Defense III Flashcards
vaccination history
- 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
Types of adaptive immunity
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
Vaccine types
- 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
MRNA vaccine works by
- Lipid coat with genetic material of virus enters host
- Produce proteins then present them to MHC to be used to mount an immunological response
Viruses
- 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
sources of infection
- 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
retroviruses
- 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
virion
- 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
HIV background
- 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
HIV process
- HIV recognizes the CD4 receptor on T-helper lymphocytes using his surface glycoprotein gp120
- Once HIV binds to the CD4 receptor gp120 undergoes a conformational change that results in the binding with additional receptors in the host cell
- 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
- 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
- Viral DNA can remain latent for years while replicating the whole time unseen
- After the latent phase, the virus is activated to undergo lytic cycle killing the host cell and t helper cells
Antigenic variation in HIV
- 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
These characteristics contribute to the virulence and effective propagation of the virus
- 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
HIV modes of transmission
- 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)
Vertical transmission
- 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
Mortality/Morbidity of HIV
- 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.