Vaccines/immunization Pt. 1 Flashcards
What is the purpose of vaccination?
Stimulate adaptive immune system to create MEMORY
Which cells function in creating adaptive memory?
Memory B cells
Memory helper T cells
Memory killer T cells
Which memory cell is associated with an antigen coming to a secondary lymph organ via lymph or blood?
Memory B cell
Which memory cell is associated with APC needing to present the antigen on MHC II?
Memory helper T cell
Which memory cell is associated with infected cells needed to present the antigen on MHC I?
Memory killer T cell
Can memory B and helper T cells be produced efficiently even when no immune system cells have been infected by the attacker?
Yes
Is the precise mechanism of vaccines well understood?
Currently an active area of research (so not fully)
What test is used to assess level of protection against attackers?
Antibody titers
Both antibody and T cell responses seem to depend on what part of the immune system?
Innate
Emerging evidence points to a key role of what cells in the immunological/vaccine mechanism?
T cells (examples = chicken pox and shingles)
What is the role of toll-like receptors in the innate immune system in immunity?
Regulate persistence of germinal center-memory B cell differentiation pathway
What is the role of basophils in the innate immune system in immunity?
Enhancing survival of plasma cells in bone marrow
What is the role of dendritic cells in lymph nodes in the innate immune system in immunity?
Provide instructive cues for migration of activated T and B cells to mucosal tissues
What is the role of macrophages in the innate immune system in immunity?
Regulate differentiation of antigen-specific T and B cells at mucosal sites
What is the definition of immunization?
Process of eliciting a long-lived state of protective immunity against a disease-causing pathogen
What is another way to achieve immunization besides vaccination?
Exposure to the actual pathogen followed by recovery
Does vaccination always ensure immunity?
NO
What needs to happen in order to have immunity against a pathogen?
Development of memory B and T cells against the pathogen
What are some examples of passive immunity?
Mother to fetus
Injection of antisera (produced in horse or human)
Is passive immunity permanent?
No, temporary
What is passive immunity?
Transfer of preformed antibodies conferring temporary immunity
Does disease always lead to immunity?
No
What are examples of diseases that do not guarantee immunity?
Respiratory syncytial virus, malaria
What is a live attenuated vaccine?
Weakened version of the pathogen that can mimic protective immunity
What are examples of some live attenuated vaccines?
Smallpox, yellow fever, measles, mumps, rubella (German measles), and chicken pox
Are live attenuated vaccines generally successful in creating long term immunity?
Yes
What is the first group of vaccines?
Live attenuated vaccines
What is the second group of vaccines?
Subunit, toxoid, CHO, and conjugate vaccines
What extra thing is included in the second group of vaccines?
Various adjuvants
What type of vaccine is the one against recombinant hepatitis B?
Subunit vaccine
What type of vaccines are those for diphtheria and tetanus?
Toxoid (inactivated toxins) vaccines
What type of vaccine is the one for pneumococcus?
CHO vaccine
What type of vaccine are the ones for Haemophilus influenzae type B or meningococccus?
Conjugate vaccines
What are the three TYPES (not groups) of vaccines?
Non-infectious, attenuated, carrier
Killed vaccines, bacterial toxins, and parts of the pathogen make up what type of vaccine?
Non-infectious
Which memory cells are UNABLE to be produced by non-infectious vaccines?
Memory killer T cells
Which memory cells ARE able to be produced by non-infectious vaccines?
Memory B and helper T cells (NOT MEMORY KILLER T CELLS)
Which type of vaccine is designed NOT to infect the host?
Non-infectious
Common flu, typhoid, and pertussis vaccines are what type?
Killed, non-infectious vaccines
What chemical is an example of one used to kill microbes for killed, non-infectious vaccines?
Formaldehyde
What are the two pathways that formaldehyde can take in the body?
1 attach to protein or DNA (not cool)
2 metabolize to formate, then CO2, then water (cool)
What is an example of a toxoid used to weakened bacterial toxins for a vaccine?
Aluminum
What is the strategy behind using parts of a pathogen for a non-infectious vaccine?
Removed harmful parts and keep non-harmful portions to create protection
What kind of vaccine is the acellular pertussis vaccine?
Non-infectious vaccine with parts of the pathogen removed (bacterial proteins)
What kind of vaccines are those for hepatitis B and HPV?
“Parts of the pathogen” technique as non-infectious vaccines (proteins used to make subunit vaccine)
Do non-infectious vaccines infect OUR cells?
No
Do non-infectious vaccines work well with poliovirus and hepatitis B vaccines?
Yes
Do non-infectious vaccines work well with measles and mumps vaccines?
No
Do the poliovirus and hepatitis B vaccines generate memory killer T cells?
No
Whether memory CTLs are required for protections depends on what?
Particular microbe and its lifestyle
Live attenuated vaccines result in the formation of which memory cells?
Memory B cells, helper T cells, and killer T cells
Smallpox, yellow fever, measles, mumps, rubella, and chicken pox vaccines are what type of vaccine?
Live attenuated
Why was the polio vaccine produced by Sabin weaker?
