Pathology of IMMUNO DEFICIENCY DISEASES.pptx

Pathology of IMMUNO DEFICIENCY DISEASES.

1. IMMUNODEFICIENCY DISEASES Mithun Venugopal

2. DISEASES OF IMMUNITY The diseases of the immune system are broadly classified into the following 4 groups Immunodeficiency disorders characterized by deficient cellular and/or humoral immune functions. Hypersensitivity reactions characterized by hyperfunction of the immune system. Autoimmune diseases occur when the immune system fails to recognize ‘self’ from ‘non-self’. Possible immune disorders in which the immunologic mechanisms are suspected in their etiopathogenesis.

3. IMMUNODEFICIENCY DISEASES Failure or deficiency of immune system, which normally plays a protective role against infections, manifests by occurrence of repeated infections in an individual having immunodeficiency diseases. Immunodeficiency diseases are classified into 2 types: Primary immunodeficiencies are usually the result of genetic or developmental abnormality of the immune system. Secondary immunodeficiencies arise from acquired suppression of the immune system.

4. ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) EPIDEMIOLOGY Although AIDS was first described in the US, the disease has now attained pandemic proportions involving all continents. Presently, developing countries comprise majority of cases and Africa alone constitutes 50% of all positive cases globally. According to a rough estimate, 1 in every 100 sexually active adults worldwide is infected with HIV. Half of all serologically positive cases are in women while children comprise 5% of all cases. About 2.5 million new cases are getting added every year. In India, epicentre of the epidemic lies in the states of Maharashtra and Tamil Nadu which together comprise about 50% of all HIV positive cases (mostly contracted sexually), while North-East state of Manipur accounts for 8% of all cases (mostly among intravenous drug abusers).

5. ETIOLOGIC AGENT AIDS is caused by an RNA retrovirus called Human Immunodeficiency Virus (HIV). CD4 molecules present on subpopulation of T cells which are the particular targets of attack by HIV. Two forms of HIV have been described, HIV1 being the etiologic agent for AIDS in the US and Central Africa, while HIV2 causes a similar disease in West Africa and parts of India.

6. HIV VIRUS HIV virion or virus particle is spherical in shape and 100- 140 nm in size. It contains a core having core proteins, chiefly p24 and p18, two strands of genomic RNA and the enzyme, reverse transcriptase. The core is covered by a double layer of lipid membrane derived from the outer membrane of the infected host cell during budding process of virus. The membrane is studded with 2 envelope glycoproteins, gp120 and gp41.

7. ROUTES OF TRANSMISSION Sexual transmission Parenteral (Transmission via blood and blood products, sharing of needles, accidental needle stick injury, organ transplantation) Perinatal transmission Occupational transmission AIDS cannot be transmitted by casual non-sexual contact like shaking hands, hugging, sharing household facilities like beds, toilets, utensils etc. HIV contaminated waste products can be sterilized and disinfected by most of the chemical germicides used in laboratories at a much lower concentration. These are: sodium hypochlorite ( liquidchlorine bleach), formaldehyde (5%), ethanol (70%), glutaraldehyde (2%), β- propionolactone . HIV is also heatsensitive and can be inactivated at 56°C for 30 min.

8. PATHOGENESIS Selective tropism for CD4 receptor : Gp120 envelope glycoprotein of HIV has selective tropism for cells containing CD4 molecule receptor on their surface; these cells most importantly are CD4+ T cells (T helper cells)

9. PATHOGENESIS Internalization : gp120 of the virion combines with CD4 receptor, but for fusion of virion with the host cell membrane, a chemokine coreceptor (CCR) is necessary. Once HIV has combined with CD4 receptor and CCR, gp41 glycoprotein of envelope is internalized in the CD4+ T cell membrane.

10. PATHOGENESIS Uncoating and viral DNA formation: Once the virion has entered the T cell cytoplasm, reverse transcriptase of the viral RNA forms a single-stranded DNA. Using the single stranded DNA as a template, DNA polymerase copies it to make it double-stranded DNA, while destroying the original RNA strands. Viral DNA so formed has frequent mutations making the HIV quite resistant to anti-viral therapy.

11. PATHOGENESIS Viral integration: The viral DNA so formed may initially remain unintegrated in the affected cell but later viral integrase protein inserts the viral DNA into nucleus of the host T cell and integrates in the host cell DNA. At this stage, viral particle is termed as HIV provirus.

12. PATHOGENESIS Viral replication: HIV provirus having become part of host cell DNA, host cell DNA transcripts for viral RNA with presence of tat gene.

13. PATHOGENESIS Latent period and immune attack: In an inactive infected T cell, the infection may remain in latent phase for a long time, accounting for the long incubation period. However, this period is short and the virus soon overpowers the host immune system.

14. PATHOGENESIS CD4+ T cell destruction: Viral particles replicated in the CD4+ T cells start forming buds from the cell wall of the host cell. As these particles detach from the infected host cell, they damage part of the cell membrane of the host cell and cause death of host CD4+ T cells by apoptosis.

15. PATHOGENESIS Viral dissemination: Release of viral particles from infected host cell spreads the infection to more CD4+ host cells and produces viraemia. Through circulation, virus gains entry to the lymphoid tissues (lymph nodes, spleen) where it multiplies further, and are the dominant site of virus reservoir rather than circulation.

16. STAGES

17. CLINICAL MANIFESTATIONS OF HIV/AIDS Due to viral infection directly Due to opportunistic infections Due to secondary tumours Due to drug treatment

18. DIAGNOSIS