Immunology Of The GI Tract Flashcards
MALT definition
Mucosal surfaces that are exposed to external infectious agents.
- therefore these areas need lymphoid tissues at these areas to combat immediately
GALT
Specialized epithelial cells and their products that are found in the GI tract.
- specifically in the Lamina propria layer for he GI tract
Possesses scattered IELs with intraepithelial lymphocytes. Specifically CD8+ T-cells
What are regional/sentinel lymph nodes for most GALT tissues?
Mesenteric lymph nodes
What areas of the gut tract possess highest thickness levels of mucus?
From highest to lowest
Colon
Ileum
Antrum of stomach
Duodenum and corpus of the stomach
Jejunum
corpus/antrum of stomach and the terminal colon are the only sites for firmly adherent mucus, the rest is loosely adherent
Goblet cells vs paneth cells
Both are found in the GALT tissues and throughout GI tract
Goblet:
- produces mucus
- inner layer of mucus = defenses and IgA are adhered
- outer layer of mucus = comensal bacteria are adhered
Paneth cells
- produce defensins (usually into crypts for them to float around in the GU tract and adhere to mucus)
Crohn’s disease pathogenesis
Patients dont produce as many paneth cells
- means less defensins and increases in inflammatory pathogen presence
Eventually leads to ulcers in the GI tract/gut with chronic exposure to the pathogens
also is believed that the commensal bacteria also trigger an inappropriate mucosal immune response that is never enough to kill infectious bacteria, but is enough to chronic all damage intestinal tissues
What bacteria do defensins bind to?
Gram (+) bacteria
- binds to the carbohydrates of the peptidoglycan wall, poking holes in them (bacteriocidal)
is innate immunity
Peyer patches
Unencapsulated follicles of lymphoid tissues that is found in the lamina propria of the ilium and rectum primarily
Contains specialized M cells that sample and present antigens to immune cells
- if APC’s are present morphs resident dormant B-cells into secreting IgA plasma cells
*are the prime movers is innate defense in gut tissue *
IgA is produced due to production of TGF-B in the follicle when stimulated
M cells
Are the prime APC’s in the gut tissues
- take bacteria antigens and M-cells upregulated them and present them to T-cells/B-cells
TLR signaling in GALT tissue
A little bit different and results in 4 main functions:
1) produces factors that promote motility and repair epithelium
2) participates in promoting B-cell production of IgA
3) maintains tight junctions integrity
4) increase expression of defensins
Why are there no immune responses to the commensal bacteria present in GALT?
TLR’s are absent from the apical membrane (lumen surface) on the epithelial cells
- TLR signaling only initiates if bacteria crosses the epithelial cells
- also DC’s only are weakly activated by commensal bacteria so instead produces Tregs vs defensins
GALT adaptive immunity
Initiates when the antigens cross the internal mucosa
- 2 ways this occurs*:
1) transcytosis of antigens through M-cell’s -> Peyer’s patch
2) dendritic cells capture antigens and transport them to secondary lymphatic tissues by transporting between adjacent cells
What do Tcells release in result to both pathogenic and commensal bacteria?
Pathogenic = T-helper cells and CTL’s
Commensal = Tregs
Why is IgA the prime antibody in GI tract?
Because it is attached to a J-chain that allows it to bind to epithelial tissues and cross tight junctions
- only one that can do this
What are the typical GI microbiome bacteria?
Enterobacteria except for
- campylobacter
- vibrio
- yersinia
- shigella
- salmonella
LOTS of gram (-) rods anaerobic bacteria
Streptococci
Staph aureus
Yeasts
Do male or female sex hormones produce a more inflammatory GI environment?
Females
- hence why females tend to get IBS/IBD easier
What factors can affect GI microbiome
Genetics
Diet
Antibiotics
- should take probiotics with it
Metabolic disease
Autoimmunity Issues
Increased susceptibility
What is fecal microbiome transplant (FMT)?
Transplant fecal matter from one person to another
Done in patients with autoimmune disorders, recurrent c. Diff infections and type 2 diabetes, etc.
What 3 factors lead to autoimmunity in the gut?
Genetics
Environmental factors
Gut Dysbiosis
What two disorders are included in IBD?
Crohn’s disease
Ulcerative colitis
Difference between ulcerative colitis and Crohn’s disease
Ulcerative colitis
- involves only colon and rectum
- almost always produces bloody diarrhea
- not much ab pain
- NO fistula And perianal disease
- “lead pipe” appearance on imaging with loss of haustra
- deep ulcers with friable mucosa and crypt abscesses is always present.
- continuous ulcer lesions are present
- is TH2 mediated
- associated with p-ANCA antibodies
- smoking is actually protective
Crohn’s disease
- involves any part of the GI tract EXCEPT rectum. Usually affects terminal ileum and colon though
- presents with fistula and perianal disease
- usually no bloody diarrhea and severe ab pain
- shows aphthoid and deep ulcers with cobblestone mucosa and creeping fat pouches
- “string sign” on affected portion with RLQ mass
- tranmural lesions and crypt abscesses
- smoking worsens condition
- common associated with Anti-Saccharomyces antibodies (ASCA)
Treatment for both Crohn’s disease and ulcerative colitis
Crohn’s:
- corticosteroids
- azathioprine (halts purine synthesis)
- antibiotics or biological
Ulcerative colitis:
- colonectomy
- 5-aminosalicyclic
- 6-mercaptopurine
Most common symptoms of Crohn’s disease
Severe RLQ pain
Non-bloody diarrhea
Weight loss
Most common symptoms of ulcerative colitis
Bloody diarrhea
Mild ab pain and cramping
(+/-) weight loss
