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29 Cards in this Set
- Front
- Back
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In whatway is the diagnosis of HIV infection usually made and what should youunderstand by the term confirmation in this context? |
Combinedtests – serum anti-HIV and p24 antigen - Testsmust be confirmed by a qualified lab, as although they are specific, there arequite a few false positives. Confirmation is done by PCR of a second samplefrom the patient. - Newbornbabies need to have direct virus detection – anti-HIV antibodies may have comefrom the mother. |
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By whatroute is HIV transmitted between individuals and how may these be controlled orinfluenced? |
- Unprotectedsex – condom use - Motherto child – drug treatment, no breast feeding - Bloodtransfusion – screening and viral inactivation protocols -Injectingdrug use – needle exchange programmes -Increasingnational awareness and surveillance of infections |
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What are the major classes of anti-retroviral drugs in use against HIV? |
1) ReverseTranscriptase inhibitors – NRTIs or NNRTIs 2) Proteaseinhibitors 3) Fusion inhibitors 4) Chemokine receptor antagonists 5) Integrase inhibitors |
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How do reverse transcriptase inhibitors (RTI) against HIV work?
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NRTIs = nucleoside & nucleotide analogues, bind competitively to RT NNRTIs = nonnucleoside RTI - bind non-competitively to RT & so prevent HIV ssRNA conversion to dsDNA |
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What is raltegravir and what does it do? |
= HIV integrase inhibitor Blocks HIV integrase & prevents provirus formation in CD4+ cell DNA |
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What is HAART? |
Highly active anti-retroviral therapy (HAART) = 2 or more NRTIs with NNRTI or PIs. We need to use multiple drugs because HIV mutatesquickly and can develop resistance. |
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How is the efficacy of antivirals against HIV monitored? |
by HIV viral load and CD4 T cell count. If CD4count drops and viral load increases despite therapy, it suggests resistance tothe therapy. |
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What is the clinical courseof HIV infection and what are the stages of, and major AIDS defining illnessesin, clinical progression? Briefly describe how HIV causes disease |
1) Afterprimary infection, the level of viremia settles to the set point (equilibriumpoint). This is the latency period, and it is asymptomatic but with decreasing CD4 count. 2) As CD4count decreases AIDS develops, as there is a reduction in the adaptiveresponse. 3) Also, Tc cells kill CD4 cells that presentwith a viral peptide. This destroys the number of CD4+ cells in the body. |
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What are AIDs patients more prone to? |
AIDS patients are more prone to tumours and opportunistic infections – viruses (e.g. cytomegalovirus), bacteria (e.g. TB), fungi (e.g. pneumocystis jiroveci), parasites (e.g. toxoplasmosis) |
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What isthe cause of Kaposi’s sarcoma? |
is a common neoplasm (tumour) in HIV-affectedindividuals. It is an opportunisticinfection causes by human herpesvirus 8 (HHV8) that occurs due to lowered CD4 Tcell levels (i.e immune compromise) |
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How does Kaposi's sarcoma present? |
It is usually found on the skin as lumps, but lesions can also be found on the gums. Lesions are usually violet in colour. In more advanced cases, they can form in the internal organs e.g. stomach, intestines, lymph nodes. |
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Why is it proving difficult to have a vaccine against HIV? |
- Continuous anti-genic drift due to high mutation rates is problematic for HIV vaccine development |
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What happens in Hep B infection?
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Liver fibrosis -> inflammation ->cirrhosis
Inflammation in labile liver cells causeseither mutations due to rapid replication which can lead to hepatocellularcarcinoma or decompensation of blood. (labile cell = multiplies constantly throughout life) |
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What is the causative agent of Hep B? |
Hepadnaviradae (hepa – liver, DNA – genome)making it a type 7 enveloped virus - Partially double-stranded circular DNA genomethat is small - Has 3 antigen types |
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What are the 3 antigen types found on Hepadnaviradae? |
1. Core antigen(HbcAg) 2. Surfaceantigen (HbsAg) on lipid membrane3. Eantigen (HbeAg) soluble protein released from infected cells, non-capsulatedform of core antigen, produced in vast amounts |
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What happens after hepadnaviradae enters into a susceptible cell via a receptor anduncoating of the viral genomelanguage? |
synthesis of the missing part of the positiveDNA strand, to form a complete ds DNA molecule. A number ofspecies of RNA are transcribed from the DNA, encoding viral proteins, butimportantly, there is also a RNA copy of the whole genome. This RNA is packagedwithin newly synthesized core protein, together with the viral polymerase, toform immature new virus particles |
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What is the final step in viral maturation of the Hep B virus? |
the reverse transcription of the pregenomic RNAinto a DNA copy, followed by synthesis of an incomplete complementary DNAstrand to yield partial dsDNA. |
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How does hep B spread through the body? |
Once inside the bloodstream, the virus travels to the liver and infectshepatocytes. Within the hepatocytes, the virus replicates and new virusparticles are released directly into the blood and can access all bodycompartments including the genital tract. |
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How is Hep B spread?
