This document discusses primary immune deficiency diseases. It covers the general features, etiology, and types of congenital immune deficiencies including defects of B lymphocytes like X-linked agammaglobulinemia and common variable immunodeficiency. It also discusses defects of T lymphocytes including severe combined immunodeficiency. Other conditions mentioned include DiGeorge syndrome, Wiskott-Aldrich syndrome, and complement deficiencies. Multiple choice questions are provided to test understanding of these conditions.

1. PRIMARY IMMUNE DEFICIENCY
DISEASES
Dr IRA BHARADWAJ
MCI TEACHER ID: PAT 2300569
KUHS FACULTY ID: M21512

2. TEXT BOOK REFRENCES
• ROBBINS BASIC PATHOLOGY
• HARSH MOHAN TEXTBOOK OF PATHOLOGY
• DAVIDSON’S PRINCIPLES AND PRACTISE OF MEDICINE
• OTHER STANDARD REFRENCES

3. SLO
• GENERAL FEATURES OF IMMUNE DEFICIENCY DISEASES
• ETIOLOGY OF IMMUNE DEFICIENCY DISEASES
• CONGENITAL IMMUNE DEFICIENCY – GENERAL FEATURES
• CONGENITAL IMMUNE DEFICIENCY – ETIOLOGY
• DEFECTS OF B LYMPHOCYTES
• DEFECTS OF T LYMPHOCYTES
• OTHER DEFECTS
• MCQs

4. IMMUNE DEFICIENCY DISEASES
GENERAL FEATURES
LEADS TO INCREASED SUSCEPTIBILITY TO INFECTIONS &
CERTAIN FORMS OF MALIGNANCY
• DEFECT IN B CELLS, COMPLEMENT, PHAGOCYTOSIS ---
PYOGENIC BACTERIAL INF
• DEFECT IN T CELLS --- VIRAL, FUNGAL,INTRACELLULAR
BACTERIAL INF, INCREASED INCIDENCE OF TUMORS

5. IMMUNE DEFICIENCY DISEASES
ETIOLOGY
•CONGENITAL (PRIMARY) IMMUNODEFICIENCY,
uncommon
•SECONDARY/ACQUIRED IMMUNE DEFICIENCY,
commoner, especially HIV associated

6. CONGENITAL IMMUNODEFICIENCY
GENERAL FEATURES
•Caused by mutation in genes involved in lymphocyte
maturation or function – B L, T L, BL+TL or innate
immunity
•Clinically present as increased susceptibility to
infection in early life (6mths – 2yrs), after maternal
Abs are depleted

7. CONGENITAL IMMUNODEFICIENCY
GENERAL FEATURES
•OFFER IMPORTANT INSIGHT IN FUNTIONING OF
IMMUNE SYSTEM
•GENE REPLACEMENT THERAPY MAY BE CURATIVE
•PRONE TO AUTOIMMUNE DISEASE ALSO

8. CONGENITAL IMMUNODEFICIENCY
ETIOLOGY
DEFECTS OF B LYMPHOCYTES
• Burton disease
• Isolated IgA deficiency
• Hyper IgM syndrome
• Common variable immunodeficiency
DEFECTS OF T LYMPHOCYTES
• Severe combined immunodeficiency – autosomal & X linked
• Thymic hypoplasia

9. CONGENITAL IMMUNODEFICIENCY
ETIOLOGY

10. PRIMARY IMMUNODEFICIENCY
DEFECTS OF B LYMPHOCYTES

11. PRIMARY IMMUNODEFICIENCY
DEFECTS OF B LYMPHOCYTES
X-LINKED AGAMMAGLOBULINEMIA-BURTON DISEASE –
• Defective maturation of pre B cell, due to decreased tyrosine
kinase activity
• Leading to absence of plasma cells & antibodies
(Immunoglobulin)
• Affects males ( X linked )
• Intravenous Immunoglobulin therapy may be helpful

