Immunologic deficiency syndrome
Learning objectives: At the end of the lecture, the students should be able to:
1- Mention types of immunologic deficiency syndromes.
2-Define primary immunodeficiencies.
3-Classify primary immunodeficiencies.
4-Explain the mechanism of X-linked agammaglobulinemia.
5-Discuss the mechanism of common variable immunodeficiency.
6-Clarify the mechanism of isolated IgA deficiency.
7-Explain the mechanism of hyper IgM syndrome.
Immunologic deficiency syndrome
Types:
1-Primary immunodeficiency disorders.
2-Secondary immunodeficiency disorders.
Primary immunodeficiency disorders
Definition:
Most primary immunodeficiency diseases are genetically determined and affect specific immunity (i.e. the humeral and cellular arms of adaptive immunity) or nonspecific host defense mechanisms mediated by complement proteins and cells such as phagocytes or natural killer cells (innate immunity).
Primary immunodeficiency diseases
Classification:
a- B cell defects.
b- T cell defects.
c- Mixed B and T cell defects.
d- Complement system defects.
e- Phagocytes defects.
a- B cell defects.b- T cell defects.c- Mixed B and T cell defects.d- Complement system defects.e- Phagocytes defects.
X-linked agammaglobulinemia
Concept:
- One of the more common forms of primary immunodeficiency.
-characterized by the failure of pro-B cells and pre-B cells to mature B cells.
- One of the more common forms of primary immunodeficiency.-characterized by the failure of pro-B cells and pre-B cells to mature B cells.
Mechanisms:
-block in differentiation of B cell precursor to mature B cells is due to mutations in a cytoplasmic tyrosine kinase, called B-cell tyrosine kinase (Btk ).
-Btk is associated with the antigen receptor complex of B-cell precursors. It is needed to tranduce signals from antigen receptor that are critical for driving maturation when it is mutated, the pre-B cell receptor can not deliver signals, and maturation stops at this stage.
-Btk is associated with the antigen receptor complex of B-cell precursors. It is needed to tranduce signals from antigen receptor that are critical for driving maturation when it is mutated, the pre-B cell receptor can not deliver signals, and maturation stops at this stage.
Common variable immunodeficiency
*Concept:
-characterized by hypergammaglobulinemia, generally affecting all the antibody classes but sometimes only IgG.
Mechanisms:
-B-cells are not able to differentiate into plasma cells.
-The molecular basis of abnormal B-cell differentiation is not understood.
-Some authorities, there is no evidence of any intrinsic B-cell defects. Rather, there are several different defects in the ability of T cells to send appropriate activation signals to B cells.
-Others, there are intrinsic B-cell defects as well as defects of T cell-mediated regulating of B cells.
Isolated IgA deficiency
*Concept:
-Patient have extremely low levels of both serum and secretory IgA.
*Mechanism:
-The basic defects in IgA deficiency in the differentiation of naïve B lymphocytes to IgA-producing cells.
.In patient, the number of IgA-positive B cells is normal.
.In vitro, few of IgA-positive B cells can be induced to differentiate into IgA plasma cells.
-Patient have extremely low levels of both serum and secretory IgA.*Mechanism:-The basic defects in IgA deficiency in the differentiation of naïve B lymphocytes to IgA-producing cells..In patient, the number of IgA-positive B cells is normal..In vitro, few of IgA-positive B cells can be induced to differentiate into IgA plasma cells.
Hyper-IgM syndrome
Concept:
-Patient make IgM antibodies but are deficient in their ability to produce IgG,IgA, and IgE antibodies.
-Abnormal T cells fail to induce B cells to make antibodies of isotypes other than IgM and to active macrophages to eliminate intracellular microbes.
Mechanisms:
-Concept of mechanisms of antibodies of different isotypes formation.
-Definition of isotype switching.
-The contact-mediated signals are delivered by physical interaction between the CD40 molecule of B cells and CD4o Ligand (CD40L) expressed on activated helper T cells
Questions
1- Write short notes on diagnosis, manifestation, and treatment of immunologic deficiency syndrome.
2- Discuss the histological and blood findings of:
a- X-linked agammaglobulinemia.
b- Common variable immunodeficiency.
c- Isolated IgA syndrome.
d- Hyper-IgM syndrome.
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 .