Antibody structure
Heavy chain constant region determines antibody class
B cell development
B cell development
Heavy chain gene rearrangement
B cell development
Light chain gene rearrangement
Human heavy chain gene-segment pool
51 x 27 x 6 = 8262 possible H chain variable regions
40 x 5 = 200 possible light chain variable regions 116 possible chain variable regions
2.6 million possibleantigen binding sites from gene segment combinations
IgM IgD IgG IgE IgA
Human light-chain gene rearrangement
Ab gene usage in a pre-B cell (allelic exclusion)
Memory cells:
Somatic hypermutation in V regions
Class switching
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?
T cell receptor(TCR genes are rearranged as antibody genes are in B cells)
T cell activation
TH cell activation
Antigen-presenting cells:Dendritic cells (shown)B cellsMacrophages
Antigen-presenting cells activate TC and TH cells
Cytotoxic T cell killing an infected cell
Apoptosis is mediated by an intracellular proteolytic cascade
Cell-surface death receptors regulate the extrinsic pathway of apoptosis
How cytotoxic T cells kill target cells
How cytotoxic T cells kill target cells
Antigen-presenting cells activate TC and TH cells
Antigen-presenting cells activate T cells
Dendritic cells activate TH cells, then TH cells activate B cells
MHC (Major Histocompatibility Complex) proteins
Human MHC (Major Histocompatibility Complex) genes
Highly polymorphic in populationClass I - Expressed in almost all cells of bodyClass II – Expressed in antigen-presenting cells
MHC I binds peptides
T cell receptor recognizes MHC + peptide
MHC I displays intracellular antigens on the cell surface
TC cells only act in hosts with the “right” MHC molecules
MHC II displays endocytosed antigens on the cell surface
TH cell activation
Coreceptors for MHC proteins:
CD4: MHC II (TH cells)CD8: MHC1 (TC cells)
HIV uses CD4 to infect TH cells
T cell selection in the thymus
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)
Wednesday, April 28th – Bring questions
Exam: Monday, May 3, 12:00-2:00, 201 Coker Hall