Immune System and Disease PDF

Can the immune system be a source of disease?  What kind of structures do antibodies recognize? Why don’t antibodies recognize these structures on our cells? Lymphocyte development generates a very large pool of lymphocytes, each with a unique specificity. The...

Can the immune system be a source of disease?  What kind of structures do antibodies recognize? Why don’t antibodies recognize these structures on our cells? Lymphocyte development generates a very large pool of lymphocytes, each with a unique specificity. The size of this pool is what protects you from the variety of different pathogens.  Immune tolerance: self-reactive lymphocytes are normally deleted during development, or they are made non-responsive. Also called ‘negative selection’. As B cells develop in the bone marrow they rearrange immunoglobulin gene segments to generate a large number of different specificities. If the immunoglobulin expressed by a B cell binds to self-antigens then this B cell is induced to die or is inactivated.  Human ABO Antigens and Blood Types Individuals express glycolipids on red blood cells with terminal carbohydrate structures identified as either ‘A’ or ‘B’, or in the absence of the terminal structure, identified as ‘O’. Since individuals express both alleles there are 4 blood types: A, B, AB, or O. Individuals produce antibodies that bind A or B antigens because they have been exposed to microbial pathogens which also have these structures. Why don’t individuals have antibodies that bind their own ABO antigen? Mismatched blood transfusions can lead to serious complications as antibody can bind to rbcs and cause complement-mediated hemolysis in recipients. Anti-A antigen antibody Blood typing using anti-A, anti-B antibodies. RBC clustering shows antibody binding Rhesus (Rh) is another red blood cell antigen whose expression differs between individuals and can be recognized by antibodies. Anti-Rh antibodies do not pre- exist, but are induced by exposure, as happens during delivery of an Rh+ fetus by an Rh- mother. Development of anti-Rh antibodies in the mother can damage rbcs of a subsequent Rh+ fetus. Treatment with anti-Rh antibodies directly after the initial pregnancy can prevent sensitization.  Immunopathology associated with pathogen infection Effects of inflammatory signals on blood vessels is typically a local event helping bring additional immune mediators to a site of infection. What would happen if the infection was in the blood and the response was not localized? Sepsis System-wide infection with bacteria can lead to systemic inflammatory response. Inflammatory cytokines act on blood vessels throughout the body, increasing permeability and leading to a loss of blood volume. Severe cases of sepsis lead to shock which can be fatal. Allergy - strong immune response directed to otherwise innocuous, but abundant substances, e.g. pollen, foods. Pollen grain These responses occur rapidly following allergen exposure. Allergens bind IgE antibody which is bound to Fc-Epsilon receptors on the surface of mast cells. This leads to the release of granules containing allergic mediators. Mast cells are found in mucosal and connective tissue and play an important role in protection against larger pathogens. Allergic responses require sensitization. Initial allergen exposure induces adaptive immunity; this includes B cells producing IgE, which binds to FcE receptors on mast cells. Subsequent allergen binding by the IgE on mast cells causes release of allergic mediators, e.g. histamine and prostaglandins, that induce symptoms. What drugs block allergic responses? Allergic mediators released by mast cell degranulation promote inflammatory responses and enhance clearance mechanisms at mucosal surfaces. Symptoms depend upon the site of exposure, e.g. respiratory tract, gastrointestinal tract. hives What would happen if allergen exposure was systemic? Allergic responses are potentially lethal if there is systemic release of mediators. This is known as anaphylaxis. There is increased blood vessel permeability causing a rapid loss of blood volume, coupled with induced airway constriction. When might an allergen be present throughout the body? Can you develop an immune response to particular drugs? Drugs are not typically antigenic, but if they attach to host proteins, as penicillin can, then they are able to create antigenic structures that may elicit the production of antibodies. Antibody binding to a drug can cause a severe systemic response Why would the response get worse with repeated exposure? T cells can also mediate hypersensitivity Contact dermatitis: Substances, (e.g. nickel, catechols from plant oils) modify host proteins, which are recognized as antigens by T cells. After sensitization, effector T cells mediate an inflammatory response at the site of exposure to the substance. T cell-mediated inflammation requires several days - known as ‘delayed-type hypersensitivity’