MHC Molecules Our immune system has the remarkable ability, and responsibility, of responding appropriately to a wide variety of potential pathogens in our environment. The proteins that are used as cell-markers to “flag” self from non-self are called MHC molecules, and are coded for by a group of genes called the major histocompatibility complex (MHC). MHC genes are diverse, and vary greatly from individual to individual. Our adaptive immune system has the remarkable ability to respond to at least a billion different epitopes Genetic recombination is the shuffling and rearranging of a few hundred versions of several small gene segments

MHC Molecules There are two general classes of MHC molecules, and at least one or the other, or both, are found on the surface of all nucleated cells in the body. Class I molecules (MHC-I) are built into almost all body cells and are used to present non-self proteins (from bacteria or viruses, for example) to cytotoxic T cells. Class II molecules (MHC-II) are only found only on APCs. Both classes are important for antigen processing and presentation. Genetic recombination is the shuffling and rearranging of a few hundred versions of several small gene segments

MHC Molecules When APCs come across foreign antigens, they are broken down and loaded onto MHC-II molecules of APCs. The Class II MHC molecules on the APCs present the fragments to helper T cells, which stimulate an immune reaction from other cells. Clones of activated T cells (and the antibodies from plasma cells) are now “competent” to recognize similar antigenic fragments displayed by infected cells throughout the body and respond harshly.

MHC Molecules Infected body cells present antigens using 22_14

MHC Molecules Cytotoxic T cell destruction of an infected cell by release of perforins that cause cytolysis Microbes are destroyed by granulysin. 22_14

Clonal Selection Clonal selection is the process by which a lymphocyte proliferates and differentiates in response to a specific antigen. A clone is a population of identical cells, all recognizing the same antigen as the original cell. Lymphocytes undergo clonal selection to produce: Effector cells (the active helper T cells, active cytotoxic T cells, and plasma cells) that die after the immune response. Memory cells that do not participate in the initial immune response but are able to respond to a subsequent exposure - proliferating and differentiating into more effector and memory cells. Memory cells have long life spans

Cytokines Cytokines are chemical signals from one cell that influences another cell. They are small protein hormones that control cell growth and differentiation: Interferon Interleukins Erythropoietin Tumor necrosis factor

Antibodies Antibodies (also called immunoglobulins or Igs) are produced by plasma cells through antibody-mediated immunity. Antibodies are composed of 4 peptide chains: Two heavy chains and two light chains Disulfide bonds link the chains together in a Y-shaped arrangement. The variable region (antigen-binding region) gives an antibody its specificity. The stem is similar for each class of antibody.

Antibodies Single-Unit antibody structure 22_19

Antibodies Some of the ways antibodies are effective include: Neutralizing a bacterial or viral antibody, or a toxin by covering the binding sites and causing agglutination and precipitation (making what was soluble, insoluble) Activating the classical complement pathway Enhancing phagocytosis - a process called opsonization

Antibodies The complement system is a series of blood proteins that often work in conjunction with antibodies – it can be activated by multiple pathways in a step-wise or cascading fashion. It encourages vasodilation and inflammation, antigen opsonization, and antigen destruction. The main proteins are C1-C9.