Adaptive Immunity David, “Bubble Boy” 1980 from 2011 CBS News 40-year retrospective 2011

Innate vs Adaptive immune systems Innate immune systemAdaptive immune system Response is non-specificPathogen and antigen specific responseantigen No immunological memoryimmunological memory Exposure leads to immunological memory Found in nearly all forms of lifeFound only in jawed vertebratesjawed vertebrates Immediate, maximal response Lag time of 1-2 weeks after initial exposure

Evolution of the adaptive immune system Nadia Danilova MIT OpenCourseWare

Adaptive Immunity: Homeland Security What are the detectors and weapons? How can the adaptive immune system recognize millions of different molecules it has never before seen? How does vaccination confer long-term protection? (immune memory)

Properties of the adaptive immune response: specificity and memory Campbell & Reece, Biology, 8 th ed.

Humoral and cell-mediated branches of the adaptive immune system Antibodies produced by plasma (B) cells –Soluble IgG in blood and lymph –Secretory IgA in mucus, tears, milk, saliva –Rarer antibody types: IgM, IgD, IgE Cytotoxic T cells attack and eliminate –virus-infected cells –cancer cells –foreign (non-self) cells

Immune specificity: antigen receptors are modular proteins H L V C V C Antibody = immunoglobulin T-cell receptor complex

How can our cells make over 10 million different antigen receptors?

Antibody and T-cell receptor diversity by combinatorial joining of DNA segments Immunoglobulins (antibodies): 2 identical heavy chains + 2 identical light chains heavy chain: V + D + J light chain: V + J T-cell receptors: 1 alpha chain + 1 beta chain alpha chain: V + J beta chain: V + D + J

Clonal selection theory Population of T-cells, B-cells each with own antigen receptor generated by random combinatorial DNA rearrangement Antigen binding selects cells to reproduce preferentially

But wait, antigen has to be processed and presented to T-cells! Class I MHC On all cells Present to CTLs Class II MHC On APCs & B cells Present to helper T cells

Launching the immune response: antigen processing and presentation Produces signal molecules Proliferates Produces memory T helper cells

Activating antibody production by B cells APCs B cells T H cell CD4+ T cell Proliferation Differentiation of plasma cells Production of memory B cells

Activation of cytotoxic T cells Cytotoxic T cell Perforin Granzymes TCR CD8 Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Dying target cell

Helper T cells assist both antibody production and cytotoxic T cell activation Campbell & Reece, Biology 8 th ed.