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Flashcards in Mucosal Immunity Deck (31):
1

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

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

2

What do mucosal dendritic cells produce from vitamin A?

Retinoic acid through expression of retinal dehydrogenases

3

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

TGF-beta

4

How do T cells recognize antigens?

1st signal: T-cell receptor
2nd signal: co-stimulatory molecule (CD28) recognizes co-stimulatory receptor (CD80/86) on APC

5

How do B cells recognize antigens?

1st signal: membrane bound IgM
2nd signal: costimulation -- complement receptor, toll like receptor

6

How much IgA does the gut secrete per day?

2-4 grams

7

A molecule that induces an immune response

Immunogen

8

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

Antigen

9

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

Tolerogen

10

Specific unresponsiveness to an individuals SELF antigens

Immunologic tolerance

11

What does mucosally induced tolerance help to prevent?

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

12

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

Th17 response

13

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

Regulatory T cells

14

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

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+)

15

What are the three things that contribute to autoimmunity?

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

16

What causes hypersensitivity?

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

Mast cells and eosinophils, vasoactive amines, cytokines
IgE mediated

Type I

18

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

Type II

19

Complement and Fc recruitment of leukocytes
Mediated by Immune complexes

Type III

20

CD4: macrophage activation, inflammation
Mediated by T cells

Type IV

21

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

Nod2
ATG16

22

How might mutations in MHC contribute to autoimmune diseases?

Inefficient displaying of self-antigens
Poorly stimulated regulatory T cells

23

How are autoimmune diseases treated??

Systemic immune suppression

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

Plasmapheresis or competitive FcR inhibition

24

Loss of oral tolerance to wheat (gluten)
Increased levels of de-aminated gliadin peptide

Celiac disease

25

Associated HLA types with Celiac disease

HLA-DQ2 and HLA-DQ8

26

Why type of hypersensitivity is Celiac disease?

Type IV - Th1 cells and inflammatory response damage tissues

27

Loss of tolerance to microbiota

Inflammatory Bowel Disease

28

What mutations are associated with IBD?

Mutation sin Nod pattern recognition receptor gene
Mutations in autophagy (cellular homeostasis) genes

29

What HLA types are associated with IBD?

HLA-DR and HLA-B27

30

What type of hypersensitivity is IBD?

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

31

What type of hypersensitivity is food allergy?

Type I - sensitized to food antigen, immediate response