L11 - Mucosal Immunity 1

Question 1

MUCOSAL IMMUNE SYSTEM

i) what can mucosa associated lymphatic tissue (MALT) be divided into? (2)
ii) what is the estimated surface area of the mucosal imm sys and what % of all effector cells does it harbour?
iii) is it in direct contact with the outside environment?
iv) name three antigens that continuously stimulate it
v) name two things that are mucosal sites are important for

Answer 1

i) bronchus associated lymphatic tissue (BALT)
gut associated lymphatic tissue (GALT)

ii) estim SA of 400m2 and has 60% of all effector cells
iii) yes in direct contact with outside environment
iv) continously stim by food, endogenous flora and pathogens
v) port of entry for infection and target site for vaccine induced protection

Question 2

MUCOSAL SURFACES AND ENTRY OF PATHOGENS

i) what are the three main mucosal transmission routes for HIV?
ii) vaccine induced immunity of which two areas would offer the best protection about micosal transmission of pathogens
iii) approx how many deaths per year from respiratory mucosal infections?

Answer 2

i) HIV > GU, rectal and oral mucosa
ii) vaccine induced immunity at both a systemic level and in the local mucosa = good protection
iii) 4 million deaths per year from resp mucosal infection

Question 3

DEFENCE STRATEGIES OF INTES MUCOSA & OROPHARYNX

i) what is the role of endogenous gut flora? (2) approx how many bacteria are found here?
ii) why type of barrier does epithelium and mucus form? what are mucins? what do they form?
iii) name four specialised epithelial cells? what is their role?
iv) name four antimicrobial substances found in mucus
v) name two important regionalised immune areas and where they are found

Answer 3

i) endog gut flora supports general function of the gut and defence against pathogens
- approx 10^14 bacteria

ii) ep and mucus form a mechanical barrier
- mucins are extensively glycosylated proteins that form a viscous barrier

iii) specialised ep cells > goblet, absorptive epithelial, M, paneth cells > role in defence
iv) antimicrobial substances in mucus = defensins, lysozyme, lactoferrin, phospholipases

v) waldeyers ring - tonsils
peyers patches - terminal ileum

Question 4

what are the four main defence strategies of the intestinal mucosa and oropharynx?

Answer 4

1) endogneous flora
2) epithelium and mucus
3) regionalised immune system
4) gut homing of B and T cells

Question 5

EFFECTOR AND INDUCTION SITES

i) what is the term given to immune cells primed in induction sites returning to their relevant effector site?
ii) name two induction sites? what type of tissue is seen here
iii) name two effector sites? what type of tissue is seen here?

Answer 5

i) gut homing of B and T cells

ii) induction sites = peyers patches and mesenteric LNs
- organised tissue

iii) effector sites = lamina propria immune cells and intraepithelial immune cells
- scattered lymphoid cells

Question 6

EFFECT OF DIET ON THE IMMUNE SYSTEM

i) what is diet important for?
ii) what does microbiota refer to? what does microbiome refer to?
iii) what type of mucus release is idea for imm sys functioning? is it desirable to have increased or reduced antimicrobial peptides?
iv) which molecule act as a fuel for epithelial cells and strengthen gut function? which foods are rich in these? (2)
v) high levels of which two things in the diet can lead to reduced control of gut bacteria

Answer 6

i) diet is important for maintaining a healthy composition of micro-organisms living in the gut

ii) microbiota > organsism present
microbiome > genes present

iii) enhanced mucus seceretion and increased microbial peptides gives best immune functioning

iv) short chain fatty acids > fuel for ep cells
- high dietary fibre and prebiotics

v) high levels of sugar and fat > toxic bile acid and metabolites cause reduced control of gut bacteria

Question 7

DIET AND EFFECT ON THE GUT

i) when the immune response is well regulated - are tight junctions in the gut up or downregulated? is oxygen high or low?
ii) what levels of oxygen and tight junctions are seen in a proinflammatory environment? what does this lead to in the gut? (2)
iii) a diet rich in what supports healthy gut microbiota? how does this affect mucus/antimicrob peptide/TJ production?
iv) what level of diversity of bacteria is typically seen with a western diet? how is short chain fatty acid production affected? what type of disease can this lead to?

