Cambridge Immunology Lecture Notes PDF
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Uploaded by LegendaryOcean8109
Newcastle University
2024
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Summary
These lecture notes cover various aspects of immunology, including innate and adaptive defenses, the roles of different T cell types, and the differences between gram-positive and gram-negative bacteria. They discuss bacterial infections and the immune response to pathogens.
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Lecture 8 √ Friday 22 November 2024 14:08 1. Describe innate defence mechanisms Rapid Barriers, complement (alternative pathway), phagocytosis, NK cells, antimicrobial peptides. Act early: first line of defence. Non-specific In effective against many pathogens 2. Des...
Lecture 8 √ Friday 22 November 2024 14:08 1. Describe innate defence mechanisms Rapid Barriers, complement (alternative pathway), phagocytosis, NK cells, antimicrobial peptides. Act early: first line of defence. Non-specific In effective against many pathogens 2. Describe adaptive defence mechanisms Antibodies, cell-mediated immunity Take longer to develop Exhibit memory Less easily evaded by pathogens Enhances and focuses innate defences 3. What is the role of Th1? Intracellular pathogens Activate macrophages - Cytokines activate macrophages (e.g. TNFa, IFNy) Stimulate cytotoxic T cells (CD8+) 4. What is the role of Th2? Extracellular pathogens Support antibody production Class switching to IgE Activate eosinophils, basophils, mast cells 5. What is the role of Th17: Extracellular bacteria and fungi Attracts inflammatory cells (neutrophils) Induced early in infection. 6. Give examples of gram positive bacteria Staphylococcus aureus Streptococcus spp. 7. Give examples of gram negative bacteria Campylobacter Salmonella Shigella Haemophilus Neisseria 8. What is the difference between gram negative and gram positive bacteria? Gram positive: thick peptidoglycan layer, violet stain. Gram negative: thin peptidoglycan, outer membrane containing LPS, pink stain. 9. How do the components of bacterial cells walls induce innate responses? (LPS, peptidoglycan): Bind to TLR on macrophages 10 TLR genes in humans: receptors recognise PAMPs to trigger an immune response. – located on plasma membrane and endocytic vesicles. NOD-like receptors (intracellular sensors) In cytoplasm detect bacterial components to activate immune response. 10. What does binding of PAMPs to TLR (e.g. of a PRR) do? Promote inflammation Promote dendritic cell maturation Influence differentiation of T cells Activate B cells (TI-1 antigens) 11. Describe the vaccine against streptococcus pneumoniae Comprises 23 polysaccharide serotypes (91 identified) Conjugate vaccine available Strep causes pneumonia, middle ear infection, meningitis Antibodies to capsular polysaccharides protect against disease. 12. What are the roles of antibodies in bacterial infections? Opsonisation (bacteria in extracellular space) - Bind Fc receptors on phagocytes (helps phagocytes recognise and ingest bacteria) - Ingestion by macrophage Complement activation (bacteria in plasma) - Promote inflammation via C3a, C5a - Lysis of gram negative organisms (MAC C5b, C6, C7, C8, C9 - creates pores in the membrane of gram negative bacteria) Bind to and neutralise toxins e.g. tetanus, diphtheria - Ingestion by macrophage. Bind to surface structures to prevent mucosal adherence. 13. What is the role of activated macrophages? Better at phagocytosis and killing More efficient antigen presenting cells Stimulate inflammation (cytokines, prostaglandins). 14. How do T cells activate macrophages? T helper cells express CD40 ligand -> binds CD40 on macrophages, triggering their activation. T Cells (i.e. Th1) secrete IFN-y -> binds IFN-y receptor on macrophages, enhancing antimicrobial activity (increases ability to kill ingested pathogens). TNFR-I (Tumour necrosis factor receptor 1): binding of TNF-a (from T cells) to TNFR-I on macrophages stimulates further activation, inflammation. 