Porth's Pathophysiology, 9e

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UNIT IV Infection, Inflammation, and Immunity

­development of memory. Active immunity is usually long lasting but requires a few days to weeks after a first expo- sure to sufficiently develop an appropriate immunological response that culminates in the destruction of the presenting antigen. However, with subsequent exposure the immune sys- tem rapidly becomes fully activated because of the presence of memory B and T lymphocytes and circulating antibodies. The process by which active immunity is acquired through the administration of a vaccine is termed immunization . An acquired immune response can improve on repeated exposures to an injected antigen (booster vaccines) or a natural infection. Passive immunity is immunity transferred from another source. The most common form of passive immunity is that conferred from mother to fetus. During fetal development, maternal IgG antibodies are transferred to the fetus via the placenta. After birth, the neonate also receives IgG antibodies from the mother in breast milk or colostrum. Therefore, infants are provided with some degree of protection from infection for approximately 3 to 6 months, giving their own immune sys- tems time to mature. Some protection against infectious dis- ease can also be provided by the administration of Igs pooled from human or animal sources. Passive immunity produces only short-term protection that lasts weeks to months. In order for a host organism to remain healthy, the immune system must function properly. A weakened immune response may lead to immunodeficiency, but an inappropriate or exces- sive response can cause allergic reactions and autoimmune diseases. Therefore, the immune system must be capable of regulating itself. The process by which the body regulates itself is poorly understood but must involve all aspects of the innate and adaptive immune responses. Each exposure to an antigen elicits a predictable response from the immune system. Once the immune system is acti- vated, the response is amplified until it peaks and eventually subsides. This occurs because the body’s normal immune responses are self-limiting. Once the antigen is destroyed and the action of chemical mediators terminated, the immune response ceases. It is believed that anti-inflammatory cytokines and regulatory T lymphocytes play a role in this process. 34 Tolerance also plays a role in the self-regulation of the immune response. Tolerance is the ability of the immune sys- tem to react to foreign antigens but remain nonreactive to self- antigens. Tolerance to self-antigens protects the body from harmful autoimmune responses. This is exquisitely impor- tant in vital organs such as the brain, testes, ovaries, and eyes where immunological damage could be lethal to the organism. Many autoimmune diseases such as Hashimoto thyroid- itis and insulin-dependent diabetes mellitus are caused by impairment in both B and T lymphocyte (specifically cyto- toxic lymphocytes) functions resulting in direct cellular dam- age because the body immune system is no longer capable of distinguishing “self” from “nonself.” 35,36 Regulation of the Adaptive Immune Response

Spleen The spleen is a large, ovoid secondary lymphoid organ located high in the left upper quadrant of the abdominal cav- ity between the diaphragm and the stomach. The spleen filters antigens from the blood and is important in the response to systemic infections. It is divided into two systems: the white pulp and the red pulp. The red pulp is well supplied with arter- ies and venous sinusoids and is the area where senescent and injured red blood cells are removed. The white pulp contains lymphatic nodules and diffuse lymphoid tissue where con- centrated areas of B and T lymphocytes permeated by mac- rophages and DCs exist. The lymphocytes (primarily T cells) that surround the central arterioles form the area called the periarterial lymphoid sheath . There is also a diffuse marginal zone that contains the follicles and germinal centers and is rich in B cells. This separates the white pulp from the red pulp and allows lymphocytes to move easily between the blood and the lymphatic tissue. A sequence of activation events similar to that seen in the lymph nodes occurs in the spleen. Other Secondary Lymphoid Tissues Other secondary lymphoid tissues include the mucosa-­ associated lymphoid tissues , which are nonencapsulated clus- ters of lymphoid tissues located around membranes lining the respiratory, digestive, and urogenital tracts. These organ sys- tems constantly came in contact with pathogens and toxins and, therefore, require the presence of immune cells in order to respond to the potential invasion by pathogens and harmful substances. In some tissues, the lymphocytes are organized in loose, nondescript clusters, but in other tissues such as the tonsils, Peyer patches in the intestine, and the appendix, their structure is better organized. These tissues contain all the cellular components ( i.e., T cells, B cells, macrophages, and DCs) required to mount an immune response. Immunity at the mucosal layers helps to exclude many pathogens from the body and, as a result, protects the more vital internal structures. Active versus Passive Immunity The goal of the immune system is to protect the host against invasion by potentially dangerous pathogens, foreign sub- stances, and other sources of harmful antigens. Adaptive immune responses accomplish this goal through the activation of cell-mediated and humoral responses. This type of protec- tion can be induced in one of two ways: 1. After exposure to the offending substance and activa- tion of B and T lymphocytes (active immunity) 2. Through the transfer of antibodies against an antigen directly to the host (passive immunity) Active immunity is acquired when the host mounts an immune response to an antigen either through the process of vacci- nation or from environmental exposure. It is called active immunity because it requires the host’s own immune sys- tem to develop an immunological response including the