This document summarizes various immunodeficiency disorders, including both primary and secondary immunodeficiencies. It describes the main types of primary immunodeficiencies which affect phagocytic cells (18%), complement (2%), B-cells (50%), T-cells (30%) and combined defects. Specific disorders are then discussed in more detail such as chronic granulomatous disease, Chediac-Higashi syndrome, X-linked agammaglobulinemia, selective IgA deficiency, DiGeorge's syndrome, ataxia telangiectasia. Secondary immunodeficiencies can result from neoplasms, infections, decreased complement components, immunosuppressive therapies, radiation, metabolic

1. IMMUNODEFICIENCY
DISORDERS
BY
PROF. S.B ZAILANI
Chief Consultant Clinical Microbiologist
Department of medical

2. PREAMBLE
• Primary immunodeficiency
disorders
• Secondary immunodeficiency
disorders

3. I0
ID DISORDERS
• PHARGOCYTIC DEFECTS(18%)
• COMPLEMENT DEFICIENCY(2%)
• B- CELL DEFECTS (50%)
• T- CELL DEFECTS (30%)
• COMBINED DEFECTS

4. PHAGOCYTIC DEFECTS
• Qualitative defects:
-Chronic granulomatous disease
(CGD)
-Chediac-Higashi syndrome
-Job’s syndrome
-Lazy leucocytes syndrome

5. Quantitative defects:
- Hereditary neutropenia
(agranuloocytopenia)
- Congenital asplenia

6. COMPLEMENT DEFECTS
• C1 inhibitor deficiency can lead
to hereditary angioneurotic
edema
• Early complement component
(C1, C2,or C4) defects
• Individuals with C3b deficiency
are prone to infections
• Late Component defects

7. B-CELL DEFECTS
• X-linked
hypogammaglobulinaemia
• Transient
hypogammaglobulinaemia
of infancy
• Selective IgA deficiency
• Immunodeficiency with
increased IgM

8. T-CELL DEFECTS
• Digeorge’s syndrome
• Nezelof’s syndrome
• Ataxia telangiectasia
• Wiskott-Alderich syndrome

9. B and T CELL DEFECT
• Severe combined
immunodeficiency syndrome
(SCID Syndrome) also called
Swiss type of
hypogammaglobulinaemia.

10. CGD
• INTRODUCTION
-Inherited as;
(70%=x-linked,30%=Autosomal
recessive)
-It is associated with qualitative
phagocytic defect
-There is failure of phagocytes to
produce peroxides and O3
-No respiratory burst due to lack of
the formation of NADPH oxidase
subunits in N,M &E

11. CLINICAL FEATURES
• Xterised by severe infection of
skin,ears,lungs,liver and bone with
catalase +ve pyogenic org. such
Staph, Aspergillus, Burkholderia
cepacia etc.
• Granuloma formation in many
organs
• There is increased IFN γ production
and macrophage activation *

12. IMMUNOLOGIC FEATURES
• Characteristic superoxide and
H2O2 are little or not formed
• Catalase –ve organisms are less
problamatic b/c they produce
H2O2 themselves leading to
autolysis
• DIAGNOSIS; Nitroblue
tetrazolium test

13. TREATMENT
• Appropriate antibiotic treatment
• Neutrophil infusion
• IFN γ may stimulate O3
production
• Allogeneic bone marrow
transplantation is now the
current treatment of choice

14. CHEDIAC-HIGASHI
SYNDROME
• INTRODUCTION
-Inherited as autosomal recessive
trait
-Xterised by repeated pyogenic
infection affecting children
-Defective chemotaxis and impaired
degranulation of phargocytic
particles
-Phagosome-lysosome fusion is
defective b/c of abnormally large
lysosomal granules

15. CLINICAL FEATURES
• Recurrent pyogenic infections
• Partial oculocutaneous albinism
• Nystagmus
• Progressive peripheral
neuropathy
• Mental retardation

16. DIAGNOSIS
• Giant primary granules in neutrophils
and other granules bearing
cells(wright stain)
• NK cell activity is decreased
• Lysosomal enzyme levels are
depressed
• Oxygen consumption,H2O2 formation
and HMP activity are normal
• TREATMENT: Appropriate antibiotics

17. B- CELL DEFECTS
• X-LINKED AGAMMAGLOBULINAEMIA
-Also known as Bruton’s agamma
globulinaemia
-Inherited as X-linked
-It was thought that there is complete
lack of B cell lineage.
-Defective pre B cell maturation is the
whole mark of the disorder
-Molecular level of defect is at Xq22

18. CLINICAL FEATURES
• Remain well during the first 6-
9months of live by virtue of
maternally transmitted IgG,
then repeated infections with
extracellular pyogenic
organisms such as Strep.
Haemophilus due to low level of
serum Igs of all classes.
• Chronic fungal & viral infections
are not found.*