Answer 7

i) well reg > up regulation of tight junctions and low oxygen

ii) proinflamm > high oxygen and downreg of TJs
- leads to overgrowth of harmful bacteria and dysfunctional intestinal barrier

iii) diet rich in fibre supports healthy gut microbiota
- increased mucus secretion/APs/upreg TJs

iv) low diversity of bacteria seen in western diet
- less short chain fatty acids produced
- can lead to chronic disease

Question 8

INTESTINAL EPITHELIAL CELLS

i) how many types are there?
ii) what type of barrier do epithelial cells form?
iii) what do they have receptors for? (2) where is each of these found?
iv) what do tight junctions regulate? what can happen if this goes wrong?
v) where is TLR5 found? what happens when it contacts bacteria?

Answer 8

i) 4 types
ii) form a mechanical barrier

iii) receptors for TLR/NLR - both activated by bacteria
- TLR5 ound on BL surface
- NLR in cytoplasm

iv) tight junctions regulate movement of water and solutes
- dysfunction can contribute to pathogenesis of intestinal disorders

v) TLR5 is found on the basolateral surface of epithelial cells and tightens the TJs when it comes into contact with bacteria

Question 9

INTESTINAL EP CELLS - PANETH CELLS

i) what do they produce? (2)
ii) what activates these molecules?
iii) what does this molecule do?

Answer 9

i) produce human defensin 5 precursor and human defensin 6 precursor
ii) activated by trypsin
iii) defensins are cytotoxic proteins that stop bacteria reaching gut epithelia

Question 10

INTESTINAL EP CELLS - GOBLET/M CELLS

i) what do goblet cells produce? what does this act as? what type of Ig is found in this?
ii) what other antibodies do goblet cells produce? what type of peptide do they produce?
iii) what is the function of M cells? where are they found? what mechanism does this happen by?

Answer 10

i) goblet cells produce mucus that acts as a physiochemical barrier > contains secretory IgA
ii) goblet cells also produce IgG and antibacterial peptides

iii) M cells transport antigens from the gut lumen to subepithelial lymphoid structures > peyers patches
- via transcellular mechanism
- specific cells in the roof of the peyers patches

Question 11

LYMPHOID COMPLEXES ALONG GI TRACT

i) what method can be used to inspect these?
ii) which two locations is the largest amount of lymphoid tissue found?

Answer 11

i) endoscopy
ii) waldeyers ring (tonsils) and peyers patches (terminal ileum)

Question 12

PEYERS PATCHES

i) where are they located?
ii) how many PP does the fetal small intestine contain before 30wks gestation?
iii) when does the number of PP reach its max? how many approx is this?
iv) what do PP contain?

Answer 12

i) in the distal ileum in areas of follicle associated epithelium
ii) fetal SI contains 60PPs before 30wks
iii) PP number reaches max at puberty ~240
iv) PP contain germinal centres for B and T cells

Question 13

M CELLS

i) what do they have on their sruface?
ii) what is found within the cell membrane? what does this allow? what is this known as?
iii) by what method do they transport antigen? what transport method occurs at the basolateral membrane
iv) which cells do they deliver antigen to? where are these cells found?

