of the innate immune systemprompts macrophages, via the transcriptional activator nuclear factor κB (NF-κB),to produce cytokines that lead to inflammation and enzymes that enhance theclearance of microbes. These initial responses serve not only to limit infection butalso to initiate specific or adaptive immune responses. Adaptive Immunity Once in contact with the host immune system, the microorganism faces thehosts tightly integrated cellular and humoral immune responses. Cellularimmunity (Chap. 308), comprising T lymphocytes, macrophages, and naturalkiller cells, primarily recognizes and combats pathogens that proliferateintracellularly. Cellular immune mechanisms are important in immunity to allclasses of infectious agents, including most viruses and many bacteria (e.g.,Mycoplasma, Chlamydophila, Listeria, Salmonella, and Mycobacterium), parasites(e.g., Trypanosoma, Toxoplasma, and Leishmania), and fungi (e.g., Histoplasma,Cryptococcus, and Coccidioides). Usually, T lymphocytes are activated bymacrophages and B lymphocytes, which present foreign antigens along with thehosts own major histocompatibility complex antigen to the T cell receptor.Activated T cells may then act in several ways to fight infection. Cytotoxic T cellsmay directly attack and lyse host cells that express foreign antigens. Helper T cellsstimulate the proliferation of B cells and the production of immunoglobulins.Antigen-presenting cells and T cells communicate with each other via a variety ofsignals, acting coordinately to instruct the immune system to respond in a specificfashion. T cells elaborate cytokines (e.g., interferon) that directly inhibit thegrowth of pathogens or stimulate killing by host macrophages and cytotoxic cells.Cytokines also augment the hosts immunity by stimulating the inflammatoryresponse (fever, the production of acute-phase serum components, and theproliferation of leukocytes). Cytokine stimulation does not always result in afavorable response in the host; septic shock (Chap. 265) and toxic shock syndrome(Chaps. 129 and 130) are among the conditions that are mediated by theseinflammatory substances. The immune system has also developed cells that specialize in controllingor downregulating immune responses. For example, Treg cells, a subgroup ofCD4+ T cells, prevent autoimmune responses by other T cells and are thought tobe important in downregulating immune responses to foreign antigens. Thereappear to be both naturally occurring and acquired T reg cells. The reticuloendothelial system comprises monocyte-derived phagocyticcells that are located in the liver (Kupffer cells), lung (alveolar macrophages),spleen (macrophages and dendritic cells), kidney (mesangial cells), brain(microglia), and lymph nodes (macrophages and dendritic cells) and that clearcirculating microorganisms. Although these tissue macrophages andpolymorphonuclear leukocytes (PMNs) are capable of killing microorganismswithout help, they function much more efficiently when pathogens are firstopsonized (Greek, to prepare for eating) by components of the complementsystem such as C3b and/or by antibodies. Extracellular pathogens, including most encapsulated bacteria (thosesurrounded by a complex po ...