Immunodeficiency syndromes

Classification Primary:rare,B,T & combined B &T deficits Secondary: in severe infection, immunosupression(CT,RT),malnutrition,DM,renal failure, ageing, autoimmune diseases,malignancies, AIDS

AIDS Definition: disease caused by retrovirus human immunodeficiency virus ( HIV). Characterized by Depletion of CD 4+ T lymphocytes Profound immunosuppression Opportunistic infection (caused by organisms that are often non-pathogenic or low virulence) Secondary neoplasms & neurological manifestations

Epidemiology Incidence >42 million people HIV + Africa,SE Asia 5th commonest cause of death in yrs Homosexual /bisexual males IV drug abusers * Recepients of blood& blood products Heterosexual contacts ??? Paediatric –mother to child transmission

Aetiology- HIV Retrovirus Lentivirus family HIV 1,HIV 2 HIV 1 –subgroups Major (M),outlier (O),neither (N) M –clades A-K (B SE asia,C India)

Structure of HIV (Cont….) HIV genome contains Gag Pol Env Tat,rev,vif,nef,vpr, vpu Imp for HIV pathogenicity & targeted therapy

Pathogenesis of HIV infection & AIDS Viral transimission to blood (Infection of CD 4+ T cells )or macrophages,dendritic cells or CD4 + cells in mucosa Infection established in lymphoid tissues Latent period Active viral replication ↓T lymphocytes & decreased immunity AIDS

Entry/internalization of HIV in T cell, macrophage Binding of gp 120 to CD 4 +cells (T cells /macrophages/dendritic cells) Conformational change in gp 120 Binding of HIV gp 120 to coreceptors (CCR 5,CXCR 4) Membrane penetration by gp 41 Membrane fusion Virus enters the cells