Adaptive Immunity

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

Innate vs Adaptive immune systems

Innate immune system Adaptive immune system

Response is non-specific Pathogen and antigen specific response

No immunological memoryExposure leads to immunological memory

Found in nearly all forms of life Found only in jawed vertebrates

Immediate, maximal responseLag time of 1-2 weeks after initial exposure

Evolution of the adaptive immune system

Nadia DanilovaMIT 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, 8th 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 MHCOn all cellsPresent to CTLs

Class II MHCOn APCs & B cellsPresent to helper T cells

Launching the immune response: antigen processing and presentation

Produces signal moleculesProliferatesProduces memory T helper cells

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AntigenPresentation.html

Activating antibody production by B cells

APCs

B cells

TH cell

CD4+ T cell

ProliferationDifferentiation of plasma cellsProduction of memory B cells

Activation of cytotoxic T cells

Cytotoxic T cell

Perforin

Granzymes

TCRCD8

Class I MHCmolecule

Targetcell

Peptideantigen

Pore

Released cytotoxic T cell

Dying target cell

Helper T cells assist both antibody production and cytotoxic T cell activation

Campbell & Reece, Biology 8th ed.