Ch2

• molecules that are recognised by B-cell receptor (antibody) and T-cell receptor • mostly proteins, carbohydrates and lipids • with many epitopes

• substances that induce an immune response • not all antigens are immunogens as recognise is not the same as trigger (eg. self-antigen)

• membrane-bound antibody or immunoglobin (Ig) molecules (IgM and IgD isotopes) • recognise the 3D structure (conformation) of unprocessed antigens

• Y-shaped with 2 heavy and 2 light chains (include constant Fc and variable Fab regions) joined together by disulphide bonds • variable heavy and variable light chain –> antigen-binding sites

• only found on the surface of T-cell receptor membrane • only recognise processed peptide antigen fragments displayed on MHC molecules, which bind to CD4 or CD8 co-receptors (CD4 on helper T cells bind to MHC II and CD8 ono cytotoxic T cells bind to MHC I)

• millions of harmful pathogens –> millions of antigen-binding sites on B-cell and T-cell receptors are required • diversity is achieved by the rearrangement of gene segments coding for variable domains of B-cell and T-cell receptors during lymphocyte maturation • heavy chain: V (variable), D (diversity) and J (joining) genes • λ and κ light chain: V and J genes

• with 2 polypeptide chains: α and β (with constant and variable regions) • variable regions of α and β chains –> antigen-binding sites

• tissue injury triggers the release of histamine from mast cells –> vasodilation (redness and heat) and increased permeability of blood vessels (swelling and pain) • blood clotting proteins move from the blood to the tissue –> clotting begins • increased migration of phagocytes from blood to the injury site • phagocytes eliminate invading pathogens and cell debris by phagocytosis –> tissue heals

• B cells circulate in blood and lymph or reside in lymphoid tissues • respond to T-dependent and T-independent antigens

• mainly peptide Ag/ protein Ag so most antigens are T-dependent • require helper T cells which secrete cytokines (eg. interleukin-2) –> stimulate B cells differentiate into plasma cells and memory B –> production of antibody

• mainly polysaccharide or lipopolysaccharide Ag with long repeating units • bind to many B-cell receptors at the same time –> strong stimulus for B cell to proliferate and differentiate into plasma cells –> Ab production • no memory B cells –> no secondary immune response

• Ab bind to and enhance elimination of Ag • variable regions Fab of Ab –> Ag binding sites • constant regions of heavy chain –> Ag elimination (as Ab receptor will bind to Fc region)

• neutralisation –> Ab attach to microbes –> coat and inactivate bacterial toxins • agglutination –> Ag are clumped together by antibodies as each Ab has at least 2 Ag-binding sites • opsonisation –> antibody-bound Ag are more susceptible to phagocytosis as phagocytes have Fc receptor to recognise antibody –> enhance phagocytosis • complement activation –> complement bind to antibody-coated antigen –> efficient cell lysis –> cells become leaky • antibody-dependent cell-mediated cytotoxicity (ADCC) –> non-specific cytotoxic cells (eg. neutrophils, macrophages, natural killer cells and eosinophils) bind to Ab-coated Ag via Fc region of Ab –> destroy target cells by lytic enzymes (lysozyme), perforins (pore-forming enzymes) and granzymes (digestive enzymes)

• first exposure to Ag (T-dependent) • B and T cells are activated and differentiate into plasma cells, helper and cytotoxic T cells and memory B and T cells • Ab level increases from 10-14 days after exposure to Ag • IgM predominates over IgG

• second exposure to the same Ag –> involves memory B and T cells • faster (2-7 days), higher titres, more prolonged than primary response • IgG predominates over IgM

• primary regulators of immune response • operate indirectly by secreting cytokines that enhance the activity of macrophages and NK cells (innate immune response) and B cells, cytotoxic T cells and helper T cells themselves (adaptive immune response)

• responsible for killing virus-infected cells, abnormal cells and cancer cells

T cells use T-cell receptors to recognise only processed Ag presented with self MHC proteins

• to discriminate self from non-self • in thymus, T cells are educated to respond only to foreign Ag presented by self MHC

MHC I - 3α + 1β domains - located on the surface of all nucleated cells - presents peptides from intracellular Ag - recognised by CD8+ cytotoxic T cells MHC II -2α + 2β domains - located on antigen-presenting cells - presents peptides from extracellular Ag - recognised by CD4+ helper T cells

• intracellular Ag are cut into small peptides in the cytosol by proteasome (with proteases) • peptides move into endoplasmic reticulum and combine with MHC I • form peptide-MHC I complexes –> released from the ER and transport to Golgi apparatus –> plasma membrane for presentation to CD8+ T cells

• release their granules (perforins and granzymes) onto the surface of the infected cells • perforins create pores on cell membrane to create passage for granzymes (proteolytic enzymes) into the cells –> killing (digested/ lysed)

• extracellular Ag internalised by antigen-presenting cells • exogenous Ag are digested within endosome or MHC II compartment (MIIC) –> become small peptide fragments • In ER, MHC II combines with invariant chain (Ii) –> form Ii-MHC II complex –> transport to Golgi apparatus and MIIC endosome • In MIIC, Ii is degraded by proteases –> peptide Ag fragments combine with MHC II –> transported to plasma membrane for presentation to CD4+ helper T cells