Lecture 20 Flashcards
What is HIV?
human immunodeficiency virus
What does HIV attack?
immune system
- CD4 (t-helper) cells
What does the CD in CD4 mean?
clusters of differentiation
How does CD4+ work?
- cytokine signaling with B cells
- interacts directly with antigens
- bind MHC class II molecules on B cells and APCs
- T-helper secretes costimulatory molecule
What do T-helper cells produce?
cytokines into
-> T-helper 1 cells
-> T-helper 2 cells
-> T-helper 17 cells
-> memory cells
What do T-helper 17 cells produce? What does it contribute to?
IL-17
- contributes to inflammation
What do T-helper 1 cells produce? What does it do?
IFN-gamma
- activates macrophages
- enhances complement
- stimulate antibody production that promotes phagocytosis
What do T-helper 2 cells release? What does it do?
IL-4 cytokine
- activates B cells to produce IgE
- activates eosinophils
How are TH1 cells involved in HIV/AIDS?
- cell-mediated immunity
- activation of cytotoxic T cells and macrophages
- HIV leads to depletion of CD4+ TH1 cells, weakening the immune system’s ability to combat intracellular pathogens
How are TH2 cells related to HIV/AIDS?
- associated with humoral immunity
- helps B cells produce antibodies
- balance between TH1 and TH2 is disrupted in HIV (TH2 more dominant) = contributes to reduced cell-mediated immunity
How are TH17 cells related to HIV?
- mucosal immunity (defending against bacterial and fungal infections at epithelial barriers)
- HIV can impair TH17 cells (weakening of mucosal defenses and gut barrier integrity) = systemic inflammation and microbial translocation
How are memory cells related to HIV?
- HIV establishes reservoirs in memory CD4+ T cells (latent virus)
- hard to eradicate virus entirely
- memory cells harbor latent HIV and can reactivate causing ongoing infection
What is the structure of HIV?
- genus: lentivirus
- retrovirus (reverse transcription)
- 2 identical + stranded RNA genome molecules
- phospholipid envelope
- gp120 glycoprotein spikes
- capsid
How does HIV infect the body?
- spread by dendritic cells and carried to the lymphoid organs
- contacts activated T cells
- gp120 combines with CD4+ receptor and CCR5 or CXCR4 coreceptors
- CD4 molecules are carried on Th cells, macrophages, and dendritic cells
- virus fuses and enters into the cell.
How does HIV work inside the cell?
- viral RNA is transcribed into DNA using reverse transcriptase
- DNA is integrated into the host’s chromosomal DNA
- virus undergoes rapid antigenic changes and a high rate of mutation
What is an active infection?
new viruses bud from the host cells
What is a latent infection?
DNA is hidden in the chromosome as a provirus
- some become memory T cells that serve as the reservoir for HIV
What are the characteristics of HIV-1?
- related to viruses that infect chimpanzees and gorillas
- 99% of cases
- group M (majority) accounts for 90%
What are the characteristics of HIV-2?
- not often encountered outside of West Africa
- less pathogenic than HIV-1
- longer asymptomatic period with lower viral load and mortality rate than HIV-1
What suppresses viral numbers?
cytotoxic T lymphocytes (CTLs)
How is HIV transmitted?
- can survive 6 hours outside a cell and 1.5 days inside
- sexual contact
- breast milk
- transplacental infection of a fetus
- blood-contaminated needles
- organ transplants
- artificial insemination
- blood transfusion
- anal-receptive intercourse
What are the phases of HIV infection?
Phase 1: asymptomatic or lymphadenopathy
Phase 2: CD4+ cells decline steadily (only a few infected cells release the virus)
Phase 3: AIDS develops, CD4+ is below 200 cells/microliter
Who are long-term survivors of HIV exposure?
- low viral load
- effective CTLs
What are the symptoms of HIV infection?
Acute stage: flu-like symptoms, high viral load
Chronic stage: asymptomatic or mild symptoms, virus continues to replicate
AIDS: severe immune system damage, opportunistic infections occur
How can HIV be diagnosed?
- seroconversion: period of time between infection and the appearance of antibodies (takes 3 months)
- ELISA
- Western blotting or APTIMA (RNA test)
- Plasma Viral Load (PVL): determined by PCR or nucleic acid hybridization
What are some challenges with developing HIV vaccines?
- no model of natural immunity to mimic
- lack of research animal
- lack of understanding of the mechanisms of retroviruses
- high mutation rate, leading to resistant strains
What should an ideal vaccine do?
- induce immunity before reservoirs of latent virus are established
- stimulate production of CTLs
- be affordable
What are AIDS?
Acquired Immunodeficiency Syndrome
What is the origin of AIDS?
- HIV crossed over into the human populations in west and central Africa from chimpanzees
- spread throughout Africa as a result of urbanization and increased sexual promiscuity
- first known sample was from Kinshasa, DRC, in 1920
What is the most common mode of HIV transmission?
heterosexual transmission
- 1/3 of cases in Eastern Europe and Central and Southeast Asia are from injected drugs
How does HIV progress to AIDS?
1) HIV attacks and infects CD4+ T cells
2) HIV multiplies rapidly, destroying CD4+ cells over time
3) CD4+ counts drop = immune system becomes less able to fight infections
4) CD4+ levels fall below 200 cells/microliter = AIDS
How can AIDS be prevented?
- biomedical interventions (condoms, HIV testing, needle programs)
- behavioral intervention (sex education, safe infant feeding programs, counseling)
- structural interventions (making changes in social, economic, political, and environmental factors to reduce vulnerability to HIV)
How can AIDS be treated?
- Highly active antiretroviral therapy (HAART): combinations of drugs to minimize survival of resistant strains
- fusion/cell entry inhibitors: targets gp41 region of the viral envelope that prevents fusion of the virus with the cell
= enfuvirtide and maraviroc - Reverse transcriptase inhibitors
= NRTIs (tenofovir and emtricitabine)
= NNRTIs (efavirenz) - integrase inhibitors: inhibits HIV integrase that integrates cDNA into the host chromosome
= Raltegravir, dolutegravir, elvitegravir - protease inhibitors: inhibit proteases that cleave viral precursor proteins into structural and functional proteins
= Atazanavir, indinavir, and saquinavir - maturation inhibitors: stop HIV from becoming infectious by blocking the final step in the virus’ replication process, where the Gag protein is processed