15. Describe the outcome based on the type of response for mycobacterium leprae Tuberculoid leprosy: strong TH1 response, few live bacteria (organisms present at low to undetectable levels), low infectivity, granulomas and local inflammation. Peripheral nerve damage, slow progression, granulosa formation. Lepromatous leprosy: strong TH2 and antibody response, large no. Of bacteria in macrophages, disseminated infection, fatal. 16. What is a granuloma? Necrotic area: granulomas form when tissue becomes infected (e.g. with mycobacterium tuberculosis. Infection triggers localised immune response, leads to tissue damage and a necrotic (dead) core. Partial removal of M. Tuberculosis -> granuloma. - The immune system attempts to control infection by isolating the pathogen to prevent it from spreading. - Granuloma contains mycobacteria, multi-nucleotide giant cell, epithelioid cell, T cells. 17. Describe how an infection with mycobacterium leprae can result in tuberculoid leprosy strong TH1 response few live bacteria (organisms present at low to undetectable levels) low infectivity granulomas and local inflammation, Peripheral nerve damage normal serum immunoglobulin levels slow progression granulosa formation Normal T-cell responsiveness Specific response to M. Leprae antigens. 18. Describe how an infection with mycobacterium leprae can result in lepromatous leprosy Th2 response Organisms show florid growth in macrophages High infectivity Disseminated infection. Bone cartilage and diffuse nerve damage. Hypergammaglobulinemia Low or absent T cell responsiveness. No response to M. Leprae antigens. High fatality. 19. Describe cytokine patterns in leprosy lesions Tuberculoid: - Th1 cytokines (+++): high IL-2, some IFN-Y, high TNF-ß - Th2 cytokines (-): some IL-4, low IL-5, low IL-10 - Monokine (+++): TNFa, IL1ß, TGFß Lepromatous: - Th1 (-): low IL-2, low IFN-y, some TNF-ß - Th2 (+++): high IL-4, high IFN-y, med IL-10 - Monokine (-) 20. Antibodies important in protecting against ____ pathogens. Extracellular E.g. streptococcus pneumoniae, clostridium tetani. 21. T cell effector mechanisms protect against ____ organisms Intracellular E.g. Mycobacterium leprae, mycobacterium tuberculosis. 22. Name an example of a pathogen that can result in the formation of granulomas Mycobacterium tuberculosis 23. Which cytokines are involved with tipping the immune response to a TH1 predominant response IL-12: (from dendritic cells and macrophages) promotes Th1 differentiation. IFN-y (from Th1 cells) further supports the Th1 response. 24. What are TLRs and what do they bind? Are PRRs on immune cells (macrophages and dendritic cells) Bind PAMPs - E.g. LPS from gram negative bacteria - Peptidoglycan from gram positive bacteria 25. What are the roles of antibodies? Opsonization: Enhance phagocytosis - bind to pathogens and immune cell receptors. Complement activation: Leads to pathogen lysis and inflammation. Neutralization: Bind to toxins or viruses to prevent their harmful effects. Prevent mucosal adherence: Bind to pathogen surfaces to block attachment. Inflammation: Promote immune cell recruitment (via C3a, C5a). Phagocytosis: Facilitate engulfment by macrophages and neutrophils. 26. What is LPS and on what type of bacteria? Lipopolysaccharide Component of the outer membrane of gram negative bacteria Binds TLR4 on immune cells - triggering an immune response. 27. Name an infection which results in the production of a potent toxin? Clostridium tetani (produces tetanus toxin, causing muscle spasms). Clostridium botulinum (produces botulinum toxin, causing paralysis). 28. What kind of infections can Neisseria spp cause? Neisseria gonorrhoeae: Causes gonorrhea Neisseria meningitidis: Causes meningitis and meningococcemia (infections of the brain and blood). 29. Which type of bacterial infections can the MAC be particularly useful in killing the pathogen? Gram negative bacterial infection MAC forms pores in the outer membrane of gram negative bacteria - causing cell lysis. 30. Why can the same infectious agent cause different distinct pathologies? (M.leprae) Tuberculoid leprosy: strong Th1 response - controlled infection Lepromatous leprosy: strong Th2 response - disseminated infection. 12.