Week 1

Question 1

Langerhans cells function

Answer 1

• Dendritic cells of skin and mucosa - recognise antigens to become antigen-presenting cells
• Migrate to draining lymph nodes
• Recent studies have shown that Langerhans cells could have a function in immune tolerance rather than induction of adaptive immune responses, as previously thought

Question 2

Mast cells contain which preformed mediators and lipid mediators

Answer 2

Preformed mediators: histamine and TNF-alpha

Lipid mediators: leukotriens, prostaglandins

Question 3

Mast cell role in acute inflammatory response

Answer 3

Active role in early recruitment of inflammatory cells by releasing mediators which cause an increase in vascular permeability

Question 4

Mast cell model of action in Urticaria

Answer 4

1. Antigen binds IgE on the surface of mast cells
2. The mast cells degranulate and release histamine from preformed granules causing capillary leakage and vasodilation of the endothelium
3. Fluid and cells leaking into the tissue to form exudate causing oedema

Question 5

The only dendritic cells found in the epidermal layer of the skin are called

Answer 5

Langerhans cells

Question 6

Homing receptors involved in rolling (during T cell migration)

Answer 6

E-selections, P-selectins

Question 7

Homing receptors involved in activation (during T cell migration)

Answer 7

CCL17, CCL27 activated by ligands CCR4, CCR10

Question 8

Homing receptors involved in adhesion (during T cell migration)

Answer 8

ICAM-1, VCAM-1

Question 9

Production of mucus is fine-tuned by

Answer 9

by recognition of microbial products by enterocytes through TLR or intracellular sensors such as NOD2

Question 10

Major “inductive” sites

Answer 10

Peyer’s patches, isolated lymph follicles, mesenteric lymph nodes

Question 11

Role of intestinal epithelial cells

Answer 11

1. Physical barrier (tight junctions)
2. Mucus production by goblet cells - provides matrix for antimicrobial peptides and IgA
3. Antimicrobial peptide production - defensins, cathelicidins, lectin

Question 12

The vast majority of intra-epithelial cells are

Answer 12

T cells, the majority of which are CD8 T cells

Question 13

T or F:

Peyer’s patches but not isolated lymphoid follicles are formed before birth

Answer 13

True

Question 14

Function of M cells

Answer 14

Microfold (M) Cells transfer the Ag to professional Ag-presenting cells. They themselves do not process, or present the Ag.
This process is facilitated by attraction of Ag-presenting cells into the epithelial layer by production of chemokines CCL20 and CCL9 that bind to complementary chemokine receptors on the DC

Question 15

Dendritic cell tolerance induction in gut mucosa mechanism

Answer 15

DC in the gut mucosa in the steady state are geared towards tolerogenic responses, which requires exposure to a number of cytokines including TSLP produced by enterocytes.
Anti-inflammatory cytokines such as IL-10 and TGF-β may be produced by macrophages that ingest commensal bacteria.

Question 16

α4β7 on T and B cells binds to

Answer 16

MAdCAM-1 on HEV

Question 17

CCR9 on T and B cells binds to

Answer 17

CCL25 on small intestinal epithelial cells

Question 18

CCR10 on B cells binds to

Answer 18

CCL28 on colonic epithelial cells

Question 19

Major function of IgA

Answer 19

Inhibition of microbial adherence

Neutralisation of toxins/enzymes

Question 20

Secretion of the IgA into the gut lumen requires

Answer 20

Transepithelial IgA transport conducted by polymeric immunoglobulin receptor (plgR) which binds the dimeric IgA via the J chain.
Cleavage of the extracellular pIgR domain (secretory component, SC) that is still attached to IgA transforms IgA into secretory IgA (IgA + SC)

Question 21

Gluten is composed of

Answer 21

50% gliadin (alcohol-soluble) and glutenin (polymeric structure)

Question 22

Genes associated with Coeliac disease

Answer 22

HLA DQ2.5, DQ2.2, DQ8

Absence of these genes excludes coeliac disease (strong negative predictive value)

Question 23

Homozygosity for A105 alpha chain and B102 produces how many possible DQ2.5 dimers?

Answer 23

Four

Question 24

Heterozygosity for A105 alpha chain and B102 produces how many possible DQ2.5 dimers?

Answer 24

One

Question 25

Mechanism of post-translation modification of Gluten

Answer 25

Post-translational modification is essential for efficient antigen binding to HLA
Tissue transglutaminase (TG2) introduces site specific glutamate (E) residues (“deamidation”)
Deamidation of gluten peptides significantly increases the stability of the gluten peptide: MHC complex

Question 26

Gluten inflammation response

Answer 26

When T cell binds gluten peptide, it causes an TH1 inflammatory response, characterised by pro-inflammatory cytokines IFN-γ and IL-21.
HLA-DQ restricted CD4+ gluten-specific T cells are CD-specific and express α4β7+, an integrin important for homing to MAdCAM expressed on HEV within the lamina propria

Question 27

What confers resistant to gastric (pepsin) and pancreatic (trypsin) proteases?

Answer 27

Proline - Humans lack endogenous proline endopeptidases

Toxic immunogenic regions can survive digestion

Question 28

What drives villous atrophy?

Answer 28

Intra-epithelial lymphocytes

Question 29

Model of pathogenesis in CD

Answer 29

Gluten-specific Th1 cells presented with a gluten peptide on the surface of an Ag-presenting cell expressing DQ2/8 are essential in liberating IFN-gamma, a pro-inflammatory cytokine.
The innate response, characterised by IL-15, inhibit Treg function which would usually dampen the Th1 response. IL-15 impairs immunosuppressive effects of TGF-β via inhibiting Smad3 signalling.

Question 30

Coeliac disease treatment

Answer 30

Transglutaminase inhibitors
HLA-DQ binders
Zonulin antagonist - reduces transepithelial uptake
Immunotherapy - induction of Treg cells and depleting gluten-specific T cell repertoire