Immunologic deficiency syndrome
Learning objectives: At the end of the lecture, the student should be able to:
1- Discuss the mechanism of DiGeorge syndrome(Thymic hpoplasia).
2- Clarify the mechanism of sever combined immunodeficiency diseases(SCID).
DiGeorge syndrome(Thymic hypoplasia)
Concept:
-Digeorge syndrome is an example of T-cell deficiency that results from failure of development of the third and fourth pharyngeal pouches.
-Digeorge syndrome is an example of T-cell deficiency that results from failure of development of the third and fourth pharyngeal pouches.
-Loss of of T cell-mediated immunity (lack or hypoplasia of the thymus)infections.
-Digeorge syndrome is an example of T-cell deficiency that results from failure of development of the third and fourth pharyngeal pouches. -Digeorge syndrome is an example of T-cell deficiency that results from failure of development of the third and fourth pharyngeal pouches.
Tetany (lack of parathyroids)
Congenital defects of the heart and great vessels
Abnormalities of the mouth , ears, and facies.
Immunoglobines(Ig) may be normal or reduced depending on the severity of the T-cell deficiency.
* Partial DiGeorge Syndrome.
DiGeorge syndrome(Thymic hypoplasia)
Mechanism:
It is not a familial disorder
It is not a familial disorder.
It results from the deletion of a gene that maps to chromosome 22q11 ( a component of the 22q11 deletion syndrome)( a member of the T-box family of transcription factors)
Sever combined immunodeficiency disease(SCID)Concept:
Common defects in both humeral and cell-mediated immune response.
Patients are extremely susceptible to recurrent sever infection.
- Treatment by bone marrow transplantation.
Types:
A- Classic form.
B- Sever combined immunodeficiency disease (SCID) defect reside in the T cell compartment with a secondary impairment of humeral immunity ( more common form).
C- X-linked sever combined immunodeficiency disease(SCID).
. Mutation in more common gamma chain (gamma c) of cytokine receptors (most common form).
D- Autosomal recessive sever combined immunodeficiency disease(SCID).
- Deficiency of the enzyme adenosine deaminase(ADA).
Mechanism
Deficiency of adenosine deaminase(ADA) lead to accumulation of deoxyadenosine and its derivatives (e.g deoxy ATP) which are particularly toxic to immature lymphocytes especially those of T-cell lineagesreduction in number of T lymphocytes than of B lymphocytes.
Other causes of autosomal recessive SCID.
Mutation in recombinase-activating gene Prevent the somatic gene rearrangements essential for assembly of T-cell receptor and immunoglobulin gene blocks the development of T and B lymphocytes.
-Mutation in an inteacellular kinase called Jak3 (essential for signal transduction through common cytokine receptor gamma chain).
- Mutation that impair the expression of class II MHC molecules prevent the development of CD4+ T cells (bare lymphocyte syndrome).
Questions:
1- Discuss the mechanism of Autosomal sever combined immunodeficiency disease (SCJD).
2- Describe the histopathological findings in sever combined immunodeficiency disease (SCID).
3-Write short notes on DiGeorge syndrome (Thymic hypoplasia).
References:
1-MacSween R.N.;and Whaly K.(Murs Textbook of pathology); 13th edition,Arlond.1997.
2-Kumar V.;Abbas A.; and Fausto N.(Robbin and Cortan, Pathologic basis of disease).7th edition. Elsevier Sounder. 2004.
3-Rosal J. (Ackerman s surgical pathology); 9th edition.Mosby.2003.
4-Walts J.B.,Talbot L.c.(general pathology ); 7th edition ,Churchill Livingstone; 1996 .
5-Krishna V.(Text book of pathology );Orient Longman Private limited. 2004 .