1. Angela Mitchell BIO422 2013 mitcheam@email.unc.edu

3.  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

8.  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. Figure 24.2

10.  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

12. Cellular ImmunityHumoral Immunity  Main cells are T cells  Useful against intracellular pathogens  B cells and antibodies  Useful against extracellular microbes and toxins

13. T cell Mediated Immunity

14. CD8 + CD4 +

15.  T cell receptor  Recognizes small parts of proteins “presented” on MHC molecules  MHC is present on antigen presenting cells

16.  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. Figure 24.21

19.  Professional antigen presenting cells  Dendritic cells, macrophages, and B cell  Offer activating signals to T cells—primes for activity, causes proliferation

20.  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. Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

22. Th1 cells: activate phagocytes Th2 cells: activate B cells

23. What do cytotoxic T cells recognize? A.Exogenous peptides on MHCI B.Endogenous peptides on MHCI C.Exogenous peptides on MHCII D.Carbohydrates on bacteria cells E.Endogenous peptides on MHCII

24. T helper 1 cells (Th1) are important for defense from… A.Extracellular pathogens B.Fungi only C.Viruses only D.Cytoplasmic pathogens E.Phagocytosed/Endosomal pathogens

25. Epitopes and Antigens MHCI and MHCII Activation of T cells

26. Figure 24.2

27.  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. Croft. 2003. Nat Rev Immun. 3: 609.

30. Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

32. Th1 cells: activate phagocytes Th2 cells: activate B cells

33. Cell TypeCytotoxic T cellTh1 Helper T cellTh2 Helper Tcell Type of MHCMHCIMHCII Location of MHCAll nucleated cellsProfessional antigen presenting cells Location of antigenEndogenous— within the cytoplasm of the cell Exogenous— present in the phagosome Type of epitopeSmall linear peptide Response to initial recognition Proliferate and activate to effector Activated cell recognizing epitope releases Granules— perforins, granzymes Cytokines Which…Kill the target cellActivate phagocytes (WBC) to kill phagocytosed microbes Activate B cells to proliferate, produce antibodies, and develop memory

34. B cell Mediated Immunity

35.  Defense from extracellular pathogens and toxins  Recognize antigen in native form

36.  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.  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. Figure 24.7

41. Functional ActivityIgMIgDIgGIgAIgE Neutralization+  ++  Phagocytosis+  ++++  Natural killer cell killing  ++  Mast cell activation  +  +++ Complement activation+++  +  LocationBCR & Serum BCR (minor) Serum & tissue Mucus & tissue Mast cells Basophile activation?

42.  B cells recognize _____ with membrane bound_____. A.Peptides onlyMHCs B.Whole antigensMHCs C.Peptides onlyAntibodies D.Carbohydrates onlyTLRs E.Whole antigensAntibodies

43. Secondary responses to infection Vaccination

47.  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. Figure 24.13

49.  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

52.  When you’re exposed to a pathogen for the second time, your innate and adaptive immune responses will be A.Innate and adaptive both faster and stronger B.Adaptive faster and stronger but innate only faster C.Innate and adaptive both faster only D.Innate the same, adaptive both faster and stronger E.Innate the same, adaptive faster only

53. The roles of IgE and mast cells

54.  Symptoms or disease caused by immune activation by a normally harmless antigen (known as an allergen)  Allergies are mediated by IgE and mast cells

57.  50% of people in developed countries have allergies ◦ There are less allergies in the developing world.  Some families have high rates of allergies  Environmental factors: the hygiene hypothesis ◦ Lower levels of childhood disease, especially parasite infections ◦ Immune system is not “trained” correctly ◦ Therefore, the immune system responds inappropriately to harmless antigens

58. Nature Reviews Immunology 2001 (1) 69-75

61. A B C