Mucosal immunology

Question 1

All of the organised and diffuse lymphoid tissues found in submucosal regions of body can be viewed as a single functional unit - MALT (mucosa associated lymphatic tissue)

What are the morphological divisions of this?

Answer 1

• BALT (Bronchus associated lymphatic tissue

- GALT (Gut associated lymphatic tissue)

Question 2

State 3 reasons why the mucosal immune system is important

Answer 2

1. biggest immune compartment
2. direct contact with outside environment –> continuous antigen stimulation
3. they are the ports of entry for infection and target site for vaccine-induced protection

Question 3

Consider the main defence strategies of intestinal mucosa and oropharynx

Which methods are employed by the epithelium and mucus

Answer 3

• mechanical barriers (ep. cells and tight junctions)
• mucus producing goblet cells, absorptive ep. cells, M cells transport antigens to supep. lymphoid structures, Paneth cells produce HD5 and HD6 precursors and trypsn (HD5/6 activator)
• antimicrobial substances
• mucins

Question 4

Consider the main defence strategies of intestinal mucosa and oropharynx

What methods are employed other than the epithelium and mucus

Answer 4

• endogenous flora (of different species)
• ‘regionalised’ immune system and gut homing of B/T cells: Waldeyers ring, Peyers patches, mesenteric lymph nodes, intraepithelial immune cells , lamina propria immune cells
• lymphoid complexes along GIT

Question 5

Where are TLRs expressed?

What happens when they meet their ligand?

Answer 5

• TLR5 is expressed on the basolateral surface and intracytoplasmic NLR for bacterial flagellins are activated only upon access of bacterial to cytosol (invasion)
• Surface TLR ligation causes tightening of epithelial junctions, increased proliferation, epithelial motility and enhances barrier function BUT not inflammation

Question 6

Where is the largest amount of lymphoid tissue in oropharynx and terminal ileum found?

Answer 6

In Waldeyers ring

Question 7

Describe peyers patches

Answer 7

Contain germinal centres for B and T cells. They are located in the distal ileum in areas of follicle associated epithelium (FAE)

• 60 peyers patches by week-30 of gestation, by puberty: 240
• They are the induction site for immune response

Question 8

How are follicle associated epithelium different to normal epithelium

Answer 8

• Microvilli regularity and length
• Presence of infiltrating immune cells

Lymphoid follicles with germinal centre containing proliferating B cells, follicle dendritic cells and macrophages

Question 9

How are peyers patches connected to lymphatics and blood vessels

Answer 9

Peyers patches connected to circulation by endothelial venules (from blood to PPs) and lymphatic vessels (from PPs to mesenteric LN)

• Naive lymphocytes immigrate into the PPs via specialised high endothelial venules. They leave the PPs via efferent lymphatic vessels at the serosal side of the PP

Question 10

Describe mesenteric lymph nodes

location, function

Answer 10

• located at the base of the mesentery and collect lymph, cells and antigens from intestinal mucosa
• main site for oral tolerance induction, sometimes
  protective immune responses need to be raised
• they drain lymph but some food antigens bypass lymphatic tissue and go to liver via portal vein. Immune cells in liver sinuses have important function in protection from microbes in portal vein

Question 11

Describe intraepithelial immune cells (IEL)

(location, shape, contents)

How can intraepithelial T cells be classified?

Answer 11

• basolateral part of epithelium
• irregular shape (large extensions in close contact with neighbouring ep. cells)
• 12% eosinophils
• TCRalphabeta+CD8aa+ cells followed by TCRalphabeta+CD8ab+ cells

1. TCRalphabeta+CD8ab+
2. TCRalphabeta+CD4ab+
3. TCRalphabeta+CD8aa+

Question 12

What happens when an epithelial cell becomes infected?

Answer 12

• becomes stressed as a result of damage, toxic peptides –> expression of MIC-A and MIC-B
• NKG2D on IEL bind to these and activate IE. CD8aa+ T cells also bind to thymus leukaemia antigen (TL)
• Activated IEL kills the stressed cell via perforin/granzyme pathway

Question 13

How do the following cells influence T cell differentiation

1. Treg
2. TH1
3. TH2
4. TH17
5. Dendritic cells

Answer 13

1. Produce IL10 and are crucial in establishing and maintaining food tolerance and class switch, including TGF-b
2. TH1 cells produce IFN-y and are important in killing virally infected ep. cells
3. Induced by worm infection. IL4 and IL13 increase fluid secretion, mucus secretion, bowel motility and smooth muscle contraction
4. Produce IL17 and IL22. They interact with receptors on epithelial cells to regulate production of mucins or defensins
5. Sit in lamina propria with their long extensions used to ‘sample’ contents of intestinal tube. Such antigens are presented to T cells.

Question 14

How is IgA transported across the endothelium?

What is the function of this?

Answer 14

• the ‘secretory component’ (poly-Ig- receptor) binds to the J chain enabling trans-endothelial transport of dimeric IgA
• localise secreted IgA in mucus

Question 15

Describe IgA

functions, secretion

Answer 15

• the main antibody in secretions
• against food antigens provides immune exclusion
• activates complement system weakly
• secretion (coupled to J chain) depends on a trans-cellular transport mechanism

Question 16

How do activate t cells and memory cells enter and leave circulation?

Answer 16

• Activated T cells and circulating memory cells exit the lymph node via efferent lymphatics and return to circulation through thoracic duct. They reach target tissues via blood stream
• Different combinations of homing receptors will guide effector cells to different tissues
• Integrin and chemokine signals direct their emigration into tissues. Imprinted t cells have a specific key that allows access to restricted tissues (gates) under normal homeostatic conditions.