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GI- WK 1-3 > Mucosal Immunity > Flashcards

Mucosal Immunity Flashcards

1
Q

What is the difference between transcelluar and paracellular transport?

A

Transcellular- Movement through the cell, crossing the apical and basolateral membranes

Paracellular- Movement across an epithelium by passing through the intercellular space between adjacent cells

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2
Q

What are the distinct features of the gut mucosal immune system in respect to- 1. Anatomical relationship 2. Effector mechanisms 3. Immunoregulatory environment

A
  1. Anatomical - Special relationship between mucosal epithelia and lymphoid tissue - Organised lymphoid structure - Antigen uptake mechanisms
  2. Effector mechanisms - activated/memory T cells predominate - Effector T cells also present
  3. Immuno-regulatory environment - Active down regulation of immune response - Inhibitory macrophages and tolerating dendritic cells
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3
Q

What are the two ways in which lymphocytes are present I the GI tract?

A
  1. Scattered Lymphocyte cells- Lymphocytes scattered around the epithelium and the lamina propria.
  2. Organised lymphocyte tissue- GALT (gut associated lymphoid tissue) Payer cells and mesenteric lymph nodes.
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4
Q

What are Peyers patches?

A

Organised lymphoid follicles, found in the organised lymphoid tissue of the gut.

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5
Q

Peyers patches contain M cells, which serve what function?

A

Take up antigen by endo or phagocytosis from extracellular lumen to inside the gut basal surface

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6
Q

The function of M cells allow dendrites to do what?

A

Dendrites at the basal surface bind to the antigens to present them to T cells to activate them/

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7
Q

What special characteristic of dendritic cells allow them to trap antigens in the gut lumen?

A

Dendritic cells can extend finger like projections that can cross the epithelium to catch antigens from the gut lumen.

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8
Q

The epithelium of the gut membrane only contain CD8 T cells? T/F?

A

True

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9
Q

The lamina propria layer has a greater variety of immune cells, which are? (6)

A
  1. CD8 2. CD4 3. Macrophage 4. Mast cells 5. Dendrites 6. Plasma cells
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10
Q

Chemokines found in the epithelium bind to which molecule receptors of T cells? (2)

A

CCR7 and L-Selectin

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11
Q

What are the two things that can happen to naive T lymphocytes once they enter the gut membrane?

A
  1. Do not see their antigen, exit the gut via lymphatics to return to the bloodstream 2. Encounter antigen and become activated- they Loe their CCR7 receptors, so they cannot the gut lining the same way.
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12
Q

How do lymphocytes initially activated by the gut renter the gut lining from the bloodstream? (2 Receptors)

A

Lymphocytes express the receptor a4b7-Integrin, which binds to MAdCAM-1, which is found in endothelial cells of the gut wall. Chemokine’s found in the gut also express receptors for CCR9 found only on gut primed lymphocytes

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13
Q

What is the effect of the “Common mucosal immune system”?

A

MAdCAM-1 is a molecule produced in the vasculature of all mucosae, which allows lymphocytes produced in one lymphoid organ to help fight infection in other lymphoid organs too

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14
Q

Which Ig is the most common in the humoral Intestinal response? (3)

A
  • IgA (80%) - IgM - IgG
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15
Q

How do IgA’s secreted in the lamina propria of the gut reach the lumen of the gut? (2)

A
  1. Bind to receptors on basolateral face of epithelial cell 2. Endocytosed to apical face of epithelial cell
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16
Q

What are the 3 different functions that IgA’s carry out in the gut lumen?

A
  1. IgA on lumenal surface can directly bind to and neutralise toxins and pathogen 2. Can bind and neutralise antigens internalised in endosomes 3. Can transport pathogens from the lamina propria to the lumenal surface
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17
Q

Intraepithelial lymphocytes (IEL’s) are found in which layer of the gut membrane?

A

Epithelial lining

18
Q

The IEL’s are mostly what type of T cell?

