Resistance, immunity, and vaccines Flashcards
What is Natural, active immunity?
Is it necessary to know that you have been ill?
Is it long or short lasting?
Natural, active: this is the usual immunity that results from real-life exposure to a pathogen.
It is not necessary to know that you’ve been ill; for example, 60% of mumps contacts will become immune to mumps without getting the disease.
Natural is usually the most long-lasting immunity, and some people believe that getting sick (‘testing in the fire’) is the best thing for a child; but if there is a vaccine, it is bad practice to allow a child to contract a disease that might leave permanent damage or even be fatal.
Mention 4 ways in which you can generate immunity:
1- You could have had it before, in other words, being exposed to the disease to get immunity (Natural, Active)
2- You could be 3 months old and you have neutralizing antibodies from your mom floating around your system. Maternal transfer of antibodies (Natural, Passive)
3- We could have given you neutralizing antibody against it (Artificial, Passive)
4- We could have exposed you to a weakened version of the same virus or just the important parts of the virus ahead of time (Artificial, Active)
Describe natural, passive immunity?
What are some Igs that can be passed from the mother to the baby?
Natural, passive: passive means that you are benefitting from the products of someone else’s immune response.
In humans, the fetus gets IgG passively across the placenta from its mother, and the baby gets IgA in mother’s milk if she nurses it (this is, of course, one of the best reasons for nursing babies rather than feeding them on cows’ milk or squished soybeans.)
Nursing has been shown to protect kids from infections.When immunogens are presented in the mother’s gut, antibodies to them appear in her milk.
Describe artificial, passive immunity:
What type of immunopthology could caused by artificial, passive immunity with animal antisera?
Human serum is used for what diseases?
What do you screen human serum for?
Why is it important to give as ordered?
Artificial, passive: the use of immune serum or antibodies to protect a patient at risk from a particular disease.
Before the antibiotic era, horse antiserum against pneumococci (Streptococcus pneumoniae) was given to pneumonia patients, and similarly with diphtheria patients, and it often pulled them through. We still use animal antisera to snake venom. But: there is a risk of serum sickness (see Type III Immunopathology).
Now when possible we use human antisera: tetanus, rabies, hepatitis, and chicken pox are most common; rattlesnake is available.
They must be screened for hepatitis and AIDS viruses, of course, but we can’t screen for everything. Remember: Unless it has been specifically (and expensively!) formulated for intravenous use, IgG will aggregate in the bottle; aggregated IgG activates complement; complement is anaphylatoxic; so never give these human immune globulins . (Curiously, horse and sheep antibodies activate human complement only poorly, so these antivenins can be given i.v.) ¡Nevertheless, Always Read the Package Insert!
Describe artificial, active immunity?
Do live or killed vaccines provide a better immunity?
What is some of the risk of live vaccines?
Artificial, active: immunity resulting from intentional immunization with vaccines, toxoids, or other antigenic preparations.
-The ‘dirtier’ a vaccine is, that is, the more complex the mixture of molecules in it, the more likely it is to cause unpleasant side effects.
Thus killed whole bacteria (the former pertussis and typhoid vaccines) were painful to receive, and often caused fever or worse. Tetanus and diphtheria toxoids, being relatively pure, are innocuous. With viruses, it has repeatedly been shown that ‘live’ (infectious but attenuated, that is, grown in culture or animals long enough that it is still antigenic but no longer causes disease) vaccines provide much better immunity than do killed preparations.
Why, do you think?
The fear is, of course, that an infectious vaccine may revert to a virulent condition. With new DNA technology it is possible to tailor the genome of viruses so that the virulence factor genes are missing or so altered that reversion to virulence is impossible. The ultimate in vaccines may very well be the products of specific genes, cloned in yeast or bacteria or totally synthetic, completely purified and then if necessary coupled to a powerful immunogenic carrier. Most now get a synthetic peptide vaccine containing the epitopes that immunize T cells best against the hepatitis B virus, grown by recombinant DNA technology in yeast cells.
What are the three different type of artificial, active immunity components?
