ملخص

IMMUNE DEFICIENCY

characterized by recurrent infections, autoimmunity, and susceptibility to malignancy.
The immune deficiency disorders are either primary (with intrinsic defect ) or secondary iatrogenic to infections, drug therapy, malignancy or aging).

Types of immune deficiency

1. Antibody deficiency
2. T-lymphocyte deficiency
3. Combine B- and T-cell deficiency
4. Complement deficiency
5. Phagocyte deficiency

General presenting problems of immunodeficiency

Severe infection, caused by unusual, low virulent or commensal organisms that occur at unusual sites.

Primary antibody deficiency

1-Infancy or early childhood
X-Linked agammaglobulinaemia (Bruton’s disease)
occurs in male .There arrest of the B cell development at pre-B cell stage , results in very low IgG level and absence of other immunoglobulins (IgM, IgA, IgD, and IgE) and mature B-cells/plasma cell. Patients usually present with recurrent infections of the respiratory tract, and very tiny tonsils (a major diagnostic feature). Treatment by immunoglobulin replacement therapy .


2-Adulthood Antibody Deficiency

Common Variable Immune Deficiency (CVID)

There is defect in B-cells maturation related to genetic susceptibility and T-cells regulatory function. It is characterized by low serum total immunoglobulin and low IgG levels and failure to make antibodies to exogenous pathogens; low or absent IgA and IgE, but normal or low IgM. The numbers of B- and T-cells are variable. The CVID is frequently accompanied by antibody-mediated autoimmune diseases

Selective IgA deficiency

This is the most common ID The IgA is absent or very low ,with compensatory high serum IgG level, and normal numbers of both B- and T-cells, present with recurrent mild respiratory and gastrointestinal infections. The patients are susceptible to allergic and autoimmune diseases and malignancy
Management: Antibiotics; NOT immunoglobulin

Management of primary antibody deficiency

1. Therapeutic and prophylactic antibiotics
2. The mainstay of treatment is immunoglobulin replacement therapy .
Investigations of primary antibody deficiency
1. Total serum immunoglobulin concentration
2. Measure specific antibody response against H. influenza, and Strep. Pneumonia; if low,
4. Protein and urine electrophoresis
5. Flow cytometry for quantitation of B- and T-cells numbers

Secondary antibody deficiency (SAD)

Secondary antibody deficiency is due to other diseases such as:
1. Multiple myeloma, chronic lymphocytic leukaemia
2. Splenectomy/hyposplenism which may prone the patient to an acute life- threatening septicaemia. This is due to
1-loss of splenic macrophages (clear circulation from m.o.) and
2-inadequate antibody response to polysaccharide antigens.
Primary T-lymphocyte deficiencies (PTLD)


These deficiencies are characterized by recurrent viral, protozoal and fungal infections. Many of these deficiencies are also associated with antibody deficiency due to the control of B-cells by T-cells.
Defects in T-cells function may result in:
1. Reactivation of latent viral infections
2. Mucocutaneous candidiasis and systemic fungal infection
3. Pneumocystis jirovicii (carinii) pneumonia.
4. Mycobacterium tuberculosis
5. Protozoa infections caused by Toxoplasma and Cryptosporidium

Tow type :

Bare lymphocyte syndrome
There is failure of expression of class I HLA in the thymus which affect CD8 development, and class II HLA which affect CD4 maturation. Failure of HLA class II expression results in systemic vasculitis due to uncontrolled NK cells activation.

DiGeorge’s syndrome

This syndrome results from failure of development of the 3rd/4th pouches , It is characterized by very low numbers of mature T-cells in spite of normal bone marrow

Management of PTLD

1. Anti-Pneumocystis and anti-fungal prophylaxis
2. Aggressive anti-microbial therapy
3. Immunoglobulin replacement
4. Stem cell transplantation for Bare lymphocyte syndrome
5. Thymic transplantation for DiGeorge syndrome


Investigations of PTLD
1. Flow cytometry for lymphocyte count
2. Functional tests for T-cell activation and proliferation
3. Test for HIV if T-cells are deficient
4. Serum immunoglobulin measurement

Complement pathway deficiencies (CPD)

Genetic deficiencies of almost all complement proteins. These patients are susceptible to capsulated microorganisms, high prevalence of autoimmune disases .
Management of CPD
1. Long life prophylactic penicillin
2. Vaccination against Strep. Meningitides or pneumonia, and H. influenza

Investigation of CPD

1. Measurement of serum C3 and C4 level
2.Classical haemolytic pathway 50 (CH50) is a screening test for determination of the function of the classical complement pathway
3. AP50 for the alternative complement pathway function.

Primary phagocyte deficiencies (PPD)

presented by recurrent bacterial and fungal infections of unusual sites .
3. Defects in cytokines and cytokine receptors
results in failure of intracellular killing. This leads in particular to susceptibility to infections by Mycobacterium.
Special tests are available for cytokines and their receptors by ELISA , and PCR


2. Chronic Granulomatous Disease (CGD)
There is a failure of oxidative killing of phagocyte cells leads to susceptibility to infections in the form of granuloma formation
The best test for this disorder is Nitro blue tetrazolium reduction test .

1. Leucocyte Adhesion deficiencies (LAD)

Defect in phagocyte cells migration . present with recurrent bacterial infections without pus formation and neutrophil infiltration. This is reflected on by a very high count of these cells in the peripheral blood. Specialized tests for adhesion molecules

Management of PPD

1. I.V. antibiotic for infections
2. Prophylactic cotrimoxazole, and anti-fungal agents
3. Surgical drainage of abscesses
4. Bone marrow transplantation is conducted during childhood.

Secondary phagocyte defects

1-Neutropenia due to bone marrow diseases
2-Abnormal phagocyte functions in certain conditions such as diabetes mellutis, chronic renal failure or alcoholic individuals.