Acquired Immunity Lecture Notes PDF

Acquired Immunity Dr Ashik Srinivasan School of Medical Sciences Thank You: Dr Belal Chami, author of the previous version of this lecture Last update: 2024-05-20 Lecture date: 2024-05-21 Learning objecti...

Acquired Immunity Dr Ashik Srinivasan School of Medical Sciences Thank You: Dr Belal Chami, author of the previous version of this lecture Last update: 2024-05-20 Lecture date: 2024-05-21 Learning objectives Antibodies-antibody structure; antibody diversity; function of antibodies; immunological memory Class Switching of antibodies Characteristics of antigen presenting cells Mechanism of activation of T cells Mechanism of activation of B cells Antibody titre following naïve and mature immune responses to same antigen stimuli Non-Specific / Innate immunity Does not have any memory Specific / Acquired Immunity Has a memory Improved protection on next exposure Basis for immunity against re- infection Basis for immunization Cells of the immune system Color Atlas of Immunology, 2003 Role of the innate immune response Reduces pathogen load Immediate Part of homeostasis Innate immune response is to - prevent infection or minimise magnitude of infection, - to reduce disruption until activation of adaptative immunity Modulates adaptive response (antigen presentation) Dendritic cells in the Vaginal Mucosa L The Antigen-presenting Cell ‘Sedentary’ in epithelium/dermis Migrate to draining lymph node Changing phenotype: Antigen processing (phagocytic) Antigen presenting (non-phagocytic)  Immune Responses - raising the alarm OVERVIEW: Dendritic cells (APC) travel in lymphatics to lymph node Present antigen to adaptive immune system Lymphocytes differentiate and proliferate in node Return to focus of infection via the blood The Antigen-presenting Cell Originates in Bone Marrow: Myeloid/monoblast origins Tissue-derived (conventional DC) or Blood-derived DC Antigen-presenting Cell Ag ‘Trap’, Ag-Processing Migratory Cytokine-producing (e.g., IL-12) Class I MHC – expressed on all nucleated cells Class II MHC (very highly effective) – expressed on the professional APCs: Dendritic cells (DC), Macrophages, B cells, Langerhans cells Antigen presentation to T- cells - MHC Antigen presentation on major histocompatibility complexes (MHC) is a fundamental link between innate and adaptive immunity. T lymphocytes recognise antigens displayed on MHC Self-antigens – MHC class I Foreign antigens – MHC class II All nucleated cells display membrane-bound MHC class I, while immune cells display both.  https://doi.org/10.1016/B978-0-12-385245-8.00006-6 Each MHC displays one High expression levels of antigen at a time peptide-MHC complexes increases propensity to activate T-cells. Mature MHC class I – 6-16 amino DCs acids; MHC class II – up to 30 amino acid residues MHC : checkpoints for activation for your interest MHC – TCR engagement requires co-stimulation – T-cell coreceptors CD28 and CD80/B7.1 and CD86/B7.2 on the APC. IL-2 is immediately released by T cells and promote proliferation. ‘Brake pads’ – following activation, T cells express CTLA-4 (CD152) which binds CD80 and CD86. Limits expansion. 3 signals T- cell activation TCR engages antigen on MHC CD4 or CD8 binds MHC CD28 binds CD80 or CD86 – proliferation Further engagement with ICOS, 4-1BB and OX40 strengthens activation British Society for immunology, 2021 ‘brakes’ applied through CD152 Cytokines direct T – cell identity Exposure to IL-12 from APC → Th1 Exposure to IL-4 from APC → Th2 Exposure to IL-6,IL-23 from APC → Th17 Must know Adaptive (Specific) Immunity - Characteristics Specificity – pathogen epitopes Every clone of T and B lymphocytes recognises a different antigen. Memory – accelerated & larger response Fewer ‘checkpoints’ required for reactivation Self-limitation Mass apoptosis of lymphocytes in absence of antigen presentation Antigen recognition – B cells and activation T-dependent antigens e.g., soluble proteins Require T cell ‘help’ i.e., Use costimulatory molecule CD40 Need cytokines T-independent antigens e.g., lipids & polysaccharides Do not require T cell help B1 cells Produce ‘natural antibody’ - IgM only Antigen recognition – B cells and activation Antigen recognition – B cells and activation Unlike T cells, B cell receptors (BCRs) recognises antigens in their native unprocessed forms (does not require peptide bound to MHC molecules). Each B-cell is decorated with IgM with a unique specificity 10 billion combinations. ‘self’ responding combinations eliminated. BCRs are membrane-bound antibodies (IgM) – low affinity, high avidity (secreted pentamer). Affinity maturation – decrease in the dissociation constant (Kd) following repeated stimulation. Involves class switching from IgM to IgG. Abbas. Cellular and Molecular Immunology 2018. 9th edition. Humoral immunity: a key component of acquired immunity Antibodies are large, complex protein molecules Antibodies bind antigens We have an amazing capacity to bind, potentially, millions of different antigens Nature has designed a clever way of producing a diversity of antibodies  VH VH VL CH CH VL CL CL FC Innate Responses - Components Proteins Immunoglobins https://tinyurl.com/1qwf4tn8  Roles of Antibodies: Bind and inactivate toxins Bind and aggregate antigens / bacteria Opsonize (Make easier for phagocytosis) Activate complement In case of IgE, activate mast cells Antibody dependent cellular cytotoxicity  Antibody Class Switching T-dependent protein antigens produce class switching IFN- stimulates IgG2a IL-4 stimulates IgG1 and IgE TGF- stimulates IgA All cytokines stimulate IgM T-independent lipid/polysaccharide antigens Do not stimulate much class switching Maintain IgM outputs No ‘helper’ cytokines/co-stimulation required  For your interest only Antibody Genes Gene components scattered through one chromosome For your interest only Must know Antibody repertoire diversity is derived from the combinatorial diversity obtained by random combination of germline V, D and J segments, from the junctional diversity obtained by random addition and deletion of nucleotides at the joints between these segments, and by somatic mutation of the entire variable region. Clonal expansion of antibody producing cells