Manipulation of Immune Response Flashcards
What is vaccination?
The deliberate administration of killed or non-pathogenic forms of the pathogen, or antigens derived from pathogen in an effort to elicit protective immune responses for that specific pathogen
What was the first vaccine and what did it consist of?
Smallpox; made of dried pustules collected from individuals that experienced mild infections
How did smallpox vaccine work?
Because cowpox and smallpox share surface antigens, immunization with cowpox induces antigens against cowpox surface antigens. Cowpox antibodies bind and neutralize smallpox viruses.
What type of vaccine is DTP/DTaP?
Killed subunits/Toxoid (deactivated toxins); Elicits an antibody response prevents disease syndrome
What type of vaccine is the inactivated polio vaccine?
Whole killed virion
What kind of vaccine is MMR?
Live attenuated virus
What kind of vaccine is Pneumococcal conjugate?
Heptavalent/Diptheria
What type of vaccine is Haemophilus B conjugate (HiBC)?
Diptheria protein conj.
What type of vaccine is Hepatitis B?
subunit
What type of vaccine is chickenpox (Varicella)?
Live attenuated
What type of vaccine is Rotavirus?
Live attenuated
What type of vaccine is Influenza?
Killed or Live Attenuated?
Why is a live attenuated virus chosen for Chickenpox, Rotavirus, and Influenza?
Immune response best for this is CD8 mediated response; killed vaccine cannot elicit a CD8 response. Live attenuated will deliver the antigen to correct pathway (MHC I –> CD8 T Cells)
What kind of vaccine is Meningococcus C?
Conjugated capsule subunit
What kind of vaccine is HPV?
Gardasil: virus-like particles
Why do we not always use attenuated vaccines?
Safety concerns
What type of vaccine is Tuberculosis?
Attenuated strain of bovine TB (BCG)
What are the 6 characteristics of an effective vaccine?
Safety, Protective, Sustained protection given, Induces a neutralizing antibody, Induces protective T Cells, and it is Practical. (Dr. Miller says protective and practical are 2 most important to him)
What is the goal of vaccination?
To trick the immune system into producing an immune response to a vaccine as if it is responding to an actual pathogen
What are the three factors that make it difficult to vaccinate?
1) Route and amount of exposure
2) Tolerance vs Responsiveness
3) Identification of Protective determinants
What level of antigen is usually required for a response to antigen/immunogen?
The physiological amount; and must reach the “threshold” amount to make immune response and too much antigen leads to decreased antibody response.
Upon second immunization with a single antigen results in what zones are recognizable on a response graph?
Low-zone and high-zone tolerance zones (threshold is important)
What the two primary routes for exposure?
Mucosal - intranasal or oral
Systemic - parenternal (SubQ, IM)
Parenternal vaccination promotes strong responses from why system but lacks to evoke a response in what system?
Systemic; Mucosal
What is the most effective in promoting a systemic response parenternally? worst?
SubQ > IP > IM > IV
Why cant a parenternal vaccine not elicit both a systemic and mucosal response?
The systems are compartmentalized
Can a mucosal immunization evoke a systemic and mucosal response?
Yes
T/F. Parenternal and mucosal immunizations both elicit a mucosal response.
False; mucosal immunizations must be given to elicit a mucosa response
What type of response does an extracellular pathogen elicit?
Humoral TH2 driven responses (antibodies), MHC Class II presentation
What type of response does an intracellular pathogen elicit?
Cell-mediated TH1 driven responses (CTL-responsiveness, MHC Class I presentation
The vaccine must supply “danger” signals, what are they? What does this “danger” signal allow the immune system to do?
PAMPs, recognized by PRRs enabling immune system to recognize it as pathogenic and upregulate B7 expression by macrophages, B cells, and dendritic cells.
Antigen presentation to naive T-Cels must be accompanied by what?
B7 costimulatory signal
Immune responsiveness to components of a pathogen do or do not ensure protective immunity?
They do NOT
What are the two broad classifications of vaccines?
Whole Pathogen Vaccines like smallpox, live attenuated, and whole killed Subunit vaccines (pathogen derived components or components of a pathogen)
What is an adjuvant?
It is a substance that is used to enhance the adaptive immune response to a vaccine immunogen
How is an adjuvant administered?
Usually coadministered with the vaccine immunogen to elicit its full effect
What is the general composition of Freund’s adjuvant and what is the mechanism of action?
Oil-in-water emulsion
Delayed release of antigen; enhanced uptake by macrophages (complete then incomplete boosters)
Which adjuvant can be used in humans? How can it be made more effective? What does the addition do?
Alum; more effective version mixed with Bordatella pertussis; it allows for induction of costimulants
What is a liposome?
A highly stable closed vesicle formed by a single layer of phospholipids
What can be incorporated into a liposome?
Immunogens
What do liposomes do?
Fuse with cell membranes, dumping contents inside
What are powerful mucosal adjuvants?
Bacterial toxins (cholera toxin, E. coli, pertussis)
What is the drawback of mucosal adjuvants?
Their inherent toxicity
What is an attenuated pathogen?
A strain of pathogen that will grow in the host and induce immunity without causing disease
True or False. Attenuated vaccines are typically more effective than killed vaccines.
True (They replicate in host giving the right amount of antigen, deliver antigen to proper compartment, and the appropriate signaling is produced to steer immune response)
True or false. Live vaccines almost never have safety concerns.
False, they do
How is a virus attenuated in vitro?
Pathogenic virus isolated from patient and grown in human cells, then used to infect monkey cells. Grows in monkey cells, acquiring mutations. Virus now no longer grows well in humans and can be used as a vaccine.
What is an iatrogenic disease?
Reversion of virus to virulent form that can result (disease caused by medical treatment)
How is a virus attenuated using recombinant DNA techniques?
Isolate the pathogenic virus, isolate the virulence gene, and mutate or delete it. It requires knowledge of the virulence gene, it is safer than in vitro (safer to delete)
What is a recent example of an attenuated recombinant viral vaccine?
Vaccine against rotovirus (Rotarix, RotaTeq)
Give a brief overview of Rotovirus.
It is similar to influenza. Has immune protection via envelop glycoprotein-specific neutralizing Abs, high mutation rate for distinct serotypes (antigenic drift), segmented genome which can be exchanged in a superinfected cell (antigenic shift)
Which delivery method is the best for mucosal surfaces?
Directly to mucosal (Intranasal, oral)
Which adjuvant is best for delivering extracellular bacteria?
Cholera toxin B
Which adjuvant is the best for delivering intracellular bacteria?
ISCOMS
How can DNA be used as a vaccine?
Recombinant plasmid DNA encoding structural proteins of a pathogen can serve as one, delivered IM or intranasally
How is DNA used as a vaccine vector?
Clone gene for influenza hemagglutinin in a plasmid, inject cloned gene, infect with virus, measure the virus titer; mice with injected DNA don’t have virus)
True of false. Signals produced by NK cells shape the immune response
False, T helper cells; proof = injection of antibody specific for particular cytokine alters response produced
Cytokines can be used as what?
Therapeutic immunomodulators
What properties of potent adjuvants do cytokines have?
Promote development of immune response and help shape immune response produced