IMMUNODEFICIENCY DISORDERS

IMMUNODEFICIENCY DISORDERS Introduction • Many infections • Many types of immunity – B cell, T cell, Phagocytic, Complement Nature of immune response vary • Normal • Overactive – autoimmunity, hypersensitivity • Underactive- IMMUNODEFICIENCY Clues of immunodeficiency • • • • • Recurrent infections Chronic infection Unusual infectious agents Poor response to antimicrobial therapy Chronic diarrhea, failure to thrive, hepatosplenomegaly, autoimmune diseases / autoantibodies, certain malignancies Types and Causes of Immunodeficiency 1. Primary ID • B cell deficiency Secondary complement D • • • T cell deficiency Phagocytic deficiency Complement deficiency Combined T and B cell deficiency Causes of Primary ID • • • • • Genetic disorder Metabolic disorders Vitamin deficiency Arrest in embryogenesis Autoimmune diseases Types of ID 2. Acquired / Secondary ID – Causes • Viral infection • Chronic infection • Immunosupressive therapy • Cancer/Tumors • Chronic renal diseases • Splenectomy • Ageing • Trauma • Malnutrition Primary ID – Phagocytic disorders 1. Quantitative disorders a. Neutropenia - Reduced production -Increased destruction b. Asplenia Phagocytic disorderds 2. Qualitative - Chronic granulomatous diseases -G6PD deficiency -Myeloperoxidase deficiency -Chediak Higashi disease -Job’s syndrome -Tuftsin deficiency - Adhesion deficiency Complement deficiency • C1esterase inhibitor deficiency – hereditary angioedema • C3 deficiency – impaired opsonisation – infections by capsulated bacteria • C5 deficiency-impaired chemotaxis • MAC deficiency – recurrent and severe Niesseria infection • C1,2,4 deficiency- reduced clearance of immune complexes B cell immunodeficiency Lack of stem cells – SCID B cell maturation deficiency – - X linked agamma globulinemia( Bruton’s disease) - Common variable ID – Affects various antibodies 3. Class switching deficiency -Hyper Ig M syndrome 4. Transient hypogammaglobulinemia of infancy- due to reduced CD4 cell help 5. Secretory component deficiency –sIg A deficiency 1. 2. T cell Deficiency 1. Congenital athymia – DiGeorge syndrome 2. Chronic mucocutaneous candidiasis – reduced macrophage MIF 3. Bare lymphocyte syndrome – defective expression of MHC II Features : recurrent viral, bacterial, fungal, mycobacterial & protozoal infections Combined immunodeficiency 1. SCID: X linked /autosomal recessive - lymphopenia and thymic hypoplasia - enzyme defects 2. Nazelof’s Syndrome 3. Wiskott Aldrich Syndrome 4. Ataxia telangiectasia WAS • DiGeorge syndrome Secondary ID More common Common Causes • • • • • • • • • Viral infection – HIV, measles Chronic infection Immunosupressive therapy Cancer/Tumors Chronic renal diseases Splenectomy Ageing Trauma Malnutrition Diagnosis of ID • Careful history – genetic factors • Evaluation of HMI -check antibody level - ELISA -assay for specific antibody (before & after antigenic challenge) Quantitation of Ig – Radial immnodeffusion -B cell estimation with monoclonal antibodies -B cell differentiation in vitro - LN biopsy Diagnosis of ID… contd • Evaluation of CMI – – – – – – – – – D H skin tests …….. Total L count Total T cell count Differential T cells- T cell subpopulation T cell proliferation assaysMigration Inhibition testing Mixed lymphocyte culture Cell mediated cytotoxicity assays Analysis of T cell functions Diagnosis of ID… contd • Complement assays – Total complement – Individual C component – Assay for neutrophil chemotaxis using test serum Diagnosis of ID… contd • Phagocytic assays – Total granulocyte and monocyte number – Assay for phagocytic index • • • • Chemotaxis Phagocytosis Bacterial killing – check for viability , staining NBT reduction test Treatment • • • • Antibiotics Antibody infusion Bone marrow transplantation Gene therapy Candida Infections Oral thrush in HIV infection Clinical Conditions • Kaposi sarcoma in AIDS