Vaccination Miller Flashcards
What is a vaccine ?
Any deliberate immunizations that induce immune responses ( if successful they weill be successful immune responses)
Define immunization
The deliberate prevocation of an acquired immune response by introducing antigen into the body
What is an attenuated virus
A weakened form of the virus
What is a subunit vaccine?
Vaccines that employ only part of the pathogen as the vaccine imunogen
What is a toxoid?
A form of bacteria that has been deactivated but can still elicite an immune response.
What do bacterial vaccines consist of ?
Whole bacteria, secreted toxins, or polysaccharide capsules.
What are inactivated bacterial toxins ?
Toxoids
What is BCG ?
BCG is an acronym for Bacille-Calmette-Gurrin which is derived from a strain of Myobacterium Tuberculosis
What do viral vaccines consist of ?
Killed, subunit, or attenuated forms of the virus as the vaccine immunogens
What is an attenuated virus ?
One that has been killed, or weakened but its ability to replicate in the host still remains.
What is an adjuvant ?
Is any substance that enhances the immunogenecity of an antigen. They often lengthen the exposure of the immune system to an antigen by releasign the antigen slowly over an extended period of time.
How do adjuvants cause inflammation ?
They promote uptake of the antigen by macrophages. An example is Freunds Adjuvant which is composed of mineral oil and myobacterial cell components.
What is a liposome ?
It is a highly stable closed vesicle formed by a single bilayer of phospholipids. Immunogens can be incorporated into and they can fuse with the cell membrane and dump their contents into the cytosol.
How can you attenuate a virus ?
You can grow the viral pathogen in non human cells. The non human cells select for virus that grown well in them. The virons will not be as strong when they are transferred to human tissue.
How can viruses be genetically modified to attenuate them ?
Viruses can be attenuated using recombinant DNA or RNA. To do this you need to identofy virulance genes that are giving the virus its pathogeneticty. The critical point for this method is the ability to identify the virulance gene that is aiding the bacteria’s pathogenecity
How can recombinant DNA be used as a viral or bacterial vaccine?
Recombinant DNA techniques can be used to clone viral or bacterial genes into nonpathogenic bacteria and viruses and can then be used to immunize a patient.
How could you use a plasmid as a vaccine ?
Recombinant genes from a bacteria or a plasmid can be cloned into a DNA plasmid and given nasally or IM
What is a risk factor in using attenuated strains of a vaccine ?
They can revert back to their pathogenic strain
What is a clinical example of an attenuated virus used as a vaccine ?
Rhotovirus
How is rotovirus similar to influenza?
- It has a segmented genome
- It has antibody responses directed against surface proteins of the virus that are protective and can be used for neutralization.
How can cytokines shape an immune response?
They can direct the differentiation between Th-1 and Th-2 cell types
What will the cytokines produced by the TH-1 cell types promote ?
Th-1 cells promote the development of immune responses that are effective against clearing intracellular immune responses and will inhibit the development of Th-2 cytokine responses.
What do the cytokines produced by TH-2 cells promote?
TH-2 effector cells promote the development of immune responses that are best for clearance of extracellular pathogens. These cytokines also inhibit the development of TH-1 effector cells.
Can TH-1 and Th-2 alter the effect of an infection.
Yes depending if the pathogen is an intracellular or extracellular pathogen
What promotes Th-1 development ?
IL-12 and INF-Gamma
What does IL-4 promote
Differentiation of TH-2 cells
What is a toxoid ?
A form of bacteria that has been attenuated to reduce its pathogenecity
What are the most two aspects of a vaccine ?
Safety and effectiveness. They must provide the patient with prolonged protection from the virus. It is best to induce neutralizing antibodies to prevent the virus from destroying cells that can not be replaced.
What is one thing every vaccine must do ?
Generate protective T cells
What is the goal of vaccination ?
To trick the immune system to generate an immune responses to vaccine particles
What is the antigen dose threshold
You plot the level of antibody responses to antigen presentation. There is a plateu that is reached where more antigen will not result in more antibody produced
What happens when antigen is presented at very high doses?
There is a level of antigen that will not result in more antibody production.
What results when there is alow dose exposure to antigen initially?
Mice that have been immunized will display a secondary response that is ten to the 4 times the initial response will show very little immune response.
What are the ways you can administer a vaccine?
Parental, Oral, Muccosal
What kind of response do extracellular pathogens elicit ?
