1. Adaptive Immune System
Angela Mitchell
BIO422
2013

2. “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

3. Overview of Host Response to Pathogens

4. Time Course of an Immune Response

5. Levels of the Immune Response

6. Levels of the Immune Response

7. 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

8. Epitopes are small parts of antigens
Figure 24.2

9. 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

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

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

12. Cellular Immune Response
T cell Mediated Immunity

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

14. 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

15. 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

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

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

18. 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

19. 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

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

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

22. 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

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

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

25. T cell summary Cell Type Cytotoxic T cell Th1 Helper T cell
Type of MHC
MHCI
MHCII
Location of MHC
All nucleated cells
Professional antigen presenting cells
Location of antigen
Endogenous—within the cytoplasm of the cell
Exogenous—present in the phagosome
Type of epitope
Small linear peptide
Response to initial recognition
Proliferate and activate to effector
Activated cell recognizing epitope releases
Granules—perforins, granzymes
Cytokines
Which…
Kill the target cell
Activate phagocytes (WBC) to kill phagocytosed microbes
Activate B cells to proliferate, produce antibodies, and develop memory

26. Humoral Immune Response
B cell Mediated Immunity

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

28. 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

29. 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

30. Antibody Structure
Figure 24.7

31. Structure of Different Antibody Types

32. Functions of Antibodies

33. Types of Antibodies Functional Activity IgM IgD IgG IgA IgE
Neutralization +  ++
Phagocytosis
+++
Natural killer cell killing
Mast cell activation
Complement activation
Location
BCR &
Serum
BCR (minor)
Serum & tissue
Mucus & tissue
Mast cells
Basophile activation?

34. Immunological Memory
Secondary responses to infection
Vaccination

35. Timing of Adaptive Response

36. Immunological Memory

37. Secondary Immune Response

38. 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

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

40. 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

41. Smallpox vaccine led to the eradication of smallpox

42. Now many vaccines!

43. Allergies
The roles of IgE and mast cells

44. What is an allergy?
Symptoms or disease caused by immune activation by a normally harmless antigen (known as an allergen)
Allergies are mediated by IgE and mast cells

45. Allergies are mediated by IgE and mast cells

47. Why are allergies increasing?
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

48. The hygiene hypothesis
Nature Reviews Immunology 2001 (1) 69-75 

49. Immune System Summary

50. Adaptive Immune System