L11-17 Questions Flashcards
How does the structural composition of EBV contribute to its ability to establish latency in B cells?
EBV has a linear dsDNA genome that circularizes upon infection, allowing it to persist in B cells without integrating into the host genome. This circularization, along with the expression of latency-associated proteins, helps the virus evade the immune system and establish long-term latency.
Compare the infection cycles of EBV and CMV, focusing on the cells they infect and their routes of entry and exit.
EBV primarily infects B cells and enters through saliva, colonizing the oropharynx, salivary glands, and tonsils. It exits through saliva. CMV infects epithelial and mononuclear cells, entering through various bodily fluids like blood, saliva, and urine, and exits through similar routes.
What are the key differences in the clinical presentations of primary and reactivated EBV infections?
Primary EBV infection often presents with fever, pharyngitis, and lymphadenopathy, especially in teens and adults. Reactivated EBV infections may be asymptomatic or present with more severe complications, such as lymphoproliferative disorders, especially in immunocompromised individuals.
Explain the diagnostic methods for EBV and their limitations.
EBV can be diagnosed using heterophile antibody tests (Monospot), viral-specific antibody tests (VCA, EA, EBNA), PCR, and blood smears showing atypical lymphocytes. Limitations include false negatives early in the infection and less sensitivity in children for the Monospot test.
Describe the clinical manifestations and potential complications of mumps.
Mumps typically presents with fever, headache, muscle aches, fatigue, anorexia, and painful swelling of the parotid glands (parotitis). Complications can include orchitis, oophoritis, meningitis, encephalitis, deafness, and pancreatitis.
How does the immune response to EBV contribute to its clinical manifestations?
The immune response, particularly the proliferation of CD8+ T cells and cytokine release, leads to the clinical manifestations of EBV infection, such as fever, pharyngitis, and lymphadenopathy. The presence of atypical T cells on blood smears is also a result of this immune response.
What are the uses and limitations of virus-specific antibody tests in diagnosing CMV?
Virus-specific antibody tests for CMV, such as IgM and IgG, help diagnose primary and past infections. Limitations include the inability to distinguish between primary and reactivated infections and the potential for false positives or negatives depending on the timing of the test.
Discuss the significance of the ‘Owl Eye’ appearance in CMV diagnosis.
The ‘Owl Eye’ appearance refers to the characteristic intranuclear inclusions seen in cells infected with CMV. This histopathological feature is a key diagnostic marker, indicating CMV infection and helping differentiate it from other viral infections.
What are the contraindications for the mumps vaccine, and why are they important?
Contraindications for the mumps vaccine include pregnancy, immunocompromised individuals, and those sensitive to neomycin. These are important to prevent adverse reactions and ensure the safety of individuals who may be at higher risk of complications from the live attenuated vaccine.
How does the latency of EBV in B cells contribute to its association with certain cancers?
Latently infected B cells can proliferate indefinitely, a hallmark of cancer. The expression of viral gene products during latency can lead to uncontrolled cell growth and the development of cancers such as Burkitt’s lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma.
What are the primary differences between the clinical manifestations of EBV and CMV mononucleosis?
EBV mononucleosis typically presents with fever, pharyngitis, and lymphadenopathy, while CMV mononucleosis is often asymptomatic or presents with milder symptoms. CMV mononucleosis is more common in older individuals and may include systemic symptoms like fatigue and myalgia.
Explain the role of CD8+ T cells in controlling EBV infection and maintaining latency.
CD8+ T cells recognize and kill EBV-infected B cells, controlling active replication and maintaining latency. This immune response helps prevent the virus from causing symptomatic infection and reduces the risk of complications associated with reactivation.
How does the MMR vaccine contribute to the prevention of mumps outbreaks?
The MMR vaccine, which includes a live attenuated mumps virus, induces immunity and reduces the incidence of mumps. High vaccination coverage helps achieve herd immunity, preventing outbreaks and protecting those who cannot be vaccinated.
What are the potential long-term health problems associated with congenital CMV infection?
Congenital CMV infection can lead to long-term health problems such as hearing loss, developmental delays, vision impairment, seizures, and motor disabilities. Early diagnosis and intervention are crucial to managing these complications.
Describe the infection cycle of mumps and how it leads to its clinical manifestations.
Mumps enters the body through direct contact with saliva or airborne droplets, colonizes the upper respiratory tract and local lymphatics, and causes parotid gland swelling (parotitis). Viremia disseminates the virus to other tissues, leading to systemic symptoms and complications.
How does the use of amoxicillin in EBV-infected patients lead to a maculopapular rash?
Amoxicillin can trigger a hypersensitivity reaction in EBV-infected patients, leading to a maculopapular rash. This reaction is not an allergic response but rather a drug-virus interaction that causes widespread rash.
What are the key factors that contribute to the high seroprevalence of EBV in adults?
