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Immunity

Immunity. State of protection against foreign organisms or substances ('antigens') Defence against disease Defence against tumours. Figure 1. Immune responses are directed at our barriers with the environment. Innate Immunity.

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Immunity

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  1. Immunity • State of protection against foreign organisms or substances ('antigens') • Defence against disease • Defence against tumours

  2. Figure 1 Immune responses are directed at our barriers with the environment

  3. Innate Immunity • Non specific immune responses which include anatomic, physiologic, phagocytic and inflammatory barriers that help prevent the entrance and establishment of infectious agents. • These keep the invading pathogen at bay until a specific response can be made.

  4. Acquired Immune responses • Specific response made against a particular pathogen or ‘agent’ • Diverse - responses can potentially be made against any pathogen etc. • Memory - the immune system can remember a pathogen that has previously infected the body • Escalating response - and generates a faster more effective response next time!

  5. How is this achieved? • 2 inter-related events: • recognition of ‘antigen’ • response to ‘antigen’

  6. Figure 2 The immune system is compartmentalised to enable lymphocytes to come into contact with pathogens/antigens.

  7. Antigen Presentation • Antigen presenting cells (dendritic cells, macrophages), B lymphocytes and T lymphocytes are involved in the generation of immune responses. • Both B and T lymphocytes possess antigen receptors in their cell membrane.

  8. B lymphocyte receptors (BCR) • Antibody molecules bound to the cell membrane form the B cell receptor (BCR) • BCR can recognise and internalise intact 'antigen'. (antigen here can be a 3-dimensional structure)

  9. Figures 3 and 4 Structure of the B cell receptor

  10. T lymphocyte receptors (TCR) • T lymphocytes only recognise 'antigen' associated with MHC class I and class II molecules • antigen here is a short linear peptide - primary structure

  11. Figures 5, 6 and 7 Structure of the TCR and it’s interaction with MHC/peptide complexes

  12. How are immune responses DIVERSE? • Each T and B lymphocyte has a DIFFERENT antigen receptor • Clonal expansion of a single cell results when the lymphocyte receptor meets its specific antigen. • Expanded lymphocytes then develop different effector and memory functions

  13. Function of T lymphocytes I • There are 2 major sub-populations. Helper T cells (Th) and cytotoxic T cells (Tc). • Th cells express CD4 and recognise 'antigen'+ class II MHC(on antigen presenting cells). • 'Antigen' is a peptide of 18-22 amino acids, and is derived from proteins from outside the cell.  fight extracellular pathogens. (can produce soluble mediators = cytokines….)

  14. ‘Helper’ CD4 T lymphocytes

  15. Functions of T lymphocytes II • Tc cells express CD8 and recognise 'antigen' + class I MHC (on all body cells). • 'Antigen' is a peptide of 9 amino acids, and is derived from proteins synthesised inside the cell. Normally self peptides are expressed in class I MHC.  fight intracellular pathogens. (can lyse body cells!!!)

  16. Cytotoxic CD8 T lymphocytes

  17. Functions of B lymphocytes • B cell antigen receptor - membrane bound antibody molecule • Activated B cells become plasma cells and secrete antibody - potent soluble effector molecues (IgM, IgG, IgA, IgE, IgD) • Need T cell help to become activated • Express class II MHC and can activate CD4+ T cells

  18. Functions of B lymphocytes

  19. Where do immune response take place? • Specific lymphocytes need to come into contact with specific pathogen/antigen to make an immune response • This occurs in the specialised micro-environment of the lymph node • Figure 8. Structure of a lymph node

  20. Where do pathogens enter the body? • Barriers - skin, nasopharynx, gut, lungs (mucosa) a) recognise pathogen b) make an immune response • The mucosa contains organised lymphoid tissue (eg peyers patches in the gut) and many lymphocytes

  21. Class exercise • What happens if I vaccinate you? • Why do I do this? • How does it work? • Why is it effective • What happens when you eat food? • What happens to food? • Where does it go? • Do you make an immune response to food? • Why might you have rheumatoid arthritis or multiple sclerosis • what are the symptoms? • what is happening? • what is the cause?

  22. So why don't you respond to self antigen?

  23. Tolerance • T and B lymphocytes have unique antigen receptors • The T cell receptor (TCR) is produced by the genetic organisation germ-line DNA • There are approximately 10 17 different TCRs!!!! • During development, TCRs go through 2 selection procedures

  24. Thymic education Pre- T cell  into the thymus: Positive selection: TCR binds to MHC= GROW  Negative selection: TCR has high affinity for MHC+self peptide = DIE mature T cell

  25. Figure 9 Structure and function of the thymus

  26. What happens if I vaccinate you? • Intentional administration of a harmless or less harmful form of a pathogen to induce a specific immune response that protects the individual against later exposure to the same pathogen. Stimulate specific adaptive immune response (antibodies; T cells) Memory

  27. Figures 10, 11 and 12 Vaccination protocols, effect on disease prevalence and immune response

  28. What happens when you eat food? • Ingest kilogram quantities of foreign 'antigen' • Digest and absorb nutrients etc • Do not make an immune response against food (except in disease eg) • coeliac disease - respond to gluten • The mucosal immune system functions to switch off responses to ingested / inhaled 'antigens'.

  29. THIS IS ORAL TOLERANCE

  30. Why might you have rheumatoid arthritis? • Immune mediated destruction of joints. • Inflammatory disease, and it is thought that T cells are recognising self-antigens. • THIS IS AN AUTO-IMMUNE DISEASE • Current theories suggest that 'molecular mimicry' may be responsible for the disease.

  31. Why might you have multiple sclerosis • MS is an auto-immune disease affecting the central nervous system. • Auto-reactive T cells participate in the formation of inflammatory lesions along the myelin sheaths of the nerve fibres. • Myelin is destroyed, nerve fibres lose insulation and this results in numerous neurological dysfunctions.

  32. fight disease  destroy self Immune responses

  33. Fight Disease eradicate pathogens response immunity Don’t fight your ‘natural’ environment ignore food / commensals non-response tolerance Healthy balancing act

  34. Balance vs Dysregulation • Both requires a functional immune system • Auto-immunity is caused by T cell responses to self antigen (egs) • Pathogenic T cell responses vs Benign T cell responses

  35. Immune regulation • There are clearly physiological mechansims of response and non-response. • Can these be switched on and off to resolve disease….?

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