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Questions and Answers
Which T cell type is primarily involved in enhancing the effector functions of macrophages and neutrophils?
Which T cell type is primarily involved in enhancing the effector functions of macrophages and neutrophils?
What is the result of IL-12 being produced by activated APCs?
What is the result of IL-12 being produced by activated APCs?
Which cytokine is responsible for the proliferation of both CD4 and CD8 T cells?
Which cytokine is responsible for the proliferation of both CD4 and CD8 T cells?
What role does Interferon-gamma (IFN-γ) play in T cell responses?
What role does Interferon-gamma (IFN-γ) play in T cell responses?
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Th17 cells produce which of the following cytokines?
Th17 cells produce which of the following cytokines?
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How do CD8 T cells contribute to the immune response?
How do CD8 T cells contribute to the immune response?
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Which cytokines are involved in the differentiation of CD4 T cells into Th2 cells?
Which cytokines are involved in the differentiation of CD4 T cells into Th2 cells?
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What is the primary function of the antimicrobial proteins produced by CD8 T cells?
What is the primary function of the antimicrobial proteins produced by CD8 T cells?
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What cytokine level significantly increases in HIV seropositive individuals?
What cytokine level significantly increases in HIV seropositive individuals?
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Which response is primarily responsible for the control of intracellular infections under normal conditions?
Which response is primarily responsible for the control of intracellular infections under normal conditions?
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What is the result of the loss of CD4 helper T cells in HIV infection?
What is the result of the loss of CD4 helper T cells in HIV infection?
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What is the primary role of CD8 T cells in the immune response to HIV infection?
What is the primary role of CD8 T cells in the immune response to HIV infection?
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Why do cytotoxic T cells become less effective against mutant strains of HIV?
Why do cytotoxic T cells become less effective against mutant strains of HIV?
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Which of the following stages of HIV infection reflects a complete failure of the immune system?
Which of the following stages of HIV infection reflects a complete failure of the immune system?
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The differentiation of T0 cells into the Th2 subset is primarily stimulated by which cytokine?
The differentiation of T0 cells into the Th2 subset is primarily stimulated by which cytokine?
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What characterizes the CD8-positive lymphocytes in the immune response to HIV?
What characterizes the CD8-positive lymphocytes in the immune response to HIV?
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What is the first step in the entry of HIV into a host cell?
What is the first step in the entry of HIV into a host cell?
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Which chemokine receptor does the T-cell-tropic strain of HIV specifically bind to?
Which chemokine receptor does the T-cell-tropic strain of HIV specifically bind to?
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What is the result of the cleavage of the Pol polyprotein during HIV replication?
What is the result of the cleavage of the Pol polyprotein during HIV replication?
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What shift occurs in T cell responses due to HIV infection?
What shift occurs in T cell responses due to HIV infection?
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Which of the following accurately describes the role of CD8 T cells in HIV infection?
Which of the following accurately describes the role of CD8 T cells in HIV infection?
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Where does the initial infection of HIV occur in the host?
Where does the initial infection of HIV occur in the host?
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What is the consequence of HIV infection of CD4-positive helper T cells?
What is the consequence of HIV infection of CD4-positive helper T cells?
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What type of receptors are required for HIV entry into CD4 T cells?
What type of receptors are required for HIV entry into CD4 T cells?
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What is the primary goal of antiretroviral therapy (ART) for individuals with HIV?
What is the primary goal of antiretroviral therapy (ART) for individuals with HIV?
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According to the 2016 WHO recommendations, when should ART be initiated in HIV patients?
According to the 2016 WHO recommendations, when should ART be initiated in HIV patients?
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Which cell subset is primarily affected by HIV-induced depletion, impacting immune response?
Which cell subset is primarily affected by HIV-induced depletion, impacting immune response?
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What is a significant opportunistic infection associated with AIDS?
What is a significant opportunistic infection associated with AIDS?
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What is the role of CD8 T cells in HIV infection?
What is the role of CD8 T cells in HIV infection?
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What is considered a hallmark of late-stage HIV infection, known as AIDS?
What is considered a hallmark of late-stage HIV infection, known as AIDS?
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Which opportunistic infection is most commonly associated with AIDS?
Which opportunistic infection is most commonly associated with AIDS?
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Which laboratory test is primarily used to diagnose early HIV infections?
Which laboratory test is primarily used to diagnose early HIV infections?
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An individual is diagnosed with AIDS if they suffer from an opportunistic infection, regardless of what factor?
An individual is diagnosed with AIDS if they suffer from an opportunistic infection, regardless of what factor?
