Immunologic deficiency syndrome
Learning objectives: At the end of the lecture, the students should be able to:
1- Explain the concept and mechanism of Wiskot-Aldrich syndrome (Immunodeficiency with thrombocytopenia and eczema).
2- Discuss the concept and mechanism of complement system disorders (especially hereditary angioedema).
Wiskott-Aldrick syndrome (Immunodeficiency with thrombocytopenia and eczema Concept:
It is an X-linked recessive disease characterized by thrombocytopenia, eczema, and a marked vulnerability to recurrent infection, ending in early death.
Mechanism
The Wiskott-Aldrick syndrome protein(WASP) maps to Xp11.23,where the gene encoding wiskott-Aldrick syndrome protein is located.
WASP is blieved to link membrane receptors (such as antigen receptor) to cytoskeletal elements.
WSAP is important in maintaining the integrity of the cytoskeleton as well as signal transduction. It is responsible for normal lymphocyte and platelet Function.
Genetic deficiency of complement system
Concept:
The various components of the complement system are important in inflammatory and immunologic responses.
All components of complement system and two of the inhibitors are affected (protease inhibitors).
A deficiency of C1 inhibitor(protease inhibitor) give rise to hereditary angioedema.
Mechanism
It is autosomal dominant disorder.
The C1 inhibitor is a protease inhibitor whose target enzymes are C1r and C1s of the complement cascade, factor XII of the coagulation pathway,and the kallikrein system.
These pathways are closely linked, and their unregulated activation can give rise to vasoactive peptides such as bradykinin.
- Patients have episodes of edema affecting skin, and mucosal surfaces such as the larynx,and gasterointestinal tract.
- Clinical features include asphyxia or nausea, vomiting, and diarrhea after minor trauma or emotional stress.
Another example of deficiency of other complement regulatory protein is the cause of Paroxysmal nocturnal hemoglobinuria.
Mechanism
Mutations in enzymes required for glycophosphatidyl inositol (GPI) linkages.
Many proteins are expressed on cell surfaces in a GPI-linked form(e.g two of complement regulatory proteins, decay accelerating factor and CD59).
In the absence of these proteins, complement deposited on red cells is not controlled, resulting in hemolysis and hemoglobinuria.
Questions
1- Discuss the concept and mechanism of phagocyte disorder (especially Chediak-Higashi syndrome.
2-Write short note on treatment of hereditary angioedema.
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 .