T-Cells
The Inflammatory Response
Some researchers believe that the
disease develops in people who have a genetic susceptibility that enables an agent
such as a virus or bacteria to trigger an abnormal immune response.
The Immune System's Infection Fighters. The primary infection-fighting
units are two types of white blood cells: lymphocytes and leukocytes.
Lymphocytes include two subtypes known as T-cell s and B-cells.
Both types of cells are designed to recognize foreign invaders (antigens) and
to launch an offensive or defensive action against them:
- B-cells produce antibodies,
which are separate agents that can either ride along with a B-cell or travel
on their own to attack the antigen.
- T-cells have special receptors
attached to their surface that recognize the specific antigen. T-cells are
further categorized as killer T-cells or helper T-cells (TH cells).
- Killer T-cells directly attack
antigens that occur in any cells that contain a nucleus.
- Helper T-cells also recognize
antigens, but their role is two-fold. They stimulate B-cells and other white
cells to attack the antigen. They also produce cytokines, powerful
immune factors that have an important role in the inflammatory process
.
- Helper T-Cells and Inflammatory
Bowel Disease. The actions of the helper T-cells are of special interest
in inflammatory bowel disease:
- TH-cells stimulate other
white blood cells called B-cells to produce antibodies. In this case, however,
they appear to direct the B-cells to produce autoantibodies, which
are directed against the body's own cells.
- TH-cells also secrete or
stimulate the production of powerful immune factors called cytokines.
In small amounts, cytokines are indispensable for healing. If overproduced,
however, they can cause serious damage, including inflammation and cellular
injury. Cytokines, particularly specific ones known as tumor necrosis factor
, interferon-gamma, and interleukins, cause intestinal inflammation
and damage, which, in a vicious cycle, attract even more helper-T cells
Helper T-cells are further categorized
as TH1 and TH2. An imbalance in these two types appear to occur in Crohn's disease:
- Crohn's disease patients
have increased activity in Th1 helper cells, which activates interleukin-2
(IL-2) and interferon-gamma that affect intestinal cells. Tumor necrosis factor
(TNF) may be a particularly potent immune factor in Crohn's disease. It has
important properties that regulate inflammation and cell proliferation. If
genetic or other factors increase production of TNF, it can lead to great
harm.
- Ulcerative colitis patients
favor a Th2 response, which activates the interleukins IL-4, IL-5, IL-6, and
IL-10 that mostly affect mucosal areas in the intestine.
The interleukin 6 appears to play
a part by inhibiting a natural mechanism called apoptosis, a process whereby cells
self-destruct. In such cases, cells proliferate faster than they die, causing
an excessively strong immune response.
Adhesion Molecules. Increased levels of certain molecules called E-selectin
and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role
in the inflammatory process by causing certain damaging immune factors to accumulate
on intestinal cells. E selectin may be involved in the early stages of the disease
(especially ulcerative colitis) and ICAM-1 in the persistence of either inflammatory
bowel disease.
Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase
has been detected in the colons of patients with IBD. Such increased levels tend
to break down the extracellular matrix, a barrier composed of structural proteins
and elastic fibers that surrounds and supports cells, in this case in the colon.
Researchers suggest that this activity may cause persistent damage once the inflammatory
process has triggered IBD.
Genetic Factors
Although the causes of inflammatory
bowel disease are not yet known, genetic factors certainly play some role. Up
to 25% of people with IBD also have family members with the disease. The inherited
risk is higher in Crohn's disease than in ulcerative colitis, but genetic factors
are involved with both. The inherited risk is highest if a mother has the condition,
followed by a sibling. A father with IBD poses the least inherited risk to his
children.
Specific Genes Involves. Researchers in Europe and the US independently
identified a gene called NOD2, which might be involved in 15% of Crohn's disease
cases. Those with one copy of the mutated gene had twice the average risk of developing
Crohn's, and those with two defective genes faced 20 to 40 times the risk. The
mutation appears to alter the immune system so that it launches an over-reaction
in response to bacteria, causing inflammation.
Infectious Agents
Some research indicates that infectious
agents, either viruses or mycobacteria, may be responsible for triggering the
inflammatory process leading to Crohn's disease. Studies have found that children
with IBD are likely to have more and earlier childhood infections, so they have
become a focus of some interest.
Measles. Of particular notice is the measles virus. Some research has found
a link between a history of childhood measles and a higher risk for IBD. One small
study reported an association between wild strains of the virus and Crohn's disease
patients. Recent studies have found no higher risk for inflammatory bowel disease
with the measles vaccine. And, in fact, one found some protection with the vaccine.
Mycobacteria. Another suspect for Crohn's disease may be mycobacteria that
cause a form of tuberculosis.
Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under
suspicion as a contributor to severe cases of IBD.
On behalf of learning, and use as teaching tools for those of us who need to
know about our disease, I have tried to supply you with as much information as
I could find on all of the drugs, treatments and disorders associated with
Inflammatory Bowel Diseases. I have tried to blend all facts supported by research
and also from personal experiences of other IBD sufferers into one readable webpage, and any and all information presented here is not entirely
from one source. Most information contained within these pages is found in the public domain.
At times you may find information used from another site, and as with all copyrighted materials you may find on these pages, I claim fair use under sections 107 through 118 of the Copyright Act (title 17, U.S. Code). Click here for more info
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