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Chapter 5

10 textbook HLTa01 lecture Aids&HIV [chapter 5] .docx

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University of Toronto Scarborough
Health Studies
Caroline Barakat

Chapter 5- A Modern Plague, AIDS Aids stalks the continent of Africa, but isn’t confined to it st st  It is a global disease and the 1 pandemic of the 21 century  It is a deadly disease for which there is NO cure or vaccine  The threat of polio and smallpox are nonexistent because of effective vaccines, and diphtheria, whooping cough are rare because children are immunized with DPT shot Aids transcends economies, and according to the WHO it afflicts 15 million people worldwide and occurs in both developed and less developed countries Worldwide estimated that 12.9 million were infected, 20 years later 30-40 million people were infected and 18 million died from AIDS since 1999, 15000 new infections every day A Look Back  Aids began as most epidemics do with small number of cases, fewer # of deaths and almost geometric increase in # of cases and deaths virus that causes AIDS is called “human immunodeficiency virus [HIV]” 1981, center for disease control [CDC] began receiving increased numbers of requests for pentamidine, drug used to treat an unusual type of pneumonia  Dr. Micheal Gottlieb; Caused by fungus “Pneumocytis carinii”  Usually found in leukemia, or adults with lymphomas or immunosuppressive drugs  He found them in young, male homosexuals  GRID was used to name the syndrome, which collected all the characteristics of the disease for gay related immune deficiency  2 labs found causative agent for GRID, Luc Montagnier and Robert Gallo: a virus named HLTV II and LAV, o today both known to be same virus  virus renamed human immunodeficiency virus [HIV] and the disease complex it produced was called “acquired immunodeficiency disease” [AIDS] HOW are they related? o HIV is a virus, an entity o Virus such as HIV is spherical in shape, resembling a 20 sided soccer ball, o Cannot be seen with naked eye, or light microscope, but only with electron microscope which magnifies 100,000x o Viruses aren’t cells, but are able to reproduce themselves by taking over the machinery of living cell o Ultimate parasite o Composed of DNA or RNA, and viral nucleic acid is packaged within a protein wrapper called the core, then outer virus coat or capsid then layer; envelope partly of host origin o In the case of HIV the genetic material is in the form of RNA, NOT DNA o In order for virus to use the machinery of eukaryotic host cell, it must subvert the cell’s machinery to copy viral RNA to DNA o Information is written as: RNADNARNAprotein, basically flow of info is in reverse of what is typically found in cells; retroviruses HIV discovered  Discovery began more than a century ago [1884] with development of porcelain filter by Charles Chamberland, who worked in the lab of Louis Pasteur; the infectious agent had to be smaller than bacterium which is a VIRUS  AIDS described in 1891, 2 years later Luc and Gallo discovered the retrovirus responsible for destruction of lymphocytes [HIV]  Upon virus replication, the host immune system was crippled, leading to clinical syndrome of AIDS  Hitchings and Elion were chemist-pharmacologists who had produced active compounds against smallpox  When pandemic of AIDS began, burroughs-wellcome had a wide array of antitumor compounds  One was AZT, 1964, it became the first line of treatment for AIDS  Both received Nobel prize, HIV’s Target: the Immune System Chemokines are soluble chemical messengers that attract or activate other white cells especially the T and B lymphocytes and macrophages To be activate, these white cells must have on their surface a receptor for the chemokine One chemokine receptor called alpha is an entry cofactor for the invasion of T cells by HIV, Another called beta is an entry factor for the invasion of macrophages by HIV and it activates monocytes, lymphocytes, basophils and eosinophils T lymphocytes, the cells that can be infected with HIV The glyproteins of the HIV capsid resemble lollipops; the stick is called gp41 and the candy ball gp120 o The function of the 2 viruses is to bind and anchor HIV to the surface of the cell, CD4 on surface allows for docking of gp120, which changes its shape so that it can bind and then a fusion takes place, with entry of HIV o If person has mutation in the chemokine receptor that individual would not be susceptible to HIV because the virus cannot enter the T CELL o Only 1% of Caucasians have this trait and it is absent from western and central Africans and Asians o CCR5 acts as a receptor for HIV also as well as smallpox virus o People with 2 normal CCR5 genes can easily contact HIV, those with one copy of the mutation can be infected but will develop AIDS more slowly, and HIV will never affect those with 2 copies of delta-32 gene Once HIV enters the cell, capsid breaks down and coat is lost and virus RNA and reverse transcriptase are released, then begins to synthesize viral DNA from viral RNA and then transported to nucleus of t lymphocyte Following assembly, the viruses leave the cell by budding, in the process the host lymphocyte is destroyed The released viruses then travel via blood to various lymphoid organs, 10 viruses are produced and cleared from blood every day, every 2-3 days host cell is destroyed Antibody to HIV is produced, found in the serum cannot eliminate the virus because it is unable to act on viruses hidden away in t lymphocytes The antibody is used as a diagnostic test, [1985] o If serum contains antibody to HIV the person must have been infected with HIV, said to
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