Immunology Lecture 3 2024 PDF

Adaptive immunity Lecture 3 14th November 2024 Introduction to the immune system  Learning outcomes today Introduction to the important cells and molecules in Adaptive immunity Differences between innate and adaptive immunity Concept of presenting antigen on...

Adaptive immunity Lecture 3 14th November 2024 Introduction to the immune system  Learning outcomes today Introduction to the important cells and molecules in Adaptive immunity Differences between innate and adaptive immunity Concept of presenting antigen on a SELF protein to another cell Importance of diversity Appreciate ‘time’ in adaptive immunity  Adaptive immunity Antigen presenting cells – Dendritic cells, Macrophages and B-cells The importance of ‘SELF receptors’ presenting antigen to other cells – Major Histocompatibility Complex (MHC) Lymphocytes – B-cells and plasma cells and antibodies – T-cells Helper, Cytotoxic The importance of diversity Memory Innate vs Adaptive immunity Basic strategy in Adaptive immunity Detection system Foreign peptide/protein Self receptor Presentation system Epithelial cells Antigen and phagocytes Presenting cell Innate immunity Adaptive immunity  Why would you detect a SELF protein in combination with a foreign protein? A way of spying on the inside (or the general state) of the cell from the outside! A way of generating memory A way of making copies of the correct cell  Antigen presenting cells Many cells can present antigen Professional and non professional APC Professional: – Dendritic cells, Macrophages, and B-cells – Self receptor is Class 2 Non professional – Other nucleated cells – Self receptor is Class 1  Major histocompatibility complex (MHC) - the self receptor A receptor / antigen binding site Genetically diverse glycoproteins Cell membranes Two versions MHC Class I-all nucleated cells in vertebrates MHC Class II-professional APC MHC  Dendritic cells Make contact with pathogens and communicate to T-cells in lymph nodes The major antigen presenting cell (APC):SENSING Link innate and adaptive immunity Respond to pathogens: secrete chemokines and cytokines Results in attraction and activation of immune cells Ingest pathogens and digests them Present on cell surface on Class 2 MHC  Lymphocytes Principal players in adaptive immune system 20-40% of WBC 99% of cells in lymph Approximately 1 trillion (1012) circulate 3 types: B-cells, T-cells and NK cells  B-cells and plasma cells Mature in BM Synthesis and display of B-cell receptor (BCR) BCR-membrane bound antibody, ~15- 30,000 molecules /cell Each B-cell has a unique antibody Activated B-cells become plasma cells – Lose cell surface and secrete antibody – 200-1000 molecules/sec – 1-2 week lifespan  T cells Mature in thymus Expresses a unique antigen binding receptor TcR TcR recognises processed antigen bound to MHC At least two types of T cells: – T-helper (TH) cells, CD4 glycoprotein and recognise MHC Class 2 – T cytotoxic (TC) cells, CD8 glycoprotein and recognise MHC Class 1 Ratio of CD4+ to CD8+ is 2:1 CD4 and CD8 T cells APC ‘MHC restriction’ of T-cell recognition-the conditions must be right.  Importance of MHC To display self Class 1 to demonstrate the cell is healthy To display foreign peptide in Class 1 to show that the cell is infected and activate T-cytotoxic cells To display a self peptide in Class 1 and 2 to test T-cells for autoreactivity To display a self peptide in Class 1 and 2 to maintain tolerance to self-proteins To display a foreign peptide in Class 2 to show the body is infected and activate T-helper cells  Generation of diversity Favour of ‘random’ generation of recognition molecules Each lymphocyte expresses many receptors of one specificity The whole group of lymphocytes in the body can theoretically bind to any antigen Make many combinations and delete the ones with the incorrect specificity Generation of diversity Clonal selection of lymphocytes: 1) effector cells 2) memory cells  Collaboration between innate and adaptive immunity 1) Pathogen introduced Phagocytic response 2a Transfer to a lymph node 3) Presentation to T and B cells and activation of appropriate specificity. Release of cells into circulation. 2b) Homing to infectious stimulus 4) Continued interactions in the lymph node differentiation and proliferation of lymphocytes 5a) Antibody production to label pathogens 5b) Some T and B cells remain as memory cells  Summary-adaptive immunity Uses huge diversity to recognise antigens Requires presentation of antigen on an APC to T- cells DCs are the major antigen presenting cell Mature B cells produce antibodies If all conditions are met there is cell activation – Proliferation of clones of lymphocytes with a defined specificity Generates memory