11/6/12 Flashcards
function of mhc molecules
present peptides for recognition by TCR
mhc I get peptides from where and how?
intracellular Ag that are digested by protease
peptide transported to ER and loaded onto MHC as it is synthesized/secreted to plasma membrane
mhc II gets peptides from where and how?
protein phagocytosed, degraded into peptides in phagolysosome.
mhc II syn in golgi buds off and fuses with phagolysosome where mhc II binds peptide
transported to plasma membrane
what expresses mhc I
almost all cells except RBC
less-so on neurons
what expresses mhc II
APC
B cells, macrophages, DC, thymic epithelium
implications of mhc I?
problem in cells
i.e. APC infected. Get rid of cell.
implications of mhc II?
problem outside cells
i.e. APC has detected an infection. Don’t necessarily get rid of cell
What do t cells do that recognize mhc I?
CD8 T cells are cytotoxic to mhc I presenters
what do t cells do that recognize mhc II?
CD4 t cells help activate APC via cytokines, cell-surface contact mediated stimulation
Also, recognize B cell MHC II (Ab that binds Ag) and help B cell activate
what are the two cells that are cytotoxic?
CD8 T cells
Natural Killer cells
mechanism of cytolysis?
specific recognition
release of lytic granules via cytoplasmic rearrangement and release
what kinds of cells are lysed?
virally infected cells
infected cells with cytoplasmic bacteria
neoplastic cells
what are the two main categories of helper T cells?
Th1
Th2
Th1 do what?
post-regulatory molecules and cytokine release that help cells do cell-mediated responses
Th2 do what?
help Ab-mediated responses (or humoral responses)
what are the two major cytokines that differentiate?
Th1 – IFN-gamma –> cell-mediated responses
Th2 – IL-4 –> Ab-mediated response (also release IL-10 for plasma cell differentiation effect)
what are the choices for B cell development
- become a plasma cell
2. become a memory b cell
how does B cell become plasma cell
Th2 produces IL-10 and B cell becomes short-lived plasma cell that produces Ab
how does B cell become memory B cell
Th2 cell produces IL-4 and B cell becomes long-lived memory cell
discuss somatic hypermutation during B cell development
during b cell/t cell interaction, b cells modify their DNA for Ab.
in area that encodes the binding site
dependent on activation-induced cytidine deaminas (AID)
discuss affinity maturation in b cell development
select for B cells that express Ab’s w/ high affinity for Ag and remove those that do not
discuss isotype switching in b cell maturation
Th2 produce cytokines that induce b cell to change the heavy chain of Ig (maintain same Ag binding site)
DNA recombination
isotype functions
IgM/IgG - trigger complement pathway
IgG - binds Fc receptors on NK cells and triggers antibody-dependent cell-mediated cytotoxicity (ADCC)
-from mother is able to cross placenta
IgA - transported across epithelial surfaces (important for immunity at mucosal surfaces)
IgE - triggers degranulation by Mast cells (allergic responses).
cytokines and their effect
IL-4 (Th2) = promotes IgE (anti-helminth responses and allergy)
IFN-gamma (Th1) = promote IgG sub-classes (cell-mediate responses)
how do T cells take on their specific cytokine production?
DC determine polarization of T cells via its own cytokine production
DC produces IL-12 –> Th1 cytokines by T cell
DC produces low IL-12 –> Th2 cytokines by T cell
how do you favor cytotoxic cell differentiation in adaptive
CD4 Th1 cells can produce IL-2 that help activation CD8 T cells favoring cell-mediated responses.
IL-12 from DC also trigger this
what determines DC IL-12 production?
The nature of the PRR stimulation
Thus, the initial, innate stimulation (type of pathogen) determines the characteristics of the adaptive immune response
