Zwickey 5/15 lecture on the GUT

[liveonearth]

--the GI tract has 400 square meters of surface area and over 500 species of bacteria
--less TLR's on macrophages and DC's in gut
--some enteric microbes no longer bind TLR's (bifidus)
--food in lumen crosses mucosa to peyers patches, mesenteric lymph nodes
--peyers patches and mesenteric lymph nodes constitute 80% of a person's immune system
--always active
--eating oil with food causes it to be absorbed lower in the tract, increasing the odds of allergy because there are more allergens down there
--TGFbeta is the 2nd signal to shut down T cells ???
--M cells are between peyers patch and lumen
--M cells transport food via endosome to PP
--epithelial cells also take in food, have MHC-I

There are four types of hypersensitivity reactions
1) IgE mediated "allergy"
2) IgG response to surface proteins (penicillin)
3) IgG response to soluble proteins
4) T cell response (wheat)

Type II
--IgG vs sfc prot
--ex: penicillin: some RBC's have a surface protein that binds penicillin. We make antibodies for penicillin. The anibodies bind the penicillin on the RBC: opsinize it, and then a macrophage with Fcgamma receptor EATS THE RBC --> hemolytic anemia

Type III
--IgG response to soluble antigen
--Ab's bind prot, macrophages release ROS
--if the protein the Ab's bind is stuck to a blood vessel wall, the ROS damage the BV
--neutrophils hang onto BV walls
--over response --> damage self
--can cause a deposit in BV wall when macrophages and neutrophils attack
--this rxn can also happen in skin, ex: TB test causes an arthus reaction (possible danger, normal under 2 days?)(TB test, vacine too shallow?)(PPD tests close togther, increased rxn the 2nd time)
--extreme rxn --> hypersensitivity

Type IV = DTH = delayed type hypersensitivity rxn
--this is our intended reaction to a microbe (Th1: GM-CSF, TNFalpha, IFNgamma)
--takes about 2 days
--is local
--inflammatory cytokines cause swelling, redness etc
--ex: nickel modifies self protein, get immune response
--celiacs have a DTH response to gluten (gliadin, a prolamine in gluten)
--type I diabetics have more gliadin sensitivity
--aa sequence of gliadin is known
--??? agglutinin globs Ab's together?
--MCH-I and II involved
--leaks = weakened tight junctions (flashback to SSL)

TWO TYPES OF TOLERANCE IN THE GUT: LOW AND HIGH DOSE
--low dose = foods rarely consumed --> CD4 response, TGFbeta shuts down response, no macrophages or CD8's involved
--high dose = eat it daily = body kills T & B cells specific for that food
--feeding --> develop a tolerance because increase Th3 response
--not working well yet experimentally
--collagen fed to rheumatoid arthritis pts--small improvement, narrow therapeutic window
--Th1-->TNFalpha-->leaky gut, crohns, colitis, increased intestinal permeability
--colitis: too much Th1 response, colon too acidic, too much IgG response to normal gut flora
--crohns: not enough cathelicidins (neutrophils)