Immunodeficiency states

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IMMUNODEFICIENCY DISORDERS BY PROF. S.B ZAILANI Chief Consultant Clinical Microbiologist
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Transcript of Immunodeficiency states

  • IMMUNODEFICIENCY DISORDERS

    BY

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

  • PREAMBLEPrimary immunodeficiency disorders

    Secondary immunodeficiency disorders

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

  • PHAGOCYTIC DEFECTSQualitative defects:

    -Chronic granulomatous disease (CGD)-Chediac-Higashi syndrome -Jobs syndrome-Lazy leucocytes syndrome

  • Quantitative defects:- Hereditary neutropenia (agranuloocytopenia)- Congenital asplenia

  • COMPLEMENT DEFECTSC1 inhibitor deficiency can lead to hereditary angioneurotic edemaEarly complement component (C1, C2,or C4) defectsIndividuals with C3b deficiency are prone to infectionsLate Component defects

  • B-CELL DEFECTSX-linked hypogammaglobulinaemiaTransient hypogammaglobulinaemia of infancySelective IgA deficiency Immunodeficiency with increased IgM

  • T-CELL DEFECTSDigeorges syndromeNezelofs syndromeAtaxia telangiectasia Wiskott-Alderich syndrome

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

  • CGDINTRODUCTION

    -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 FEATURESXterised 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 organsThere is increased IFN production and macrophage activation *

  • IMMUNOLOGIC FEATURESCharacteristic superoxide and H2O2 are little or not formedCatalase ve organisms are less problamatic b/c they produce H2O2 themselves leading to autolysis

    DIAGNOSIS; Nitroblue tetrazolium test

  • TREATMENTAppropriate antibiotic treatmentNeutrophil infusionIFN may stimulate O3 productionAllogeneic bone marrow transplantation is now the current treatment of choice

  • CHEDIAC-HIGASHI SYNDROMEINTRODUCTION

    -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 FEATURESRecurrent pyogenic infectionsPartial oculocutaneous albinism NystagmusProgressive peripheral neuropathyMental retardation

  • DIAGNOSISGiant primary granules in neutrophils and other granules bearing cells(wright stain)NK cell activity is decreasedLysosomal enzyme levels are depressed Oxygen consumption,H2O2 formation and HMP activity are normal

    TREATMENT: Appropriate antibiotics

  • B- CELL DEFECTSX-LINKED AGAMMAGLOBULINAEMIA

    -Also known as Brutons 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 FEATURESRemain 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/DIAGNOSISLow serum levels of all IgsLack of circulating B cellsLack of germinal/plasma cell in lymph nodesAbsent or hypoplastic tonsils/payers patchesIntact T cell functions

  • TREATMENTLife long replacement therapy with pooled human globulin. FFP may be usedAvoidance of infection( prophylaxis) and administration of antibiotics are essential

  • SELECTIVE IgA DEFICIANCYINTRODUCTION

    -Is an isolated absence or near absence (i.e.

  • CLINICAL FEATURESSome are asymptomaticSome have occasional resp/GI infectionsRarely patients have severe infections leading to permanent airway and intestinal damage

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

  • TREATMENTPatients should NOT be treated with pooled globulin b/c anaphylactic sensitivity may be inducedAggressive antibiotic therapy to control the infections must be used

  • T CELL DEFECTSDigeorges 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 FEATURESHypocalcaemic seizures during neonatal periodRight sided aortic arch Oesophageal atresiaAtrial/ventricular septal defect Hypertelorism,mandibular hypoplasiaLow set ear

  • IMMUNOLOGIC FINDINGSLymohopenia is usually foundDelayed hypersensitivity reactionMost patients have normal Ig levels

  • TREATMENT Transplantation of a thymusHypocalcaemia can controlled by administration of calcium and Vit. DIn most patient the condition improves with age

  • ATAXIA TELANGIECTASIAINTRODUCTION

    -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 FEATURESClinically, 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 translocationEBV infection is common

  • TREATMENTAntibiotic therapyFetal thymus and bone marrow transplantation may be helpful

  • SECONDARY IMMUNODEFICIENCY(ID) STATESINTRODUCTION

    1.NEOLPLASM INDUCED IMMUNODEFICIENCY

    2.INFECTION INDUCED IMMUNODEFICIENCY

    3.IMMUNODEFICIENCY SECONDARY TO DECREASE COMPLEMENT COMPONENT

  • CONTD4. IMMUNODEFICIENCY SECONDARY TO THERAPY

    5. OTHERS

  • Neoplasm Induced I DBenign monoclonal gammopathyMultiple myelomaNon Hodgkins lympomaCLLHodgkins disease

  • Infection Induced IDAcute Infections; measles, malaria, EBV, CMVChronic Infection; TB, HIV, MalariaCombined Infections; malaria / EBV

  • ID Secondary to Decreased Complement ComponentNephrotic syndromeBurnsMalnutrition

  • ID Secondary to Therapy Antibiotics (Lurias law)Cytotoxic drugsSteroidsSurgery

  • Miscellaneous Radiation Metabolic; (DM,uraemia,cushing) GIT; Crohns diseaseAutoimmune Diseases; SLE, RAStress

  • Thank you for your attention.