The adaptive immune system an introduction - Dr Alexander Strachan (2024-25).pptx

Adaptive immunity; an introduction [email protected] Learning objectives Describe the cellular and soluble components of the adaptive immune system Discuss the key functions of the adaptive immune system Distinguish between humoral and cell mediated immunity Compare and c...

Adaptive immunity; an introduction [email protected] Learning objectives Describe the cellular and soluble components of the adaptive immune system Discuss the key functions of the adaptive immune system Distinguish between humoral and cell mediated immunity Compare and contrast innate and adaptive immunity Session aim: To introduce key concepts in adaptive immunity in preparation for more in depth coverage of humoral and cell-mediated immunity in later sessions. Adaptive immunity; an Session outline: Re-cap on innate immunity (5 minute exercise) How is the adaptive immune system different to the innate immune system? Introduction to adaptive immunity: – What does adaptive immunity mean? – Why do we need an adaptive immune system? What is the adaptive immune system made of? – Anatomy of the adaptive immune system – Cellular and soluble components – Functions of adaptive cells and components Adaptive immunity quiz (2x 5 minute exercises) Any questions Adaptive immunity; an What do we know about the innate immune system? 5 minute activity Write down: 3 examples of mechanical barriers and their functions 2 examples of circulating effector proteins and their functions 4 examples of key inflammatory cytokines and their functions 3 examples of effector cells and their functions Innate immunity: 3 examples of mechanical barriers and their functions: Epithelial layers: Prevent microbial entry Enzymes / low pH: Break down microbial structures Commensal microbes: Outcompete pathogens 2 examples of circulating effector proteins and their functions Cytokines: Messenger molecules that can regulate immune cells and responses Complement: Opsonisation, neutralisation, coagulation, MAC formation C-reactive protein: Opsonisation, activation of complement Innate immunity: 4 examples of key inflammatory cytokines and their functions TNFα: Key inflammatory mediator, potent stimulator of inflammation, multiple roles incl. neutrophil and endothelial cell activation, apoptosis IL-1β: Key inflammatory mediator, multiple roles incl. activates endothelial cells, induces coagulation IFNγ: Anti-viral response; activates MΦs, NK cells. Also important in anti- tumour responses IL-8: Chemotactic for neutrophils 3 examples of effector cells and their functions: Macrophage: Phagocytosis, antigen presentation, regulation of inflammation, cytokine production Neutrophil: Phagocytosis, early inflammation Dendritic cell: Antigen presentation, cytokine production NK cells: Kill infected cells, recognise tumour cells Eosinophils & basophils : Granulocytes which release membrane damaging granules, important in anti-parasite responses Mast cells: Release potent inflammatory mediator, histamine.Innate immunity: What are the key characteristics of the innate immune system? RAPID None No memory specific Why do we need an adaptive immune system? Adaptive immunity; an Innate and adaptive immunity Lines of defence Innate Adaptive Physical Non-specific Specific, barriers defences choreographed defences Adaptive immunity; an  The innate immune system talks to the adaptive immune system for help Adaptive immune cells wait for antigen in the lymph nodes and spleen… Adaptive immunity; an What does adaptive immunity mean? Adapts to fight the particular pathogenic challenge Must be specific Must be robust Adaptive immune system has properties distinct from the innate immune system… Adaptive immunity; an What is the adaptive immune system made of? Components the adaptive  What is the adaptive immune system made of? Image courtesy of Akiko Iwasaki (Creator) & Jung-Hee Lee Components the adaptive  Where are cells of the adaptive immune system found? Lymphocyte s Components the adaptive T and B cells are kept apart in the lymph nodes to minimise inappropriate activation 24 hr Components the adaptive T and B cells are kept apart in the lymph nodes to minimise inappropriate activation …and in the spleen Components the adaptive Specificity: Ensures that distinct antigens elicit responses that specifically target those antigens YY Y Characteristics of adaptive Diversity: Enables immune system to recognise a vast variety of antigens B Y B T Characteristics of adaptive Memory: Leads to rapid and enhanced responses upon re-exposure to Y Y Y the same antigen Y Y YY Y Y Y Y Y Y Y B Y Y Primary exposure (~10 Secondary exposure (~5 days) days)Characteristics of adaptive Clonal expansion: Expands the number of pathogen specific lymphocytes to keep pace with the microbes Y Y B Y Y Y Y B Y Y Y Y Y Y B Y Y Characteristics of adaptive Specialisation: Generates responses that are optimal for defence against different types of organisms B Y Bacteri Viru Fungi a s T B T Characteristics of adaptive Specialisation: Switches off responses when infection is resolved B Y T B T Characteristics of adaptive Non-reactivity to self: Non-reactivity to self: Prevents injury to the host by the immune system https://www.genscript.com/self-tolerance.html Exercise 2: 5 minutes…………. 