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 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

Human k light-chain gene rearrangement

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

Clonal selection

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 cells Macrophages

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

Apoptosis

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 population Class I - Expressed in almost all cells of body Class 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