Adaptive Immunity_1_2023.pptx

The Adaptive Immune system (1) Aim: This lecture will explore the components of the adaptive immune system: · Definition and classification of B-cells and T-cells · compare and contrast B-cell and T-cell maturation · The role of B-cells and T-cells in generating an immune response Learning outcomes...

The Adaptive Immune system (1) Aim: This lecture will explore the components of the adaptive immune system: · Definition and classification of B-cells and T-cells · compare and contrast B-cell and T-cell maturation · The role of B-cells and T-cells in generating an immune response Learning outcomes: Understand the similarities and differences between B-cells and T-cells and their inter-dependency in mounting an effective immune response Chris Pepper : [email protected] Recognition of lymphocyte subsets T cell differentiation B and T cell development Comparison of B cell and T cell development Lymphocyte stages of development B cells T cells Common stages of B and T cell development 1st phase: generation of an antigen receptor • V(D) J gene rearrangement – producing a new antigen receptor 2nd phase: refinement of the antigen receptor repertoire • Antigen receptor is tested for antigen recognition (self antigens) • Only those receptors that recognise self antigen are selected – POSITIVE SELECTION • Those receptors which bind strongly to self antigen are deleted – NEGATIVE SELECTION 3rd phase: Stimulation by foreign antigen • Clonal selection of lymphocytes • Generation of effector and memory lymphocytes Summary (1.1) B cells and T cells are the lymphocyte components of the adaptive immune system Their critical function is to produce immunological memory B cells and T cells begin life in the bone marrow – T cells complete their development in the thymus All lymphocyte development is guided by interactions with stromal cells All undergo both positive and negative selection There are many subsets of T cells but the most important are CD4+ Thelper and CD8+ Tcytotoxic T cell development B cell Antigens T cell independent responses Simple, repetitive antigens Mostly IgM (no class switching) Modest affinity No memory (plasma cells are short lived) B cells activated by direct BCR crosslinking B cells still require a second activation signal – often this is via Toll-like receptor (TLR) engagement Antigen recognition by B cells vs T cells Both produce a diverse array of antigen receptors by V(D)J recombination • B cell receptor (BCR) consists of 2 HC and 2 LC (membrane and secreted Ig) • T cell receptor (TCR) consists of ab heterodimer (membrane form only) Both signal by associating with signaling complex in membrane: • Ig-a and Ig-b for B cells; CD3 complex for T cells • B cells can bind intact protein antigen in solution • T cells bind peptides displayed on the surface of another cell - an “antigen presenting cell” (dendritic cell, macrophage, or B cell) - in the context of MHC I or MHC II molecules T-independent and T-dependent B cell activation Antigen engagement of the B cell receptor (BCR, “signal 1”) is not sufficient to activate B cell. Also need co-stimulatory signal (“signal 2”) classically, this would come from toll-like receptor recognition of antigen B cell-T cell interactions •Required for antibody response to complex antigens – proteins/peptides •Requires direct, physical B-T interaction •Involves multiple cell surface receptors on T and B cells •Both B and T cell must recognise antigen (but not necessarily the same epitope) •Both B and T cells need signal 1 (through antigen receptor) and signal 2 (costimulation) T-dependent B cell Sequence of events: response CD80/CD86 •Antigen binding to BCR provides “Signal 1” to B cell •Antigen is internalised, processed and antigenic peptides are displayed on MHC for T cell recognition •TH (helper T-cell) recognises antigen-MHC complex via the T cell antigen receptor (TCR): provides “Signal 1” to T cell •CD80/CD86 on B cell binding to CD28 on T cell provides “Signal 2” to T cell •T cell activation leads to up-regulation of CD40L which bind to CD40 providing “Signal 2” to B cell •Cytokine production by activated T cell also help to activate B cell…“Signal 3” •B cell proliferates and differentiates into antibody secreting B cell (plasma cell) or becomes a memory B cell Primary and Secondary Antibody Responses Summary (1.2) Some B cells are capable of responding to antigen without T cell help – most are not T-independent antigens usually contain repeating epitopes classically polysaccharides, glycolipids and nucleic acids Cross-linking of the B cell receptors is the first signal for activation, but a second signal is required e.g., from tolllike receptor engagement T-dependent antigens are usually proteins/peptides This type of T-dependent activation requires 3 signals – B cell receptor engagement (signal 1), Binding of CD40L to CD40 (signal 2) and cytokine stimulation (signal 3) Suggested reading Parham The Immune System Chapters 4-7 Janeway Immunobiology Chapters 7, 8 and 10 (Ed. 8) LeBien and Tedder. B lymphocytes: how they develop and function. Blood 2008; 112: 1570-1580. Coming next… Adaptive immunity 2.1 – How to B and T cells generate antigen receptor diversity – V(D)J recombination Any questions send me an email: [email protected] Also, see the revision notes I have produced for you: Key learning outcomes – things you should know These can be found Student Central T-independent B cell activation https://www.youtube.com/watch?v=iIJulGXWm6Q T-dependent B cell activation https://www.youtube.com/watch?v=_qF2jEe7ZWc