HLTB21H3 Chapter Notes - Chapter 5: Pentamidine, Immunodeficiency, Pneumocystis Jirovecii
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Chapter 5: A Modern Plague, AIDS Page 89 – 115
- According to World Health Organization (WHO), AIDS afflicts 15 million people and occurs both in developed and less developed
- In 1981, 12 cases in U.S., 1994 there were 400 000 cases, now maybe more than 1 million cases.
- Worldwide, in 1992, it was estimated that 12.9M were infected. Twelve years later = 30-40M and 18M dead by AIDS.
- Since 1999, 15 000 new infections every day.
A Look Back (90)
- AIDS started in 1981 where around 10 000 were infected worldwide by the virus: Human Immunodeficiency (HIV).
- In 1981, Centers for Disease Control (CDC) started receiving higher # of request for pentamidine, a drug used to treat an unusual
type of pneumonia (PCP) (requests mainly from Dr. Michael Gottlieb who saw more people with this disease (caused by fungus,
Pneumocystis carinii)). At first, he noticed that these were not people with the criteria for PCP; instead they were young, male, and
homosexual. The appearance of a rare cancer of the skin and blood vessels that were signalled by a red-purple blotching of the skin,
called Kaposi’s sarcoma. At that time, the syndrome was called GRID (Gay-related Immune Deficiency). In 1983, Robert Gallo
identified the causative agents – HLTV III (Human Lymphotropic T-cell Virus) and LAV (lymphadenopathy virus). These two viruses
were both the same and were named HIV and the disease it caused was named AIDS.
- HIV is a virus spherical in shape, resembling a 20-sided soccer ball.
- HIV can only be seen with the electron microscope.
- Normal: DNA RNA protein. In the cause of HIV: RNA DNA RNA protein; HIV has genetic material in RNA form and the
machinery of the eukaryotic host cell copies only DNA, so it must change it to DNA first. This flow of information is the reverse of
normal cells, so therefore these viruses are called retroviruses.
HIV Discovered (92)
- As Biologists explore nature of living things, they ask three kinds of questions: structural, functional, and evolutionary.
- Roberto Gallo and Luc Montagnier identified the retrovirus responsible for the destruction of lymphocytes (HIV).
- Upon virus replication the host immune system was crippled, leading to clinical syndrome of AIDS.
- At first, HIV had no treatment, but George Hitchings and Gertrude Elion, who had produced compounds against smallpox virus, had
helped in creating the antitumor compounds. AZT, azidothymididne, was the first treatment for AIDS.
HIV’s Target: the Immune System (96)
- White blood cells are responsible for the body’s defence system and play a key role in immunity.
- Three kinds of granule-bearing white cells: eosinophils, basophils, and neutrophils.
- Two kinds that lack granules in cytoplasm: lymphocytes and monocytes (macrophages) – both produced in bone marrow.
- Two kinds of lynphocytes: A and B. B lymphocytes make antibodies on their own or by being activated by T-helper cells, called T4 –
have a receptor molecule on their surface, CD4, as well as macrophages.
- T8 lymphocyte, killer cell, is also activated by T4-helper cell.
- T cells, unlike B cells, do not make antibody, they are involved in what is referred to as cell-mediated immunity – responsible for
transplant rejection and for delayed hypersensitivity reactions (i.e. reaction after being stung by a bee).
- T cells communicate with one another using soluble chemicals called chemokines.
- For these white cells to be activated, they must have on their surface a receptor for the chemokine.
- One chemokine receptor, called alpha (α) is an entry cofactor for the invasion of T cells by HIV, and it also activated neutrophils.
- Another chemokine receptor, called beta (β), is an entry factor for the invasion of macrophages by HIV, and it activates monocytes,
lymphocytes, basophils, and eosinphils.
-T lymphocytes can be infected by HIV.
- Glycoproteins of HIV capsid resemble lollipops: “stick” is called gp41, and the “candy ball” is gp120.
- Functions of these viral proteins are to bind and anchor the HIV to the surface of the cell.
- CD4 on the surface of the T cell allows for the docking of gp120; once docked the gp120 changes its shape so that it can bind to the
chemokine receptor, and after binding there is a fusion and entry of HIV.
- If a person has a mutation in the chemokine, they would not be susceptible to HIV.
- The decedents of the bubonic plague in Eyam, had a mutation in their chemokine receptor called delta-32 which alters the β
chemokine receptor (CCR5). This mutation also protected them against smallpox and does so against HIV as well.
- Delta-32 can be considered the “AIDS resistance gene”.
- Once HIV enters the cell, the capsid breaks down, its coat is lost, and virus RNA and reverse transcriptase are released.
- Following virus assembly, the viruses leave the cell by budding, and in the process the host lymphocyte is destroyed.
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