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Questions and Answers
Which process primarily occurs as the immature virion buds from the cell membrane?
Which process primarily occurs as the immature virion buds from the cell membrane?
What occurs first after the initial infection of HIV in the genital tract?
What occurs first after the initial infection of HIV in the genital tract?
What is the role of CD8 T cells in the context of HIV infection?
What is the role of CD8 T cells in the context of HIV infection?
What change occurs in CD4 T cell responses as a result of HIV infection?
What change occurs in CD4 T cell responses as a result of HIV infection?
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What function do CD4 T cells primarily serve in the immune response?
What function do CD4 T cells primarily serve in the immune response?
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Which of the following best describes the initial detection of HIV in the body?
Which of the following best describes the initial detection of HIV in the body?
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Which statement regarding the integration of viral DNA is accurate?
Which statement regarding the integration of viral DNA is accurate?
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What type of T cells recognize processed antigen peptides on APC associated with MHC class II?
What type of T cells recognize processed antigen peptides on APC associated with MHC class II?
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What is the primary function of CD8 T cells in the immune response?
What is the primary function of CD8 T cells in the immune response?
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Which cytokine is primarily responsible for the differentiation of CD4 T cells into the Th1 subset?
Which cytokine is primarily responsible for the differentiation of CD4 T cells into the Th1 subset?
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What role does IFN-γ play in the immune response?
What role does IFN-γ play in the immune response?
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Which subset of CD4 T cells produces IL-5 for B cell differentiation?
Which subset of CD4 T cells produces IL-5 for B cell differentiation?
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What is the significance of IL-17 produced by Th17 cells?
What is the significance of IL-17 produced by Th17 cells?
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How does IL-2 contribute to T cell responses?
How does IL-2 contribute to T cell responses?
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Which cytokines are produced by Th2 cells to induce B cell differentiation?
Which cytokines are produced by Th2 cells to induce B cell differentiation?
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What effect does IFN-γ have on the Th2 response?
What effect does IFN-γ have on the Th2 response?
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What type of immune response is typically utilized to control intracellular infections under normal conditions?
What type of immune response is typically utilized to control intracellular infections under normal conditions?
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What is the effect of HIV infection on Th1 and Th2 cytokine levels in individuals?
What is the effect of HIV infection on Th1 and Th2 cytokine levels in individuals?
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Which cytokine is notably elevated in HIV seropositive individuals, contributing to the Th2 response?
Which cytokine is notably elevated in HIV seropositive individuals, contributing to the Th2 response?
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What role do CD8 T cells play in response to HIV infection?
What role do CD8 T cells play in response to HIV infection?
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How do mutant strains of HIV affect the ability of cytotoxic T cells?
How do mutant strains of HIV affect the ability of cytotoxic T cells?
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What happens to the immune system as a result of the shift from a Th1 response to a Th2 response in HIV infection?
What happens to the immune system as a result of the shift from a Th1 response to a Th2 response in HIV infection?
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What proteins do CD8 T cells produce to induce apoptosis in infected host cells?
What proteins do CD8 T cells produce to induce apoptosis in infected host cells?
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What is the consequence of cytotoxic T cell failure in controlling HIV infection?
What is the consequence of cytotoxic T cell failure in controlling HIV infection?
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What does the 2016 WHO report recommend regarding the initiation of ART?
What does the 2016 WHO report recommend regarding the initiation of ART?
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Which cell type is primarily targeted and depleted by HIV leading to immune deficiency?
Which cell type is primarily targeted and depleted by HIV leading to immune deficiency?
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What is the role of opportunistic infections in individuals with AIDS?
What is the role of opportunistic infections in individuals with AIDS?
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Which of the following is NOT considered an opportunistic infection associated with AIDS?
Which of the following is NOT considered an opportunistic infection associated with AIDS?
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In the context of HIV infection, what shift occurs in CD4 T cell responses?
In the context of HIV infection, what shift occurs in CD4 T cell responses?
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What is the primary function of reverse transcriptase in HIV?