The high seroprevalence of EBV in adults is due to its efficient transmission through saliva, the ability to establish lifelong latency, and the fact that primary infection often occurs in childhood, leading to widespread exposure and immunity.
Explain the significance of atypical lymphocytes in the diagnosis of EBV infection.
Atypical lymphocytes, which are larger T cells with abundant cytoplasm, are a hallmark of EBV infection. Their presence on blood smears indicates an active immune response to the virus and helps differentiate EBV from other causes of lymphocytosis.
How does CMV establish latency, and what triggers its reactivation?
CMV establishes latency by persisting in CD34+ progenitor cells and their CD14+ monocyte derivatives without producing viral progeny. Reactivation can be triggered by immunosuppression, stress, or other factors that weaken the host immune response.
Describe the genomic structure of Hepatitis A Virus (HAV) and explain how it influences the virus’s replication process.
HAV is a (+) ssRNA virus belonging to the picornavirus family. Its single-stranded RNA genome allows it to directly serve as mRNA for protein synthesis upon entering the host cell, facilitating rapid replication.
What are the primary clinical signs and symptoms of acute viral hepatitis, and how do they progress over time?
Acute viral hepatitis often starts with flu-like symptoms such as fever, headache, muscle aches, fatigue, anorexia, nausea, and vomiting, followed by abdominal pain, bilirubinuria, and jaundice.
Explain the changes in liver enzymes associated with viral hepatitis and their clinical significance.
Early in viral hepatitis, AST and ALT levels rise significantly, indicating hepatocyte damage. GGT and AlkPhos levels are usually near-normal initially but may increase later due to biliary obstruction.
Discuss the epidemiology and modes of transmission of Hepatitis E Virus (HEV) and compare them with those of Hepatitis A Virus (HAV).
HEV is primarily transmitted through contaminated drinking water, especially in East and South Asia, whereas HAV is transmitted fecal-orally with a global distribution and sporadic epidemics.
What are the outcomes of HAV infection, and what methods are used for its prevention?
Most HAV infections are self-limited with no chronic carrier state. Prevention includes vaccination, improved sanitation, and post-exposure prophylaxis with anti-HAV IgG.
How would you evaluate the results of serological assays used in the diagnosis of HAV?
Serological assays for HAV include detecting IgG anti-HAV, which is present by symptom onset and confers lifelong protection. RT-PCR can also be used to confirm the diagnosis.
Diagram the replication cycle of Hepatitis B Virus (HBV) and explain its significance in chronic infection.
The HBV replication cycle involves the formation of covalently closed circular DNA (cccDNA) in the host cell nucleus, allowing the virus to evade immune responses and maintain long-term infection.
Compare and contrast the clinical presentation of acute and chronic viral hepatitis.
Acute viral hepatitis presents with flu-like symptoms, liver swelling, and jaundice, while chronic hepatitis may be asymptomatic but can lead to cirrhosis and hepatocellular carcinoma.
Identify the pathogens that cause viral hepatitis and describe their genomic structures.
Pathogens causing viral hepatitis include:
* HAV (ssRNA)
* HBV (gapped dsDNA)
* HCV (ssRNA)
* HDV (ssRNA)
* HEV (ssRNA)
What are the key differences in the pathogenesis of HAV and HEV?
Both HAV and HEV are transmitted fecal-orally and cause similar acute symptoms. However, HEV has a higher risk of severe disease in pregnant women and those with underlying liver conditions.
Explain the significance of elevated AST and ALT levels in viral hepatitis.
Elevated AST and ALT levels indicate hepatocyte damage and are early markers of viral hepatitis. Their levels can help assess the extent of liver injury and monitor disease progression.
Describe the role of CD8+ cytotoxic T cells in the pathogenesis of HAV.
CD8+ cytotoxic T cells target and eliminate infected hepatocytes, contributing to liver damage and the clinical symptoms of hepatitis.
What are the risk factors for severe HEV infection, and how do they influence disease outcomes?
Risk factors for severe HEV infection include pregnancy, underlying liver disease, and immunosuppression, leading to higher mortality rates and more severe disease outcomes.
How does the immune system respond to HAV infection, and what are the implications for disease resolution?
The immune response to HAV includes CD8+ cytotoxic T cells and antibody-mediated cytotoxicity, leading to the elimination of infected cells, resulting in no chronic carrier state and lifelong immunity.
What are the diagnostic criteria for acute viral hepatitis, and how are they applied in clinical practice?
Diagnostic criteria for acute viral hepatitis include clinical suspicion based on symptoms, liver function tests showing elevated AST and ALT levels, and serological assays for specific viral antigens or antibodies.
Discuss the role of vaccination in the prevention of HAV and HEV, and the challenges associated with vaccine implementation.
Vaccination is crucial for preventing HAV and HEV infections. HAV vaccines are widely available, while the HEV vaccine, Hecolin®, is available only in China. Challenges include vaccine availability and public awareness.
Explain the significance of bilirubinuria and jaundice in viral hepatitis and their underlying mechanisms.
