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Immunology > Lec13 Mucosal Immunity > Flashcards

Lec13 Mucosal Immunity Flashcards

1
Q

What is largest lymphoid organ in body

A

gastrointestinal mucosa

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2
Q

2 parts of mucosal immune system

A

inductive sites effector sites

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3
Q

function of innate immune mech in mucosal immune system? what makes it up?

A

function is to keep microbiota contained - antimicrobial peptides produced by epithelial cells - regulatory cytokines [TGF-beta and IL-10] help control inflammation in intestine - specialized cytokine-producing innate lymphoid cells in intestine - unique features of intestinal dendritic cells that promote induction of regulatory T cells

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4
Q

function of adaptive immune response in gut? what makes it up?

A

regulatory/suppressive function = immune tolerance - IgA keeps antigens from being absorbed - regulatory T cells keep immune response contained

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5
Q

What antigens are in gut?

A

dietary protein: 100 g daily bacteria: 10 bacteria cells per human cell in body

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6
Q

What separates mucosal immune system from intestinal lumen?

A
  • single layer epithelial cells act as gatekeepers - secreted mucins and antibodies - digestive enzymes that break down antigens
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7
Q

What are the inductive sites of mucosal immune system?

A

where initial immune response takes place - lymphoid structures where immune cells found - peyer’s patches - isolated lymphoid follicles - mesenteric lymph nodes

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8
Q

What are the effector sites?

A

GI mucosa where B/T lymphocytes, macrophages, dendritic cells, eosinophils, mast cells densely scattered in normal intestine

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9
Q

Can intact protein antigens get from GI lumen into body? How?

A

Yes - cross epithelial cells - taken up by M cells, specialized antigen sampling cells, and taken to peyer’s pathces - taken up by dendritic cells that reach into lumen

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10
Q

Which cytokines are involved in gut innate immune?

A

TGF-beta IL-10

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11
Q

Why are oral vaccines not often successful?

A

It is difficult to generate a good protective response in the intestine

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12
Q

What do adjuvants do to adaptive immune response?

A
  • Adjuvants can break oral tolerance and allow the gut to generate an immune response
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13
Q

Celiac disease

A
  • innapropriate innate and adaptive immune reactivity to gluten that causes to attack epithelial cells — from Il-15 by intestinal epithelial cells, IFN-gamma by T cells - flattening of villi on upper small intestine, crypt hyperplasia, intraepithelial lymphocytes - due to DR3/7-DQ2/8 genetic mut - get fat and vit malabsorption, weight loss, osteoporosis, iron deficiency, diarrhea, abdominal bloating - most effective therapy: avoid gluten
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14
Q

Food allergy mech

A

hypersensitivity reaction to food

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15
Q

Oral tolerance

A
  • don’t get reaction to antigen taken orally - this is what allows to separate commensal from pathogen - soluble antigen better at producing tolerance
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16
Q

peyer’s path

A
  • oval or round lymphoid follicle in lamina propria/submucosa - contain T and B cells
17
Q

What antibodies in mucosal immunity?

A

IgA production in setting of suppression of systemic IgG/IgM

18
Q

adjuvant and antigen experiment with mouse

A

treat mouse with antigen subcutaneously then 10 days later give antigen and adjuvant subcutaneously –> immunity treat moust with antigen orally then 10 days later give antigen and adjuvant subcutaneously –> tolerance - transfer T cell from tolerance mouse to another mouse then give antigen and adjvuant subcutaneously –> tolerance

19
Q

Factors involved oral tolerance

A

Nature of antigen: protein >> carb >> lipid Form of antigen: soluble protein is best at producing tolerance, particulate does not give as much tolerance Genetics of host: some mouse strains harder to tolerize Dose of antigen: – low dose –> regulatory T cells turn on – high dose –> anergy and deletion of T cells Age of host: neonates do not tolerize well

20
Q

What specific changes in immune cells [macrophages, lymphocyes, dendritic cells] occur in gut to make gut immune less reactive?

A

macrophages/dendritic cells: fewer toll like receptors, less signaling lymphocytes: difficult to activate, undergo apoptosis after activation Treg cells: activated to suppress response

21
Q

What is immune exclusion?

A
  • IgA binds bacteria and neutralizes them
22
Q

What is function of SIgA?

A
  • inhibits adhesion of virus and bacteria to the epithelium, protects epithelial cells
23
Q

3 Methods Antigens captured from gut into body?

A
  1. Dendritic cells telescoping: dendritic cells telescope through and can see antigen in lumen and takes some in, eventually dendritic cells exit lamina propria and go to lymph nodes 2. M cells: M cell overlies peyer’s patch and transports antigen in and brings it to peyer’s patch, leading to formation of larger immune rxn 3. antigen transports through or between epithelial cells
24
Q

Th1 cell cytokine

A

IFN-gamma

25
Q

Th2 cell cytokines

A

IL-4, IL-13, IL-5

26
Q

TH17 cell cytokine

A

IL-17

27
Q

3 types of Tregs and their cytokines

A

CD4+Foxp3+CD25+ TR1: produce IL10 TH3: produce TGFB

28
Q

Cause of IBD

A
  • Inflammatory bowel disease caused by dysregulated mucosal immune response to enteric bacterial antigens in genetically susceptible host - 2 types: crohns, ulcerative colitis
29
Q

Effect of extra TH1 response

A
  • get extra IFN-gamma and IL-2 - cell-mediated granulomas
30
Q

Effect of extra TH2 response

A
  • get extra IL-4, IL-5, IL-10 - hypersensitivity reactions
31
Q

Effect of lack of TR1 cells?

A
  • not as much TGF-B and IL-10 - get increase in both TH1 and TH2 response - granulomas and hypersensitivity
32
Q

Function of IL-17/IL-22

A
  • normally expressed by immune cells to repair - help recruit neutrophils - reduce expression of microbicidals
33
Q

Crohn’s Disease

A
  • Faulty genes and specific bacterial antigen –> lots of inflammation, granuloma - due to TH1/TH17 problem
34
Q

Ulcerative collitis

A
  • segmented disease - sometimes goes through whole wall of gut - happen in colon - ulcerates = lose epithelial cells from surface - dense inflammation - unconfrolled reaction to bacteria in context of genetic predispostion - due to TH2/TH17
35
Q

Food allergy

A
  • food specific - contrary to other allergic rxns: not always associated with eosinophils - affects many parts of bowel - associated wtih urticaria [hives] - elevated IgE, tryptase - get diarrhea or anaphylaxis - vasoactive compounds released

Immunology (17 decks)

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