Lecture 33 HIV and AIDS Review Can this pill end the AIDS Epidemic PrEP is PreExposure Prophylatic one a day more than 90 effective at preventing an HIV infection Only FDA approved PrEP is Truvada an HIV medicine that combines 2 NRTI s Nucleoside Reverse Transcriptase Inhibitor Must take 7 days before effective take once a day throughout period of high risk exposure and continue 28 days after high risk exposure Best to use condom and PrEP 98 and 90 effective backup plan World Health Guidelines September 2015 recommends that anyone at high risk for acquiring an HIV infection take an approved form of PrEP Boosting Production of generic neutralizing Antibodies Scientists found existing antibodies capable of attacking a weakness in the virus Now the trick is getting our immune systems to create more of them Engineering Human Genes for Immunity People are using expensive inexpensive technology to mutate mess up the virus Major Viral Components Gp120 and Gp41 make up the 72 spikes on the HIV particle Embedded in the stolen lipid bilayer of whatever CD4 cell it came from How Does HIV Bind to Target Cells GP120 binds to CD4 receptor CD4 receptor brings HIV closer to the surface of the target cell closer to the CCR5 receptor on the cell surface CCR5 is what makes the initial infection It extends out and into the target cell membrane The membranes meld together and the inside enters the target cell Binding of HIV to CD4 T Cell Virus directly infects helper T cells Stalk of the envelope pierces the target cell membrane and the membranes fuse It interacts with CD4 receptors that are unique to this type of cell together and the genetic material is injected into the host cell Replication of HIV It needs to enter the host cell 1 2 Membranes fuse together 3 Single stranded RNA is released into the cell 4 The protein reverse transcriptase comes into the cell and reverse transcribes the 5 Two strands of DNA complementary looking like our DNA It can interact with HIV RNA into DNA the genome 6 Integrase carries the DNA into the nucleus randomly chops away a piece of DNA and inserts that piece of HIV DNA right into the host cell DNA chain 7 HIV uses the host cell s machinery to transcribe the DNA back into RNA Some RNA will slip away and become single stranded Some will go straight to the ribosome and become transcribed 8 Protease cutting the polypeptides into viable proteins is crucial for the HIV virus to become fully mature 9 Virus pops off the cell and is mature Syncytia Fusion of different T helper cells Sometimes after a certain point T helper cells who have been expressing lots of HIV viruses it has all these gp120 spikes it engages with an uninfected T cell Once fused they cannot function normally Can be made up of 50 cells Usually happens around year 5 It s a sign of faster progression to AIDS What is Screening Systematic search for cancer before any symptoms are evident Targets general population who have NO symptoms Goal 1 Increase odds of early detection of cancer or pre metastases What about cancer is the actual killer Ultimate goal Decrease cancer specificity mortality What are Pitfalls of Screening False negatives More false positives than accurate correct detection of cancer Overdiagnosis treating a cancer that does not need to be treated Health risk of screening techniques Cancer label Trade offs exist between Sensitivity and Specificity Sensitivity of people with a given cancer accurately identified during Note Sensitive increased false negatives Specificity of people without cancer that are correctly identified as being Not specific increased false positives False negatives or not catching enough people who have cancer low sensitivity False positives or saying people have cancer when they don t High sensitivity screening cancer free high specificity low specificity Positron Emission Tomography PET Screens areas of the body with high metabolic activity why cancer is growing So there will be a metabolic rate where there really shouldn t be The cancer will be metabolic active An imaging technique that produces a 3 D image of picture of metabolic processes in the body Detects gamma rays emitted radioactive tracer which is introduced into the body on a molecule which cells will use in process of growing 3D images of tracer concentrations within the body are constructed Often the active molecule choesne for PET is a glucose analogue The high concentration of tracer will identify spots of active growth tumor development Use of PET Scan to identify possible metastases is the most common type of PET scan in standard medical care 90 of current scans Review Facts Cancer s cure What is the recent hypothesis for why elephants do not get cancer as much as us P53 and preference for apoptosis with DNA damage What is the long time standard triad for treatment with cancer surgery radiation chemotherapy excise the rogue cells and kill the rogue cells How does chemotherapy work Kills actively growing cells or recent versions now kill targeted cells Why does hair fall out during chemotherapy hair follicles are fast growing cells so the chemotherapy will target it How do most cells exposed to radiation die apoptosis unspecific targeting of cells
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