UNIT1_GI_ImmuneSys

Question 1

Talk to me about the Lone Star Tick. What can’t you eat after you are bitten by one of these buggers!?

Answer 1

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!

Question 2

____________ cells: recognize antigen, attract macrophages

Answer 2

Th1 T helper

Question 3

What do Th1 T helper cells secrete?

Answer 3

IFNy → activate M1 (inflammatory, “angry”) macrophages

IL-2 → helps CTL get activated when they recognize antigen

Question 4

What kind of T-cells do you need to get rid of TB infection → without them get disseminated TB.

Answer 4

Need Th1 & M1-macrophages

Question 5

_____________ cells: inflammatory role, more potent than Th1 cells

Answer 5

Th17 helper T-cells!

Question 6

Th17 helper T-cells secrete what?

Answer 6

IL-17

Question 7

○ Dendritic cells can make ___what IL___ → pushes differentiation into Th17.

Answer 7

IL-23;

IL-23 considered a central cytokine in Crohn Disease and UC.

Question 8

______________ cells: stimulate macrophages to become M2 (alternatively activated) → wall off pathogens, promote healing.

Answer 8

Th2 helper T-cells

Question 9

What is so special about M2 Macrophages?

Answer 9

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

Question 10

M2 Macrophages make IL-4 → attract ___________ & ___________

Answer 10

eosinophils and macrophages

Question 11

_____________ 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

Answer 11

Follicular helper T cells (Tfh)

Question 12

What do Follicular helper T cells (Tfh) do?

Answer 12

help B cells get activated and make IgM, IgG, IgE, and IgA

Question 13

Follicular helper T cells (Tfh) are stimulated by what cells/signals?

Answer 13

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

Question 14

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?

Answer 14

Regulatory T cells (Treg)

Question 15

What are the predominant T-cell type in a healthy gut?

Answer 15

Regulatory T cells (Treg)

Question 16

_____________ cells: destroy any body cell they identify as foreign or abnormal antigen on surface presented on class I MHC.

Answer 16

Cytotoxic killer T cells (CTL):

○ Make IFNy → attract macrophages that eat cells induced to die via apoptosis.

Question 17

What are the actions of CTLs?

Answer 17

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.

Question 18

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:???)

Answer 18

a. thymus

1. Non-selection
2. Negative-selection
3. Positive-selection

Question 19

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

Answer 19

1. random V(D)J

2. T-Cell Receptor (TCR)

Question 20

w.r.t T-cell development:

Which type of “selection” occurs when there is no affinity between the TCR and MHC?

Answer 20

Non-Selection: no affinity between TCR and MHC

Question 21

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.

Answer 21

Negative-Selection: high affinity for self peptide in MHC → T cell dies by apoptosis (prevent autoimmunity) OR turns into a Treg

Question 22

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.

Answer 22

Positive selection: low affinity, T cell selected to mature

Question 23

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

Answer 23

1. paracortex

2. antigen

Question 24

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)

Answer 24

○ Th1

○ Th17

○ Th2

○ Tfh

○ Treg

Question 25

Determinants of differentiation: ?

Answer 25

Determinants of differentiation: conditions in periphery when APC was stimulated, what TLRs were engaged, and what cytokines/chemokines predominate

Question 26

Th17 is a strong inflammatory T cell. What is a typical target of Th17? and what is Th17 activated in?

Answer 26

Th17 targets Candida.

Activated in IBD, psoriasis.

Question 27

Which inflammatory T cell targets Helminths (worms)?

Answer 27

Th2.

Th2 is mistakenly activated in asthma and allergy.

Question 28

In the GI Peyer’s Patches, Th0 in gut binds peptide/MHC in presence of what?

Answer 28

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

Question 29

Describe the recognition of normal commensal gut organisms?

Answer 29

○ 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.

Question 30

What makes a Peyer’s Patch abnormal?

Answer 30

• 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

Question 31

From an Immunology POV, what are possible causes of IBD?

Answer 31

• 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

Question 32

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)

Answer 32

HLA-DQ2, HLA-DQ8.

→ B cells with anti-TTG2 antibodies activated by Tfh cells to make IgA anti-tTG.

Question 33

is Celiac disease an Auto-Immune disease?

Answer 33

HELLS to the NO!

Question 34

Is Dermatitis Herpetiformis an Auto-Immune disease?

Answer 34

YES!

Question 35

People with HLA-DQ8 (and DQ2) are at an increased risk of getting what other disease?

Answer 35

DM1

Question 36

What are the signs & Sx ~w/ non-celiac gluten sensitivity?

Answer 36

• 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