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HIV & AIDS LCHS Mark Ewoldsen, Ph.D. Immunology 2 Significance of the Immune System • Beneficial –Protection from Invaders –Elimination of Altered Self • Detrimental –Discomfort • inflammation • allergies –Damage to self (autoimmunity) 3 Pathogens • Microbes that cause disease –constantly in the environment –evolved to spread in a variety of ways • Four types –Bacteria –Fungi –Viruses –Protozoa 4 Bacteria Concentrations Part of body Bacteria Head (scalp) 1,000,000 /cm2 Surface of skin 1000 /cm2 Saliva 100,000,000 /g Nose mucus 10,000,000 /g Feces over 100,000,000 /g 5 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Antigen • Non-self molecule –on the surface of every foreign cell –unique set of characteristics –generally fragments of protein or carbohydrate molecules 6 Balance between Infection and Immunity Infection Immunity 7 Innate vs Adaptive Innate Adaptive Antigen independent No time lag Not antigen specific No Immunological memory 8 8 Eyes • Tears –wash out pathogens –contain enzyme that can kill bacteria 9 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Nose • Mucus traps pathogens –swallowed –blown out in coughs and sneezes 10 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Mouth • Friendly bacteria help to prevent the growth of harmful pathogens • Saliva cleans and removes bacteria. 11 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Lungs • Mucus in lungs traps –bacteria –fungal spores –Tiny hairs, called cilia move mucus • up to the back of the throat • it is swallowed 12 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Stomach • Acid helps to sterilize the food 13 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Skin • Outer layer of skin –dead –difficult for pathogens • grow on • Penetrate • Cuts allow pathogens to gain entry to the body 14 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Reproductive system • Slightly acid conditions –vagina – urethra –help to stop the growth of pathogens 15 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Large intestine • Friendly bacteria – stop the growth of harmful pathogens • Feces contains over 30% live bacteria 16 http://www.abpischools.org.uk/res/coResourceImport/resources04/immune/immune3.cfm Innate vs Adaptive Innate Adaptive Antigen independent No time lag Not antigen specific No Immunological memory Antigen dependent A lag period Antigen specific Development of memory 17 17 18 What is HIV? HIV (human immunodeficiency virus) is the virus that causes AIDS. + HIV = AIDS A positive HIV test result does not mean that a person has AIDS. A diagnosis of AIDS is made by a physician using certain clinical criteria I Heard It through the Grapevine AIDS Mythology Fact or Fiction? You can get AIDS from a mosquito bite Fact or Fiction? You can get AIDS from a mosquito bite Fiction HIV is not transmitted by insects Fact or Fiction? You can get AIDS by having oral sex with an infected person Fact or Fiction? You can get AIDS by having oral sex with an infected person Fact It is possible for either partner to become infected with HIV through performing or receiving oral sex. While no one knows exactly what the degree of risk is, evidence suggests that the risk is less than that of unprotected anal or vaginal sex. Fact or Fiction? HIV survives well in the environment, so you can get it from toilet seats and door knobs Fact or Fiction? HIV survives well in the environment, so you can get it from toilet seats and door knobs Fiction Scientists and medical authorities agree that HIV does not survive well in the environment - so forget about those toilet seats! Fact or Fiction? You can get AIDS by hugging a person with HIV who is sweating Fact or Fiction? You can get AIDS by hugging a person with HIV who is sweating Fiction Contact with saliva, tears, or sweat has never been shown to result in transmission of HIV. Fact or Fiction? You can get AIDS by kissing someone who is HIV infected Fact or Fiction? You can get AIDS by kissing someone who is HIV infected Fiction It would be extremely unlikely to get HIV from kissing, even open-mouth deep kissing. HIV is transmitted through blood, semen, vaginal fluids, and breast milk and these fluids are not usually present during kissing. Fact or Fiction? Condoms are not really effective in preventing HIV transmission Fact or Fiction? Condoms are not really effective in preventing HIV transmission Fiction •The protection that proper use of latex condoms provides against HIV transmission is most evident from studies of couples in which one member is infected with HIV and the other is not. •In a study of discordant couples in Europe, among 123 couples who reported consistent condom use, none of the uninfected partners became infected. •In contrast, among the 122 couples who used condoms inconsistently, 12 of the uninfected partners became infected Fact or Fiction? There is a connection between other STDS and HIV infection Fact or Fiction? There is a connection between other STDS and HIV infection Fact Having a sexually transmitted disease (STI) can increase a person's risk of becoming infected with HIV up to 10x Fact or Fiction? Patients in a dentist or doctors office are at risk for getting HIV Fact or Fiction? Patients in a dentist or doctors office are at risk for getting HIV Fiction Studies of more than 22,000 patients of 63 health care providers who were HIV-infected have found no evidence of transmission from provider to patient in health care settings HIV/AIDS Quick Facts QuickTime™ and a BMP decompressor are needed to see this picture. 