GI Immunology (continue w/ handout on page2) Flashcards
Th1
type I helper T cells
recognize antigen and make a lymphokine that attracts thousands of
macrophages
-make IFN gamma, attracts and activates M1 mac and IL2 which helps CTL get activated
-M1 mac are aggressive; “classically activated”
mistakenly activated in IBD, RA, T1D
Th17
- more powerful than Th1
- make IL17
- DC make IL23 that helps differentiation into Th17
- imp for CANDIDA, Listeria, and other org
- IL-23 is imp in IBD, psoriasis
important cytokine in crohns, uc
IL-23
Th2
stimulate mac to become M2 alternatively activated
- help wall off pathogens and promote healing
- imp in parasite immunity if Th1 M1 can’t kill invader
- Th2 makes IL-4 (attracts mac and eosinophils)
-involved in asthma
Follicular helper T cells
Tfh
stimulated by antigen and migrate from T cell areas of lymph nodes into the B cell follicles, where they help B cells get activated and make the IgM, IgG, IgE
and IgA antibody subclasses.
Treg
-make cytokines (IL10, TGF-beta) that suppress activation and function of Th1, Th17, and Th2– keep immune response in check
CTL
Cytotoxic or killer Tcells
-destroy any body cell bearing a foreign or abnormal antigen on its surface, presented on Class I MHC.
They can also make IFNγ which attracts macrophages
CD8 on surface
look for antigen on MHC Class I
CD4
marker on TH1, 2, 17, fh, reg -these all look for antigen on MHC class II on mac, DC, and B cells
CTL have CD8, look for antigen on MHC Class I on all nucleated cells
Th0
In thymus:
- binds peptide/MHC with HIGH affinitiy:
- dies by apop or turns into a Treg cell (tTreg)
Th0 in gut:
binds peptide/MHC in presence of TGF-beta ONLY turns into a Treg (iTreg)
but in presence of TGFbeta and IL-6 turns into a Th1, Th2, or Th17
**gut should be Treg dominant
T cell development
Pre-T cells in the thymus proliferate rapidly and express a randomly assembled (from T-cell receptor V(D)J libraries) (TCR). Then
examine the surfaces of stromal cells.
Non-selection: If there is essentially no affinity between the TCR and the MHC on the stromal
cells (which are always loaded with a self-peptide of some sort).
Negative selection: If there is high affinity for a self-peptide in MHC, the developing T cell is
autoimmune, and dies by apoptosis. ►BUT A significant proportion of these cells
can turn into Tregs! They are called tTreg, and they serve to suppress Th1/2/17 as well as CTL
that are mistakenly recognizing self tissues.
Positive selection: If there is low affinity (above a certain threshold, but not high enough to
activate the T cell) it is selected to mature and become part of the T cell repertoire. ( takes place usually when the CDR 1s and CDR2s of both the TCR α and β chains interact adequately with amino acid residues on the alpha-helical sides of the peptide-binding MHC groove)
–>then in periphery, strong contacts with CDR3s leads to T cell stimulation
T cells involved in celiac
Th1 and Th17 against gliadin peptides
Are there TTG2 self reactive B cells?
yes, but it is ok if there isn’t self reactive T cells to react.
Gliadin:TTG2 could serve as stimulus for antiTTG2 autoantibody by formation of hybride self-foreign antigen.
(IgA)
Tfh then may help B cell, and then there is Ab against TTG2
-binds to TTG2 in gut, but then cross rxn with TTG3 by epitope spreading–> dermatitis herpetiformis
In the gut, what T cell is highly abundant and why?
Treg
B/c abundance of TGFbeta in the submucosal Peyer’s patches and DC make IL-10.–> both stim Treg devel
(Tfh are also common in Peyer’s patches and drive B cells to make IgA creating an almost sterile mucus layer)
What happens with combination of TFGbeta AND IL-6?
Downregulation of Treg and upreg of Th1 and Th17
-IL6 produced by epi cells in resp to stress/damage
Treg in thymus vs gut
thymus: tTreg
gut: iTreg (induced by exposure to normal gut flora)
