HIV/AIDS - Life Sciences Outreach Program - Harvard University

HIV/AIDS: The Status of theEpidemic Today“The greatest single public healthchallenge that humanity has ever faced.”Dr. Robert Lue, Harvard UniversityKristine Thyng, HHMI-MCB WorkshopSummer 2004

Worldwide• 3 million deaths in 2003• Over 21 million deaths since thebeginning of the epidemic• 17.5 million adults• 4.3 million children (under 15years old)Image fromhttp://www.freegraphics.com/images/downloads/worldaids/index3.html(www.avert.org/worldstats.htm)

Worldwide cont’d• Approximately 40 million people living withAIDS worldwide in 2003• Approximately 14 million children orphaned byAIDS by the end of 2002• Number of orphans expected to rise to 25 millionby 2010(www.avert.org)

Adult Prevalence of AIDSImage from http://www.hivaidssearch.com/hiv-aids-links.asp?id=811

People With HIV/AIDS, by RegionEnd 2002Sub-SaharanAfrica71%Latin America4%South andSoutheast Asia14%Caribbean1% North Africaand MiddleEast1%WesternEurope1%East Asia andthe Pacific3%North America2%EasternEurope/CentralAsia3%Australia andNew Zealand

United States• By the end of 2002: 384, 906 people living withAIDS– 46% White– 34% Black– 18% Hispanic– 298,248 men– 82,764 women(www.avert.org/statsum.htm)

United States Cont’d• Of the 298, 248 U.S. men living with AIDS,• 57% were men who had sex with men (MSM)• 23% were I.V. drug users• 10% were exposed through heterosexual contact• 8% were both MSM and IV(www.avert.org/statsum/htm)

United States Cont’d• Of the 82,764 U.S. women living with AIDS,• 61% were exposed through heterosexual contact• 36% were I.V. drug users(www.avert.org/statsum/htm)

Image from http://www.cdc.gov/hiv/graphics/images/l178/l178-3.htm

United States Cont’d1999: Estimated that 800,000 to 900,000Americans were infected with HIV(www.avert.org/statsum/htm)

Image from http://www.hivaidssearch.com/hiv-aids-links.asp?id=936

How A Healthy Immune SystemWorks• Physical Barriers: skin, mucus, etc.• Innate Immune System: body’s immediateresponse to a pathogen. Not antigen specific.Immunity a person is born with.• Acquired Immune System: Body takes a fewdays to build this immunity. Antigen specific.Immunity that is acquired through life.

Key Structures of theImmune SystemImage from http://health.allrefer.com/pictures-images/immunesystem-structures-1.html

Physical BarriersSkinimage fromhttp://health.allrefer.com/picturesimages/skin-layers.htmlMucosaimage fromhttp://www.health.allrefer.com/health/mucosa-info.html

Innate ImmunityIf pathogenspenetrate physicalbarriers,phagocytic cellsin the area beginto engulfpathogen.Image from http://health.yahoo.com/health/ency/adam/000821/i9478

Innate Immunity Cont’d• Phagocytes also release chemical signals (cytokines) to“call” other phagocytes to the area, resulting ininflammation (redness, heat, swelling). The pus that weoften observe is a combination of dead pathogen, whiteblood cells, and injured body cells.Image fromhttp://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl/chapter43/deluxe.html

Acquired Immunity• If pathogens are not completely eliminated by the innateimmune system, the acquired immune system is activated.• Key Players: Lymphocytes (T and B cells)Image fromhttp://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl/chapter43/deluxe.html

Acquired Immunity Cont’d•Phagocytes active in the innateimmune system display some ofthe proteins from the pathogen ontheir surfaces, “advertising” thatthe pathogen is present.Macrophage (yellow) attackingbacteria (blue)Image from http://www.rit.edu/~photo/IFS/index-pages/IFS-37.html• These cells then travel to thelymph nodes and spleen, wherethey help to activate T and B cells.The increase in T and B cellproduction when you are ill canoften be detected by swollenlymph nodes (glands).

Acquired Immunity Cont’dB cells – Defend againstpathogens located outsideof body’s cells. *• Plasma cells – produceantibodies which attach toantigens and help todestroy them, or block theharmful effects of theantigen• Memory cells – Can reactquickly to produceantibodies upon additionalexposures to the antigenImage from http://www.accessexcellence.org/AB/GG/Antibody.html*Dr. Starnbach lecture 7/13/04

Acquired Immunity Cont’d• T cells – Defend againstpathogens located inside ofbody’s cells.*– Helper T cells: secretecytokines to call in other T,B, and phagocytic cells,activate B cells to produceantibodiesT cell (SEM)– Killer T cells: recognize aninfected cell and lyse it– Memory T cells: remain inbody to react when pathogenis encountered again.Image from http://ca.encarta.msn.com/media_461519550/Lymphocyte.html*Dr. Starnbach lecture 7/13/04

How it all works togetherImage fromhttp://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl/chapter43/deluxe.html

Immune Response SummaryImage fromhttp://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl/chapter43/deluxe.html

How does HIV interrupt thenormal functioning of theimmune system?HIV infected T-cellImage fromhttp://ca.encarta.msn.com/media_461518877/TLymphocyte_Infected_With_HIV.html