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1) Mother to baby transmission, at birth throughexposure to infected maternal blood/ genital tract secretions. This is the mostimportant route of infection 2) Sexual transmission 3)Direct blood to blood (parenteral), bloodtransfusion and intravenous drug use |
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What is the response to Hep B in an immunocompetent host? |
can generally develop all antibodies (anti HBsare particularly important as these antibodies are potentially neutralising andcan prevent further viral spread within the body) and clear the infection The acute response can involve CD8+ T cellswithin the liver killing infected cells via MHC class I |
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What is the disease pathogenesis of Hep B due to? |
mostly due to the host response as the HBVvirus is not cytolytic |
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When does chronic inflammation of Hep arise? |
generally arises following verticaltransmission or in the immunosuppressed |
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What is the course of the chronic inflammation of Hep B? |
1) Immunotolerance Mother’s IgM initially protects the child 2) Immune active Mother’s Ab are used up and new onesare being generated 3) Immune control Ab against the e Ag are formed soviral load decreases, in some cases surface antigen may serotype convert andcan be targeted by antibody 4) Reactivation Only in immune active and reactivation stagesof chronic HBV does liver function decrease and ALT levels rise |
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What are the virulence characteristics of Hep B? |
- DNA type, cccDNA that can’t be targeted - Tropism to liver cells |
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What % of HBV infections don't result in disease? |
5% of HBV infections result in no detectabledisease phenomenon, asymptomatic seroconversion |
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What is the clinical presentation of acute Hep B? |
1) Pre-icteric (jaundice) = non-specific,lethargy, anorexia, nausea, alcohol and cigarette intolerance and fever. Rightupper quadrant abdominal pain may signify liver damage 2) Acute icteric = Jaundice, (liver unable toprocess pigments derived from haemoglobin in the blood leading to excess ofcirculating bilirubin -> yellow discolouration of skin, most easily seen bylooking at the sclera of the eyes. The pigments are filtered in the kidney andexcreted in the urine which becomes very dark, the absence in the faeces meansit becomes very pale 3) Fulminant hepatitis = acute liver failure, highmortality with only therapy a liver transplant, very rarebase |
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What happens in chronic Hep B?
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1) Virus continues to replicate in infectedhepatocytes, and is continually released from cells into the bloodstream 2) May not be symptomatic due to the size of thefunctional reserve of the liver 3) Infected cells may be killed by the CTL causingchronic inflammatory hepatitis -> fibrosis -> cirrhosis 4)Hepatocellular carcinoma, HBV carriers are 300xmore likely to develop HCC than non-carriers |
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What is the diagnosis of Hep B? |
- Depends on antigens and antibodies - HBsAg – if present the patient has beeninfected with HBV - To distinguish between chronic and acute, lookat ATL levels and antibody response to the core antigen. - IgM anti-HBc will bepresent only in acute infection. - If HbsAg persist for longer than 6 months, thenthe patient is a chronic carrier - HbeAg carriers are more at risk of long-termdisease -HBV DNA is a true marker of viral replicationand infectivity. Monitoring is key for patients undergoing antiviral therapy |
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What is the management and prevention of Hep B?
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- Vaccination containing HBsAg, prepared byrecombinant DNA technology - No cure, however people can be induced intoimmune—control - IFN-alpha acts as an immunomodulatorydrug inducing the express of class I MHC on hepatocytes allowing therecognition by virus-specific CTLS. (Only in immunocompetent) - Nucleotide analogues (NUCs) mimic bases likeadenosine and bind to the viral genome preventing replication. Combinationtherapy of these including lamivudine, adefovir, entecavir and tenofovir areused. |
