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 25-44 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, vpuImp 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