RT Book, Section
A1 Blumberg, Richard S.
A1 Snapper, Scott B.
A2 Greenberger, Norton J.
A2 Blumberg, Richard S.
A2 Burakoff, Robert
SR Print(0)
ID 1119985013
T1 Inflammatory Bowel Disease: Immunologic Considerations & Therapeutic Implications
T2 CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 3e
YR 2016
FD 2016
PB McGraw-Hill Education
PP New York, NY
SN 9780071837729
LK accessmedicine.mhmedical.com/content.aspx?aid=1119985013
RD 2024/04/18
AB ESSENTIAL  CONCEPTSGut-associated  lymphoid  tissues  (GALT)  are  characterized  by  a  unique  structure,  physiologic  inflammation,  a  tendency  to  suppress  immune  responses  (oral  tolerance),  and  production  of  secretory  immunoglobulins.The  immune  response  has  two  major  arms:  innate  (rapid,  hard-wired)  and  adaptive  (delayed  in  onset  with  memory).Inflammatory  bowel  disease  (IBD)  offers  a  paradigm  for  understanding  and  treating  intestinal  inflammatory  diseases.IBD  is  a  dysregulated  immune  response  of  GALT  to  normal  commensal  microbes  within  the  intestine;  risk  of  IBD  is  altered  by  genetic  susceptibility  and  by  specific  environmental  factors  (eg,  tobacco).Numerous  genetic  loci  and  environmental  elements  defined  as  risk  factors  for  IBD  regulate  innate  and  adaptive  immunity,  the  epithelial  barrier,  and  the  relationships  of  each  of  these  with  normal  commensal  microbiota  (bacterial  and  nonbacterial).IBD  is  ultimately  caused  by  overproduction  of  proinflammatory  mediators  relative  to  anti-inflammatory  mediators,  both  of  which  are  derived  from  cells  associated  with  adaptive  immunity  (T  helper  [Th]  cells)  and  innate  immunity  (macrophages  and  dendritic  cells)  that  excessively  infiltrate  the  intestinal  tissues.Although  Crohns  disease  (CD)  may  preferentially  exhibit  overactivity  of  Th1  and  Th17  cells,  and  ulcerative  colitis  (UC)  may  exhibit  overactivity  of  Th2  cells,  there  is  significant  overlap  in  the  immunopathogenesis  of  these  disorders.Excess  production  of  cytokines  derived  from  innate  immune  pathways  (tumor  necrosis  factor  [TNF]  and  interleukin-6  [IL-6])  occurs  in  both  CD  and  UC.T  regulatory  cells  secrete  anti-inflammatory  cytokines  (eg,  IL-10,  transforming  growth  factor-β  [TGFβ],  and  IL-35)  that  inhibit  proinflammatory  cytokine  responses  from  innate  and  adaptive  immune  cells.Increased  understanding  of  IBD  immunopathogenesis  has  led  to  development  of  therapeutic  agents  that  are  increasingly  being  administered  in  a  logical,  mechanism-based  manner.