TH-2 driven antibody response
What kind of response do intracellular pathogens elicite
TH-1 driven CTL response
What kind of immune response can a parenteral immune response generate?
It can elicite a strong systemic response but will not generate a mucosal response
To get a mucosal immune response what must you do ?
Give the vaccine in a mucosal route
How do you circumvent the eolerance response of the body?
You have to activate B-7 expression by APC’s. The vaccine must elicit the appropriate danger cells.
How can the vaccine activate the T cell ?
The efficacous vaccine must elicite B-7 co expression or the t cell will become anergic and die when activated by the APC
What are the two primary formats of vaccines
Whole pathogen vaccines (Live attenuated or whole killed ) Subunit Vaccines (individual or mixture of pathogen derived components.
What is adjuvant ?
Any substances used to adapt an immune response to a vaccine immunigen. To exert its effect the adjuvant is co-administered with the immunogen
Describe the process of how a vaccine toxoid can make its way to a MHC-1 cell ?
The toxoid is engulfed into liposome. More or less emulsified by a polar head and a hydrophobic tail. And this liposome fuses with the APC and releases the toxoids into the cytoplasm of the APC where they are degraded by the proteosome and bound to MHC-1 cells.
What kind of toxins have a powerful adjuvants for mucosal responses?
Bacterial Adjuvants
What is the drawback of muccosal adjuvantacy that is associated with bacterial toxins ?
The adjuvancy can also lead to toxicity
What is the goal when designing adjuvants ?
You have to balance toxicity vs adjuvanticity
What is an attenuated pathogen ?
Is a strain that will grow and induce immunity without causing disease.
What is more effective, killed or attenuated ?
Attneuated is an actual live pathogen that will produce physiological amounts of antigen. You will get the correct amount of processing and presentation. There will also be an appropriate array of cytokine and chemokine responses. ( Killed Vaccines will not do this & Live is way to dangerous )
Describe the process of in vitro attenuation
Take a viral pathogen from human cells, purify the cells, add the cells to monkey cells. The virus is not initially adapted to survive in monkey cells so they will mutate and adapt to live in the monkey cells. After they adapt to the monkey cells they will not be all that great in human cells. Thus, there virulance has been decreased and can be reintroduced to humans. ( This is not really that safe because they can switch back to their virulent form )
How would you make an attenuated virus with recombinant DNA ?
The Virulence gene must be known. You can use recombinant DNA to delete the gene and replace it with DNA of your choice. The Virulance gene will not be there. The virus can undergo their life cycle and the body can form an immune response but the virus will not undergo the diseased state.
What are the two options using recombinant DNA ( Virus Attenuation )
Deletion and mutation. Deletion is safer but again you will need to know the virulence gene
What is a common example of a recombinant attenuated vaccine ?
Rotovirus
How is rotovirus like influenza ?
They are recognized through identification of glycogen specific neutralizing antibodies.
- High mutation rate of envelope glycoproteins (VP4 and VP7) give rise to immunologically distinct serotypes ( Antigenic Drift )
- They have s segmented genome which can be exchanged in a superinfected cell ( antigenic shift )
* * 5 of the types of rotovirus account for the majority of infections
What are the 2 recombinant attenuated strains of rotovirus vaccines
Rotarix- attenuated human virus.
RhotaTeq- Derived from cattle viruses. They express the most common variants of VP-4 and VP-7.
What would you use to vaccinate against intracellular Listera monocytogenes
The most important aspect of Listeria is a CD8 response ( you need CD4-Th1) it lives in a macrophage that takes it up.
***LMAg is the Listera vaccine, If you put it in ISCOMS it is more likely to go to the APC, B- Pertussis is a danger signal that will increase the activation of T cell responses
What is ISCOMS ?
A liposomal formation that can deliver a vaccine to an APC to generate a Class 1 response
Which subunit strategy would you use to vaccinate against S Pneumo
?
What is a powerful adjuvant for administering a nasal vaccine?
Cholera Toxin B
What is a DNA vaccine ?
They elicite a great immune response but it is difficult to generate a vaccine that will give long lived protection. You give the gene to the host on a plasmid ( IM, Sub-Q, Intra-N) you need a promoter but the gene will be expressed and the antigen will be generated.
Can tumor cells be recognized by your immune system ?
Yes, the tumor cells can be transfected with B7 cells so that they can provide co-stimulation to T cells.