4. Which innate immune cells collect antigen from the mucosal tissues to the lymph nodes to present antigen to lymphocytes? 5. Where in the body do T cells mature? 6. Where in the body do B cells mature? What different types of pathogen might the immune system need to defend against? The origin of a microbe in relation to the cells dictates what kind of immune response is required  Types of Adaptive Immunity Fig. 1-2 Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright © 2012 by Saunders, an© imprint Copyright of Elsevier 2011 by Saunders, Inc. an imprint of Elsevier Inc. Examples of defective humoral and cell mediated immunity in dentistry Cell mediated – Lichen planus: T cells targeted to host cells – Sjogren’s syndrome Humoral – Pemphigus/pemphigoid: Antibodies targeted to host cells – Sjogren’s syndrome Associated pathologies Lichen planus Cells appear shrunken bullae formation Epithelium Mostly CD8+ T cells Basal cells (no B cells) ? Epidermal Soames & Southam. Oral Pathology. 4th Ed. Oxford. 2005 hyperplasia Aetiology: Idiopathic Can occur as reaction to dental materials (lichenoid reaction) Idiopathic and lichenoid reaction are clinically and pathologically indistinguishable Lichenoid reaction resolves on removal of offending material Associated pathologies Mechanism of action: Antigenic challenge Cytokine release Epithelial cells express ICAM-1 basal cell T cell chemotaxis and accumulation Tissue destruction Liquefactive degeneratio n Associated pathologies Pemphigous Autoantibod ies Stratum spinosum Basal layer Intraepithelial vesicle in pemphigous vulgaris Autoantibodies to desmogleins (cell adhesion molecules in desmosomes) Associated pathologies Mechanism of action: ADCC Y Eosinophil, basophil and mast cell activation Complement activation Associated pathologies Sjogren’s syndrome Autoimmune tissue destruction of exocrine glands BOTH humoral and cell-mediated mechanisms: Autoantibodies to MMPs and muscarinic receptors. Cell mediated destruction of acinar and ductal cells Further information: https://www.bssa.uk.net/pdfs/information-sheet.pdf Associated pathologies Exercise 3: 5 minutes…………… 7. What are the main effector functions of B cells? 8. What are the two major subsets of T cells? 9. What are the main effector functions of T cells? 10. Which adaptive immune cells are the major effectors in the humoral immune response? 11. Which adaptive immune cells are the major effectors in the cell-mediated immune response? 12. Give two examples of a pathogen that would initiate a humoral immune response 13. Give two examples of a pathogen that would initiate a cell-mediated immune response 14. Give an example of an oral condition that involves a humoral response 15. Give an example of an oral condition that involves a cell- mediated response Summary Key characteristics of adaptive immunity: – Specificity – Memory – Clonal expansion – Robust response – Primary and secondary responses The cellular and soluble components of adaptive immunity are: – B cells, T cells, antibodies and cytokines Adaptive immunity has two branches: – Humoral (B cells & antibodies, extracellular pathogens) – Cell mediated (T cells, intracellular pathogens) Adaptive immunity is the last line of defence against pathogens Suggested reading: Chapter 1  Glossary of terms Antigen presenting cells: Internalise and process antigen and present it to adaptive immune cells (lymphocytes) Antigen: Initiates an immune response B cell receptor: Antigen receptor (membrane bound antibody) on the surface of a B cell Cell mediated response: Adaptive response involving T cells and cytokines (intracellular pathogens) Chemokine: cell- cell messenger molecule that induces chemotaxis Chemotaxis: Attraction of a cell to a particular site following a concentration gradient Clonal expansion: Production of identical progeny Cytokine: Cell – cell messenger molecule Humoral response: Adaptive response involving B cells and antibodies (extracellular pathogens) T cell receptor: Antigen receptor on the surface of a T cell. Only recognises antigen when presented by APC  Types of T cell CD8 Cell mediated T CD4 Cytotoxic T cells T T helper cells Humoral Corripio-Miyar, Y., Hayward, A., Lemon, H. et al. Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal. Sci Rep