MCMP422 Immunology and Biologics

1. MCMP422Immunology and Biologics Immunology is important personally and professionally! Learn the language - use the glossary and index RNR - Reading, Note taking, Reviewing All materials in Chapters 1-3 are examinable (with exceptions) plus extra material from class

2. Chapter 1 Elements of the Immune System and their Roles in Defense Summarizes all of immunology Foundation for the rest of the course The rest is all details

3. Chapter 1 Concepts What components make up the immune system? Cells, organs, cytokines and other molecules involved in the immune system What is the goal of the immune system? To clear pathogens in our body How do we classify immune responses? Innate and adaptive immune responses What are the side effects of the immune system? Autoimmune diseases, Allergies, Transplantation Rejection

4. Immunology: the science of how the body responds to foreign organisms (e.g. pathogens) or substances (e.g. allergen) • Immune system: the organs, cells and molecules that defend and respond to pathogens/allergens • 1. Tissues/organs • bone marrow, thymus, spleen, lymph nodes • 2. Cells • lymphocytes, dendritic cells, macrophages, natural killer cells, granulocytes (neutrophils, basophils, eosinophils), mast cells • Blood borne proteins complement and mannose-binding proteins

5. Origin of Immunology - individuals who survived a disease seemed to be untouched upon re-exposure Vaccination/Immunization - procedure where disease is prevented by deliberate exposure to infectious agent that cannot cause disease.

6. Figure 1-2

7. Diversity of Pathogens • Four Classes • Opportunistic pathogens Pneumocystis carinii • Pathogen-Host relationship

8. How Clean are You? Part of bodyBacteria Head (scalp) 1,000,000 /cm2 Surface of skin 1000 /cm2 Saliva 100,000,000 /g Nose mucus 10,000,000 /g Faeces over 100,000,000 /g

9. Defenses against Pathogens Physical Defenses 1. Skin - Tough water-proof Barrier - Pathogen Penetration is difficult - Breached by wounds/mosquito 2. Mucosal surfaces - line body cavities - epithelial cells covered with mucus - e.g. mucus in lungs traps pathogens Immune Defenses 1. Innate 2. Adaptive

10. Figure 1-4 Physical Barriers

11. Innate and Adaptive responses Innate • Pathogen independent • Immediate (hours) • Neutrophils • NK cells • Macrophages • Mast cells • Eosinophils • Basophils Adaptive • Pathogen-dependent • Slower (days) • Dendritic cells • B cells • T cells (CD4 or CD8) Both systems “talk” to each other to modulate response

13. Recognition (Binding event) Immune disorders Signal (Self) Effector mechanisms Effector Cells Complement Innate immunity - “naïve”, immediate, everyday immunity Acquired immunity - “specialized”, late, immunity Immunity: Three Basic Parts Pathogen (Foreign)

14. Figure 1-5 part 1 of 2 One way Immunity Works Complement Effector cell Endocytosis

15. Figure 1-5 part 2 of 2

16. Figure 1-6 Innate Immunity Cytokines Inflammation Phagocytosis Inflammatory cells

17. Inflammation • Inflammation - local accumulation of fluid and cells involved in the immune response - State of Inflammation is induced - increased swelling, pain, heat and redness. • Blood capillary dilation = heat = redness • Vascular dilation = swelling = pain • Extravasation - change in adhesiveness of the endothelial tissue allowing immune cells to attach and migrate into the connective tissue

18. What if Innate Immunity is not Enough? • Innate immunity keeps us healthy most of the time • Some pathogens escape the innate immune process • Need a specific system to adapt to a specific pathogen • Adaptive immune response

19. Figure 1-7 Characteristics of Innate vs Adaptive Immunity Lymphocytes - white blood cells that increase the immune response to ongoing infection

20. INNATE ADAPTIVE Genes are constant Genes rearrange NO Longterm immunity Longterm immunity

21. Innate vs Adaptive Molecular Recognition • Most important difference: Receptors used to recognize pathogens • Innate immunity: Receptors recognize conserved structures present in many pathogens • Pathogen-associated Molecular Patterns: LPS, peptidoglycan, lipids, mannose, bacterial DNA and viral RNA • Adaptive immunity: Receptors recognize a specific structure unique to that pathogen

23. Figure 1-11 part 1 of 2 Flowchart of Hematopoiesis

24. Figure 1-11 Flowchart of Hematopoiesis

25. Myeloid Lineage

26. Figure 1-9 part 3 of 6 Granulocytes (Myeloid progenitor) Polymorphonuclear leukocytes (PMLs) Neutrophils: Most abundant Phagocyte Effector cells of Innate Immunity Short-lived - Pus Eosinophils: Worms/intestinal parasites Amplify inflammation Bind IgE Very Toxic - Pathogen and host Chronic asthma Basophils: Rare Unknown function Bind to IgE

27. Figure 1-9 part 5 of 6

28. Figure 1-13

30. Lymphoid Lineage Cells

31. Figure 1-9 part 2 of 6 Lymp

32. Figure 1-9 part 1 of 6

33. Erythroid Lineage

34. Figure 1-9 part 6 of 6

35. Figure 1-11 part 2 of 2 Lymphoid Myeloid Erythroid

36. Figure 1-12

38. Figure 1-14

39. Figure 1-15 Sites of Lymphoid Tissue Primary and Secondary GALT, BALT, MALT Lymph Recirculation

40. Figure 1-16 Draining Lymph node Edema Afferent and Efferent

41. Figure 1-17 part 1 of 2

42. B-cell area (follicle)

44. Figure 1-19 Anatomy of immune function in the Spleen

45. Figure 1-19 part 1 of 2

46. Figure 1-19 part 2 of 2

47. Figure 1-20

49. Adaptive Immunity • Vertebrates only • Specificity - recognition modules - BCR, Ab and TCR - gene rearrangement is the source of diversity - clonal selection • Small lymphocytes - types and sub-types - functions

50. Recognition concept Receptor or Antibody molecule Antigen - structure recognized by an Ab, BCR or TCR Epitope - particular sub-structure of the Ag that is bound Affinity - how much a molecule likes to bind to a structure