UNIT1_GI_ImmuneSys Flashcards
Talk to me about the Lone Star Tick. What can’t you eat after you are bitten by one of these buggers!?
NO RED MEAT!!!
Tick bites you –> foreign sugar gets inside you –> you mount an immune rxn to the sugar –> sugar is similar to molecule in red meat (mammals) –> you become allergy to red meat –> your life sucks from then on!
____________ cells: recognize antigen, attract macrophages
Th1 T helper
What do Th1 T helper cells secrete?
IFNy → activate M1 (inflammatory, “angry”) macrophages
IL-2 → helps CTL get activated when they recognize antigen
What kind of T-cells do you need to get rid of TB infection → without them get disseminated TB.
Need Th1 & M1-macrophages
_____________ cells: inflammatory role, more potent than Th1 cells
Th17 helper T-cells!
Th17 helper T-cells secrete what?
IL-17
○ Dendritic cells can make ___what IL___ → pushes differentiation into Th17.
IL-23;
IL-23 considered a central cytokine in Crohn Disease and UC.
______________ cells: stimulate macrophages to become M2 (alternatively activated) → wall off pathogens, promote healing.
Th2 helper T-cells
What is so special about M2 Macrophages?
wall off pathogens, promote healing
○ Typically occurs after pathogen killing Th1 response.
○ Important in parasite immunity if Th1’s M1 macs can’t kill invader.
○ Make IL-4 → attract eosinophils and macrophages
M2 Macrophages make IL-4 → attract ___________ & ___________
eosinophils and macrophages
_____________ cells: stimulated by antigen and migrate from T cell areas of lymph nodes into B cell follicles → help B cells get activated and make IgM, IgG, IgE, and IgA
Follicular helper T cells (Tfh)
What do Follicular helper T cells (Tfh) do?
help B cells get activated and make IgM, IgG, IgE, and IgA
Follicular helper T cells (Tfh) are stimulated by what cells/signals?
Tfh cells are stimulated by antigen and migrate from T cell areas of lymph nodes into B cell follicles
→ help B cells get activated and make IgM, IgG, IgE, and IgA
Make cytokines (IL-10, TGF-B) → suppress activation and function of Th1, Th17, and Th2 cells → keep immune response in check.
This are the actions of what immune cells?
Regulatory T cells (Treg)
What are the predominant T-cell type in a healthy gut?
Regulatory T cells (Treg)
_____________ cells: destroy any body cell they identify as foreign or abnormal antigen on surface presented on class I MHC.
Cytotoxic killer T cells (CTL):
○ Make IFNy → attract macrophages that eat cells induced to die via apoptosis.
What are the actions of CTLs?
destroy any body cell they identify as foreign or abnormal antigen on surface presented on class I MHC.
○ Make IFNy → attract macrophages that eat cells induced to die via apoptosis.
w.r.t T-cell development:
Pre T cells in the ____a____ proliferate → express T cell receptor via random V(D)J → use TCR to examine stromal cell surfaces with 3 possible outcomes:
(which are:???)
a. thymus
- Non-selection
- Negative-selection
- Positive-selection
w.r.t T-cell development:
Pre T cells in thymus proliferate → express T cell receptor via ____1____ → use ____2____ to examine stromal cell surfaces
- random V(D)J
2. T-Cell Receptor (TCR)
w.r.t T-cell development:
Which type of “selection” occurs when there is no affinity between the TCR and MHC?
Non-Selection: no affinity between TCR and MHC
w.r.t T-cell development:
Which type of “selection” occurs when there is a high affinity for self peptide in MHC → T cell dies by apoptosis (prevent autoimmunity) OR turns into a Treg.
Negative-Selection: high affinity for self peptide in MHC → T cell dies by apoptosis (prevent autoimmunity) OR turns into a Treg
w.r.t T-cell development:
Which type of “selection” occurs when there is a low affinity of the TCR to the MHC, T cell selected to mature.
Positive selection: low affinity, T cell selected to mature
Most cells begin as undecided precursors (Th0) located in ____1____ of lymph nodes → APC presents correct ____2____ in lymphoid tissues → divide and differentiate into Th1, Th17, Th2, Tfh, or Treg
- paracortex
2. antigen
Most cells begin as undecided precursors (Th0) located in paracortex of lymph nodes → APC presents correct antigen in lymphoid tissues → divide and differentiate into what types of immune cells? (5)
○ Th1
○ Th17
○ Th2
○ Tfh
○ Treg
Determinants of differentiation: ?
Determinants of differentiation: conditions in periphery when APC was stimulated, what TLRs were engaged, and what cytokines/chemokines predominate
Th17 is a strong inflammatory T cell. What is a typical target of Th17? and what is Th17 activated in?
Th17 targets Candida.
Activated in IBD, psoriasis.
Which inflammatory T cell targets Helminths (worms)?
Th2.
Th2 is mistakenly activated in asthma and allergy.
In the GI Peyer’s Patches, Th0 in gut binds peptide/MHC in presence of what?
TGF-B → ONLY turns into a Treg (iTreg)
○ Abundant TGF-B → favor Th0 differentiation into Treg
○ Local dendritic cells made IL-10 → favor Treg development
Abundant Tfh cells that drive B cells towards IgA production
Describe the recognition of normal commensal gut organisms?
○ Recognition of normal commensal gut organisms: recognition of organisms by innate immunity via pattern recognition receptors that bind PAMPs → formation of iTregs (induced by exposure to normal flora) → prevent chronic inflammation.
What makes a Peyer’s Patch abnormal?
- Abnormal Peyer’s Patches:
- TGF-B + IL-6 → downregulate Treg and upregulate Th1 and Th17
• IL-6 produced in response to stress or damage
Th0 cell in gut binds peptide/MHC in presence of TGF-B + IL-6 turns into a Th1, Th2, or Th17
From an Immunology POV, what are possible causes of IBD?
• Hygiene hypothesis (old friends hypothesis) - not exposed to bacteria when you are growing up
○ Missing stimulation by “old friends” → not enough Tregs
○ → Normal bacteria (harmless) → more aggressive response via Th1, Th17, Th2
• Genetic causes: hundreds gene loci associated with IBD
• No difference in Th subgroup involvement between UC and CD
○ Th1/Th17 related expression, with little Th2 differentiation dominated both diseases
In Celiac disease: what HLA type is needed to → specially present peptides derived from gliadin to Th1 and Th17 cells (MUST have these HLA to get Celiac’s)
HLA-DQ2, HLA-DQ8.
→ B cells with anti-TTG2 antibodies activated by Tfh cells to make IgA anti-tTG.
is Celiac disease an Auto-Immune disease?
HELLS to the NO!
Is Dermatitis Herpetiformis an Auto-Immune disease?
YES!
People with HLA-DQ8 (and DQ2) are at an increased risk of getting what other disease?
DM1
What are the signs & Sx ~w/ non-celiac gluten sensitivity?
- Negative blood tests for celiac disease AND no sign of damage on intestinal biopsy
- Symptoms improvement when gluten is removed from diet
- Recurrence of symptoms when gluten is reintroduced
- No other explanation for symptoms
- NOT HLA-DQ2 and 8 associated but may be a food allergy
