Lecture 3.2 - Adaptive Immunity PDF

Adaptive immunity: ◦Adaptive immunity is the process by which a specific immune response is elicited. The immune response: Cells of the immune system: Adaptive immunity: secureserver.ae assessments ◦T cells and B cells reside in...

Adaptive immunity: ◦Adaptive immunity is the process by which a specific immune response is elicited. The immune response: Cells of the immune system: Adaptive immunity: secureserver.ae assessments ◦T cells and B cells reside in peripheral lymphoid tissue including lymph nodes ◦Each T cell has a T cell receptor which is specific to a single antigen from an invading microorganism ◦Each B cell has a B cell receptor which is specific to a single antigen from an invading microorganism ◦Dendritic cells phagocytose the invading microorganism at the site of infection and exhibit antigen from them on MHC II molecules. They travel to the lymph nodes where they find the T cell (CD4+ T cell) which recognises the antigen and is activated ◦The particular T cell then proliferates into CD4+ Helper T cells and interacts with the B cells which also recognise the specific antigen. ◦The B cells then mature into plasma cells which produce antibodies against the specific antigen. ◦The T cells also produce cytokines which cause proliferation of cytotoxic T cells (CD8+ T cells) ◦The CD8+ cytotoxic T cells recognise antigens presented on MHC I molecules and can kill virus infected cells directly or induce apoptosis through activation of the Fas molecule. T cells: ◦So called because they mature in the Thymus ◦Originate as haematopoietic stem cells (HSCs) in the bone marrow ◦In the thymus they are screened for their ability to recognise ‘self’ antigens. Those that do are directed towards apoptosis. Major histocompatability complex: ◦These are proteins that exist on the surface of cells  ◦It uses signposts on each cell. These are known as MHC I and MHC II. ◦MHC complexes are tissue antigens which display proteins which are being made within that cell. This allows the immune system to determine if it’s observing ‘self’ or ‘non-self’. ◦This is critical for T cell tolerance ◦MHC I interacts with CD8 on cytotoxic T cells ‣ This can be important for cancer cell detection and clearance as well as virally infected cells ‣ Present on all nucleated cells ◦MHC II interacts with CD4 on helper T cells ‣ This displays antigens which have been processes by antigen presenting cells and leads to the adaptive immune response. Immune tolerance: Antigen presentation: ◦Antigen presentation is a two-step process which occurs in the lymph node - although, it is worth noting that presentation to CD8+ T cells causes the T cell to kill the infected cell without secondary antigen presentation. Equally, B cells are sometimes able to recognise antigen without T cell help. ‣ Presentation of the antigen by an antigen presenting cell (macrophage, dendritic cell, professional antigen presenting cells) to T cells ‣ Helper T cells activate B cells expressing a specific B cell receptor (Ig) for the antigen. Antigen processing pathways: earth to asersederses Antigen presentation:  ◦T cell receptors are specific to a single antigen - they don’t just recognise everything that is presented to them ◦Any given B cell will only produce specific antibody to specific antigen. V(D)J recombination: ◦Process of gene rearrangement whereby variable, diverse and joining regions are rearranged in different combination to produce a vast range of unique receptors. adobe.ee T cell/B cell interaction: ◦In order for the immune response to proceed down the adaptive route, T cells must then “help” B cells to effectively respond to this same antigen. ◦B cells, like T cells, have receptors which are specific to a single antigen. ‣ B cell receptor is essentially an immunoglobulin ◦B cells will encounter the antigen on their own, but this isn’t sufficient to activate the B cell. Instead, the B cell internalises the antigen and then presents it on MHC II. ◦Primed (activated) T cells secrete more IL2 (T cell growth factor) causing expansion of the population of T cells which recognises the antigen. ◦Primed T cells then encounter B cells. If they come across a B cell displaying the antigen that they recognise, they bind to it causing activation of the B cell. B cells: Immunoglobulins: ◦ Immunoglobulins are proteins produced by B cells which have an affinity for a unique antigen.  Opsonisation: ◦“The process of labelling/flagging a pathogen for clearance by phagocytes” ◦An opsonin is a molecule which can attach to an antigen on the surface of a bacteria (or virally infected cell). ◦It acts as a beacon for phagocytes which will come in and ‘eat’ the pathogen. ◦They can be: ‣ Complement proteins (innate immunity) ‣ Antibodies (adaptive immunity) seersceressed BEE IgG and complement: ◦IgG (and IgM) can activate the complement pathway once it has bound to its antigen. ‣ Classical pathway ‣ Alternative pathway ‣ Lectin pathway Clearance of opsonised pathogen: ◦Complement can “punch holes” in the cell membrane of the pathogen, leading to death. ◦Phagocytes such as macrophages and neutrophils have Fc receptors on their surface which bind to the Fc region of an antibody which has formed a complex with an antigen. ‣ This leads to internalisation of the pathogen which has been coated in antibody. ‣ The macrophage produces reactive oxygen species to destroy the pathogen.  Immunological memory: ◦Memory cells are vital to long term immunity to common infections ◦Once T and B cells have encountered an antigen for the first time and are prompted to proliferate, some will become effector cells which combat the infection. Others don’t proliferate and reside predominantly in the spleen (45% of memory B cells) and some in the circulation awaiting a second encounter with their specific antigen. ◦A second challenge from the same pathogen with unaltered antigens elicits a much swifter immune response as mature effector memory cells are already present. ‣ These just need to be instructed to proliferate and migrate out of the lymph node. ◦Immunological memory is the foundation principle of immunity which allows vaccination to work. Vaccines: Cytotoxic T cells and NK cells: ◦Both types of cell interact with infection cells to kill them directly or drive those cells towards apoptosis. ◦CD8+ cells recognise antigen in the same way as CD4+ cells, except they recognise antigens presented on MHC I. ◦They still have a two-step verification system in place and won’t kill directly or induce apoptosis without interaction of Fas ligand (FasL) on the T cell surface with Fas on the surface of the infected cell. ◦NK cells can use FasL/Fas too. ◦NK and Tc cells are also able to secrete performing and granite which produce pores in the infected cell membranes leading to cell death. Natural killer cells: ◦Natural killer cells are activated by cytokines and interferon released from macrophages during an infection. ◦Natural killer cells recognise infected cells and abnormal cells without requiring MHC or other types of receptors. ◦Natural killer cells release interferon gamma which activates macrophages resulting in an inflammatory response.