MHC Molecules

1. 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.

2. 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.

3. 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.

4. MHC Molecules • Infected body cells present antigens using MHC-1 molecules

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

6. 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.

7. 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

9. 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.

10. Antibodies • Single-Unit antibody structure

11. 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

12. 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.