Chronic Frustrated Immune Response Flashcards
What goes on in Peyer’s Patches normally and abnormally?
Normally: Epithelia in gut submucosa produce a lot of TGFbeta, which favors differentiation of T0 cells into Treg. Peyer’s Patches also make Tfh that drive B-cells to make IgA.
Resident dendritic cells secrete IL-10 which also favors Treg differentiation.
Abnormally: In response to stress/damage, epithelial cells secrete IL-6. IL-6+TGFbeta downregulate Treg and UPREGULATE Th1, Th2, Th17.
Inflammatory Bowel Diseases - Crohns
affects large and small intestine, particularly at the terminal ileum.
Microabscesses, generalized inglammation, and “patchy” disease progress
Inflammatory Bowel Disease - Ulcerative Collitis
More superficial than Crohns disease, can erode the surface and lead to intestinal bleeding
Mechanism of Inflammatory Bowel Diseases
Involve dysregulation of immune response to commensal bacteria.
Theory: early genetic event increased gut permeability so some defensins can penetrate back into the tissue. There, acting as DAMPs, stimulate macrophages to produce cytokines such as IL-6.
Patient has activated Th1, Th2, and Th17 to normal organisms, which may even change the population of microorganisms in the gut!
Celiac Disease (gluten sensitive enteropathy)
Infants present w/ malabsorption, diarrhea and failure to thrive
Adults present w/ symptoms secondary to malabsrption (osteoporosis, anemia, rash) as villi in gut atrophy
Diagnosis: biopsy, antibody to gut endomyseum (transglutaminase 2 - TG2)
TG2 makes protein crosslinks through glutamines, can’t release wheat peptide, turns itself into B-cell autoantigen
T-cell immunity causes most issues. Strong HLA correlates.
90% of ppl have HLA-DQ2, 10% HLA-DQ8
Some people w/ poorly controlled Celiac will present w/ skin condition called dermatitis herpetiformis (transreaction with skin TG3!)
Chronic Beryllium Disease
pulmonary and fibrotic disease caused by inhaled beryllium dust
Becomes covalently bound -> generates response from Th1 and later the scarring Th2
Can’t be removed by macrophages, so condition is chronic after a single dose! :(
Strongly linked to HLA-DP alleles
Psoriasis
chronic inflammatory skin condition, innapropriate T-cell response
associated w/ HLA-Cw 06:02 (HLA gene that affects skin differentiation and IL-23, a Th17 cytokine)
Periodontal disease
major cause of tooth loss. Many similar characteristics as IBD, such as shift from TGFbeta to TGFbeta+IL-6
Discuss hygiene hypothesis and old friends hypothesis
Hygiene hypothesis : newborns start w/ Th2 response dominanted system which gradually balances out w/ Th1 due to exposure to environmental dirt and infections. Help immune system develop normally. Incomplete.
Old friends Hypothesis: certain harmless organisms have been in humans for a long time that we rely on their presence to instruct our immune systems not to overreact. Balance between Th1 and Th2 via TREG!!!! (whipworms - eat em! they cause an increase in Treg)
