Immunodeficiencies

      - Congenital: Due to defective or missing genes

      - Acquired: Develop during an individual's life

      - Due to drugs, cancers, and infections

      - Hodgkins’ disease lowers cell-mediated response

      - Damage to or removal of certain organs can decrease immunity (e.g., the spleen)

 

Check Understanding

      - Is AIDS an acquired or a congenital immunodeficiency?

 

AIDS

      - 1981: In United States, cluster of Pneumocystis and Kaposi's sarcoma was discovered in young homosexual men

      - The men showed loss of immune function

      - 1983: Discovery of virus causing loss of immune function

 

HIV and The Origin of AIDS

      - Crossed the species barrier into humans in Africa in the 1930s

      - Patient who died in 1959 in Congo is the oldest known case

      - Spread in Africa as a result of urbanization

      - Spread worldwide through modern transportation and unsafe sexual practices

      - Norwegian sailor who died in 1976 is the first known case in Western world

 

HIV Virus and disease cycle

 

Clades (Subtypes) of HIV

      - HIV-1

      - M (main)

      - A to D, F to H, J, and K

      - O (outlier)

      - N (non M or O)

 

Clades (Subtypes) of HIV

      - Clade B

      - North and South America and Europe

      - Clade C (half of all HIV infections)

      - Central Africa down to South Africa

      - India and southeast Asia

      - Parts of China

      - Clade E

      - Southeast Asia

 

The Stages of HIV Infection

      - Phase 1: Asymptomatic or chronic lymphadenopathy

      - Phase 2: Symptomatic; early indications of immune failure

      - Phase 3: AIDS indicator conditions

 

Diseases Associated with AIDS

      - Cryptosporidium hominis

      - Toxoplasma gondii

      - Isospora belli

      - Cytomegalovirus

      - Herpes simplex virus

      - Varicella-zoster virus

      - Mycobacterium tuberculosis

      - M. avium-intracellulare

      - Pneumocystis jirovecii

      - Histoplasma capsulatum

      - Cryptococcus neoformans

      - Candida albicans

      - Kaposi’s sarcoma

      - Hairy leukoplakia

      - Cervical dysplasia

 

Survival with HIV Infection

      - Exposed, but not infected

      - CCR5 mutation

      - Effective CTLs

      - Long-term nonprogressors

      - Mechanism not known

 

Check Understanding

      - On what continent did the HIV-1 virus arise?

      - What is the primary receptor on host cells to which HIV attaches?

      - Would an antibody against the coat of HIV be able to react with a provirus?

      - Would a CD4+ T-cell count of 300/?l be diagnostic of AIDS?

      - Which cells of the immune system are the main target of an HIV infection?

 

Diagnostic Methods

      - Seroconversion takes up to 3 months

      - HIV antibodies detected by ELISA

      - HIV antigens detected by Western blotting

      - Plasma viral load (PVL) is determined by PCR or nucleic acid hybridization

 

HIV Transmission

      - HIV survives 6 hours outside a cell

      - HIV survives less than 1.5 days inside a cell

      - Infected body fluids transmit HIV via

      - Sexual contact

      - Breast milk

      - Transplacental infection of fetus

      - Blood-contaminated needles

      - Organ transplants

      - Artificial insemination

      - Blood transfusion

 

AIDS Worldwide

      - Heterosexual intercourse (85%)

      - Injected drug use (IDU)

      - Women comprise 42% of infected

 

Preventing AIDS

      - Use of condoms

      - Use of sterile needles (IDUs)

      - Circumcision

      - Health care workers use Universal Precautions

      - Wear gloves, gowns, masks, and goggles

      - Do not recap needles

      - Risk of infection from infected needlestick injury is 0.3%

 

Vaccine Difficulties

      - Mutations

      - Clades

      - Antibody-binding sites “hidden”

      - Infected cells not susceptible to CTLs

      - Proviruses

      - Latent viruses

 

Chemotherapy

      - Nucleoside reverse transcriptase inhibitors

      - Non-nucleoside reverse transcriptase inhibitors

      - Protease inhibitors

      - Fusion inhibitors

 

HAART

      - Highly active antiretroviral therapy

      - Combinations of nucleoside reverse transcriptase inhibitors plus

      - Non-nucleoside reverse transcriptase inhibitor or

      - Protease inhibitor

 

Check Understanding

      - What form of nucleic acid is detected in a plasma viral load test for HIV?

      - What is considered to be the most dangerous form of sexual contact for transmission of HIV?

      - What is the most common mode, worldwide, by which HIV is transmitted?

      - Does circumcision make a man more or less likely to acquire HIV infection?