immunodeficiency states
TRANSCRIPT
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IMMUNODEFICIENCY DISORDERS
BY
PROF. S.B ZAILANI Chief Consultant Clinical Microbiologist Department of medical microbiology University of Maiduguri
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PREAMBLE
• Primary immunodeficiency disorders
• Secondary immunodeficiency disorders
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I0 ID DISORDERS• PHARGOCYTIC DEFECTS(18%)• COMPLEMENT DEFICIENCY(2%)• B- CELL DEFECTS (50%)• T- CELL DEFECTS (30%)• COMBINED DEFECTS
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PHAGOCYTIC DEFECTS
• Qualitative defects:-Chronic granulomatous disease
(CGD)-Chediac-Higashi syndrome -Job’s syndrome-Lazy leucocytes syndrome
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Quantitative defects:- Hereditary neutropenia
(agranuloocytopenia)- Congenital asplenia
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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
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B-CELL DEFECTS
• X-linked hypogammaglobulinaemia• Transient
hypogammaglobulinaemia of infancy
• Selective IgA deficiency • Immunodeficiency with increased
IgM
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T-CELL DEFECTS
• Digeorge’s syndrome• Nezelof’s syndrome• Ataxia telangiectasia • Wiskott-Alderich syndrome
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B and T CELL DEFECT
• Severe combined immunodeficiency syndrome (SCID Syndrome) also called Swiss type of hypogammaglobulinaemia.
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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
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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 *
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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
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TREATMENT
• Appropriate antibiotic treatment• Neutrophil infusion• IFN may stimulate O3 production• Allogeneic bone marrow
transplantation is now the current treatment of choice
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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
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CLINICAL FEATURES
• Recurrent pyogenic infections• Partial oculocutaneous albinism • Nystagmus• Progressive peripheral neuropathy• Mental retardation
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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
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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
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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.*
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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
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TREATMENT
• Life long replacement therapy with pooled human globulin. FFP may be used
• Avoidance of infection( prophylaxis) and administration of antibiotics are essential
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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
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CLINICAL FEATURES
• Some are asymptomatic• Some have occasional resp/GI
infections• Rarely patients have severe
infections leading to permanent airway and intestinal damage
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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
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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
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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
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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
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CLINICAL FEATURES
• Hypocalcaemic seizures during neonatal period
• Right sided aortic arch • Oesophageal atresia• Atrial/ventricular septal defect • Hypertelorism,mandibular
hypoplasia• Low set ear
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IMMUNOLOGIC FINDINGS
• Lymohopenia is usually found• Delayed hypersensitivity reaction• Most patients have normal Ig
levels
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TREATMENT • Transplantation of a thymus• Hypocalcaemia can controlled by
administration of calcium and Vit. D
• In most patient the condition improves with age
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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
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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
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TREATMENT
• Antibiotic therapy• Fetal thymus and bone marrow
transplantation may be helpful
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SECONDARY IMMUNODEFICIENCY(ID) STATES• INTRODUCTION
1.NEOLPLASM INDUCED IMMUNODEFICIENCY
2.INFECTION INDUCED IMMUNODEFICIENCY
3.IMMUNODEFICIENCY SECONDARY TO DECREASE COMPLEMENT COMPONENT
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CONTD
4. IMMUNODEFICIENCY SECONDARY TO THERAPY
5. OTHERS
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Neoplasm Induced I D• Benign monoclonal gammopathy• Multiple myeloma• Non Hodgkin’s lympoma• CLL• Hodgkin’s disease
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Infection Induced ID• Acute Infections; measles,
malaria, EBV, CMV• Chronic Infection;
TB, HIV, Malaria• Combined Infections;
malaria / EBV
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ID Secondary to Decreased Complement Component• Nephrotic syndrome• Burns• Malnutrition
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ID Secondary to Therapy • Antibiotics (Luria’s law)• Cytotoxic drugs• Steroids• Surgery
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Miscellaneous • Radiation• Metabolic; (DM,uraemia,cushing) • GIT; Crohn’s disease• Autoimmune Diseases; SLE, RA• Stress
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• Thank you for your attention.