Fig.5.3 Theinflammasome.Theinflammasomeisaproteincomplexthat recognizesproductsofdeadcellsandsomemicrobesandinducesthesecretionofbiologicallyactiveinterleukin-1.Itisacomplexofmultiplecopiesof asensorprotein(aleucine-richproteincalledNLRP3),anadapter,andthe enzyme caspase-1, which is converted from an inactive toanactive form. The structure of the inflammasome as shown is simplified from known crystal structures.The formation of the inflammasome complex proceeds byaprion-likemechanismofpropagation,inwhichoneproteinalteredby activation induces conformational changes in other proteins of the same type.The net result is the activation and assembly of a large number of identicalpolypeptides,formingfilament-likebundlesofadaptersandenzymes.
Reactions of Innate Immunity
The innate immune system provides host defense by the following two main reactions:
Inflammation. Cytokines and products of complement activation, as well as other mediators, are produced during innate immune reactions and trigger the vascular and cellular components of inflammation. The recruited leukocytes destroy pathogens and ingest and eliminate damaged cells. This reaction was described in Chapter 3.
Anti-viral defense. Type I interferons produced in response to viruses act on infected and uninfected cells and activate enzymes that degrade viral nucleic acids and inhibit viral replication.
In addition to these defensive functions, the innate immune system generates signals that stimulate the subsequent, more powerful adaptive immune response. Some of these signals are described later.
The adaptive immune system consists of lymphocytes and their products, including antibodies. In contrast to the limited repertoire of the innate immune system, the adaptive immune system can recognize a vast array of foreign substances.
There are two types of adaptive immunity: humoral immunity, mediated by soluble proteins called antibodies that are produced by B lymphocytes (also called B cells), and cell-mediated (or cellular) immunity, mediated by T lymphocytes (also called T cells). Antibodies provide protection against extracellular pathogens in the blood, mucosal surfaces, and tissues. T lymphocytes are important in defense against intracellular microbes. They work by either directly killing infected cells (accomplished by cytotoxic T lymphocytes) or by activating phagocytes to kill ingested microbes, via the production of soluble protein mediators called cytokines (made by helper T cells). We next turn to the main properties and functions of the cells of the immune system.
The cells of the immune system consist of lymphocytes, most of which have specific receptors for antigens and mount adaptive immune responses; specialized APCs, which capture and display microbial and other antigens to the lymphocytes; and various effector cells, whose function is to eliminate microbes and other antigens. Some of the remarkable features of the immune system are the expression of highly diverse and specific antigen receptors on B and T cells, the specialization of the cells that that enable them to perform many different functions, and the precise control mechanisms that permit useful responses when needed and prevent potentially harmful ones.
Lymphocytes are present in the circulation and in various lymphoid organs. Although all lymphocytes are morphologically similar, they actually consist of several functionally and phenotypically distinct populations (