15: Manipulation of Immune Responses Flashcards
Variolation
Delivery of initial smallpox vaccine either intranasally or intradermally (via a scratch on the arm)
Vaccinia
Another name for the virus used to vaccinate against smallpox
Vaccination
Deliberate immunization that induces immune responses
Immunization
Deliverate provocation of an acquired immune response by introducing antigen into the body
By what methods are inactivated vaccines killed?
Chemical treatment, heat, or irradiation
What is an attenuated vaccine?
A vaccine that employs weakened pathogens as the immunogen so that the pathogen’s ability to cause disease is weakened or destroyed
What is a subunit vaccine?
A vaccine that employs only part of the pathogen as the vaccine immunogen
Toxoid
Inactivated toxin used as a vaccine immunogen whose toxic activity has been destroyed
How was the first completely effective vaccine formulated?
- Jenner noticed that cowpox produced effects that looked like a milder version of smallpox
- Cowpox was used as a vaccine for smallpox
- This induced antibodies against cowpox surface antigens, which could bind to and neutralize the smallpox virus too
Bacterial vaccines can be composed of __________.
Whole bacteria, secreted toxins, or polysaccharide capsule material
T or F: Most bacterial strains are attenuated.
F: Very few attenuated bacterial strains currently exist
What is the most widely used whole live bacterial vaccine?
BCG vaccine – derived from a bovine strain of Mycobacterium tuberculosis
What type of vaccine is the DTP (diphtheria-tetanus-pertussis) vaccine?
Killed subunits/toxoids
What type of vaccine is the inactivated polio vaccine?
Whole killed virions
What type of vaccine is MMR (measles/mumps/rubella)?
Live attenuated virus
What type of vaccine is pneumococcal conjugate?
Heptavalent/diptheria
What type of vaccine is Haemophilus B conjugate?
Diptheria protein conjugate
What type of vaccine is the hepatitis B vaccine?
Subunit
What type of vaccine is the varicella vaccine?
Live attenuated
What type of vaccine is the rotavirus vaccine?
Live attenuated
What type of vaccine is the flu shot?
Killed or live attenuated
What type of vaccine is the meningococcus C vaccine?
Conjugated capsule subunit
What type of vaccine is the HPV vaccine?
Gardasil – virus-like particles
T or F: Killed viruses elicit a large CD8 T cell response.
F: Attenuated viruses elicit a large CD8 T cell response, and killed viruses don’t
What type of vaccine is the yellow fever vaccine?
Live attenuated virus
What type of vaccine is the typhoid fever vaccine?
Vi polysaccharide subunit vaccines or live-attenuated oral vaccine
What type of vaccine is the meningitis vaccine?
Purified capsular polysaccharide or H.influenzae polysaccharide conjugated to protein (depending on the strain)
What type of vaccine is the bacterial pneumonia vaccine?
Purified capsular polysaccharide
What type of vaccine are the cholera and plague vaccines?
Killed bacteria or cell extract
What is unique about the Tuberculosis vaccine?
It is an attenuated vaccine, which is surprising since attenuated vaccines are typically for CD8 T cell response and TB mostly uses a TH1 immune response (to activate macrophages and form granulomas).
What 6 characteristics are important for an effective vaccine?
- Safe
- Protective
- Gives sustained protection
- Induces neutralizing antibody
- Induces protective T cells
- Practical considerations (cost, side effects, administration)
Why would you want a vaccine to induce neutralizing antibodies?
Some pathogens infect cells that cannot be replaced, and neutralizing antibodies prevent infection of such cells
What is the goal of vaccination?
To trick the immune system to produce responses to a vaccine like it’s responding to a pathogen
What are the 3 big factors that make creating an effective vaccine difficult?
- Route and amount of exposure
- Tolerance vs. responsiveness
- Identification of protective determinants
T or F: Most anti-viral vaccines are live-attenuated vaccines.
T
Production of strong immune responses to an antigen almost always requires that the antigen be mixed with ______ prior to administration.
An adjuvant
Adjuvant
Any substance that enhances the immunogenicity of an antigen
T or F: Parenteral immunization promotes strong systemic response, but it cannot prime mucosal responses.
T
T or F: Mucosal immunization can produce strong mucosal response, but it cannot prime systemic responses.
F: Mucosal can elicit both mucosal and systemic responses
What is the most effective parenteral route for eliciting immune response? Least effective?
Most effective: SubQ
Least effective: IV
Antigen presentation to naive T cells must be accompanied by ______.
Co-stimulation
T or F: Immune response to components of a pathogen does not ensure protective immunity.
T
What are two broad classifications of vaccines?
- Whole pathogen viruses
2. Subunit vaccines
What are subunit vaccines?
- Individual or mixtures of pathogen-derived components
- Recombinant forms of pathogen-derived components
- Recombinant live vectors expressing components of a pathogen
What does depot formation do?
Increases the length of exposure of the immune system to an antigen by releasing the antigen slowly over an extended period of time
T or F: Often adjuvants turn a soluble protein antigen into a particulate antigen that is more readily ingested by antigen-presenting cells.
T
What are some adjuvants that specifically elicit mucosal immune responses?
Cholera toxin, tetanus toxin, and E.coli lymphotoxin
What is Freund’s adjuvant composed of?
Mineral oil (depot formation) and mycobacterial cell wall components (source of PAMPs for inflammation induction)
What is a liposome?
Highly stable closed vesicle formed by a single bilayer of phospholipids
What do ISCOMs do?
Deliver immunogens directly to the cytoplasm of host cells
T or F: Attenuated vaccines are typically more effective than killed vaccines.
T
What are 2 methods of attenuation?
- Grow human viral pathogen in cells of non-human origin
2. Mutate viruses using recombinant DNA (so that virulent genes can be deleted or mutated)
How are DNA vaccines typically administered?
Intramuscularly or intranasally
What is an example of a recombinant attenuated viral vaccine that is efficacious?
Rotovirus vaccine (Rotarix and Rotateq)
How is rotovirus similar to influenza?
- Segmented genome
2. Antibody responses directed against surface proteins of the virus are protective via neutralization
How can cytokine environment shape developing acquired immune responses?
Two types of effector CD4 T cells perform different roles in the development of acquired immunity
T or F: Cytokines can be administered therapeutically to alter the outcome of an infection.
T (example: Leishmania and IL-4)
