1.07 Mucosal Immunology Flashcards
What kind of cells produce antimicrobial peptides in the intestinal lumen?
Paneth cells
Where is secretory IgA produced at the intestinal mucosa?
Lamina propria (plasma cells)
How are intestinal epithelial cells held together to maintain a first line of defense/physical barrier?
Tight junctions
What are some immune stimuli that can increase mucin production?
IL1, IL4, IL6, TNFa, Interferons (Type 1)
Intestinal epithelial cells produce what two anti microbial substances?
Paneth cells + defensins
Why do IECs express TLR 2,4, 5, 6, 7, 9, and engage in signaling?
Increase tight junction strength, motility and replication, & defensin secretion
Do IECs also have Nod like Receptors?
Yup to recognize pathogens
When are TLR and NLR activated at IECs (why not all the time)?
TLR only activated past basolateral surface (past epi) and NLR only activated at cytosol
What is included in the adaptive immune defense at the mucosa?
GALT, Peyer’s patches, mesenteric lymph node
What’s in a Peyer patch?
B, T, DC cells and Macrophages
What delivers antigens from lumen to GALT to be recognized by adaptive immune system?
M cells (with short irregular micro ills)
Where does antigen presentation to the T cells happen?
Lymph nodes (GALT, Peyer, mesenteric)
How are effector T cells distributed in the mucosa?
CD8 = epithelium (kill)
CD4 = peyers patches + nodes (orchestrate)
Where do al the Th responses happen at mucosa?
Lamina propria
What helps enhance fluid and mucus secretion, smooth muscle contraction, and bowel motility?
IL-4, IL-13
What immune response against intestinal helminth infections?
Th2 (IL4, IL13, IgA)
What immune response maintains mucosal epithelial barrier function?
Th17 (IL17, IL22, IgA)
What process allows activated T cells to go from the mucosal Lamina propria to lymph nodes?
Imprinting
What is essential to allow the expressions of integrins and chemokine receptors for imprinting process?
Retinoic acid (via DCs)
What immune responses is typically found in the gut?
Th2 (immunosuppressive)
What kind of cells are found in the gut almost 2 fold?
Tregs
Peripheral Tregs are reliant on what two factors?
Retinoic acid and TGFb
TGFb is also necessary factor for what other immune component in the gut?
IgA (isotype switching)
What autoimmune disorder is associated with Treg dysfunction?
IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X linked)
A mutation where leads to a loss of Tregs?
Foxp3
Where are B cells activated in the gut?
GALT
What’s the most abundant antibody in the human body?
IgA
What is the GALT ration of B:T cells versus normal lymph nodes?
5:1
What antibody is most abundant in the blood?
IgG
IgA is able to get to the mucosal layer via transcytosis because of what?
Poly-Ig receptor (on IECs)
It also gets cleaves and joins IgA afterwards to protect it a bit
How to infants get IgA?
Breastfeeding
Most common immunoglobulin deficiency that leads to decreased levels of IgA and normal IgM and IgG?
Selective IgA deficiency
Clinical presentation of selective IgA deficiency?
Increases respiratory, gastrointestinal and GU infections + giardiasis risk (most asymptomatic)
Short chain fatty acids produced by commensal gut bacteria have what role in immunity?
Stimulate Treg production + inhibit neutrophil activation
When an immune response is elicited in the gut, what do IECs produce?
IL1, TNFa, IFNy
What live attenuated vaccine is delivered orally to stimulate musical IgA response?
Polio live (Sabin)
What is activated and where in an allergic food response that causes nausea, vomiting, diarrhea, and abdominal pain?
Mast cells in Lamina propria
Why does an allergic food response also led to anaphylactic/systemic symptoms too?
Antigens activate mast cells in different tissues too
What are the antibodies in a pernicious anemia directed against?
Intrinsic factor (via parietal cells of stomach needed for B12 absorption at intestine)
What is the leading theory on what causes IBDx?
Inadequate Treg mediated suppression to commensal invasion — Th1 — Inflammation
Crohn’s disease illicit what kind of reaction in the gut that is thought to cause defect in inflammasome mediated intracellular signaling to bacterial products?
Granulomatous reaction
Can affect any part of GI tract, NOD2 loss of function mutation, and Th1 mediated (IFNy + IL12) granulomatous inflammation?
Crohn’s Dx
Colon only, IL-10 suspectibility mutation, Th2 mediated (IL5)?
Ulcerative colitis
What is triggering the immune responses in celiacs disease?
Deamidated gliadin (presented to DC and activate T cells that are intolerant)
What CD4 T cells are implicated in celiacs?
HLA DQ2
HLA DQ8
What antibodies are associated in celiacs?
Anti-tTG, antiendomysial, antigiladin
What kind of antibodies should you look for if patient suspected with celiacs tests negative for IgA?
anti tTG-IgG
Celiacs and Crohn’s are what kind of hypersensitivity reaction?
IV
Chronic gastritis associated with H. Pylori infections can lead to what?
MALT lymphomas
Painful swollen tongue, hyper segmented neutrophils in blood smear, macrocytic anemia, neurological symptoms, and hashimoto thyroiditis hint at a deficiency of what?
Intrinsic factor
What will differentiate/hint a folate versus a B12 deficiency in a clinical stem?
Autoimmune disease (B12 autoantibody hint)
