Defense III Flashcards

1
Q

vaccination history

A
  • Edward Jenner in 1798 developed the first vaccine
  • He observed that milkmaids who had previously caught cowpox did not catch smallpox because they had already made antibodies/t/b cells that could recognize virus
  • He inoculated cowpox and demonstrated that it protected against inoculated smallpox but didn’t understand the mechanism
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2
Q

Types of adaptive immunity

A

o Active: create own antibodies
1. Artificial: injected or received a drug, vaccine, inoculation, modified virus, proteins from virus
2. Natural: body mounts immunological response, memory cells, create own antibodies
o Passive: receive antibodies
1. Artificial: serum, where give antibodies that recognize virus to patient
2. Natural: breast feeding delivers antibodies

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3
Q

Vaccine types

A
  • Protein subunit: injected with a component of viral protein
  • Virus like particle: contain something of virus but not genetic material
  • DNA or RNA based vaccine with genetic material of virus
  • Viral vectors: replicating or non-replicating that are no longer infectious
  • Inactivated: “kill” render virus unable to function so recognized by system
  • Live attenuated: copies of virus made weaker so can’t harm us but body can recognize and create antibodies
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4
Q

MRNA vaccine works by

A
  • Lipid coat with genetic material of virus enters host
  • Produce proteins then present them to MHC to be used to mount an immunological response
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5
Q

Viruses

A
  • Small infectious agents, obligate intracellular parasite, not a “life” b/c cant exist on own
  • can infect all types of life forms like animals, plants, eubacteria and archaea
  • Can be very diverse
    o the simplest virus is composed of a nucleic acid core (RNA or DNA with + or - strand) surrounded by a coat of proteins (capsid)
    o more advanced viruses may have a phospholipid envelope they stole
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6
Q

sources of infection

A
  • During our evolution the risk of viral infections increased dramatically
    o many viruses that infect humans are derived from domesticated animals
    o Problems of waste disposal and hygiene
    o Pathogens have evolved in relationship to the host and to the vectors they rely on for their survival and fitness
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7
Q

retroviruses

A
  • Single stranded RNA virus
  • With an envelope
  • Contains the info to create an integrase enzyme to integrate its own DNA into the host’s genome to create more virions
  • Infects t helper cell
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8
Q

virion

A
  • Envelope: composed of lipids and glycoprotein (env). Important for: Protection & Infection
  • RNA: contain two identical single-stranded RNA molecules 7–10 kb in length, codes for virion proteins:
  • most common are Gag, Pol, Env,
  • more are integrase , Tat and others
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9
Q

HIV background

A
  • HIV (human immunodeficiency virus) infection has now spread to every country in the world.
  • Approximately 40 million people are currently living with HIV infection
  • Approx. 39 million have died from this disease.
  • In the United States, approximately 1 million people are currently infected.
  • Every 10 minutes one person in the US is infected with HIV
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10
Q

HIV process

A
  1. HIV recognizes the CD4 receptor on T-helper lymphocytes using his surface glycoprotein gp120
  2. Once HIV binds to the CD4 receptor gp120 undergoes a conformational change that results in the binding with additional receptors in the host cell
  3. The viral glycoprotein gp41 is then able to mediate the fusion of the viral envelope with the cell membrane which allows RNA to enter into cell
  4. The viral reverse transcriptase converts the viral RNA into DNA, which enters the nucleus and is inserted into the cellular genome by the viral integrase
  5. Viral DNA can remain latent for years while replicating the whole time unseen
  6. After the latent phase, the virus is activated to undergo lytic cycle killing the host cell and t helper cells
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11
Q

Antigenic variation in HIV

A
  • HIV has a great **genetic heterogeneity **
    o caused by the error prone nature of reverse transcription
  • HIV being a highly mutable virus
    o exhibits frequent antigenic variations, nucleotide variations, cell tropism, growth characteristics and cytopathology
  • Differences can be identified between:
    o sequential isolates from the same person
    o between **isolates obtained from different sites **of the same person at the same time
  • highly intergenic so error prone by reverse transcriptase make the surface proteins look somewhat different so we cant make vaccines to attack them cause they change so fast
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12
Q

These characteristics contribute to the virulence and effective propagation of the virus

A
  • It is not possible to develop antibodies that can recognize the virus for a prolonged time
  • The virus can enter the body as infected cells, in which the virus is protected because cant be recognized by antibodies inside cells
  • Virus readily establishes lifelong latent infection hiding from antibodies while replicating
  • This tendency to accumulate mutations has contributed to the fast evolution of the virus
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13
Q