What is HIV?• HIV – humanimmunodeficiency virus– Works by infecting the cells ofthe immune system, using themto make more virus, and thenkilling them.– The immune system is able tobattle this virus fairlysuccessfully for up to 8-10years, before the virus eventuallywins.Image fromhttp://medlib.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS001.html

HIV Structure• HIV is composed ofthree main layers:– Envelope– Viral Matrix– CoreImage fromhttp://www.brown.edu/Courses/Bio_160/Projects1999/hiv/images/Virion2.jpg

Overview of how HIV works• HIV attacks cells of the body, especially thehelper T cells. (Approx. 100 billion new HIVparticles generated/day during clinical latency)• When the number of helper T cells is depleted, thebody cannot fight infection• Death results from infection or cancer that thebody can’t fight off, not from AIDS itself.(Dr. Lue’s lecture 7/16/04)

HIV infection• Animation of HIV infection(http://www.galaxygoo.org/hiv/hiv_lifecycle.html)

HIV proteins attach to receptors on cell membraneHIV inserts genetic material (RNA)Reverse transcriptase used to make viral DNA from RNAViral DNA inserted into one of the cell’s chromosomesCell manufactures viral proteins and RNANew copies of virus bud off of host and infect new cells

Progression of HIV in the BodyImage from http://www.hivaidssearch.com/hiv-aids-links.asp?id=936

Do some people have resistance• Resistance to HIVto HIV?• Mutations to HIV – will those without the ccr5receptor still be resistant?(www.teachersdomain.org/9-12/sci/life/gen/hivimmunity/index.html)

Why is HIV so hard to fight?• Some antibodies that the body produces actually work toenhance HIV replication.• Some antibodies that work to neutralize HIV replicationcan become enhancing antibodies when the virus mutates.• Cells other than helper T-cells can be infected, thereforethe virus can colonize many tissues of the body.• HIV can kill cells that it doesn’t even infect.(Dr. Lue’s lecture 7/16/04)

Growth of the AIDS EpidemicPeople With HIV/AIDS, Cumulative Regional TotalsMillions4540353025201510501981 1986 1991 1996 2001Highly Industrialized* Sub-Saharan Africa South and East AsiaLatin America/CaribbeanEastern Europe, other***North America, Europe (except Eastern Europe), Japan, Australia, and New Zealand.**Eastern Europe, Central Asia, Middle East, and North Africa.Source: UNAIDS, “Twenty Years of HIV/AIDS: Fact Sheet,” 2002, and unpublished data.© 2003 Population Reference BureauImage from http://www.prb.org/presentations/d_growth-aids-epidemic.ppt

• Drug TherapyIs there any reason to beoptimistic?– “Old” drugs - reverse transcriptase and protease inhibitors. BUT,many strains of the virus are becoming resistant.– Salvage drugs• T-20 in phase III trials (prevents fusion of HIV with T-cell)• T-1249 in phase II trials (prevents fusion of HIV with T-cell).• Both are promising, but already see some resistance.(Dr. Lue, 7/22/04)

Availability of Drugs• Widely available in U.S and other industrializednations, but cost tens of thousands of dollars/year.• Clearly not feasible in developing countries.• Problems of patent infringement to producegeneric versions.(Dr. Lue, 7/22/04)

HIV/AIDS is a preventabledisease, but controllingthe epidemic will requirebehavioral changesworldwide

References• TEXT SOURCES:• “Averting AIDS and HIV”, www.avert.org• Lue, Dr. Robert, “Evasion and Destruction of the Immune System by HIV”, Department ofMolecular and Cellular Biology, Harvard University. Lecture July 16, 2004, July 22, 2004.• Starnbach, Dr. Michael, “Adaptive Immune responses to bacterial pathogens”, Department ofMicrobiology and Molecular Genetics, Harvard Medical School. Lecture July 13, 2004.• IMAGE SOURCES: All images were obtained from the web between the dates of 7/13/04 –7/22/04• “Access Excellence @ the national health museum”,http://www.accessexcellence.org/AB/GG/Antibody.html• “Bio 160, Development of Vaccines to Infectious Disease” Brown University,http://www.brown.edu/Courses/Bio_160/Projects1999/hiv/• Campbell and Reece, Biology, 6 th editionhttp://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl/chapter43

References cont’d• “Centers for Disease Control and Prevention”, http://www.cdc.gov/hiv/graphics/images/l178/l178-3.htm• “Free Graphics”, http://www.freegraphics.com/images/downloads/worldaids/index3.html• “Galaxy Goo, An Online Exploration of Science and Community”,http://www.galaxygoo.org/hiv/hiv_lifecycle.html• “Health”, AllRefer.com, http://health.allrefer.com• “The HIV/AIDS Search Engine”, http://www.hivaidssearch.com/hiv-aids-links.asp• “MSN Encarta: Multimedia”, http://ca.encarta.msn.com/media• “Population Reference Bureau”, http://www.prb.org• Rochester Institute of Technology, http://www.rit.edu/~photo/IFS/index-pages/IFS-37.htmleluxe.html• Spencer S. Eccles Health Sciences Library, University of Utah,http://medlib.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS001.html

References cont’d• “Teachers’ Domain, Multimedia Resources for the Classroom and ProfessionalDevelopment”, www.teachersdomain.org/9-12/sci/life/gen/hivimmunity/index.html• “Yahoo Health” http://health.yahoo.com/health/ency/adam/000821/i9478