A

CD8+

19
Q

CD8 cells are important against viral infection? What are the steps involved in its action mechanism? (3)

A
  1. Virus affects mucosal epithelial cell
  2. Infected cell displays viral peptide to CD8 via MHC class I
  3. CD8 cell kills infected cell. (Fas pathways)
20
Q

How do IEL’s kill stressed epithelial cells? (3)

A
  1. Stressed epithelial cells express M1C A & B (MHC class 1 A&B)
  2. NKG2D on IEL’s bind to M1C A, M1CB to be activated
  3. Activated cells kill the stressed cell via perforin/ granzyme pathway
21
Q

There are developed was to distinguish between pathogens and inoculant antigens in mucosal immunity. T/F?

A

True. Important to ensure that mucosal immunity is not hyper-responsive

22
Q

What are the 3 ways in which mucosal hyporesponsiveness is maintained?

A
  1. Commnesal organisms regulate local hypo-responsiveness
  2. Deletion of antigen specific T cells
  3. Generation of regulatory T cells (immunosuppressive)
23
Q

What is the standard response of mucosal immunity to infection? (don’t memorise)

A
  1. Actiavtion of pattern recognition receptors
  2. PRR’s activate the NFkB pathway
  3. Production of cytokines and chemokines
  4. These mediators stimulate underlying immune response
24
Q

What happens when mucosal immunity becomes dysregulated?

A
  1. Dendritic cells are infected
  2. They transport virus from site of infection to regional lymph node
  3. Virus particles infect effector T cells (CD4)
25
Q

Infected effector T cells can destroy 90% of gut epithelium. T/F?

A

True

26
Q

What primary immunodeficiencies are associated with mucosal disorder? (5)

A
  1. Selective IgA deficiency
  2. CVID- low antibody production, Ig differentiation problem
  3. XLA- No B cells
  4. CGD- excessive granulomas due to lack of ROS production needed to kill pathogens
  5. SCID- defected T & B cells
27
Q

Most common systemic effects of these primary immunodeficiencies?

A
  1. Recurrent sinopulmonary, GI, infections (pneumonia)

CGD- Inflammatory granulomas and abccess formation in liver, skin etc

28
Q

Which of the previous 5 immunodeficiencies is heavily linked with Coeliac disease?

A

Selective IgA deficiency- makes one 10x more likely to get Coeliac’s

29
Q

_ antibodies construct an allergic response by binding to Fc receptors of _ cells which release _.

A

IgE, mast, histamine

30
Q

What are three clinical effects of IgE mediated mast cells on intestinal epithelium?

A
  1. Vomiting- contraction of smooth muscle
  2. Diarrhoea- fluid outflow into gut
  3. Urticaria - antigen diffusion and dissemination into blood vessels.
31
Q

Coeliac disease is an autosomal dominant condition. T/F?

A

False. Can be dominant or recessive

32
Q

Define coeliac disease.

A

Immune disorder which causes damage to the small intestine leading to malnutrition

33
Q

Coeliac is an allergic response. T/F?

A

False

34
Q

What is the pathophysiology of Coeliac?

A
  1. Gamma interferon from Gluten specific T cell activate epithelial cells. (Gliadin peptide activate Gliadin specific T cells)
  2. Epithelial cells produce IL-5 which proliferate & activate T cells
  3. T cells and IEL’s kill epithelial cells by releasing cytokines.
35
Q

What are the two effects of Coeliac on lining of the small intestine?

A
  1. Flattened epithelium- reduced surface area, loss of function 2. Vili atrophy (wasting)
36
Q

What 3 methods are used to diagnose Coeliac’s disease?

A
  1. Biopsy- not used in kids 2. Serology- 1st choice in kids (detects IgA autoantibodies in gluten) 3. Genetics
37
Q

Crohns disease can affect any part of the GI tract, but the two most common areas affected are the distal _ and _ .

A

Ileum and Colon

38
Q

What happens in Crohns disease? (effect, mediators and genetic)

A

Focal discontinuous inflammation with deep eroding fissures. +/- granulomas Mediated by TH1 CD4 cells, gamma interferon, IL-12, TNFa. Multiple genetic deficiencies.

39
Q

Ulcerative colitis is restricted to the _ and _

A

Rectum and colon

40
Q

What happens in ulcerative colitis?

A

Inflammation of the rectum and colon leading to ulcers that can bleed to produce pus.

GI- WK 1-3 (25 decks)

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