Chapter 28: Immune Deficiency, Immune Deficiency disorders

IMMUNE DEFICIENCY

Definition:

1. Immune Deficiency is a failure in the immune system to perform the normal function.
2. OR Clinically relevant illness resulting from a defect or deficiency in one or more immune system components, which may be congenital (primary) or acquired (secondary).
3. Immune deficiency disorders may be caused by a defect in the quality or quantity of lymphocytes, which may be congenital or acquired.
4. This may be combined disorders of B and T lymphocytes or either T lymphocytes or B lymphocytes.
5. Immune deficiency disorders reflect an impairment in the mechanism of immunity  like:
   1. 1. The defensive  part of the body like:
         1. Skin.
         2. Respiratory mucosa and its lining.
         3. GIT mucosa and lining.
      2. Defective phagocytosis and inflammatory response, including complement and other biological components.
      3. Cell-mediated delayed hypersensitivity reaction.
      4. The major congenital or inherited causes are rare.
6. B-lymphocytes defect (deficiency):
   1. B-L defect appears after 6 months of the age, that period is covered by the maternal antibodies.
   2. Defective B-L function is characterized by a recurrent bacterial infection like the sinopulmonary area:
      1. Staphylococcal.
      2. Streptococci.
      3. Hemophilus.
   3. Intestinal infestation with G lamblia.
   4. Opportunistic infections are common by fungi and viruses.
7. T-lymphocytes  defect (deficiency):
   1. T-L deficiency patients are susceptible to viral, fungal, and protozoal infections.
   2. These diseases present at an early age often in the neonatal period.
   3. These cases are often associated with B-L deficiency to a certain level.
8. Severe combined immunodeficiency (SCID):
   1. This is a syndrome characterized by decreased or absent T-L function, low or undetectable immunoglobulins level, and thymic dysplasia.
   2. This will lead to life-threatening immunodeficiency that is only treated by bone marrow transplantation.
   3. This disease is due to genetic abnormalities like:
      1. 50% of the cases are X-linked recessive and due to defects in the IL-2.
      2. Rest 40% of the cases are autosomal recessive and are due to an enzyme deficiency of adenosine deaminase.
      3. The third is JAK3 deficiency, purine nucleoside phosphorylase, CD3 deficiency, and RAG1/RAG2 deficiency.

B-L and T-L disorders:

The immunodeficiency may be:

1. Primary: Due to a defect in congenital or genetic abnormality.
2. Secondary: More common and is due to other conditions or therapy like steroids or immunosuppressive therapy.

Deficiency diseases of B and T lymphocytes (Primary/secondary immune deficiency diseases):

Primary immune deficiency diseases are:

B-lymphocytes related diseases:

1. Selective IgA deficiency diseases associated with:
   1. Allergy.
   2. Autoimmune diseases.
   3. Gastrointestinal diseases.
   4. Central nervous system diseases.
   5. Pulmonary infections.
   6. Malignancy.
2. Selective IgM deficiency.
3. IgG subclasses deficiency.
4. X-linked infantile aggamaglobulinmeia.
5. X-linked immunodeficiency with hyper-IgM
6. Common variable hypogammaglobulinemia

T-lymphocytes related diseases:

1. Thymoma.
2. DiGeorge’s syndrome.
3. Ataxia telengiactasia.
4. Wiskott-Aldrich syndrome.
5. Chronic mucocutaneous candidiasis.
6. Leukocytes adhesion deficiency.
7. Combined immune deficiency:
   1. Swiss-type.
   2. Thymic alymphophasia.
   3. Adenosine deaminase deficiency.
   4. Nezelof syndrome.

Complement deficiencies related diseases:

These are mostly congenital in origin. These patients are more susceptible to recurrent infections.

Secondary causes of immune deficiency diseases:

1. Hematological and lymphoproliferative diseases:
   1. Leukemias.
   2. Hodgkin’s lymphoma.
   3. Multiple myeloma.
   4. Sickle cell disease.
   5. Aplastic anemia.
   6. Agranulocytosis.
2. Viral infections:
   1. Acquired immune deficiency syndrome (AIDS).
3. Immunosuppressive drugs:
   1. Corticosteroids.
   2. Radiation.
   3. Antimetabolites
4. Metabolic and other systemic diseases:
   1. Diabetes mellitus.
   2. Malnutrition.
   3. Aging.
   4. Nephrotic syndrome.
   5. Renal failure (uremia).
   6. Protein-losing enteropathy.
   7. Liver diseases.
5. Surgical procedure:
   1. Splenectomy.
6. Surgical procedure:
   1. In case of burns.

Classification of immune deficiency:

It is preferable to classify the immune deficiency state according to the immune system’s component rather than classify it as primary or secondary. 

Table XXVI – Immune Deficiency Disease
Diseases caused by the immune deficiency of B and T lymphocytes:

Deficiency of B and T lymphocytes

Distribution of the immune deficiency diseases:

1. The most common immune deficiency diseases are due to B-lymphocytes disorders is 50%.
2. This is followed by severe immune combined deficiency  (SCID) is 23%.
   1. This disorder develops in infants resulting from a lake of both B and T lymphocytes. As a result, there is no formation of immunoglobulins (antibodies).
3. Disorders of the phagocytic cells are 14%.
4. While T-lymphocytes deficiency is hardly 7%.
   

   Immune deficiency diseases distribution

Clinical Features of immunodeficiency diseases:

1. Immune deficiency may arise at any age, but infections associated with them have several typical features:-
2. There is often chronic or recurrent infection.
3. These may resolve only partially with conventional therapy.
4. Infections are usually severe.
5. The organisms involved may be unusual.
6. The chances for opportunistic malignancies are more.

Causes of recurrent infections in immunodeficiency:

Table-XVIII – Infection suggesting immune deficiency (Recurrent infection)

Infective microorganisms in various immune deficiency disorders:

Table XXVII – Pattern of infectious organisms encountered in immune deficiency
Diagnostic Approach

1. Take detail H/O patient, including family history.
2. Look for the lymphocytes and other parameters in:
   1. Peripheral blood.
   2. Bone marrow.
   3. Lymph nodes.
   4. Spleen.
   5. Thymus.
   6. Tonsils.

3. Enumerate B-cells, T-cells, and macrophages.
4. Look for products by the immune response like:
   3. Ig level.
   4. Complement assay.

5. Look for immune responsiveness like:-
   5. Mitogenic response.
   6. Specific Ab-response.
   7. Rate of H₂O₂ productions.
   8. Cytochrome b. content.
      

Functions of B and T – lymphocytes and their functional tests:

Table XXVIII – Useful Screening Tests for the Assessment of Immune Function in Diagnosing Immune-Deficiency