What is the primary function of reverse transcriptase in HIV?
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Which CD4 T cell subset is particularly depleted in the context of HIV infection?
Which CD4 T cell subset is particularly depleted in the context of HIV infection?
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What is the general purpose of ART in the treatment of HIV?
What is the general purpose of ART in the treatment of HIV?
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What is a significant consequence of the loss of Th1 CD4 helper T cells during HIV infection?
What is a significant consequence of the loss of Th1 CD4 helper T cells during HIV infection?
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During which stage of HIV infection do antibodies to HIV typically appear?
During which stage of HIV infection do antibodies to HIV typically appear?
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Which symptom is NOT typically observed during the acute stage of HIV infection?
Which symptom is NOT typically observed during the acute stage of HIV infection?
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What is the primary reason for the potential for false-negative serologic tests during the acute stage of HIV infection?
What is the primary reason for the potential for false-negative serologic tests during the acute stage of HIV infection?
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What happens to the level of viremia after the resolution of the acute stage in HIV infection?
What happens to the level of viremia after the resolution of the acute stage in HIV infection?
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Which characteristic is true regarding the acute stage of HIV infection?
Which characteristic is true regarding the acute stage of HIV infection?
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What should be done if HIV infection is suspected but antibody tests return negative?
What should be done if HIV infection is suspected but antibody tests return negative?
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Which immune component is primarily responsible for combating HIV during the acute stage?
Which immune component is primarily responsible for combating HIV during the acute stage?
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What does ART stand for in the context of HIV treatment?
What does ART stand for in the context of HIV treatment?
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When should ART treatment be initiated according to the latest WHO recommendations?
When should ART treatment be initiated according to the latest WHO recommendations?
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What is a key reason for combining therapy with ART in HIV treatment?
What is a key reason for combining therapy with ART in HIV treatment?
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Which of the following is NOT classified as an opportunistic infection associated with AIDS?
Which of the following is NOT classified as an opportunistic infection associated with AIDS?
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What role do CD4 T cells primarily serve in the immune response against HIV?
What role do CD4 T cells primarily serve in the immune response against HIV?
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How many individuals worldwide were estimated to be living with HIV or AIDS as of 2015?
How many individuals worldwide were estimated to be living with HIV or AIDS as of 2015?
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What happens to CD4 T cell responses in individuals infected with HIV?
What happens to CD4 T cell responses in individuals infected with HIV?
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What is the role of the CD8 T cells in relation to HIV infection?
What is the role of the CD8 T cells in relation to HIV infection?
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What is the primary reason individuals with AIDS become susceptible to opportunistic infections?
What is the primary reason individuals with AIDS become susceptible to opportunistic infections?
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Which population is most affected by HIV infections worldwide?
Which population is most affected by HIV infections worldwide?
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What characteristic distinguishes HIV-1 from HIV-2?
What characteristic distinguishes HIV-1 from HIV-2?
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What role does reverse transcriptase play in the HIV life cycle?
What role does reverse transcriptase play in the HIV life cycle?
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What is the normal range of CD4 T cell counts in healthy individuals?
What is the normal range of CD4 T cell counts in healthy individuals?
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Which of the following is NOT a cell type infected by HIV?
Which of the following is NOT a cell type infected by HIV?
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How many copies of RNA are contained within the HIV genome?
How many copies of RNA are contained within the HIV genome?
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What is the fourth leading cause of death worldwide?
What is the fourth leading cause of death worldwide?
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What is formed after the cleaving of the Pol polyprotein during the maturation of the virion?
What is formed after the cleaving of the Pol polyprotein during the maturation of the virion?
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Which cells act as the initial site of HIV infection in the genital tract?
Which cells act as the initial site of HIV infection in the genital tract?
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What type of immune response do CD4 T cells primarily enhance?
What type of immune response do CD4 T cells primarily enhance?
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During HIV infection, which cytokine shift occurs in CD4 T cells?
During HIV infection, which cytokine shift occurs in CD4 T cells?
