This document provides an overview of immunodeficiency diseases. It describes how immunodeficiencies can be primary, due to abnormalities in immune system development, or secondary, resulting from other diseases or conditions. The major types of primary immunodeficiencies are then classified and examples in each category are outlined, including humoral deficiencies affecting B cells, cellular deficiencies affecting T cells, combined deficiencies, and disorders of complement and phagocytosis. Clinical features, diagnostic tests, and treatment approaches are summarized for several specific immunodeficiency syndromes.
2. INTRODUCTION
Defence mechanism of the body impaired
Repeated microbial infections
Enhanced susceptibility to malignancy
Specific – Humoral, Cell mediated
Non specific – Phagocytosis and Complement
4. CLASSIFICATION OF PRIMARY
IMMUNODEFICIENCY SYNDROMES
Humoral Immunodeficiencies
Cellular Immunodeficiencies
Combined Immunodeficiencies
Disorders of Complement
Disorders of Phagocytosis
5. HUMORAL IMMUNODEFICIENCIES (B
CELL DEFECTS)
X linked agammaglobulinemia
Transient hypogammaglobulinemia of infancy
Common variable immunodeficiency
Selective Immunoglobulin deficiency
Immunodeficiencies with hyper – IgM
Transcobalamin II Deficiecy
6. X LINKED AGAMMAGLOBULINEMIA
Bruton’s disease
Disease not apparent till 6 months of age
Recurrent bacterial infection with Pneumococci, Streptococci,
Meningococci, Pseudomonas and H. influenza
Patient respond normally to viral infections
All classes of immunoglobulins are grossly depleted
Tonsils and Adenoids are atrophic
Depletion of cells in bursa depenent areas of Lymph nodes.
7. Marked decrease of B cells in circulation
Antibody formation does not occur even after injection of antigen
CMI is not affected
Allograft rejection is normal
Arthritis, haemolytic anemia and atopic manifestations
300 mg/Kg of Gamma globulin in 3 doses followed by monthly injections
of 100 mg/kg
Whole Plasma infusion
8. TRANSIENT HYPOGAMMAGLOBULINEMIA OF
INFANCY
Abnormal delay in Immunoglobulin G synthesis
Maternal Ig G are catabolised by the second month.
Recurrent Otitis media and Respiratory infections
Spontaneous recovery occur between 18 and 30 months of age.
Prophylaxis with Gamma globulin is not recommended
9. COMMON VARIABLE IMMUNODEFICIENCY
Late onset Hypogammaglobulinemia
15 – 35 years of age
Recurrent pyogenic infection and increased incidence of autoimmune
disease.
Malabsorption and Giardiasis
The total immunoglobulin level is low
Defective B cell in circulation
Increased suppressor T cell and diminished helper T cell activity
10. SELECTIVE IMMUNOGLOBULIN
DEFICIENCIES
Reported in 1% of all patients with recurrent infection
Isolated Ig A deficiency reported in 0.2% of normal population
Increased susceptibility to respiratory infections
Steatorrhea
Atopic disorders
Anti IgA antibodies present
Preventive antibiotics
Selective Ig M deficiency associated with Septicemia
11. IMMUNODEFICIENCIES WITH HYPER
IgM
X linked
Autosomal recessive
Low Ig A and Ig G levels are seen with elevated Ig M
Infections
Thrombocytopenia, Neutropenia, Hemolytic anemia and renal lesions
Congenital Rubella
Intravenous Immunoglobulin therapy
14. THYMIC HYPOPLASIA (DIGEORGE
SYNDROME)
Developmental defect
Aplasia or Hypoplasia of the thymus and Parathyroid gland
Not hereditary
Intrauterine infection
Fallot’s tetrology
Neonatal tetany
viral, fungal and bacterial infection
15. DIGEORGE SYNDROME
The thymus dependent areas of the lymph node and spleen are depleted
of lymphocytes
Circulating T cells are reduced in number
Delayed hypersensitivity and graft rejection are depressed
Transplantion of fetal thymus tissue
16. CHRONIC MUCOCUTANEOUS
CANDIDIASIS
Abnormal immunological response to Candida albicans
Severe Chronic Candidiasis of mucosa, skin and nails
Endocrinopathies
CMI to candida is deficient
Transfer factor + Amphotericin B
18. COMBINED IMMUNODEFICIENCIES
Nezelof syndrome
Ataxia Telengiectasia
Wiskott Aldrich Syndrome
Immunodeficiency with Thymoma
Episodic lymphopenia with lymphocytotoxin
Severe combined immunodeficiencies
19. COMBINED IMMUNDEFICIENCIES
Nezelof Syndrome
Ataxia telangiectasia
Wiskott Aldrich Syndrome
Immunodeficiency with thymoma
Immunodeficiency with short limbed dwarfism
Episodic lymphopenia with Lymphocytotoxin
Severe combined immunodeficies
20. NEZELOF SYNDROME
Cellular immunodeficiency with abnormal immunoglobulin synthesis
Recurrent infections
Abundant plasma cells are seen in the spleen, lymph nodes and intestines
Thymic dysplasia with lymphoid depletion
Antigenic stimuli do not induce antibody formation
Histocompatible bone marrow transplant, transfer factor & Thymus
transplantation
Antimicrobial therapy
21. ATAXIA TELANGIECTASIA
Autosomal recessive
Cerebellar ataxia
Chorioatethoid movements
Telengiectasia
Ovarian dysgenesis
Sinopulmonary infection & malignancy
Absence of IgA & low IgE
Transfer factor therapy and fetal thymus transplants
22.