12. PRIMARY IMMUNODEFICIENCY
DEFECTS OF B LYMPHOCYTES
ISOLATED IgA DEFICIENCY
• It is the commonest primary immune deficiency disease seen
in clinical practice
• Due to defective maturation of immature B cells into IgA
secreting mature B cells resulting in decreased mucosal
defense

13. PRIMARY IMMUNODEFICIENCY
DEFECTS OF B LYMPHOCYTES
HYPER IgM SYNDROME –
• Due to defective maturation of immature B cells into mature
B cells secreting IgG, IgA, IgE antibodies & increased
maturation into mature IgM secreting B cells
• 70% cases are X linked,
• Some cases are associated with defect of T cells also

14. PRIMARY IMMUNODEFICIENCY
DEFECTS OF B LYMPHOCYTES
COMMON VARIABLE IMMUNODEFICIENCY-
• Due to variable defect of maturation of B cells into plasma cells,
leading to defects in Antibody production
• Usually seen in adults
• Cause is unknown, so far
• It is a diagnosis of exclusion

15. PRIMARY IMMUNODEFICIENCY
DEFECTS OF T LYMPHOCYTES

16. PRIMARY IMMUNODEFICIENCY
DEFECTS OF T LYMPHOCYTES
AUTOSOMAL [AR] SCID (Severe Combined Immune
Deficiency)
• Due to defective maturation of common precursor lymphoid
cell, leading to failure of T cell and secondary failure of B
cells
• 50% cases have ADA (adenosine deaminase) mutation
leading to accumulation of toxic metabolites which affects
lymphocyte maturation & proliferation
• Lymphoid organs are hypoplastic & lymphopenia is present
• Rx – bone marrow transplant & gene therapy

17. PRIMARY IMMUNODEFICIENCY
DEFECTS OF T LYMPHOCYTES
X – LINKED SEVERE COMBINED IMMUNODEFICIENCY
• Due to defective maturation of pro T cell caused by mutation in
gamma chain of cytokine receptor
• Leading to failure of T cell and secondary failure of B cells
• Affects males ( X linked)
• Rx gene therapy may be helpful

18. PRIMARY IMMUNODEFICIENCY
DEFECTS OF T LYMPHOCYTES
Di GEORGE SYNDROME (velocardiofacial syndrome) –
THYMIC HYPOPLASIA – AD
• D 22q11 leads to defective maturation of immature T cells,
associated with defective thymic development & T cell
function,
• It is also associated parathyroid hyoplasia & hypo function,
cardiac, facial & other congenital defects
• Thymic transplant may improve immune status of the baby

19. PRIMARY IMMUNODEFICIENCY
OTHER CAUSES
WISKOTT-ALDRICH SYNDROME, characterized by:
• Immune deficiency
• Thrombocytopenia
• Eczema
• X linked, recessive disorder caused by defective cytoskeleton
• IgG & IgA are normal, IgM is decreased and IgE is raised
• Rx bone marrow transplant

20. PRIMARY IMMUNODEFICIENCY
OTHER CAUSES
• COMPLEMENT DEFICIENCY
• DEFECTIVE LEUKOCYTE FUNCTION
• MANY MORE

21. MCQ
The commonest primary immunodeficiency is
• AIDS
• Isolated IgA deficiency
• Wiskott-Aldrich syndrome
• Common variable immunodeficiency

22. MCQ
Thymic hypoplasia is seen in
• Burton disease
• DiGeorge syndrome
• Wiskott – Aldrich syndrome
• AIDS

23. MCQ
Primary decreased T cell immunity is a feature of
• Burton disease
• DiGeorge syndrome
• Wiskott – Aldrich syndrome
• AIDS

24. MCQ
Wiskot – Aldrich syndrome is associated with all except
• IgE is increased
• IgG is normal
• Platelets are normal
• IgM is decreased

25. MCQ
Severe combined immune deficiency is associated with all
except
• Adenosine deaminase deficiency
• Autosomal dominant
• Defective T cell maturation
• Lymphoid hypoplasia