Answer 13

i) microvilli

ii) fenestrations which allow antigen uptake from the gut lumen
- known as fluid phase endocytosis

iii) transport antigen transcellularly
- exocytosis at BL membrane

iv) deliver antigen do dendritic cells of underlying lymphatic structures (follicle assoc epithelia)

Question 14

PEYERS PATCHES STRUCTURE

i) what covers peyers patches?
ii) what proliferating cell type does the follicular area contain? which specific area are these found it? what other cells does it contain? (2)
iii) name four cell types found in the interfollicular/subepithelial dome? what class of cells are these?
iv) label diagram

Answer 14

i) follicle associated epithelium

ii) follicular area contains proliferating B cells in germinal centre
- also contains follicular dendritic cells (fix antigen on surface but arent APCs) and macrophages (are APCs)

iii) interfollicular area/subep dome = B cells, T cells, MPs and dendritic cells - all APCs
iv) A - follicular area, B - follicle associated epithelium, C - interfollicular area

Question 15

PEYERS PATCHES CELLS

i) what type of cell is A? what does it facilitate?
ii) what is B? where does antigen bind this?
iii) what is a plasmablast?
iv) what type of T cells are C and D?

Answer 15

i) M cells - facilitates antigen from gut lumen to peyers patch
ii) B is secretory IgA - binds antigen in gut lumen
iii) plasmablast = primed antibody producing B cell

iv) C - lamina propria T cell
D - intraeptihelial T cell

Question 16

LYMPHOCYTE HOMING

i) what is it?
ii) in the first step - how do B cellls enter peyers patches? what do they do once in the PP? (3)
iii) which type of T cells also enters the PP? what cells do they contact once inside and what does this cause?
iv) what happens once T and B cells have encountered eachother? (2) what does B cell class switch from?
v) where do T and B cells then leave to? (3)
vi) what Ig do B cells produce in the PP? which two molecules influence this? which cells provide them?

Answer 16

i) events leading to naive cells being antigen primed, leaving the PP and moving to the effector tissue

ii) B cells enter PP by high endothelial venules
- once in the PP they recog antigen from the gut lumen, recog antigen by IgD and prolif/increase in number

iii) naiive T cells also enter the PP via high endothelial venules
- once inside they contact dendritic cells presenting antigen
- this causes T cell activation/prolif and increase chance of encountering a B cell that presents the same antigen

iv) once T and B cells have encountered eachother the T cell can help the B cell and gives B cell signal to class switch from IgM
v) T and B cells then drained to mesenteric LNs > blood via thoracic duct > effector site in gut
vi) B cells produce IgA in the PP due to influence of nitric oxide and TGFb provided by dendritic cells

Question 17

SUMMARY PART 1

i) what type of barriers do immune defences in the gut involve?
ii) name two accumulations of lymphatic tissue in the GI tract and where they are found
iii) name two important inductive sites
iv) name two important effector sites

Answer 17

i) mechanical - spec and non spec
ii) Waldeyers ring (tonsils) and peyers patch (terminal ileum)
iii) inductive sites = peyers patch and mesenteric LNs
iv) effector sites = lamia propria and epithelium

Question 18

SUMMARY PART II

i) what is the dome of a peyers patch covered in? what type of cells are found here? what is function of these cells?
ii) which type of cells do PP give rise to? which two molecules cause the cell to produce a specific Ig?
iii) which cells do naiive B cells recognise antigen on? where are these found?
iv) which cells do T cells recognise antigen on?

Answer 18

i) dome of PP is covered in epithelia that contains M cells
- M cells deliver gut antigen to the PP

ii) PP give rise to IgA producing plasma cells
- NO and TGFb cause B cells to predominantly produce IgA

iii) naiive B cells recognise antigen on follicular dendritic cells in the follicles (not professional APCs)
iv) T cells recognise antigen on dendritic cells (profesh APCs)

Question 19

SUMMARY PART III

i) what increases chance of B and T cells meeting? (2)
ii) what really gets the immune system going?
iii) how to T and B cells leave the PP? where do they return to? how do they get there? (2) does this depend on high endothelial venules?
iv) what is the cellular recirculation pattern referred to?

Answer 19

i) proliferation and increase in number following antigen recognition
ii) B and T cell co-operation

iii) B and T cells leave the PP via afferent lymphatics
- return to the gut via thoracic duct and bloodstream
- does not depend on HEV like naiive B and T cells

iv) cellular recirculation pattern = homing