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What enables the replication of viral mRNA from proviral DNA?
What enables the replication of viral mRNA from proviral DNA?
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How does HIV affect the Th1 and Th2 balance within the immune system?
How does HIV affect the Th1 and Th2 balance within the immune system?
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What role do CD8 T cells play in the context of HIV infection?
What role do CD8 T cells play in the context of HIV infection?
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What is a direct consequence of CD4 T cell depletion due to HIV infection?
What is a direct consequence of CD4 T cell depletion due to HIV infection?
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What typically characterizes the latent stage of HIV infection?
What typically characterizes the latent stage of HIV infection?
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What is the most characteristic manifestation of AIDS?
What is the most characteristic manifestation of AIDS?
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Which symptom is commonly associated with AIDS-related complex (ARC)?
Which symptom is commonly associated with AIDS-related complex (ARC)?
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During which stage do individuals typically become symptomatic after HIV infection?
During which stage do individuals typically become symptomatic after HIV infection?
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What typically occurs in untreated patients during the latent stage of HIV infection?
What typically occurs in untreated patients during the latent stage of HIV infection?
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What typically occurs during the acute stage of HIV infection?
What typically occurs during the acute stage of HIV infection?
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What change occurs in CD8 T cells during the resolution of HIV acute stage?
What change occurs in CD8 T cells during the resolution of HIV acute stage?
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Why can false-negative serologic tests occur during the acute stage of HIV infection?
Why can false-negative serologic tests occur during the acute stage of HIV infection?
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What is the initial clinical signs of HIV infection in the acute stage?
What is the initial clinical signs of HIV infection in the acute stage?
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What implication does the inability to detect antibodies at the time of testing have?
What implication does the inability to detect antibodies at the time of testing have?
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What is a significant consequence of the death of Th1 CD4 helper T cells in HIV infection?
What is a significant consequence of the death of Th1 CD4 helper T cells in HIV infection?
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Which assay should be done if a person is suspected to be infected with HIV but antibody tests are negative?
Which assay should be done if a person is suspected to be infected with HIV but antibody tests are negative?
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What happens to the level of viremia following the acute stage of HIV infection?
What happens to the level of viremia following the acute stage of HIV infection?
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Study Notes
Immune Response to HIV
- CD8 T cells, also known as cytotoxic T cells, are crucial for combating viral infections and cancer by producing perforin, granulysin, and granzymes.
- CD4 T cells differentiate into subsets (Th1, Th2, Th17) based on polarizing cytokines from antigen-presenting cells (APCs).
- Interleukin-12 (IL-12) leads to differentiation of CD4 T cells into Th1 cells, which secrete IL-2 and interferon-gamma (IFN-γ).
- IL-2 promotes proliferation of CD4 and CD8 T cells, enhancing immune responses.
- IFN-γ amplifies the Th1 response, enhances macrophage and neutrophil functions, and is vital for activating cytotoxic T cells.
- IL-10 and IL-4 encourage differentiation into Th2 cells, which secrete cytokines that promote B cell functions but are less effective against intracellular pathogens.
- IL-23 causes differentiation into Th17 cells, producing IL-17 to recruit neutrophils during bacterial infections.
HIV Life Cycle
- HIV RNA is transcribed into double-stranded DNA by DNA polymerase before integrating into host DNA.
- Integration can occur at various host DNA sites, allowing for multiple copies of viral DNA.
- Viral mRNA is synthesized from proviral DNA and translated into polyproteins, forming immature virions that mature through proteolytic cleavage.
Immunopathogenesis of HIV
- HIV infects CD4 T cells, leading to their depletion and resulting in weakened immunity and susceptibility to opportunistic infections.
- Initial infection predominantly occurs in dendritic cells and spreads to local CD4 T cells, with HIV detectable in the blood 4-11 days post-infection.
- CD8 T cells play a key role in controlling HIV, but the effectiveness declines as HIV mutations arise.
