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GI > Mucosal Immunity > Flashcards

Mucosal Immunity Flashcards

1
Q

What are the 3 traffic signals that bring immune cells to the gut??

A

alpha4beta7 and CCR9 - immune cells
MadCAM - endothelium
CCL25 - epithelium

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2
Q

What do mucosal dendritic cells produce from vitamin A?

A

Retinoic acid through expression of retinal dehydrogenases

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3
Q

What drives class switching to IgA in T-depending class switching in the gut?

A

TGF-beta

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4
Q

How do T cells recognize antigens?

A

1st signal: T-cell receptor

2nd signal: co-stimulatory molecule (CD28) recognizes co-stimulatory receptor (CD80/86) on APC

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5
Q

How do B cells recognize antigens?

A

1st signal: membrane bound IgM

2nd signal: costimulation – complement receptor, toll like receptor

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6
Q

How much IgA does the gut secrete per day?

A

2-4 grams

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7
Q

A molecule that induces an immune response

A

Immunogen

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8
Q

A molecule that binds to (is recognized) by antibody (B cells) or T cells

A

Antigen

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9
Q

A molecule that induces immune unresponsiveness to subsequent doses of the molecule

A

Tolerogen

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10
Q

Specific unresponsiveness to an individuals SELF antigens

A

Immunologic tolerance

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11
Q

What does mucosally induced tolerance help to prevent?

A

Intestinal disorders – food allergy, celiac disease, inflammatory bowel disease

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12
Q

What is the predominant T-cell mediated immune response in the gut?

A

Th17 response

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13
Q

What cell mediates the non-responsiveness to food and microbiota?

A

Regulatory T cells

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14
Q

How do mucosal dendritic cells regulate the induction of tolerance in the gut?

A

Gut DCs take up antigens from the gut (food or microbiota) travel to mesenteric lymph nodes and present Ag to T cells –> Cell produces retinoid acid and TGFbeta –> drives differentiation of CD4+ naive T cells to become regulatory T cells (FoxP3+)

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15
Q

What are the three things that contribute to autoimmunity?

A

Genetic susceptibility - susceptibility genes (HLA and non-HLA)
Environmental triggers - smoking
Uncontrolled immune response - hypersensitivity

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16
Q

What causes hypersensitivity?

A
  1. dysregulated or uncontrolled response to foreign antigens resulting in tissue damage and injury
  2. failure of self-tolerance followed by immune responses directed against “self” antigens (autoimmunity)
17
Q

Mast cells and eosinophils, vasoactive amines, cytokines

IgE mediated

A

Type I

18
Q

Opsonization/phagocytosis, complement and Fc recruitment of leukocytes
IgM and IgG mediated

A

Type II

19
Q

Complement and Fc recruitment of leukocytes

Mediated by Immune complexes

A

Type III

20
Q

CD4: macrophage activation, inflammation

Mediated by T cells

A

Type IV

21
Q

What are some non-HLA genes that contribute to autoimmunity?

A

Nod2

ATG16

22
Q

How might mutations in MHC contribute to autoimmune diseases?

A

Inefficient displaying of self-antigens

Poorly stimulated regulatory T cells

23
Q

How are autoimmune diseases treated??

A

Systemic immune suppression

Non-systemic immune suppression – Antibodies to TNF (Infliximab) and soluble TNFR (Etanercept)

Plasmapheresis or competitive FcR inhibition

24
Q

Loss of oral tolerance to wheat (gluten)

Increased levels of de-aminated gliadin peptide

A

Celiac disease

25
Q

Associated HLA types with Celiac disease

A

HLA-DQ2 and HLA-DQ8

26
Q

Why type of hypersensitivity is Celiac disease?

A

Type IV - Th1 cells and inflammatory response damage tissues

27
Q

Loss of tolerance to microbiota

A

Inflammatory Bowel Disease

28
Q

What mutations are associated with IBD?

A

Mutation sin Nod pattern recognition receptor gene

Mutations in autophagy (cellular homeostasis) genes

29
Q

What HLA types are associated with IBD?

A

HLA-DR and HLA-B27

30
Q

What type of hypersensitivity is IBD?

A

Type IV - Th1 (Crohn’s) or Th2 (ulcerative colitis) –> inflammatory damage

31
Q

What type of hypersensitivity is food allergy?

A

Type I - sensitized to food antigen, immediate response

GI (34 decks)

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