Lecture 10

Lecture 10

1. Classes of Antibodies

   • Class defined by heavy chain
   • Light Chains: kappa, lambda
   • Heavy Chains: mu, gamma, alpha, delta, epsilon
   • IgM: Largest antibody molecule (pentamer). Confined to blood and lymphatics. about 10% of Ig pool. First in primary antibody response. Effective agglutinator. Efficient complement activator. Important for blood borne spread of pathogens.
   • IgG: small monomer. 70-75% of Ig pool. Diffuses into extravascular spaces. Potent antitoxin antibody. Effective barrier against viruses. Actively transported across the placenta. Good complement activator. Strongly bound by phagocytes. Enhancement of phagocytosis (opsonisation).
   • IgA: 15-20% of human blood antibodies. Predominant in sero-mucous secretions. Main role-protecting external body surfaces. Prevents potentially harmful material getting through the gut, respiratory tract and genitourinary tract.
   • IgD: only trace amount in blood and other fluids. Found exclusively on the surface of naive B cells. Main function is as a triggering receptor. Delivers activation signal to naive B cells through antigen binding.
   • IgE: generally only trace amounts in the blood. Important in allergies and some parasitic infections. Can bind strongly to mast cells (class of basophils). Allergens binding to mast-cell associated IgE, activates processes that lead to symptoms of allergy or asthma.

2. Humoral and Cell-Mediated Immunity

   • Humoral immunity: product of B cells, involves antibodies, effective against antigens outside cells. Viruses and toxins (stop attachment). Extracellular bacteria (enhance phagocytosis, activate complement).
   • Cell-Mediated Immunity: Product of T cells, no antibodies, effective against intracellular antigens (displayed on cell-surfaces). Virus infected cells, tumour cells, transplanted organs.

3. HLA Genes

   • Structure
     • Genes that code for the structures on the surface of cells which present antigens to T lymphocytes and are also recognised in graft rejection are called the MHC genes.
     • Class I: found on virtually all nucleated cells. Co-dominant. Polymorphic. Present peptides to CD8 T cells.
     • Class II: found on B cells and specialised APCs. Co-dominant. Polymorphic. Present peptides to CD4 T cells.
   • Significance
   • Products

4. Methods of Antigen Presentation

   • The way in which antigens are process within cells differ according to whether the antigens are ingested by the cell (e.g. though phagocytosis or pinocytosis) or whether they originate within the cell.
   • Antigenic fragments that associate with class I molecules are usually derived from an infectious process (such as virus infection and replication) or as a result of normal breakdown of normal cell metabolic product within the cell.
   • Antigenic determinant that associated with class II MHC molecules usually result from the processing of antigens which have been taken up (phagocytosed) and degraded by specialised antigen-presenting cells.
   • Antigen fragments can be presented to T lymphocytes by Class I and II MHC molecules on the surface of cells.
   • All T cells express receptors for antigens that recognise antigenic peptide fragments presented to them by MGC structures.

5. T Lymphocytes

   • Cytotoxic Lymphocytes Generation
     • CD8, CD3, TCR - alpha beta
     • Recognise Class I MHC Peptide on a target cell (e.g. virus infected)
     • Cytotoxic T cell precursors are selected by antigens presented to them by class I MHC structures
     • Typically the sort of cells which might present antigens to Cytotoxic precursors might be virus infected cells.
     • Cytotoxic T cell precursors with receptors which bind strongly to the presented antigens will become activated.
     • With the help of immunological hormones (cytokines) from helper T cells, these activated cells will divide and differentiate into population of effector cells which can recognise specific target cells and kill them.
   • Arise in the thymus
   • Helper T cells
     • CD4, CD3, TCR - alpha beta
     • Recognise Class II MHC Peptide on an antigen presenting cell