Clinical Stages of HIV Infection
- Acute Stage: Occurs 2-4 weeks post-infection; characterized by fever, sore throat, lymphadenopathy, and a maculopapular rash. High-level viremia and detectable HIV antibodies typically develop within 3-4 weeks.
- Latent Stage: Immune response begins to control the virus; however, HIV remains present at low levels.
- Late Immunodeficiency Stage: Progressive depletion of CD4 cells leads to AIDS.
Treatment and Prevention Strategies
- Antiretroviral therapy (ART) is a lifelong treatment that helps manage HIV but does not cure it. WHO now recommends immediate ART initiation regardless of CD4 counts.
- As of 2015, an estimated 37 million individuals worldwide are living with HIV or AIDS, with 17 million on ART.
- Importance of preventing opportunistic infections in HIV/AIDS patients is critical in management.
Opportunistic Infections Associated with AIDS
- Common infections include Pneumocystis jirovecii pneumonia, herpes simplex virus, cytomegalovirus, and various fungal infections like candidiasis and cryptococcosis.
Important HIV-Related Terms
- Retrovirus, Lentivirus, gp120, gp41, p24, integrase, reverse transcriptase, protease, CXCR4, and CCR5 are vital components in HIV infection and replication.
- The shift from a Th1 to a Th2 response in HIV infections contributes to reduced effectiveness against viruses and higher vulnerability to opportunistic infections.
HIV Overview
- HIV (Human Immunodeficiency Virus) is a retrovirus from the lentivirus subgroup, leading to AIDS (Acquired Immunodeficiency Syndrome).
- The WHO recommended initiating Antiretroviral Therapy (ART) when CD4+ T cell counts fall below 500 cells/mm³, but current guidelines advocate starting ART immediately regardless of CD4 count.
- 37 million individuals globally have HIV/AIDS, with 17 million receiving ART.
Immune Response and HIV Transmission
- HIV primarily infects and depletes CD4+ T lymphocytes and macrophages, compromising immune function and increasing susceptibility to opportunistic infections.
- Two-thirds of the 36.9 million HIV-infected individuals reside in sub-Saharan Africa, where healthcare access is limited.
- HIV transmission occurs mainly through sexual contact and infected blood transfer.
Cytokine Involvement in HIV
- Healthy individuals normally have CD4 T cell counts between 500-1500/mm³; counts drop below 200/mm³ in AIDS, linked to reduced cytokines IL-2, IFN-γ, and IL-17.
- IL-2 supports the viability of T cells; IFN-γ enhances immune responses; IL-17 provides mucosal immunity.
Stages of HIV Infection
- Acute Stage: Begins 2-4 weeks post-infection, presenting as infectious mononucleosis-like symptoms. High-level viremia makes it highly transmissible. Antibodies typically develop 10-14 days post-infection.
- Latent Stage: Can last 7-11 years in untreated patients, asymptomatic but with ongoing viral replication in lymph nodes. May present with AIDS-related complex (ARC) symptoms.
- Late Stage (AIDS): Characterized by CD4 cell counts below 200/μL, leading to frequent opportunistic infections.
Opportunistic Infections in AIDS
- The most common opportunistic infection in AIDS is pneumonia caused by Pneumocystis jirovecii.
- Other infections include Herpes simplex, cytomegalovirus, Candida albicans, and Mycobacterium tuberculosis, resulting from weakened immunity.
HIV Genetic Structure and Replication
- HIV contains two identical RNA copies and reverse transcriptase, allowing conversion of RNA to complementary DNA (cDNA).
- Viral DNA can integrate into host DNA, leading to multiple copies and subsequent production of viral proteins.
Clinical Management and Monitoring
- Continuous lifelong ART is critical for managing HIV as there is currently no cure.
- Monitoring includes tracking CD4 counts and assessing for opportunistic infections to provide timely interventions.
Studying That Suits You
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Test your knowledge on the roles of CD8 T cells in viral infections and cancer with this quiz designed by Professor Vishy Venkataraman. Understand the key functions of cytotoxic T cells and their importance in the immune response against pathogens.