38 Global • 33 million people worldwide living with HIV/AIDS in 2007 • 2.7 million people newly infected with HIV in 2008 • Deaths –more than 27 million lives to date –2 million people die every year • More than 95% in developing countries 39 40 41 42 43 Global • Children living with HIV/AIDS –2 million, 2008 figures –Most in sub-Saharan Africa • infected by their HIV-positive mothers –childbirth –breastfeeding • Almost 1200 children newly infected each day 44 Percentage of children under 18 who have lost one or both parents, in countries with HIV prevalence greater than 1 per cent, 2003-2007 45 Domestic • The U.S. HIV/AIDS epidemic began in 1981 and continues to disproportionately affect minorities, men who have sex with men of all races, women and youth • More than 1 million people in the U.S. currently are living with HIV/AIDS • 21 percent of those infected with HIV are unaware of their infection 46 Domestic • 1 million affected, with as many as 53,600 new AIDS cases reported each year. • Since the U.S. epidemic began, 565,927 people have died of AIDS 47 48 HIV Biology 50 Biology of HIV • HIV belongs to a class of viruses known as retroviruses • Retroviruses are viruses that contain RNA (ribonucleic acid) as their genetic material 51 52 HIV Devastates the Immune System • Every day, HIV destroys billions of CD4+ T cells • Overwhelming the immune system's capacity to regenerate or fight other infections 53 X 54 • Virus can hide within –the cytoplasm –integrate into DNA • HIV can hide in –Brain –Lymph nodes –Skin –peripheral blood –Reticuloendothelial system –Bone marrow –Gastrointestinal cells 55 Risk Factors 56 HIV Risk Factors HIV is found in • blood, semen or vaginal fluid Increased risk • Engage in anal, vaginal or oral sex with –men who have sex with men –multiple partners –anonymous partners without the use of a condom 57 HIV Risk Factors Increased risk • Inject drugs or steroids & share needles/syringes • STD+ – Syphilis – Genital herpes – Chlamydia – Gonorrhea – Bacterial vaginosis or trichomoniasis 58 HIV Risk Factors Increased risk • Have hepatitis, tuberculosis or malaria • Exchange sex for drugs or money • Exposed to the virus as fetus or infant before or during birth or through breastfeeding from a HIV+ mother • Received a blood transfusion or clotting factor in US from 1978-1985 • Engage in unprotected sex with someone who has any of the risk factors 59 Factors affecting Progression High Viral Load • People with high viral loads are more likely to progress to AIDS faster Viral Set Point • HIV level of in a person’s blood after the first few months of infection • Higher viral set point are much more likely to get sick faster 60 Testing and Diagnosis • Routine HIV Testing –1.1 million Americans HIV+ –21% do not know • CDC recommends HIV testing –Adults –Adolescents –Pregnant women • prevent mother-to-child HIV transmission 61 Testing and Diagnosis • Types of Testing –sample of blood for HIV antibodies • ELISA • Western blot 62 63 Testing and Diagnosis • Types of Testing –sample of blood for HIV antibodies • ELISA • Western blot • antibody tests may not detect HIV –recently infected with HIV (within one to three months of infection) • HIV DNA test 64 Treatment • Early 1980s people with AIDS were not likely to live longer than a few years 65 Treatment • Early 1980s people with AIDS were not likely to live longer than a few years • Today – 31 antiretroviral drugs (ARVs) • do not cure people of HIV or AIDS – suppress the virus » even to undetectable levels » does not eliminate HIV from the body – lead longer and healthier lives – can still transmit the virus – must continuously take antiretroviral drugs 66 Vaccine Problem • HIV continually –mutates –recombines –evolve –new strains of virus that differ slightly from the original infecting virus • Vaccine not cover all 1500 types in body • Increase risk of partners 67 Progression of HIV → AIDS 68 Clinical Progression of HIV Typical course of HIV infection that shows the relationship between the levels of HIV (viral load) and CD4+ T cell counts over the average course of 69 untreated HIV infection Acute Primary Infection • HIV enters the body • Virus infects a large number of CD4+ T cells and replicates rapidly • Blood has a high number of HIV copies (viral load) – spread throughout the body – seeding in various organs, particularly the lymphoid organs such as the thymus, spleen, and lymph nodes 70 Acute Primary Infection • Virus may integrate and hide in the cell’s genetic material • Shielded from the immune system, the virus lies dormant for an extended period of time • Up to 70 percent of HIV-infected people suffer flu-like symptoms 71 Early Symptoms • Initial stages - very few or none • Within a month or two after infection – Fever – Headache – Tiredness – Enlarged lymph nodes in the neck and groin area • Disappear within a week to a month • Highly infectious – HIV is present in large quantities in genital fluids and blood 72 Early Symptoms • Highly infectious –HIV is present in large quantities in genital fluids and blood 73 Clinical Progression of HIV Typical course of HIV infection that shows the relationship between the levels of HIV (viral load) and CD4+ T cell counts over the average course of 74 untreated HIV infection Immune System Strikes Back • Two to four weeks after exposure – immune system fights back with killer T cells (CD8+ T cells) – B-cell-produced antibodies • HIV levels in the blood are dramatically reduced • CD4+ T cell counts rebound and number may rise to original level 75 Clinical Progression of HIV Typical course of HIV infection that shows the relationship between the levels of HIV (viral load) and CD4+ T cell counts over the average course of 76 untreated HIV infection Clinical Latency • Free of HIV-related symptoms for several years despite the fact that HIV continues to replicate in the lymphoid organs where it initially seeded 77 Clinical Progression of HIV Typical course of HIV infection that shows the relationship between the levels of HIV (viral load) and CD4+ T cell counts over the average course of 78 untreated HIV infection Progression to AIDS • Immune system eventually deteriorates to the point that the human body is unable to fight off other infections – HIV viral load in the blood dramatically increases – Number of CD4+ T cells drops to dangerously low levels • AIDS diagnosis – one or more opportunistic infections – fewer than 200 CD4+ T cells per cubic millimeter of blood 79 Later Symptoms • Virus severely weakens immune system • Symptoms: – – – – – – – – – Rapid weight loss Recurring fever or profuse night sweats Extreme and unexplained fatigue Prolonged swelling of the lymph glands in the armpits, groin or neck Diarrhea that lasts for more than a week Sores of the mouth, anus or genitals Pneumonia Red, brown, pink or purplish blotches on or under the skin or inside the mouth, nose or eyelids 80 Memory loss, depression and other neurological disorders. Clinical Progression of HIV Typical course of HIV infection that shows the relationship between the levels of HIV (viral load) and CD4+ T cell counts over the average course of 81 untreated HIV infection Opportunistic Diseases • Bacterial – Tuberculosis – MAC – bacterial pneumonia – Septicaemia (blood poisoning) 82 Opportunistic Diseases • Protozoal diseases – Toxoplasmosis – Microsporidiosis – Cryptosporidiosis – Isopsoriasis – Leishmaniasis 85 QuickTime™ and a BMP decompressor are needed to see this picture. Toxoplasmosis 86 QuickTime™ and a CryptosporidiosisBMP decompressor are needed to see this picture. 87 Leishmaniasis 88 Opportunistic Diseases • Fungal diseases – PCP – Candidiasis – Cryptococcosis – Penicilliosis 89 Thrush Thrush Opportunistic Diseases • Viral diseases – Cytomegalovirus – Herpes simplex – Herpes zoster virus 93 94 Opportunistic Diseases • HIV-associated malignancies – Kaposi's sarcoma – Lymphoma – Squamous cell carcinoma. 95 Kaposi’s Sarcoma 155 97 Bibliography 1. ‘Sexually Transmitted Disease Program,’ Los Angeles County Department of Health Services - Public Health @ http://lapublichealth.org/std, 4/22/04 2. “Access Excellence @ the national health museum”, http://www.accessexcellence.org/AB/GG/Antibody.html 3. “Averting AIDS and HIV”, www.avert.org 4. “Bio 160, Development of Vaccines to Infectious Disease” Brown University, http://www.brown.edu/Courses/Bio_160/Projects1999/hiv/ 5. “Centers for Disease Control and Prevention”, http://www.cdc.gov/hiv/graphics/images/l178/l178-3.htm 6. “Free Graphics”, http://www.freegraphics.com/images/downloads/worldaids/index3.html 7. “Galaxy Goo, An Online Exploration of Science and Community”, http://www.galaxygoo.org/hiv/hiv_lifecycle.html 8. “Health”, AllRefer.com, http://health.allrefer.com 9. “MSN Encarta: Multimedia”, http://ca.encarta.msn.com/media 10. “Population Reference Bureau”, http://www.prb.org 11. “The HIV/AIDS Search Engine”, http://www.hivaidssearch.com/hiv-aids-links.asp 12. “Yahoo Health” http://health.yahoo.com/health/ency/adam/000821/i9478 13. 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Mertz KJ, McQuillian GM, Levine WC, et al. A pilot study of the prevalence of Chlamydia infection in a national household survey. Sex Transm Dis 1998; 25:225-228 48. Progress in Reproductive Health Research, Sexual Health, A New Focus for WHO No. 67, 2004. 49. Pubic Lice or "Crabs” Pthirus pubis (THEER-us pu-bis), CDC @ http://www.cdc.gov/ncidod/dpd/parasites/lice/factsht_pubic_lice.htm, 4/22/04 50. Rochester Institute of Technology, http://www.rit.edu/~photo/IFS/index-pages/IFS-37.htmleluxe.html 51. Simms I, Stephenson J. 2000. Sex Transm Infect. Bibliography 52. Spencer S. Eccles Health Sciences Library, University of Utah, http://medlib.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS001.html 53. Spiderbytes: A New Spin on Sexual Health for Teens, http://www.spiderbytes.ca/Health/Health_STIs_STIsByNames.shtml, 1/30/05 54. Starnbach, Dr. Michael, “Adaptive Immune responses to bacterial pathogens”, Department of Microbiology and Molecular Genetics, Harvard Medical School. 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