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Introduction to the immune system

Introduction to the immune system. Lisbeth N. Fink Nutritional Immunology Group – CBS - DTU. Protecting borders to the outside world. Challenges Discrimination between self and non-self bacteria fungi vira parasites (transplants) Evolution Dealing with non-pathogenic factors.

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Introduction to the immune system

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  1. Introduction to the immune system Lisbeth N. Fink Nutritional Immunology Group – CBS - DTU

  2. Protecting borders to the outside world • Challenges • Discrimination between self and non-self • bacteria • fungi • vira • parasites • (transplants) • Evolution • Dealing with non-pathogenic factors

  3. Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance

  4. First lines of defense

  5. Lymphoid organs and lymphatics

  6. Immunocompetent cells

  7. Hæmatopoesis = creation of blood cells Red blood cells Leukocytes/ White blood cells Lymphocytes Adaptivt/Specifikt Medfødt/Uspecifikt

  8. Second line of defense: Humoral factors • Humor = liquid • (From greek, 4 humors controlling health and mood: blood, phlegm, yellow and black bile) • Antibodies – specific • pathogen recognition • Complement system • – non-specific recognition • Reactive oxygen species • (ROS) – bactericidal activity

  9. Third line of defense: Immune cells

  10. Haematopoieisis Red blood cells Leukocytes/ White blood cells Lymphocytes Adaptive/Specific Innate/Non-specific

  11. Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance

  12. T cells B cells Antibodies Memory MHC - HLA Diversity Somatic hypermutation Polymorphism Granulocytes Monocytes Macrophages Dendritic cells NK cells NK T cells Complement Pattern recognition Characteristics of the two parts Adaptive/Specific Innate/Non-specific

  13. T cells B cellsAPC Antibodies Memory MHC - HLA Diversity Somatic hypermutation Polymorphism Granulocytes APC Monocytes APC Macrophages APC Dendritic cells APC NK cells NK T cells Complement Pattern recognition Characteristics of the two parts Adaptive/Specific Innate/Non-specific

  14. Inflammation – recruitment of cells

  15. What leads to an adaptive immune response

  16. Antigen uptake - phagocytosis Phagocytic cells: Granulocytes Monocytes Macrophages Dendritic cells

  17. The ”patterns” of microorganisms

  18. Pattern recognition in APC Takeda & Akira, Int. Immunol. 2005

  19. Recognition of ”pathogenic” structures • Direct recognition of pathogens – ”danger signals” (viral, bacterial, fungal, parasitic) • Innate immune system alerts the adaptive immune system in parallel with antigen-presentation • Must recognize vital structures!

  20. Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance

  21. What leads to an adaptive immune response

  22. T cells Recognizes MHC I on all cells Recognizes MHC II on APC Kills: Infected cells Tumour cells Helps: B-cells T cells Macrophages

  23. Activation of CD4+ T cells

  24. T cell receptor

  25. MHC molecules

  26. Antigen-presenting cells

  27. Antigen presentation pathways

  28. MHC I and II Tc TH

  29. Antigen presentation • 3. Signal • Cytokines ↔ Cytokine • receptors 2. 1. Activation Proliferation Help or Killing

  30. Induction of immunity • Importance of CD4+ T cells: • CD4+ T cells are central in providing help for CD8+ T cell and B cell activation

  31. Activation of CD8+ T cells

  32. Killing of virus-infected cells Apoptosis is induced due to the action of perforin (making pores), and the granule-containing granzyme B, a serine protease which activates a variety of caspases.

  33. CTLs in virus clearance

  34. Meeting places (T – APC)

  35. Second line of defense: Humoral factors • Humor = liquid • (From greek, 4 humors controlling health and mood: blood, phlegm, yellow and black bile) • Antibodies – specific • pathogen recognition • Complement system • – non-specific recognition • Reactive oxygen species • (ROS) – bactericidal activity

  36. Antibodies

  37. B cells – plasma cells - antibodies

  38. T cell help for B cell activation

  39. B cells – memory cells

  40. Antibody classes

  41. Preference for ”opsonized” bacteria Antigen uptake

  42. Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance

  43. What about ’endogenous’ challenges? • Cancer cells – tumor antigens • Immune reactions within self-tissues: autoimmunity • Discontinuation of immune responses • …and reactions to harmless environmental factors: allergy (to food, pollen, fur etc.) • Immunity vs. Tolerance

  44. The central issue: immunity versus tolerance • The immune system has the tremendous task to eliminate pathogens and eradicate arising tumours, while preventing auto-reactive responses that are harmful to the host. • In keeping with balancing this dual task, a complex interplay between immune cells exists and many stimulatory and inhibitory circuits are in place. • Deregulation of this intricate balance is directly associated with human diseases, ranging from inflammatory and autoimmune disorders to infection and cancer.

  45. Definitions • Immunity: • Effective clearance of all infectious agents and tumours by immune cells • Tolerance: • Hindering of autoimmunity, and down-regulation of immune responses after clearing of pathogens

  46. Discrimination between “self” and “non-self” Every immune response depends on regulation at the single-cell level

  47. Different lines of tolerance induction • Regulation of tolerance is two-legged: • Central regulation (thymus, bone marrow) • Peripheral regulation

  48. Central T cell tolerance Ideally, selected T cells contain TCRs with low affinity for self MHC in combination with “non-self” antigens, but usually auto-reactive T cells also exists in the periphery

  49. Peripheral tolerance • Ways of down-regulating immune responses in the periphery: • Anergy – no co-stimulatory signal • Deletion - by apoptosis • Active suppression (by naturally-arising or peripherally induced Tregs)

  50. Antigen presentation • 3. Signal • Cytokines ↔ Cytokine • receptors 2. 1. Activation Proliferation Help or Killing

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