Bilirubinuria and jaundice result from excess unconjugated bilirubin in the blood and urine due to hepatocyte infection and impaired bile excretion, causing yellow discoloration of the skin and eyes.
What are the common modes of transmission for HBV, and how do they contribute to the spread of the virus?
Common modes of transmission for HBV include blood (parenteral), perinatal, intravenous drug use (IVDU), and high-risk sexual activity, facilitating the spread through direct contact with infected blood or body fluids.
List the serological tests used for the diagnosis of HBV.
The serological tests for HBV include:
* HBsAg (hepatitis B surface antigen)
* HBsAb (hepatitis B surface antibody)
* HBcAg (hepatitis B core antigen)
* HBcAb (hepatitis B core antibody)
* HBeAg (hepatitis B e antigen)
* HBeAb (hepatitis B e antibody)
These tests help determine the stage of HBV infection.
Identify the serological markers that indicate an acute HBV infection.
Acute HBV infection is indicated by the presence of HBsAg and IgM anti-HBc.
IgM anti-HBc is a marker of recent infection.
What are the serological markers for a resolved HBV infection?
A resolved HBV infection is indicated by:
* HBsAg negative
* HBsAb positive
* HBcAb positive
This pattern indicates that the immune system has successfully cleared the virus.
Describe the prevention strategies for HBV.
Prevention strategies for HBV include:
* Vaccination with a recombinant DNA vaccine
* Passive immunization with HBIG for post-exposure prophylaxis
The vaccine is administered in three doses and is 95% effective.
Explain the importance of vaccinating against HBV within 24 hours of birth for all neonates.
Vaccinating neonates within 24 hours of birth is crucial to prevent maternal-to-child transmission of HBV, which can lead to chronic infection and severe liver disease.
Many cases involve mothers with unknown or false-negative serology.
Discuss the complications associated with chronic HCV infection.
Chronic HCV infection can lead to:
* Ongoing inflammation
* Cirrhosis
* Hepatocellular carcinoma (HCC)
* Cryoglobulinemia
* Vasculitis
* It is also the leading cause of liver transplants in the US.
These complications highlight the importance of early detection and treatment.
Describe the mechanisms of action of available therapeutic options for HCV.
Therapeutic options for HCV include:
* NS3/4A protease inhibitors
* NS5A inhibitors
* NS5B polymerase inhibitors
These drugs prevent RNA replication and are often used in combination.
Explain the role of cytotoxic T cells in the pathogenesis of HBV.
Cytotoxic T cells mediate the destruction of infected hepatocytes, leading to liver damage and the acute symptoms of HBV infection.
This immune response is crucial for controlling the infection but also contributes to liver injury.
What are the primary risk factors for HCV transmission in the US?
The primary risk factors for HCV transmission in the US are:
* Intravenous drug use (IVDU)
* Sexual transmission
Understanding these risk factors is essential for prevention strategies.
How does the presence of HBeAg correlate with HBV infectivity?
The presence of HBeAg correlates with higher levels of circulating viral DNA and higher infectivity, indicating active viral replication.
This marker is important for assessing the risk of transmission.
Discuss the significance of HBsAg in HBV diagnosis.
The detection of HBsAg indicates an active HBV infection.
It is one of the first markers to appear during infection and is used to diagnose both acute and chronic HBV.
Explain the rationale behind the use of combination therapy in HCV treatment.
Combination therapy in HCV treatment targets different viral proteins to:
* Increase cure rates
* Reduce the likelihood of resistance
This approach has led to near 100% cure rates for genotype 1 cases.
What are the serological markers for chronic HBV infection?
Chronic HBV infection is indicated by:
* HBsAg positive
* HBsAb negative
* HBcAb positive
* HBV DNA positive
This profile helps in differentiating chronic from acute infections.
How does co-infection with HDV affect the clinical course of HBV?
Co-infection with HDV leads to more severe acute symptoms than HBV alone.
Superinfection with HDV after HBV can result in severe hepatitis with a higher mortality rate (5-15%).
Describe the immune response involved in the acute symptoms of HBV infection.
The acute symptoms of HBV infection are due to the cytotoxic T cell response directed against infected hepatocytes, leading to liver damage.
This immune response is responsible for the clinical manifestations of the disease.
What are the outcomes of HCV infection in terms of liver disease progression?
Chronic HCV infection can lead to:
* Cirrhosis
* Liver failure
* Hepatocellular carcinoma (HCC)
Many adults with chronic HCV are unaware of their infection, which can progress silently over decades.
Explain the significance of HCV genotype in therapy selection.
Different HCV genotypes respond differently to therapies.
In the US, genotype 1 is the most common and directs therapy selection, predicting the response to treatment.
Discuss the importance of blood product screening in preventing HCV transmission.
Blood product screening is crucial in preventing HCV transmission through contaminated blood products.
This practice has been in place since 1982.
