Mucosal Immunity

Question 1

What is the difference between transcelluar and paracellular transport?

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

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.

Question 4

What are Peyers patches?

Answer 4

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

Question 5

Peyers patches contain M cells, which serve what function?

Answer 5

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

Question 6

The function of M cells allow dendrites to do what?

Answer 6

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

Question 7

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

Answer 7

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

Question 8

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

Answer 8

True

Question 9

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

Answer 9

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

Question 10

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

Answer 10

CCR7 and L-Selectin

Question 11

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

Answer 11

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.

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

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

Answer 14

• IgA (80%) - IgM - IgG

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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

Question 17

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

Answer 17

Epithelial lining

Question 18

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

Answer 18

CD8+

Question 19

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

Answer 19

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)

Question 20

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

Answer 20

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

Question 21

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

Answer 21

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

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

What happens when mucosal immunity becomes dysregulated?

Answer 24

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)

Question 25

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

Answer 25

True

Question 26

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

Answer 26

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

Question 27

Most common systemic effects of these primary immunodeficiencies?

Answer 27

1. Recurrent sinopulmonary, GI, infections (pneumonia) CGD- Inflammatory granulomas and abccess formation in liver, skin etc

Question 28

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

Answer 28

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

Question 29

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

Answer 29

IgE, mast, histamine

Question 30

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

Answer 30

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

Question 31

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

Answer 31

False. Can be dominant or recessive

Question 32

Define coeliac disease.

Answer 32

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

Question 33

Coeliac is an allergic response. T/F?

Answer 33

False

Question 34

What is the pathophysiology of Coeliac?

Answer 34

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.

Question 35

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

Answer 35

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

Question 36

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

Answer 36

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

Question 37

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

Answer 37

Ileum and Colon

Question 38

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

Answer 38

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

Question 39

Ulcerative colitis is restricted to the _ and \_

Answer 39

Rectum and colon

Question 40

What happens in ulcerative colitis?

Answer 40

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