Mucosal Immunity Flashcards
Describe the dual role of the digestive system in immunity
- full of microflora and food antigens but also pathogens
- thin-walled to allow exchange of nutrients
What can cause mucosal inflammation?
- endometritis
- enteritis and colitis - IBD
- recurrent airway obstruction & other respiratory inflammation
What are the key components of MALT?
- microflora/commensal bacteria
- dendritic cells
- M cells in Peyer’s Patches
- B lymphocytes/antibodies
- Үδ T lymphocytes and Treg lymphocytes
Describe microflora/commensal bacteria
- ‘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
Describe the process of enterotoxaemia
- 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
Describe recognition
- 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
What allows BCR recognition of epitopes?
DCs, FcRn and M cells do not always degrade the antigens with transport
What happens do DCs in absence of PAMPs/danger signals
- DC will provide lead to tolerised response
- induction of Treg -> anti-inflammatory response
Describe what happens to DCs in presence of PAMPs/danger signals
- DC will provide lead to inflammatory response
- still heavily regulated
Describe IgA function in mucosal surface
- prevents opportunistic infections
- main function is immune exclusion as does not activate complement cascade
- prevention of adherence of virus and bacterial to host cell
Give 3 examples of IgA function in mucosal surface
- Bordetella in dogs
- transmissible gastroenteritis in piglets - oral live vaccine
- rotaviruses - most common cause of neonatal diarrhoea in calves
Where do IgG and IgE function?
below epithelial layer - function via immune elimination
Describe IgE
- present on mast cells
- important esp for helminth infections
- evidence of IgE-associated killing infective larval forms in skin etc
Describe worm expulsion mechanisms
- non-antibody related
- changes in mucous levels/consistency, changes in motility
Describe why the antibody isotype matters in vaccines
- high IgA levels can be critical in protection
- high IgG antibody serum titres may not protect
- therefore also consider method of delivering vaccine
Describe what occurs to activated IgA-producing B cells
- 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
Describe T lymphocytes and vaccination
- 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
Describe what occurs when a virus infects a mucosal epithelial cell
- 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
Describe α/β T cells
- conventional T cells
- throughout lamina propria
- responses depend on subset - important in B cell activation
Describe ү/δ T cells
- 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
Describe ү/δ T cell interactions with MICA & MCIB
- MICA & MCIB are stresses cell molecules
- kill stressed cells
- e.g., virally infected cells, cancer
Describe ү/δ T cell interactions with PAMPs
- can directly interact with antigens
- no MHC needed
What can change in balance between Treg and pro-inflammatory molecules lead to?
- inflammatory bowel disease
- pro-inflammatory molecule can be Th1, Th2, Th17 or mixed
- e.g., enteropathy in Wheaten terriers
Describe the 3 types of antibody transfer from mother to child
- hemochorial
- endotheliochorial
- epitheliochoral
Describe hemochorial antibody transfer
- 3 layers of placenta
- fuller antibody transfer
- humans, rabbits, rats, mice
Describe endotheliochorial antibody transfer
- 4 layers of placenta
- some antibody transfer
- cats, dogs
Describe epitheliochorial antibody transfer
- 6 layers of placenta
- no antibody transfer
- ruminants, horses, whales
What is colostrum / antibody transfer important for?
- mainly IgG
- also IgA and IgM
What are the 4 types of Failure of Passive Transfer (FTP)?
- antibody absorption
- protection failure
- ingestion failure
- absorption failure
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
Describe protection failure in FPT
- premature birth - colostrum lacking high Ab levels
- variation in colostrum Ab levels
- 28% mares produce low-quality colostrum
Describe ingestion failure in FPT
- inexperienced mothers
- access to teats/colostrum amount (sheep)
- damaged teats
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
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
Which antibody is transferred more in milk?
IgA