HIV modes of transmission

A
  • Sexual contact - In the vast majority of cases transmission is by sexual contact
  • Parenteral - by blood transfusion or blood product transfusion – numbers are decreasing
  • Sharing of unsterilized needles or syringes contaminated with blood from an infected person
  • Occupational risks - accidental needle sticks in the healthcare setting
  • Organ transplantation (donors are tested for HIV to minimize this risk but latency could cause false negatives)
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14
Q

Vertical transmission

A
  • Women can transmit HIV to the fetus during pregnancy or birth, when infected maternal cells enter the baby’s circulation
  • 30% of children born to infected mothers have the acquired infection unless virus is treated by antiviral drugs before pregnancy
  • In nursing mothers’ transmission can occur through breast milk
  • In mothers taking medications, the risk is the less than 2% mostly due to birthing so need to do a C section so no blood crossover from mother during birth
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15
Q

Mortality/Morbidity of HIV

A
  • The course of HIV infection is characterized primarily by latency
  • Profound immune suppression eventually develops, and the illness appears to be almost uniformly lethal
  • Progression from HIV infection to AIDS occurs 8-10 years after infection without antiretroviral treatment
  • Since the introduction of highly active antiretroviral therapy (HAART) and prophylaxis against opportunistic pathogens, death rates from AIDS have declined significantly.
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16
Q

AIDS

A
  • AIDS (Acquired Immunodeficiency syndrome) is a collection of symptoms due to underlying infections and malignancies resulting from specific damage to the immune system caused by HIV
  • The affected patients appeared to have lost their immune competence, rendering them vulnerable to relatively avirulent micro-organisms, as well as to lymphoid and other malignancies.
  • AIDS markers: Pneumocystis pneumonia and Kaposi’s sarcoma are considered AIDS markers, since they reflect the underlying collapsed immune system
17
Q

Causes of immune deficiency

A
  • The primary pathogenic mechanism in HIV infection is the damage caused to the CD4+ T lymphocytes
  • Infected cells are unable to release cytokines and the immune response is hampered
  • T helper cells are responsible for activating and stimulating other cells of the immune system
  • AIDS patients are unable to respond to new antigens or infections or cancer
  • The impaired immune response renders the patient susceptible to life threatening opportunistic infections and malignancies
18
Q

HIV1 group M

A
  • The epicenter in Africa (Congo)
  • Using molecular clocks, the common ancestor of HIV-1 group M strains has been dated to the 1920-1940s without people knowing what it was
  • Initial characterization of two viruses from samples obtained around 1960 in Kinshasa has shown that HIV1 group M had already diversified substantially by that time
  • HIV-2 and several SIV (Simian Immunodeficeincy Virus) strains were subsequently identified
  • Phylogenetic analysis of all these lentivirus strains has provided insights into the evolutionary origins of the human viruses
19
Q

Evolution of HIV1

A
  • Env gene of SIVGSN, SIVMuS and SIVMON is closely related to that of SIVCPZ and HIV-1,
  • Gag, pol and nef genes of SIVGSN, SIVMuS and SIVMON are most closely related to SIVRCM ²
  • This suggests that SIVCPZ arose from a recombination between ancestors of SIVs that infected different primates ²
  • Additionally, most primate lentiviruses coexist in a benign relationship with their natural primate hosts and infection is usually considered apathogenic, however, the recombination of multiple strains lead to the development of the deadly HIV that we know
    o Must have been mixing of blood between monkeys to make new virus, rna from one virus and RNA from another make hybrid/mutant virus that now infects humans
20
Q

treatments of HIV/AIDS

A
  • Focus on arresting the progression of the disease within the body as measured by T cell counts and tests for viral load
  • Main approaches:
    1. Reverse transcriptase inhibitors (RTIs)
    2. Protease inhibitors (Pis) so final proteins cant be produced
    3. Fusion inhibitors – prevent fusion of virus with host
    4. Entry inhibitors (block recognition step) – inhibit insertion of viral genome into genome of human
    5. Integrase inhibitors- inhibit reverse transcribed DNA from host integration
21
Q

Combination treatment

A
  • most affective is HAART with 3 drugs un one to block infection process
  • Reverse transcriptase inhibitors and protease inhibitors address different stages of viral replication
    using both families of drugs in combination is particularly effective
  • Highly active anti-retroviral therapy (HAART):
    o A combination of two reverse transcriptase inhibitors and a protease inhibitor
    o blocks infection both before and after integration and in both activated and resting T cells