L13 - Mucosal Immunity Flashcards
Essential function of mucosal surfaces?
Gas exchange
Food absorption
Sensory activities
Reproduction
What are the mucosal surfaces for entry of pathogens?
Mouth & respiratory contract
Gastrointestinal tract
Reproductive tract
3 functions of the epithelium?
Lines mucosal surfaces defining border
Defends from invasion
selectively transports components essential for life to lamina/circulation
What are the 2 ways that mucosal tissue is defined?
Scattered - lymphocytes dotted around
Organised - B cell and T cell areas concentrated in 1 area - drain the lymph nodes
Anatomical features of the mucosal immune system?
Interactions between mucosal epithelia and lymphoid tissues
discrete compartments of diffuse lymphoid tissue and organised structures e.g. tonsils
specialised antigen-uptake mechanisms e.g. M cells in Peyer’s patches
Effector mechanisms of the mucosal immune system?
Presence of distinctive microbiota
Secretory IgA antibodies
activated ‘natural’ effector T cells present
Activated T cells predominate even without infection
Immunoregulatory environment of the mucosal immune system?
Active downregulation of immune response
Inhibitory macrophages & tolerance-inducing DCs
The 4 cells that stem cells differentiation in mucosal tissue leads to?
Enterocytes/colonocytes
Paneth cells
Goblet cells
Enteroendocrine cells
function of enterocytes/colonocytes?
absorptive
AMPs production
function of paneth cells?
AMPs
function of goblet cells?
mucus secretion - lubricate food and prevent bacteria binding
function of enteroendocrine cells?
neurohumoral factors secretion - enzymes
What are M cells?
sample environment and phagocytose pathogens
Antimicrobial protein families in intestine and skin?
REG3y - bind onto carbs
BD1/2/3/4 - produced by sebaceous gland
RNases
Lactoferrin - ferrous ions
Calprotectin - binds Ca ions
What is the dominant class of Ab on mucosal surfaces?
IgA
IgA1 - lung
IgA2 - colon
Major function of IgA?
IMMUNE EXCLUSION
IgA adsorb on the mucus layer - interactions between carbohydrates
IgA do NOT activate complement classical pathway - does NOT promote inflammation
What are IgA resistant to?
protease
What are the immune cells of the mucosa?
Intraepithelial lymphocytes (IELs)
What do IELs recognise?
epithelial cells expressing abnormal phenotypes resulting from stress/infection
What are ILCs?
Innate Lymphoid cells
Group 1 ILCs?
ILC1
NK cells
IFNy
similar to Th1
Group 2 ILCs?
ILC2
Trigger soluble antibody response
similar to Th2
Group 3 ILCs?
ILC3
Inflammatory response & epithelial type immunity
similar to Th17 & Th22
What samples the mucosal compartments?
Distinct DCs e.g. CD103+
What is MadCAM?
on vasculatare of all mucosa
Gut homing lymphocytes
Why are host-commensal interactions needed in the gut?
help to digest food
responsible for extraction & synthesis of nutrients
compete with pathogens
inhibit pathway that is required for pathogen uptake
What gut infection can arise when antibiotics are used?
Clostridium difficile
altered gut environment and pathological inflammation
What is happy equilibrium “physiological inflammation”?
Commensal bacteria constantly triggering slight inflammation
important in calming the immune response
How does salmonella cause infection?
kill M cells - infect macrophages and epithelial cells
invade luminal surface of epithelial cells
enter phagocytes cells that are sampling gut luminal contents
How does shigella cause infection?
physically kills M cells
invade basal surface of epithelial cells and spread
cell-wall peptides binds NOD1 - activate NFkB pathway
activated epithelium secretes CXCL8 - recruits neutrophils
What does shiga toxin do?
inhibit translation
What does Clostridium difficile toxin A do?
inactivates GTPase
What does rotavirus NSP4 do?
disrupts tight junctions
What response do helminth infections provoke?
Th2
IL13 - epithelial cell repair
M2 macrophages activated
Driver B cells to produce IgE
IL5 recruits eosinophils
IL3/IL9 mast cell recruitment
Aberrant mucosal immunity?
Crohn’s - NOD2, Atg16L1 - phagoctyoses intracellular bacteria
Coeliac - HLA-DQ2 - binds gliadin
C. difficile
