Clinical Immunology SCID

1. Advanced paper in Clinical
Immunology

2. Two main cell lineage important to immune function are lymphoid and myeloid .
most defect that leads to immunodeficiency .
The lymphoid cell disorder may affect T cells ,B cells (or)combine immunodeficiency
both T cell and B cell .
combine immunodeficiency both humoral immunity and cell mediated immunity are
impaired
The consequences of primary immunodeficiency depend on the number and type of
immune system components involved.Hematopoiesis impair functioning of immune-
system cells result in various immunodeficiency diseases.

3. SCID- severe combined immunodefeciency disease
SCID is actually a group of inherited disorders that cause severe abnormalities of
the immune system. These disorders lead to reduced or malfunctioning T- and B-
lymphocytes,
Human severe combined immunodeficiency (SCID) was first reported in 1950. SCID
may be best known from 1980s news stories about a “bubble boy”disease .
fatal primary immunodeficiency in which there is combined absence of T cell with
normal B cell (T-)(B+).both B cell and T cell . SCID is a group of heterogeneus
disorder associate with lack of T cell and B cell

5. SCID - Characters
A varity failure can leads to SCID . Defect in intracellular communication .
clinically very low number of circulating lymphocyte .
The thymus do not development and few circulating T cells in the SCID
patients .Not stimulation of mitogens .Cannot proliferate in repond to
antigen .
Myloid and erythorid cells apper normal in number and function . but only
lymphoid cells are depleted in SCID

6. Types of deficiency
Gamma chain defeciency ,
Recombination Activating Gene mutation(RAG -1, RAG -2) ,
Janus Kinase 3 Deficiency (JAK3) ,
Deficiency of purine salvage enzymes ;
Adenosine Deaminase (ADA)
Purine nucleotide phosporylase (PNS)
X linked SCID

7. Gamma chain deficiency
deficiency of the common gamma
chain of the IL2 receptor .
Defects in this chain impede
signaling through receptors for
IL4,-7,-9,and -15 as well as the IL-2
receptor,because the chain is
present in receptors for all of
these cytokines.

8. RAG gene mutation( Omenn’s Syndrome)
A defect in the genes that encode mediatorsof the rearrangement processes
(recombination-activatingproteins RAG-1 and RAG-2)precludes development of
B and T cells with functional receptors and leads to SCID .
JAK3;
Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino
acids with apparent molecular weights of 120-130 kDa. JAK-3, which transduces
signals from the gamma chain of the cytokine receptor
deficiency in this kinase JAK3 it leads to SCID

9. Purine salvage enzymes deficiency
• Adenosine deaminase (ADA) deficiency, was reported in 1972.
This type of SCID is referred to as ADA-SCID. The absence of ADA leads to
an accumulation of toxins within the lymphocytes resulting in
lymphopenia .
Adenosine deaminase catalyzes conversion of adenosine to inosine,and
its deficiency results in accumulation of adenosine .

10. PNP
Purine nucletide phosporylase deficiency causes on accumlation of
deoxyguanosine. which is triphosporylated to deoxy guanosine
triphosphate (deoxyGTP).
deoxyGTP has toxic effect on lymphocytes,causing their selective
depletion.
others deficiency
Class IIMHC molecules.Without these molecules,the patient’s lym-
phocytes cannot participate in cellular interactions with T helper cells.This
type of immunodeficiency is also called thebare-lymphocyte syndrome.

13. Specific defect Impaired function chromosomal defect
RAG-1/RAG-2deficiency No TCR or Ig gene rearrangment 11p13
ADA deficiency
PNP deficiency
Toxic metabolite in T and B cell 20q13
14q13
JAK-3deficiency
IL-2Rgamma-deficiency
Defective signals from
IL-2,4,7,9,15,
19p13
Xq13

14. Clinical presentation
SCID infants suffer from chronic diarrhea, pneumonia, and skin,mouth,
and throat lesions as well as a host of other oppor-tunistic infections.
The immune system is so compromised that even live attenuated vaccines
(such as the Sabin poliovaccine) can cause infection and disease.
fungal (yeast ) infection in patient with SCID may be treat very difficult .
oral thruch.
candida(OR)fungal pneumonia esophagel infection , growth failure (or)
mal absorption is a common probelm in children with SCID.

15. Diagnosis
The average lymphocyte count for patients will all types of SCID is
1,500 lymphocytes (per cubic millimeter)
The diagnosis of SCID before the baby is born .
Multiple blood tests — including a complete blood cell count(CBC).
Molecular testing of the cells from a chorionic villius sampling (CVS)
and small amount amniotic fluid which contain fetal cells it removed
from the uterine cavity.

16. TREATMENT
Gene Theraphy
Bone marrow transplantation
Patient with hypogammaglobulinemia are treated with immunoglobulin
infusion through vein . These infusion raise blood immunoglobulin leval and
protect against many infection .(IVIG)

17. Both X linked form of SCID and ADA deficiency have been corrected for gene
theraphy .
 Protocol ; Harvesting peripheral blood T lymphocyes from the patients .
transfecting the ADA gene using retro viruse vector . Transfected cells in cultuer
, and re administering them to patients .
Haematapoitic stem cell transplantation(HSCT)

19. A bone marrow transplant requires a human leukocyte antigen (HLA) match
between the donor and the recipient .
BMT can be allogenic or autologous, which means the donor and recipient of
bone marrow can be two different people or the same person, respectively. The
autologous BMT involves a full HLA match, whereas, the allogenic BMT involves
a full or half (haploidentical) HLA match .