Medical brain notes 26

  GENERAL CONCEPTS A.   Specific and Nonspecific Defenses The protection of our organism against infectious agents involves many different mecha-nisms—some nonspecific (i.e., generically applicable to many different pathogenic organ-isms) and others specific (i.e., their protective effect is directed to one single organism). Nonspecific defenses, which as a rule are innate (i.e., all normal individuals are born with them), include: ·                Mechanical barriers such as the integrity of the epidermis and mucosal membranes hysicochemical barriers, such as the acidity of the stomach fluid ·                The antibacterial substances (e.g., lysozyme, defensins) present in external secretions Normal intestinal transit and normal flow of bronchial secretions and urine, which eliminate infectious agents from the respective systems · ...

  CELLS OF THE IMMUNE SYSTEM The peripheral blood contains two large populations of cells: the red cells, whose main physiological role is to carry oxygen to tissues, and the white cells, which have as their main physiological role the elimination of potentially harmful organisms or compounds. Among the white blood cells, lymphocytes are particularly important because of their cen-tral role in the immune response. Several subpopulations of lymphocytes have been defined: 1. B lymphocytes, which are the precursors of antibody-producing cells, known as plasma cells.   2. T lymphocytes, which can be divided into several subpopulations: a. Helper T lymphocytes (T H ), which play a very significant amplification role in the immune responses. Two functionally distinct subpopulations of T helper lymphocytes emerging from a precursor population (T H  0) have been defined: 1) T H 1 lymphocytes, which assist the differentiation of cyto-toxic cells and also activate macrophages (acti...

  ANTIGENS AND ANTIBODIES Antigens are usually exogenous substances (cells, proteins, and polysaccharides) which are recognized by receptors on lymphocytes, thereby eliciting the immune response. The re-ceptor molecules located on the membrane of lymphocytes interact with small portions of those foreign cells or proteins, designated as antigenic determinants or epitopes. An adult human being has the capability to recognize millions of different antigens, some of micro-bial origin, others present in the environment, and even some artificially synthesized. Antibodies are proteins that appear in circulation after infection or immunization and that have the ability to react specifically with epitopes of the antigen introduced in the or-ganism. Because antibodies are soluble and are present in virtually all body fluids (“hu-mors”), the term humoral immunity was introduced to designate the immune responses in which antibodies play the principal roles as effector mechanism. Antibodies are...

  LYMPHOCYTES AND CELL-MEDIATED IMMUNITY Lymphocytes play a significant role as effector cells in three main types of situations, all of them considered as expression of cell-mediated immunity, i.e., immune reactions in which T lymphocytes are the predominant effector cells. A.   Immune Elimination of Intracellular Infectious Agents Viruses, bacteria, parasites, and fungi have developed strategies that allow them to survive inside phagocytic cells or cells of other types. Infected cells are generally not amenable to destruction by phagocytosis or complement-mediated lysis. The study of how the immune system recognizes and eliminates infected cells resulted in the definition of the biological role of the histocompatibility antigens (HLA) that had been described as responsible for graft rejection . Those membrane molecules have a peptide-binding pouch that needs to be occupied with peptides derived from either endogenous or exogenous proteins. The immune system does not recogniz...

  SELF VERSUS NONSELF DISCRIMINATION The immune response is triggered by the interaction of an antigenic determinant with specific receptors on lymphocytes. It is calculated that there are several millions of different receptors in lymphocytes—10 15 –10 18  on T cells and 10 11  on B cells—sufficient to respond to a wide diversity of epitopes presented by microbial agents and potentially noxious ex-ogenous compounds. At the same time, the immune system has the capacity to generate lymphocytes with receptors able to interact with epitopes expressed by self antigens. Dur-ing embryonic differentiation and adult life the organism uses a variety of mechanisms to ensure that potentially autoreactive lymphocytes are eliminated or turned off. This lack of response to self antigens is known as tolerance to self. When the immune system is exposed to exogenous compounds, it tends to develop a vigorous immune response. The discrimination between self and nonself is based the fact tha...

  GENERAL OVERVIEW One of the most difficult intellectual exercises in immunology is to try to understand the global organization and control of the immune system. Its extreme complexity and the wide array of regulatory circuits involved in fine-tuning the immune response pose a formidable obstacle to our understanding. A concept map depicting a simplified view of the immune system is reproduced in Figure 1.1.           If we use as an example the activation of the immune system by an infectious agent that has managed to overcome the innate anti-infectious defenses, the first step must be the uptake of the infectious agent by a cell capable of presenting it to the immune system in fa-vorable conditions for the induction of an immune response. In the case of T lymphocytes, APCs expressing MHC-II molecules play this role. A variety of cells can function as APCs, including tissue macrophages, B cells, and dendritic cells. Those cells adsorb...