BIOL 3155 Lecture Notes - Lecture 18: Cytotoxic T Cell, Immune System, Chemotherapy

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17 Feb 2018

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An hiv carrier name timothy brown, who had also a lymphoma. In order to cure him from lymphoma, he went under radiation and chemotherapy. This is called haematopoietic stem cell transplantation, because the chemotherapy is likely to kill his bone marrow cells low immunity. In order to restore his immunity we need to take bone marrow from a donor. Physicians in berlin decided to take the bone marrow cells from a donor who happened to be ccr5 mutated. First it was a good match to him, second this was an interesting idea to see if they can restore timothy"s helper t-cells and his immunity have a better outcome for the hiv. Donor cells were used eventually as a way to restore the immune system of timothy brown. He was recovered from lymphoma and also from hiv. Hiv was undetectable in his system, even in those hiding places.

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Some people suffer from adenosine deaminase (ADA) deficiency.ADA is an enzyme necessary for the immune systems T-cells tofunction properly. Helper T-cells activate B cells which secreteantibodies which are proteins that help fight against infection.When ADA is lacking due to an autosomal recessive mutation, theimmune system is extremely impaired and afflicted individuals aresusceptible to chronic infections. There are several differenttechniques that have been utilized in an attempt to treat ADAdeficient individuals: Chelsea received a bone marrow transplantfrom her father at four months of age. His healthy cells populatedher bone marrow, replacing her defective cells with normal, healthycells that produce the needed enzyme. She is now doing quite welland has functioning T and B cells in circulation. Michael receivedADA manufactured using recombinant DNA technology. Unfortunately,the enzyme stays in the blood for only a few minutes before beingbroken down - not long enough to restore immunity. Michael hassince passed away from a fatal viral infection. Shelley wasselected for gene therapy when a bone marrow donor could not befound for her. Her T-cells were separated and treated with aretrovirus which delivered a functional ADA gene to the T-cells.These T-cells were then re-infused back in to her body. Her immunesystem gradually began to function, but the treatment had to berepeated every few weeks as the genetically altered T-cells beganto die off. Todd had gene therapy like Shelley, but it wasperformed on hematopoietic stem cells from his bone marrow ratherthan on mature, circulating T-cells. Todd soon had many normallyfunctioning T cells and antibodies circulating in his blood for thevery first time. He even grew tonsils, which are typically absentin folks with ADA deficiency. Todd's ADA activity rose to 25% ofnormal levels, enough to provide limited immunity. To date hehasn't required any additional gene therapy.

Shelley needed to repeat her treatment (gene therapy) whereTodd and Chelsea did not because:

		Shelley s treatment altered only the phenotypic deficiency notthe genotypic mutation.
		Shelley s treatment altered the genotypic deficiency not thephenotypic mutation.
		Shelley s treatment involved germ-line therapy, which is moretransient.
		Shelley s treatment didn't activate the proper genes in herT-cells.

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BIOL 3155 Lecture Notes - Lecture 18: Cytotoxic T Cell, Immune System, Chemotherapy

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