1. Antibody structure
Heavy chain constant region determines antibody class

2. B cell development

3. B cell development
Heavy chain gene rearrangement

4. B cell development
Light chain gene rearrangement

5. Human heavy chain gene-segment pool
IgM IgD IgG IgE IgA
51 x 27 x 6 = 8262 possible H chain variable regions
40 x 5 = 200 possible k light chain variable regions
116 possible l chain variable regions
2.6 million possible
antigen binding sites from gene segment combinations

6. Human k light-chain gene rearrangement

7. Ab gene usage in a pre-B cell (allelic exclusion)

8. Clonal selection

9. Memory cells:
Somatic hypermutation in V regions
Class switching

10. T cells and MHC proteins
How does the immune system recognize cells that are infected by a virus?
Why doesn't the immune system attack uninfected cells?

11. T cell receptor
(TCR genes are rearranged as antibody genes are in B cells)

12. T cell activation

13. TH cell activation

14. Antigen-presenting cells:
Dendritic cells (shown)
B cells
Macrophages

15. Antigen-presenting cells activate TC and TH cells

16. Cytotoxic T cell killing an infected cell

17. Apoptosis is mediated by an intracellular proteolytic cascade

18. Cell-surface death receptors regulate the extrinsic pathway of apoptosis

19. How cytotoxic T cells kill target cells

20. How cytotoxic T cells kill target cells

21. Apoptosis

22. Antigen-presenting cells activate TC and TH cells

23. Antigen-presenting cells activate T cells

24. Dendritic cells activate TH cells, then TH cells activate B cells

25. MHC (Major Histocompatibility Complex) proteins

26. Human MHC (Major Histocompatibility Complex) genes
Highly polymorphic in population
Class I - Expressed in almost all cells of body
Class II – Expressed in antigen-presenting cells

27. MHC I binds peptides

28. T cell receptor recognizes MHC + peptide

29. MHC I displays intracellular antigens on the cell surface

30. TC cells only act in hosts with the “right” MHC molecules

31. MHC II displays endocytosed antigens on the cell surface

32. TH cell activation

33. Coreceptors for MHC proteins:
CD4: MHC II (TH cells)
CD8: MHC1 (TC cells)
HIV uses CD4 to infect TH cells

36. T cell selection in the thymus

37. Clonal selection
Proliferation of B and T cells that recognize a harmful antigen (positive selection)
Elimination of T cells that recognize self peptides (negative selection)

38. Wednesday, April 28th – Bring questions
Exam:
Monday, May 3, 12:00-2:00, 201 Coker Hall