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 55955091
T1 Chapter 2. Inflammatory Bowel Disease: Immunologic Considerations & Therapeutic Implications
T2 CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 2e
YR 2012
FD 2012
PB The McGraw-Hill Companies
PP New York, NY
SN 978-0-07-176848-1
LK accessmedicine.mhmedical.com/content.aspx?aid=55955091
RD 2024/04/18
AB Gut-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  intestines  of  a  genetically  susceptible  host;  this  response  is  modified  by  specific  environmental  factors  (eg,  tobacco).Numerous  genetic  loci  defined  as  risk  factors  for  IBD  regulate  innate  immunity,  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).Crohn  disease  (CD)  preferentially  exhibits  overactivity  of  Th1  and  Th17  cells,  and  ulcerative  colitis  (UC)  may  exhibit  overactivity  of  Th2  cells.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  anti-inflammatory  therapeutic  agents  that  are  increasingly  being  administered  in  a  logical,  mechanism-based  manner.