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Immunodeficiency disorders
Combined
immunodeficiencies
Combined
Immunodeficiencies
Combined immunodeficiencies /combined immunity
deficiency are immunodeficiency disorders that
involve multiple components of the immune system,
including both humoral immunity and cell-mediated
immunity
Babies with SCID can't produce IgG,so once the IgG from the mother
has gone, they easily get the types of infections that antibodies are
good at preventing.
Types
SCID is usually
inherited disorder
an
SCID Mice
In 1983, Melvin & Gayle Bosma & their colleagues describes
Autosomal Recessive Mutation.
SCID mouse
Human thymus
releases mature
human T cells into
circulation
Transplant human
thymus & lymph node
tissue under kidney
capsule. Inject with
human fetal liver
cells.
Mutations in this gene result in very low T-lymphocyte and NKlymphocyte counts, but the B-lymphocyte count is high .
Only males have this type of SCID, but females may carry the gene and
have a 1 in 2 chance (50%) of passing it on to each son as well as a 1 in 2
chance of passing the carrier state on to each daughter
ADA is essential for the metabolic function of a variety of body cells but
especially T-cells.
The absence of this enzyme leads to an accumulation of toxic metabolic byproducts within lymphocytes that cause the cells to die.
Babies with this type of SCID have the lowest total lymphocyte counts of
all, and T, B and NK-lymphocyte counts are all very low. This form of
SCID is inherited as an autosomal recessive trait. boys and girls can be
affected
However, the B-cells do not work because of the lack of T-cells. IL-7R
deficiency is the third most common cause of SCID accounting for 11%
of SCID cases.
JAK3 encodes Janus kinase 3, a tyrosine kinase that belongs to the Janus
family.
Thus, when T, B and NK-lymphocyte counts are done, infants with they are
T-, B+, NK-.
Since this form of SCID is inherited as an autosomal recessive trait both boys
and girls can be affected.
the
Three other forms of SCID are due to mutations in the genes that
encode three of the individual protein chains that make up another
component of a group of molecules on the surface of T-lymphocytes,
the T-cell receptor complex, CD3.
Deficiency of CD45
Mutation is due to a large deletion at one allele and a point mutation at the other.
Bare-lymphocyte syndrome:
Reticular dysgenesis :
Is a rare genetic disorder of the bone marrow resulting in complete
absence of granulocytes and decreased number of abnormal
lymphocytes.
In the patient with SCID, chicken pox can be fatal because it does not resolve
and can progress to cause infection in the lungs, liver and brain.
Other dangerous viruses for patients with SCID are the cold sore virus
(Herpes simplex), adenovirus, para influenza 3, Epstein-Barr virus (EBV,
the infectious mononucleosis virus), polioviruses, measles virus (rubella)
and rotavirus.
Fungal (yeast) infections in patients with SCID may be very difficult to
treats such as oral thrush.
Candida pneumonia, abscesses, esophageal infection or even meningitis
may develop in patients with SCID.
Persistent diarrhea, resulting in growth failure or mal absorption, is a
common problem in children with SCID.
Patients with SCID may also have a rash that is mistakenly diagnosed as
eczema, but is actually caused by a reaction of the mothers T-cells (that
entered the SCID babys circulation before birth) against the babys tissues.
This reaction is called graft-versus-host disease (GVHD).
Diagnosis
The average lymphocyte count for patients with all types of SCID is
1,500 lymphocytes (per cubic millimeter)
The diagnosis of SCID can also be made before the baby is born.
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HIV test
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Treatment
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Gene therapy
Recently gene therapy has been attempted as an alternative to the bone marrow transplant.
Transduction of the missing gene to hematopoietic stem cells using viral vectors is being
tested in ADA SCID and X-linked SCID.
In 1990, four-year-old Ashanthi DeSilva became the first patient to undergo successful gene
therapy.
Researchers collected samples of Ashanthi's blood, isolated some of her white blood cells,
and used a virus to insert a healthy Adenosine Deaminase (ADA) gene into them.
These cells were then injected back into her body, and began to express a normal enzyme.
However, the concurrent treatment of ADA injections may impair the success of gene
therapy, since transduced cells will have no selective advantage to proliferate if
untransduced cells can survive in the presence of the injected ADA
The bone marrow or cord blood stem cells need to come from a healthy
donor with normal immune function.
The transplant cells are inevitably contaminated with T cells from the donor.
These T cells can recognise the foreignness of the patient's tissues and start
to attack them (as would happen if the T cells were still in the donor and
were called upon to reject an invader like a tumour, skin graft or infection).
This attack causes a condition called graft versus host disease (GVHD). A
patient with GVHD might develop fever, measles like rash or diarrhoea and
it can be very serious.
Prevention of GVHD
(i)
Prevention
Practicing safe sex and avoiding the sharing of body fluids may help
prevent HIV infection and AIDS. Good nutrition may prevent
acquired immunodeficiency caused by malnutrition.
Immune system disorders occur when the immune system does not
fight tumours or harmful substances as it should. The immune
response may be overactive or underactive.