Mucosal Immunity Flashcards

1
Q

Describe the dual role of the digestive system in immunity

A
  • full of microflora and food antigens but also pathogens
  • thin-walled to allow exchange of nutrients
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2
Q

What can cause mucosal inflammation?

A
  • endometritis
  • enteritis and colitis - IBD
  • recurrent airway obstruction & other respiratory inflammation
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3
Q

What are the key components of MALT?

A
  • microflora/commensal bacteria
  • dendritic cells
  • M cells in Peyer’s Patches
  • B lymphocytes/antibodies
  • Үδ T lymphocytes and Treg lymphocytes
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4
Q

Describe microflora/commensal bacteria

A
  • ‘germ free’ mammals fail to fully develop mucosal lymphoid tissues
  • exclude pathogenic organisms
  • can release anti-microbial molecules
  • activate innate immune responses
  • can lead to Treg production
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5
Q

Describe the process of enterotoxaemia

A
  • colon colonized by large numbers of commensal bacteria
  • antibodies kill many of these commensal bacteria
  • colostridium difficile gains a foothold and produces toxins that cause mucosal injury
  • neutrophils and red blood cells leak into gut between injured epithelial cells
  • connective tissue degredation leads to colitis and pseudo-membrane formation
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6
Q

Describe recognition

A
  • how immune cells observe mucosal antigens
  • intestinal dendritic cells extend processes into lumen
  • capture commensal bacteria/antigens
  • move to lymph nodes and present to B cells
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7
Q

What allows BCR recognition of epitopes?

A

DCs, FcRn and M cells do not always degrade the antigens with transport

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8
Q

What happens do DCs in absence of PAMPs/danger signals

A
  • DC will provide lead to tolerised response
  • induction of Treg -> anti-inflammatory response
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9
Q

Describe what happens to DCs in presence of PAMPs/danger signals

A
  • DC will provide lead to inflammatory response
  • still heavily regulated
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10
Q

Describe IgA function in mucosal surface

A
  • prevents opportunistic infections
  • main function is immune exclusion as does not activate complement cascade
  • prevention of adherence of virus and bacterial to host cell
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11
Q

Give 3 examples of IgA function in mucosal surface

A
  • Bordetella in dogs
  • transmissible gastroenteritis in piglets - oral live vaccine
  • rotaviruses - most common cause of neonatal diarrhoea in calves
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12
Q

Where do IgG and IgE function?

A

below epithelial layer - function via immune elimination

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13
Q

Describe IgE

A
  • present on mast cells
  • important esp for helminth infections
  • evidence of IgE-associated killing infective larval forms in skin etc
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14
Q

Describe worm expulsion mechanisms

A
  • non-antibody related
  • changes in mucous levels/consistency, changes in motility
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15
Q

Describe why the antibody isotype matters in vaccines

A
  • high IgA levels can be critical in protection
  • high IgG antibody serum titres may not protect
  • therefore also consider method of delivering vaccine
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16
Q

Describe what occurs to activated IgA-producing B cells

A
  • not limited to specific mucosal site of infection
  • % of B cells move:
  • site -> regional lymph node -> bloodstream -> other mucosal sites
  • other mucosal sites = respiratory, mammary, urogenital etc
17
Q

Describe T lymphocytes and vaccination

A
  • present in lymphoid tissues, some present in tissues
  • key type: intraepithelial lymphocytes
  • mostly Tc
  • different from conventional CD8+ T cells as no priming requirement
  • in humans: mainly α/β T cells but some are ү/δ
18
Q

Describe what occurs when a virus infects a mucosal epithelial cell

A
  • infected cell displays viral peptide to CD8+ T cell via MHC class I
  • activated T cell kills infected epithelial cell via perforin/granzyme and Fas-dependent pathways
19
Q

Describe α/β T cells

A
  • conventional T cells
  • throughout lamina propria
  • responses depend on subset - important in B cell activation
20
Q

Describe ү/δ T cells

A
  • TCR composed of 2 transmembrane glycoprotein ү/δ chains
  • limited TCR diversity
  • mainly present just below epithelial layer
  • IFN-ү secreted
  • innate and adaptive cell
  • enigmatic functions in different species
  • some interact with MICA/MICB and PAMPs
21
Q

Describe ү/δ T cell interactions with MICA & MCIB

A
  • MICA & MCIB are stresses cell molecules
  • kill stressed cells
  • e.g., virally infected cells, cancer
22
Q

Describe ү/δ T cell interactions with PAMPs

A
  • can directly interact with antigens
  • no MHC needed
23
Q

What can change in balance between Treg and pro-inflammatory molecules lead to?

A
  • inflammatory bowel disease
  • pro-inflammatory molecule can be Th1, Th2, Th17 or mixed
  • e.g., enteropathy in Wheaten terriers
24
Q

Describe the 3 types of antibody transfer from mother to child

A
  • hemochorial
  • endotheliochorial
  • epitheliochoral
25
Describe hemochorial antibody transfer
- 3 layers of placenta - fuller antibody transfer - humans, rabbits, rats, mice
26
Describe endotheliochorial antibody transfer
- 4 layers of placenta - some antibody transfer - cats, dogs
27
Describe epitheliochorial antibody transfer
- 6 layers of placenta - no antibody transfer - ruminants, horses, whales
28
What is colostrum / antibody transfer important for?
- mainly IgG - also IgA and IgM
29
What are the 4 types of Failure of Passive Transfer (FTP)?
- antibody absorption - protection failure - ingestion failure - absorption failure
30
Describe antibody absorption in FPT
- newborn foals, lambs, calves drink within 6hrs - low protease activity in digestive tract in newborn - intestinal epithelial cells can bind maternal Ab using FcRn - these cells transport Ab into bloodstream
31
Describe protection failure in FPT
- premature birth - colostrum lacking high Ab levels - variation in colostrum Ab levels - 28% mares produce low-quality colostrum
32
Describe ingestion failure in FPT
- inexperienced mothers - access to teats/colostrum amount (sheep) - damaged teats
33
Describe absorption failure in FPT
- 25% newborn foals fail to absorb sufficient Abs from colostrum - foals need at least 400mg/dL serum IgG - <200mg/dL - susceptible to infection
34
Describe how FTP is treated in foals
- <400mg/dL and foal <18hrs old - administer oral colostrum to top up - <200mg/dL and foal >18hrs old - administer IV plasma infusion
35
Which antibody is transferred more in milk?
IgA