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Immune System Essentials: Cells, Defense Mechanisms, and Adaptive Responses

Explore the key components of the immune system, from innate vs. adaptive immunity to antigen presentation and tolerance. Learn about immune cells such as T cells, B cells, antibodies, and their crucial roles in protecting the body from pathogens and maintaining balance. Discover how the immune system differentiates between self and non-self elements, and the challenges it faces in dealing with infections, cancer, allergies, and autoimmunity. Gain insights into the intricate balance between immunity and tolerance, and the impact of immune deregulation on various human diseases.

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Immune System Essentials: Cells, Defense Mechanisms, and Adaptive Responses

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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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