23. WISKOTT ALDRICH SYNDROME
X linked disease
Eczema, thrombocytopenic purpura, recurrent infections
Death due to infection, hemorrhage, lymphoreticular malignancy
Cellular depletion of thymus and paracortical areas of lymph nodes
Low IgM levels
Specific inability to respond to polysaccharide antigen
26. EPISODIC LYMPHOPENIA WITH
LYMPHOCYTOTOXIN
Episodic but profound depression of T cell function
Complement dependent Lymphocytotoxin
Anti lymphocyte antibody
No immunological memory
familial
27. SEVERE COMBINED IMMUNODEFICIENCIES
Autosomal recessive
Primary defects are at the level of early precursors of immunocompetent
cells in the fetal liver and bone marrow
Swiss type agammaglobulinemia
Reticular dysgenesis of de Vaal
Adenosine deaminase deficiency
28. RETICULAR DYSGENESIS OF DE VAAL
Multipotent hemopoietic stem cell
Total failure of myelopoiesis
Lymphopenia, neutropenia, thrombocytopenia, anemia and bone marrow
aplasia
Invariably fatal in the first week of life
31. Chronic Granulomatous Disease
Familial disease
Recurrent infection with low grade pathogen (catalase +)
Suppurative granulomatous lesions in skin and lymph nodes
Hepatospleenomegaly
Progressive infiltration in lungs
Granulomatous Septic Osteomyelitis
32. Chronic Granulomatous Disease
NADPH Oxidase
Engulfment of bacteria is not followed by activation of oxygen dependent
killing mechanisms
Nitroblue tetrazolium test
33. CHEDIAK HIGASHI SYNDROME
Genetic disorder
Decreased pigmentation of the skin, eyes and hair
Photophobia
Nystagmus
Giant peroxidase positive inclusions in the cytoplasm of leukocytes due to
autophagocytic activity
Diminished phagocytic activity
Frequent and severe pyogenic infections
35. JOB’S SYNDROME
Multiple large Staphylococcal abscesses occurring repeatedly on the skin
and in various organs with little inflammatory response
Atopic Eczema, Chronic Nasal discharge and Otitis media
Elevated IgE
36. TUFTSIN DEFICIENCY
Leukokinin capable of stimulating phagocytosis
Tetrapeptide
Local and systemic bacterial infections
37. LAZY LEUKOCYTE SYNDROME
Defect in chemotaxis and neutrophil mobility
Normal number of Neutrophils in Bone Marrow
Peripheral neutropenia
Poor leukocyte response to chemical and inflammatory stimulation
Bacterial infection
Recurrent stomatitis, Gingivitis and Otitis
38. HYPER IgE SYNDROME
Early onset Eczema
Recurrent bacterial infections such as abscess, Pneumonia and secondary
infections of Eczema
Staphylococcus aureus
Streptococcus pyogenes
IgE levels are more than 10 times the normal level
43. CLINICAL CASE
A nine month old infant was brought to the hospital with symptoms of
fever and difficulty in breathing. The mother reported of two similar
episodes in the previous two months. At the age of 12 months, the child
was again brought in with an episode of measles, from which he recovered
after treatment. At 18 months of age, it was observed that the boy’s height
and weight were not appropriate to his age. The child was the fourth of
unrelated parents. His 3 sisters enjoyed good health and the parents did
not report of them suffering from any repeated infections, unlike the boy.
44. Tests on the boy showed the serum immunoglobulin G to be less than a
tenth and IgA and IgM to be less than a hundredth of the normal level.
Lymph node biopsy revealed depletion of cells of bursa dependent areas.
Diagnosis?
Treatment?