-Live attenuated
- Whole killed virus/bacteria
- Subunit (small portions of the infection as targets)
What is the difference between humoral and cellular immunity?
Current vaccine efficacy is almost exclusively dependent on what arm of immunity?
Antibody (humoral):
- Inhibits binding to host cells (prevents entry)
- Promotes uptake by macrophages
- Lysis
Cell Mediated:
- Destroy pathogen (neutrophils, activated macrophages)
- Inhibit growth (interferons)
- Kill infected cells
**Currently, vaccine is almost exclusively dependent on humoral immunity.
Live attenuated vaccine:
What are its advantages?
What aspects of immunity doeslive attenuated vaccine incites?
What are its disadvantages?
Advantages
–All aspects of innate immunity engaged
–There is a robust cellular (CD4 and CD8) and humoral responses
–Longer lasting humoral response with high titer and affinity.
Disadvantages.
–Higher risk of adverse events including reversion to virulence.
–Increased contraindications in population (ie. Vaccinia and atopic dermatitis).
–Production cost and stability-cold chain.
–Not all infectious agents can be attenuated… for example? HIV
Whole killed bacteria/virus:
Advantages?
Disadvantages?
There is a higher risk of ______ events due to strong local toxicity.
What kind of cell responsed could be substantially lost?
Advantages
–Endogenous ligands/agonists for innate receptors (PAMPS) produces robust innate activation.
–Strong humoral response indicative of good CD4 T cell help.
Disadvantages
–Higher risk of adverse events-strong local toxicity. “Reactogenicity”.
–Substantial loss of CD8 response.
–Production cost and stability
Sabin (live-attenuated) vs. Salk (death bacteria)
Which one induces protective IgG but no IgA?
In which one does the virus can replicate and infect others?
In which one is protection short-lived?
Which one forms humoral and cellular immunity?
Which one forms protective IgA?
Which one can provide herd immunization?
Subunit vaccine:
What is it?
Does it produce a cellular response?
CD4 responsed inferred from what?
Does it require boosting?
The requirement for adjuvant makes it what?
Using only components, or subunits, of the infectious agent in a vaccine formulation.
Advantages:
–Sufficient *humoral responses.
–Fewer reactogenicity/toxicity issues
–Lower production cost and increased shelf life.
Disadvantages:
–Little to no cellular responses. CD4 responses inferred by class switched antibody.
–Requires more frequent boosting.
–Requires adjuvant- dramatically reduced innate activation
What is an adjuvant?
They allow vaccines to be more what?
What type of immune response do they cause initially?
What is alum? What cell does it instigate, which leads to production of IL-1?
Does it produce impressive T cell responses?
These are substances added to vaccines to make them more immunogenic.
►They all seem to work by causing an innate immune response, which is a necessary predecessor to an effective adaptive response. The most common approved adjuvant in the US is alum, aluminum hydroxide plus aluminum phosphate. While alum does not stimulate any one specific innate receptor to instigate innate responses, indigestible substances like Alum tend to instigate neutrophil activation and release of damage associated molecular patterns (DAMPS) that subsequently activate the inflammasome and result in production of IL-1.
The collective influence of these and, as yet undefined, other inflammatory factors facilitates reasonable antibody responses (it is in tetanus and DaPT ) but not very impressive T cell responses.
Modern, more robust adjuvants usually target specific innate receptors like as TLR4 (by Monophosphoryl lipid A-MPLA) or TLR2 (by Pam3CYSK-4, a lipopeptide). Combinations of these also exist, good examples being the Adjuvant System 01-04 (AS01-04) made by GSK. (eg. AS04= Alum + MPLA). In Europe several firms make approved, effective adjuvants, commonly based on the steroid precursor squalene, which activate both T and B
Examples of live, dead, and subunits:
Humoral vs. Cellular immunity
Which one is easier to induce?
Which one can eradicate intracellular pathogens?
Which one required actual infection?
Which one can PREVENT illness?
Which one is THERAPEUTIC?
How does polyssacharide/protein conjugate facilitate T Cell help?
