GI immunology Flashcards
what is Payer’s patch
a specialised area where gut contents are sampled
what is Payer’s patch covered in
epithelial layer containing M cells
what are M cells
specialised cells which have characteristic membrane ruffles
what is the function of M cells
gateway for antigens into payer’s patch:
take up antigen via endocytosis and phagocytosis
where are dendritic cells located within the payer’s patch
directly under M cells
how do dendritic cells bring antigens into the payers patch
extend processes across the epithelial layer to capture antigens from the lumen of the gut
how are antigens brought into the Payer’s patch (2)
- M cells = endocytosis & phagocytosis
2. dendritic cells = extend processes
what are the 2 distinct compartments of the mucosal immune system
the epithelium
the lamina propria
what immune cells are located within the lamina propria
ALL types
what immune cells are located within the epithelia
dendritic cells
T cells
what is the percentage breakdown of the intestinal response
80% = IgA IgM = 15% IgG = 5%
describe the IgA in the intestinal response
dimeric
IgA1:IgA2 = 3:2
describe T cells role within the GI system
T cells enter Payers patch from blood vessels directed by L-selectin
They encounter antigens and are transported across M cell where they are activated by dendritic cells
activated T cells drain via mesenteric lymph nodes to the thoracic duct and return to the blood.
gut homing effector T cells bind to MAdCAM1 on endothelium
what is the role of MAdCAM
binds gut homing effector T cells on the endothelium
what does IgA bind to
poly-Ig receptor
what can IgA be replaced by and why
IgM
they are both polymers
what are intraepithelial lymphocytes (IELs)
CD8+ T cells
where are intraepithelial lymphocytes (IELs) located
lie within the epithelia lining of the gut
how do are intraepithelial lymphocytes (IELs) react to viruses
infected cells displayed viral peptide to IEL via MHC class 1
activated IEL kill the infected epithelia cell
what do stressed epithelial cells express
MIC-A and MIC-B
how do IEL bind to MIC-A and MIC-B, what happens next
via NKG2D
this then activated the IEL which then kills the stressed cell
give examples of mucosal disorders associated with primary immunodeficiency
selective IgA deficiency CVID = Common variable immune deficiency XLA = X-linked agammaglobulinemia CGD = Chronic Granulomatous Disease SCID
what condition is IgA associated with
coeliac disease
what are the symptoms of Common variable immune deficiency (CVID)
recurrent sinopulmonary and GI infections
what is the cause of Common variable immune deficiency (CVID)
failure to differentiate into Ig secreting cells
low IgG, IgA, IgM, and IgE
what are the symptoms of X-linked agammaglobulinemia (XLA)
sinopulmonary and GI infections + chronic enteroviral infections
what is the cause of X-linked agammaglobulinemia (XLA)
no B cells/ agammaglobulinemia
what is the cause of SCID
defect in T and B cell immunity
what are the symptoms of SCID
oral candidiasis
chronic diarrhoea interstitial pneumonitis
what is the cause of Chronic Granulomatous Disease (CGD)
failure of phagocyte respiratory burst
what are the symptoms of Chronic Granulomatous Disease (CGD)
staph aureus infections
perianal, liver, and skin abscess
what type of hypersensitivity is a food allergy
type 1
how are food allergies initiated
cross linking of allergen specific IgE on the surface of mast cells with the specific allergen
what Ig is involved in food allergies
IgE
describe the villi in coeliac disease
flattened with “scalloping”
villous atrophy
what genes are associated with coeliac disease
HLADQ2
HLADQ8
describe the immunological process involved in coeliac disease
Gamma interferon from gluten specific T cells activate epithelia cells which produce IL-15 which induces proliferation and activation IEL. both T cells and IEL then kill the epithelia cells
what IL is involved in coeliac disease
IL-15
how is coeliac disease diagnosed
biopsy (gold standard in kids)
serology for IgA anti-TTG
what is crohn’s disease mediated by
Th1 CD4+ T cells
gamma interferon
IL-12
TNF alpha
what gene is associated with crohn’s disease
NOD2
what IL are associated with crohn’s disease
IL-12 (main one)
IL-8
IL-23