19. IMMUNOLOGIC
FINDINGS/DIAGNOSIS
• Low serum levels of all Igs
• Lack of circulating B cells
• Lack of germinal/plasma cell in
lymph nodes
• Absent or hypoplastic
tonsils/payer’s patches
• Intact T cell functions

20. TREATMENT
• Life long replacement therapy
with pooled human γglobulin.
FFP may be used
• Avoidance of
infection( prophylaxis) and
administration of antibiotics are
essential

21. SELECTIVE IgA DEFICIANCY
• INTRODUCTION
-Is an isolated absence or near
absence (i.e. <10mg/dl) of serum &
sIgA.
-Mostly present with recurrent
sinopulmunary infections, GI disease
and allergy
-Is the most frequently recognized
selective hypogamma globulinaemia
1:700 sons
-The inheritance pattern is variable

22. CLINICAL FEATURES
• Some are asymptomatic
• Some have occasional resp/GI
infections
• Rarely patients have severe
infections leading to permanent
airway and intestinal damage

23. IMMUNOLOGICAL FINDINGS
• Serum levels of both IgAs are
low but levels of IgG & IgM are
normal or increased
• IgA bearing B-cells are present
and in normal number but
defective in their ability to
synthesize or release IgA

24. TREATMENT
• Patients should NOT be treated
with pooled γglobulin b/c
anaphylactic sensitivity may be
induced
• Aggressive antibiotic therapy to
control the infections must be
used

25. T CELL DEFECTS
Digeorge’s syndrome
• INTRODUCTION
-Congenital thymic hypoplasia or
aplasia
-Result from dysmorphogenesis of 3rd
4th
pharyngeal pouches during the
early embryogenesis leading to
hypoplasia or aplasia of thymus &
parathyroid glands

26. CONTD
-The basis for the anomaly is not
known, but an assoc.with
maternal alcoholism is evident
in some cases and autosomal
inheritance in apparent in
others

28. CLINICAL FEATURES
• Hypocalcaemic seizures during
neonatal period
• Right sided aortic arch
• Oesophageal atresia
• Atrial/ventricular septal defect
• Hypertelorism,mandibular
hypoplasia
• Low set ear

29. IMMUNOLOGIC FINDINGS
• Lymohopenia is usually found
• Delayed hypersensitivity
reaction
• Most patients have normal Ig
levels

30. TREATMENT
• Transplantation of a thymus
• Hypocalcaemia can controlled
by administration of calcium
and Vit. D
• In most patient the condition
improves with age

31. ATAXIA TELANGIECTASIA
• INTRODUCTION
-Abnormality in cerebellar/blood
vessels development
-Defective DNA repair
-The most striking neuropathologic
feature is loss of Purkinje, granule
and basket cells in the cerebellar
nuclei
-Thymic atrophy & T cell deficiency
-Progressive immunodeficiency

32. CLINICAL FEATURES
• Clinically, thus results in functional
antibody deficiency and bacterial
predisposition to acute/chronic
infection (sinopulm. Infection)
• T and B cell lymphomas are very
common and must demonstrate
specific chromosomal inversion or
translocation
• EBV infection is common

33. TREATMENT
• Antibiotic therapy
• Fetal thymus and bone marrow
transplantation may be helpful

34. SECONDARY
IMMUNODEFICIENCY(ID) STATES
• INTRODUCTION
1.NEOLPLASM INDUCED
IMMUNODEFICIENCY
2.INFECTION INDUCED
IMMUNODEFICIENCY
3.IMMUNODEFICIENCY SECONDARY TO
DECREASE COMPLEMENT
COMPONENT

35. CONTD
4. IMMUNODEFICIENCY
SECONDARY TO THERAPY
5. OTHERS

36. Neoplasm Induced I D
• Benign monoclonal
gammopathy
• Multiple myeloma
• Non Hodgkin’s lympoma
• CLL
• Hodgkin’s disease

37. Infection Induced ID
• Acute Infections;
measles, malaria, EBV, CMV
• Chronic Infection;
TB, HIV, Malaria
• Combined Infections;
malaria / EBV

38. ID Secondary to Decreased
Complement Component
• Nephrotic syndrome
• Burns
• Malnutrition

39. ID Secondary to Therapy
• Antibiotics (Luria’s law)
• Cytotoxic drugs
• Steroids
• Surgery

40. Miscellaneous
• Radiation
• Metabolic;
(DM,uraemia,cushing)
• GIT; Crohn’s disease
• Autoimmune Diseases; SLE, RA
• Stress

41. • Thank you for your attention.