A daptive I mmune S ystem

1. Adaptive Immune System Angela Mitchell BIO422 2013 mitcheam@email.unc.edu

2. “Jobs” of the Immune System

3. “Jobs” of the Immune System • Recognize that invaders are present • Recognize that these are different than self • Recruit more cells/factors to fight invaders • Kill the invaders • Block any toxins produced by the invaders • Learn from past encounters to increase future effectiveness

4. Overview of Host Response to Pathogens

5. Time Course of an Immune Response

6. Levels of the Immune Response

7. Levels of the Immune Response

8. Adaptive Responses Are Specific to Individual “Epitopes” • Antigen: the molecule recognized by the response • The epitope is the specific part of the antigen recognized • Each adaptive immune cell can only recognize one epitope

9. Epitopes are small parts of antigens Figure 24.2

10. Concept Questions • Can an antigen have more than one epitope? • Yes, almost always • Can an epitope have more than one antigen? • No (almost always…) • You found two adaptive immune cells that respond to pilin. Are these cells specific for the same epitope? • No necessarily: they could respond to two different epitopes on the same antigen

11. Adaptive Immune response relies on lymphocytes: B and T cells

12. Two Branches of Adaptive Response • Main cells are T cells • Useful against intracellular pathogens • B cells and antibodies • Useful against extracellular microbes and toxins Cellular Immunity Humoral Immunity

13. Cellular Immune Response T cell Mediated Immunity

14. Roles of T cells in Host Defense CD8+ CD4+

15. How do T cells recognize antigen? • T cell receptor • Recognizes small parts of proteins “presented” on MHC molecules • MHC is present on antigen presenting cells

16. Two types of MHC: MHCI and MHCII • MHCI is present on all nucleated cells • CD8+ cytotoxic T cells recognize MHCI • MHCII is present on professional antigen presenting cells  pAPCs • CD4+ helper T cells recognize MHCII Figure 24.20

17. Intracellular antigens are processed and displayed on MHCI for CD8+ cytotoxic T cells Figure 24.21

18. Extracellular antigens are processed and displayed on MHCII for CD4+ helper T cells Figure 24.21

19. Initial recognition by pAPCs • Professional antigen presenting cells • Dendritic cells, macrophages, and B cell • Offer activating signals to T cells—primes for activity, causes proliferation

20. Types of T cells • Cytotoxic T cells: CD8+ T cells • Recognize antigens on MHCI • Releases granules to kills target cells • Helper T cells: CD4+ T cells • Recognize antigens on MHCII • Secrete cytokines to activate other cells • Two major types: Th1 and Th2

21. CD8+ Cytotoxic T cells • Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

22. CD4+ Helper T cells (Th) Th1 cells: activate phagocytes Th2 cells: activate B cells

23. Concept Question What do cytotoxic T cells recognize? • Exogenous peptides on MHCI • Endogenous peptides on MHCI • Exogenous peptides on MHCII • Carbohydrates on bacteria cells • Endogenous peptides on MHCII

24. Concept Question T helper 1 cells (Th1) are important for defense from… • Extracellular pathogens • Fungi only • Viruses only • Cytoplasmic pathogens • Phagocytosed/Endosomal pathogens

25. Review From Friday Epitopes and Antigens MHCI and MHCII Activation of T cells

26. Epitopes are small parts of antigens Figure 24.2

27. Specificity of T cell (B and) activation • Every T cell has a different T cell receptor specific to a different epitope • Your body can make about 10^18 different T cell receptors • Developmental processes kill T cells that cannot recognize your MHC and that recognize self peptides • Initial T cell recognition of a peptide without an innate immune response (inflammation) does not activate the T cell

28. Initial response of T cells (cytotoxic and helper): proliferation and activation Croft. 2003. Nat Rev Immun. 3: 609.

29. MHCI presents cytoplasmic (endogenous) peptides to Cytotoxic T cells

30. CD8+ Cytotoxic T cells • Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

31. MHCII presents endosomal (exogenous) peptides to Helper T cells

32. CD4+ Helper T cells (Th) Th1 cells: activate phagocytes Th2 cells: activate B cells

33. T cell summary

34. Humoral Immune Response B cell Mediated Immunity

35. B cells Produce Antibodies • Defense from extracellular pathogens and toxins • Recognize antigen in native form

36. Activation of B cells • B cell receptor (BCR) recognizes antigen • Membrane bound antibody • Th2 cells help activation and are required for memory • B cell differentiates to plasma cell, which produces antibodies

37. Antibody Structure • Immunoglobulins (Ig) • “Y” shaped proteins • 4 polypeptides linked by disulfide bonds • Two identical heavy chains • Two identical light chains • Has variable and constant regions • Variable regions are responsible for recognizing the epitope

38. Antibody Structure Figure 24.7

39. Structure of Different Antibody Types

40. Functions of Antibodies

41. Types of Antibodies Basophile activation?

42. Concept Question • B cells recognize _____ with membrane bound_____. • Peptides only MHCs • Whole antigens MHCs • Peptides only Antibodies • Carbohydrates only TLRs • Whole antigens Antibodies

43. Immunological Memory Secondary responses to infection Vaccination

44. Timing of Adaptive Response

45. Immunological Memory

46. Secondary Immune Response

47. Memory Responses • Small populations of B and T cells retained from first exposure • Survive for a long time • Begin faster than first response • Stronger than first response • Vaccinations take advantage of memory responses

48. Vaccines allow for high levels of pre-existing immunity due to memory Figure 24.13

49. Vaccination • Deliberate induction of an immune response to a pathogen by introducing a dead or non-pathogenic (attenuated) form of the pathogen • Vaccination began with Edward Jenner (around 1796) • Observation that people exposed to cowpox did not get smallpox • Exposed a boy to cowpox (vaccinia) and the boy did not get sick with smallpox

50. Smallpox vaccine led to the eradication of smallpox