Polio virus was reproduced in monkey kidney cells instead of human nerve cells
What is the function of formaldehyde with the polio vaccine?
Perservative
What structure is used to inactivate the polio virus for the vaccine?
Formalin solution (warmed)
Which memory cell types are a result of carrier vaccines?
Memory B, helper T, and killer T cells
How do carrier vaccines work?
Introduction of a single gene from a pathogenic microbe into a virus that doesn’t cause disease
Carrier vaccines infect what specific cells of the host?
APCs
When infected by a carrier vaccine, what do the APCs produce?
Pathogenic microbe proteins
The pathogenic microbe protein fragments produced by APCs when infected by a carrier vaccine are presented on what molecules?
MHC I
What does adjuvant mean?
“Helper”
What is the purpose of adjuvants in vaccines?
Enhance the magnitude and modulate the quality of the immune response
What are some of the results of adjuvant in the system?
Mild inflammation
Attraction of phagocytes
Acceleration of phagocyte activation and antigen presentation to T cells
What type of immune response is associated with alum as an adjuvant?
Th2, antibody
What type of immune response is associated with MF59 as an adjuvant?
Th2, antibody
What type of immune response is associated with AS04 as an adjuvant?
Th1, antibody
What type of immune response is associated with CpG DNA aka TLR 9 or TLR 7 or TLR 8 as an adjuvant?
Th1, antibody
What type of immune response is associated with flagellin-protein fusions as an adjuvant?
Th1 AND Th2
Th1 helper T cells are associated with what kind of response?
Viral/bacterial
What response is associated with Th1 helper T cells?
Classical cytokines (TNF, IFN-gamma, IL-2)
What is the goal of Th1 helper T cells?
Activate macrophages and natural killer cells
What effect does IFN-gamma have on macrophages?
Keeps them active
What effect does IFN-gamma have on B cells?
Tells them to make IgG3
What are the functions of IgG3 produced by B cells when stimulated by IFN-gamma?
Opsonization of viruses and bacteria
Fixes complement
IL-2 regulates what cells?
Natural killer cells
IL-2 stimulates the proliferation of what cells?
CTLs, NK cells, and Th1 cells
What type of attack is associated with Th2 helper T cells?
Parasitic attack or food contaminated with pathogenic bacteria
What response is associated with Th2 helper T cells?
Intestinal attack
What cytokines are associated with a Th2 helper T cell response?
IL-4, IL-5, and IL-13
What are the functions of IL-4?
Growth factor to proliferate T cells releasing Th2 cytokines)
Growth factor for B cells making IgE
What is the function of IL-5?
Causes B cells to make IgA which is antibacterial in the GI tract
What is the function of IL-13?
Stimulates mucus in the intestine
Is mercury-containing thimerosal currently used in childhood vaccines as a preservative?
No (exception = some influenza vaccines)
What is alum?
Aluminum salts that can be emulsified with the antigen that creates a gel-like substance
Alum typically induces which biased response?
Th2
Alum induces antibody responses independently of what other form of signaling?
TLR
Alum exerts a direct effect on what substance?
IL-4 producing Gr-1 expression on cells
Gr-1 is heavily expressed by what cells, and what is believed to be its function?
Neutrophils (but also monocytes and dendritic cells); important in fighting infection (microbial ones, too)
What are other names for Gr-1?
Ly-6G/Ly-6C
What is the main importance of the use of alum in vaccines?
Essential for priming and clonal expansion and optimal antibody production of B cells in vivo
How do aluminum adjuvants work?
Induction of chemokines in macrophages, monocytes, and granulocytes to recruit other immune cells to the area
Which cells are activated by sampling the area after recruitment of chemokines by aluminum adjuvants, then uptake the vaccine, and then haul the antigen to the lymph node?
Dendritic cells
At least how many cytokines and chemokines are produced within 4 hours of aluminum adjuvant injection?
13 (examples = IL-1beta and IL-5)
What cytokine is the main stimulus for microglial activation?
IL-1beta
What is MF59 (adjuvant)?
Squalene-based oil-in-water emulsion
What is the perceived mechanism of MF59?
Enhanced uptake by APCs
What is the most potent inducer of genes encoding cytokines, cytokine receptors, and adhesion molecules involved in WBC migration?
MF59
Because aluminum is difficult to clear from the body, where does it tend to accumulate?
Mitochondria and nuclei of cells
What is the most abundant metal on Earth?
Aluminum
Is there a known physiologic need for aluminum?
No
About what percentage of orally administered aluminum is actually absorbed via the GI tract?
.3%
What organ is the major route of elimination of absorbed aluminum from the human body?
Kidneys (limited ability, however)
When intravenously infused with aluminum, who are more at risk for aluminum accumulation: adults or neonates?
Neonates (retention of 75% while only 40% in adults)
Under what two situations can aluminum accumulation result?
When GI barrier is bypasses (IV infusion) or with advanced renal dysfunction
What is the leading source of aluminum exposure?
Antacids (followed by antiperspirants)
At 18 months of age, a child may have about how much aluminum exposure due to vaccines?
Over 5000 micrograms