IMMUNODEFICIENCY DISORDERS

BY

PROF. S.B ZAILANI Chief Consultant Clinical Microbiologist Department of medical microbiology University of Maiduguri

PREAMBLE

• Primary immunodeficiency disorders

• Secondary immunodeficiency disorders

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

PHAGOCYTIC DEFECTS

• Qualitative defects:-Chronic granulomatous disease

(CGD)-Chediac-Higashi syndrome -Job’s syndrome-Lazy leucocytes syndrome

Quantitative defects:- Hereditary neutropenia

(agranuloocytopenia)- Congenital asplenia

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

B-CELL DEFECTS

• X-linked hypogammaglobulinaemia• Transient

hypogammaglobulinaemia of infancy

• Selective IgA deficiency • Immunodeficiency with increased

IgM

T-CELL DEFECTS

• Digeorge’s syndrome• Nezelof’s syndrome• Ataxia telangiectasia • Wiskott-Alderich syndrome

B and T CELL DEFECT

• Severe combined immunodeficiency syndrome (SCID Syndrome) also called Swiss type of hypogammaglobulinaemia.

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

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 production

and macrophage activation *

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

TREATMENT

• Appropriate antibiotic treatment• Neutrophil infusion• IFN may stimulate O3 production• Allogeneic bone marrow

transplantation is now the current treatment of choice

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

CLINICAL FEATURES

• Recurrent pyogenic infections• Partial oculocutaneous albinism • Nystagmus• Progressive peripheral neuropathy• Mental retardation

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

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

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.*

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

TREATMENT

• Life long replacement therapy with pooled human globulin. FFP may be used

• Avoidance of infection( prophylaxis) and administration of antibiotics are essential

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

CLINICAL FEATURES

• Some are asymptomatic• Some have occasional resp/GI

infections• Rarely patients have severe

infections leading to permanent airway and intestinal damage

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

TREATMENT

• Patients should NOT be treated with pooled globulin b/c anaphylactic sensitivity may be induced

• Aggressive antibiotic therapy to control the infections must be used

T CELL DEFECTSDigeorge’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

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

CLINICAL FEATURES

• Hypocalcaemic seizures during neonatal period

• Right sided aortic arch • Oesophageal atresia• Atrial/ventricular septal defect • Hypertelorism,mandibular

hypoplasia• Low set ear

IMMUNOLOGIC FINDINGS

• Lymohopenia is usually found• Delayed hypersensitivity reaction• Most patients have normal Ig

levels

TREATMENT • Transplantation of a thymus• Hypocalcaemia can controlled by

administration of calcium and Vit. D

• In most patient the condition improves with age

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

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

TREATMENT

• Antibiotic therapy• Fetal thymus and bone marrow

transplantation may be helpful

SECONDARY IMMUNODEFICIENCY(ID) STATES• INTRODUCTION

1.NEOLPLASM INDUCED IMMUNODEFICIENCY

2.INFECTION INDUCED IMMUNODEFICIENCY

3.IMMUNODEFICIENCY SECONDARY TO DECREASE COMPLEMENT COMPONENT

CONTD

4. IMMUNODEFICIENCY SECONDARY TO THERAPY

5. OTHERS

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

Infection Induced ID• Acute Infections; measles,

malaria, EBV, CMV• Chronic Infection;

TB, HIV, Malaria• Combined Infections;

malaria / EBV

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

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

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

• Thank you for your attention.