Lecture 1 Specific, adaptive or acquired immunity There are 2 main criteria for response: Specificity – altered response = selective. Only one type of bacterium, virus or pollen grain can trigger the response Memory – a second infection occurs, the responses will be faster so tissue damage is minor. There are 2 mechanisms of specific immunity: Antibody mediated/humoral immunity (specificity depend on antibodies) Cell mediated / cellular immunity (specificity depends on T cells) ANTIGENS - a substance capable of inducing a specific immune response Immunogenicity VS Antigenicity Immunogenicity = ability to induce immune response B cell + immunogen effector B cells + memory B cells T cell + immunogen effector T cells + memory T cells Antigenicity = ability to combine with products of immune response Antibodies Cell-surface receptors Immunogen always an antigen. Antigen not necessarily an immunogen. Antigen types: Endogenous antigens – originates inside body, recognised by cytotoxic T cells Exogenous antigens – originates outside the body, recognised by helper T cells Immunogenicity Determined by 4 properties of the immunogen: - Foreignness - Molecular size - Chemical composition and heterogeneity (synthetic copolymers = immunogenic, aromatic amino acids enhance immunogenicity) - Susceptibility to antigen processing and presentation (d-stereoisomers are not immunogenic, insolubility increase phagocytosis and processing) Antigen structure Antigenic determinant (epitope) – the site on the antigen molecule where the antibody or TCR binds non covalently. Each epitope has a small number of lymphocytes that can recognise and respond to it. It induces the production specific antibody or T cell. Antibody binds to its only particular epitope only. Hapten – a molecule too small to initiate immune response, can trigger response when linked to a carrier molecule, will react with antibody present, responsible for allergic reaction to drugs. Antigenic not immunogenic. Antibodies Gamma globulins of antibodies absorbed by antigen. Classes of antibodies: IgG – 75% of all antibodies only class that crosses placenta monomers found in blood, lymph and intestine protect against bacteria and viruses triggers complement, enhance phagocytosis, neutralise toxins IgA – 15% of all antibodies monomers and dimers found in tears, saliva, mucus, milk, blood, lymph, GI secretion provides localised protection on mucous membranes IgM – 10% pentamers and monomers on B cell surface found in blood lymph and B cell surface as antigen receptor causes lysis of microbes; antigen receptor on B cells; agglutinogens on RBC; first antibody after exposure. IgD – monomers found in blood. Lymph, B cell surface as antigen receptor involved in activation of B cells IgE – monomers found on mast cells and basophils involved in allergic reactions Antibody function Complexes neutralise or eliminate antigen by several different mechanisms: - Activation of complement (classical pathway) - Phagocytosis (through opsonisation) - Neutralisation (cross linking molecules of toxin or viruses) The immunoglobulin superfamily - B cell receptor - T cell receptor - Class I and II MHC molecules - T cell accessory proteins (CD antigens) - Poly-Ig receptor (secretory component of IgA and IgM) - Cell adhesion molecules (CAMs) Monoclonal antibodies o Normal activated antibody-producing B cell o Fused with hybridoma (hybrid cell immortalised and antibody-producing) o Inserted into myeloma cell(immortal cancerous plasma cell) Lecture 4 Lymphocytes, major histocompatibility complex and antigen presenting cells. Specific – B and T cells Non-specific – null cells (NK cells) = all differentiate in bone marrow Null cells mostly large granular lymphocyte. B and T cells start as small cells that migrate to specific regions of lymphatic tissue. The have CD markers. B lymphocytes o Clone of original B cell formed over 4-5 days plasma cells (Ig secretors) and memory cells T lymphocytes Immature t cells migrate to thymus gland divide and differentiate into cytotoxic, helper and regulatory cells. Inactive T cells aggregate in lymph nodes and spleen until activated by appropriate antigens. Recog antigens displayed on self-cells (with MHC molecules): Th – CD4+, MHC class II - restricted Tc – CD8+, MHC class I – restricted Treg – ‘suppressor’ T cells subpopulations of Th and Tc o Mostly CD4+, MHC class II – restricted o Some CD8+, MHC class I – restricted o Characterised by FOXP3 transcription factor Major Histocompatibility complex Role in intercellular recognition and discrimination b/w self/non-self MHC molecules act as antigen presenting strictures influence range of an individuals antigen response. Genes linked usually inherited together but some recombination. Antigen presenting cells Process and present exogenous antigens to Th cells B cells can recog free antigens Presenting means that a fragment of antigen is associated with an MHC protein and inserted into the plasma membrane.