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What CD4 T cell count level indicates that an individual has progressed to AIDS?
What CD4 T cell count level indicates that an individual has progressed to AIDS?
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Which of the following opportunistic infections is NOT typically associated with AIDS?
Which of the following opportunistic infections is NOT typically associated with AIDS?
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What is the most effective treatment currently available for HIV?
What is the most effective treatment currently available for HIV?
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Which condition can result in severe neurological problems in AIDS patients?
Which condition can result in severe neurological problems in AIDS patients?
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Study Notes
HIV Replication and Entry
- HIV entry begins with the binding of gp120 envelope protein to CD4 protein on host T cells or macrophages.
- Following initial binding, gp120 interacts with chemokine receptors CCR5 or CXCR4 on the host cell surface.
- The fusion of HIV's viral envelope with the host cell membrane is mediated by the virion protein gp41, allowing viral entry.
- HIV strains that bind CXCR4 are termed T-cell-tropic, while those binding CCR5 are macrophage-tropic.
- After uncoating, HIV RNA-dependent DNA polymerase transcribes viral RNA into double-stranded DNA, which integrates into host DNA.
- Integrated viral DNA can occur at various host DNA sites, allowing multiple copies.
- Viral mRNA is generated from proviral DNA by host cell RNA polymerase and translated into large polyproteins.
- Proteins such as reverse transcriptase, integrase, and protease are cleaved from the Pol polyprotein.
- The immature virion forms in the cytoplasm and matures as proteolytic cleavage occurs during budding from the cell membrane.
Immunopathogenesis and CD4 T Cell Depletion
- HIV primarily infects helper T cells (CD4-positive), leading to their destruction and reduced cell-mediated immunity.
- Initial infection occurs in dendritic cells (Langerhans' cells) in the genital tract before spreading to local CD4-positive T cells.
- HIV is detectable in blood within 4 to 11 days post-infection.
- CD8 T cells are important for controlling HIV infection and help manage viral load over time.
Th1 to Th2 Cytokine Shift
- HIV infection prompts a shift in CD4 T cell response from Th1 (cell-mediated) to Th2 (humoral).
- Th1 cells produce IL-2 and IFN-γ, enhancing immune response against intracellular pathogens.
- Th2 cells produce IL-4 and IL-5, promoting B cell function but are less effective against HIV.
- This shift results in an increase of Th2 cytokines and a decrease in Th1 cytokines in HIV positive individuals.
- IL-4 increases Th2 proliferation, leading to ineffective antibody production against HIV, contributing to viral persistence and immunodeficiency.
Role of Cytotoxic CD8 T Cells
- CD8 T cells (cytotoxic T cells) are crucial in responding to HIV by inducing apoptosis in infected cells.
- They produce perforin and granulysin, targeting both host cells and intruding viruses.
- Resistance diminishes as HIV mutates, particularly when mutations arise in the env gene.
Clinical Stages of HIV Infection
- HIV infection has three stages: early acute stage, middle latent stage, and late stage (AIDS).
- Late-stage AIDS is marked by fewer than 200 CD4 cells/μL and higher susceptibility to opportunistic infections.
Opportunistic Infections in AIDS
- Key opportunistic infections include pneumonia caused by Pneumocystis jirovecii, herpes simplex, cytomegalovirus, and fungal infections like candidiasis.
- Neurological complications may arise, leading to dementia and neuropathy in many patients.
Diagnosis and Treatment
- The HIV antigen/antibody "Combo" test detects p24 antigen and antibodies to HIV-1 and HIV-2, effective for early diagnosis.
- CD4 cell counts below 200 cell/mm³ indicate AIDS; viral load assays and drug resistance tests aid in managing HIV.
- Antiretroviral therapy (ART) is the primary treatment but requires lifelong adherence and is not a cure.
- WHO guidelines suggest ART initiation when CD4 counts drop below 500 cells/mm³, with a more recent recommendation for immediate ART regardless of CD4 levels.
- As of 2015, 37 million individuals globally live with HIV/AIDS, with 17 million receiving ART.
Key Terms
- Retrovirus, Lentivirus
- gp120 and gp41 Role in Infection
- HIV Types: T-cell-tropic and Macrophage-tropic
- Immune Response Mechanisms: CD4 and CD8 T Cells
- Opportunistic Infections: Pneumocystis jirovecii, Herpes simplex, Candida albicans, etc.
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Description
This quiz explores the mechanisms of HIV entry and replication within host cells. It covers key concepts, including the roles of envelope proteins and cellular receptors. Test your understanding of the viral lifecycle and the integration of HIV genetic material into host DNA.
