Unit 4c. Vaccination Flashcards
essentials of the Acquired Immune Response
the acquired immune system is equipped with B-cell receptors and T-cell receptors that specifically respond to an endless profile of microbial antigens during antigen presentation
this process of antigen recognition leads to an antigen specific B-cell and T-cell activation, which initiates an antibody mediated response (AbMIR) to destroy intracellular pathogens
Immunological Memory
in addition to antigen recognition and pathogen killing, the acquired immune system also has the capacity for “memory” such that subsequent exposure to antigen elicits an enhanced and more efficient immune response
without this immune capacity it would not be possible to develop and use vaccines to enhance immunity to pathogens
Factors influencing Antigen Immunogenicity
types of antigens: the most immunogenic antigens are proteins larger than 1000 DA in size
surveillance (sentinel) immune cells are well equipped to process proteins and present their antigenic peptides to T-cells via major histocompatibility complex (MHC) class I and II molecules
- MHC I will drive cell mediated response
- MHC II drive antibodies mediated response
Antigen Processing and Presentation by MHC class I And II molecules
endogenous pathway: all host cells infected with an intracellular pathogen are capable of presenting endogenous antigenic peptides on MHC class I molecules to cytotoxic T-cell (Tc) - if the TCR in the Tc recognizes the antigenic peptide, the T-cell becomes activated and sends a death signal to the infected host cell, which forces it to undergo programmed cell death
Antigen Exposure Route
Antigen exposure route influences the type of immune response that is mounted during vaccination
Genetics
mutations in genes coding for a microbial protein antigen will influence immunogenicity, and some pathogens under host selection pressure utilize this to evade the immune response
EXAMPLE: Epitopes on Influenza virus- hemagglutinin antigen
the antigenic determinants of a protein are referred to as epitopes. since there are potentially many epitopes on a single protein, some being more immunogenic than others, an immune response will be mounted against each epitope with varying effectiveness: overtime the immune response will favour an immunodominant epitope
the challenge with vaccine development is to incorporate an antigen that possesses an immunodominant epitope in order to elicit an immune response that provides immunity against the target pathogen before exposure occurs
influenza virus is constantly changing these epitopes via gene mutations to evade the host immune response, and this is why influenza vaccines are not always highly effective from one flu season to the next
Stability
increasing antigen stability increases immunogenicity
plant based vaccines for example, have been shown to increase antigen stability and immunogenicity because the plant cell wall protects the antigen as it passes through the acidic and enzyme rich gut to lymphoid tissue of the small intestine
Foreignness
the more genetically dissimilar the antigen is from the vaccine recipient, the more immunogenic it will be
complexity
the more complex an antigen is, the more immunogenic it will be
polysaccharides and lipids making up a microbial cell membrane are not very immunogenic, however, when they are conjugated to a protein, their immunogenicity is dramatically increased
Dose
a low antigen does may not be sufficient to elicit an immune response, whereas a high antigen dose may be lethal or may shut down the immune system (anergy)
examples of adjuvants
alum
calcium phosphate
freunds incomplete adjuvant - water-in-oil emulsion
monophosphoryl lip A from lipopolysaccharides
CpG oligonucleotides
cholera toxin
plant saponins
Live Attenuated Vaccines
used most frequently for preventing viral infections, in order to provide immune protection against these intracellular pathogens, the vaccine must elicit a CMIR (cell mediated immune response)
vaccines containing live pathogen are most effective for eliciting CMIR because the antigen can be processed via the endogenous antigen processing pathways, which leads MHC class I antigen presentation to T-helper cells
the most common attenuation method involves passing the virus through succession of cell coulters under limited growing conditions to weaken it
Advantages of live attenuated vaccines
fewer immunizations required to elicit longterm immunity
no requirement for an adjuvant
reduced risk for hypersensitivity reaction
induces antiviral interferon response
can be administered by natural route
provides long lasting immunity
elicits CMIR and ABMIR
Shortcomings of live attenuated vaccines
possibility of mutation occurring that will increase virulence
may cause illness in immune compromised individuals
Inactivated Vaccines
the pathogen is inactivated using heat, radiation or certain chemicals antigens are processed by exogenous antigen processing which leads to MHC class II antigen presentation to T-helper cells, and subsequent elicitation of an acquired immune response
Advantages of inactivated vaccines
longer shelf life
easier to store
less likely to cause disease or infection
no risk of pathogen increasing virulence
Shortcomings of inactivated vaccines
does not always provide long term immunity, boosters may be needed
also possibility of hypersensitivity reaction
Subunit vaccines
antigenic proteins are isolated from a pathogen and incorporated into a vaccine
immunization triggers an antigen-specific acquired immune response without causing infection
may need an adjuvant
shortcomings of subunit vaccines
isolation of the antigenic protein is costly and time consuming
also it may not always provide the long-term immunity
Vector-delivers subunit vaccines
the gene coding the antigenic protein from the pathogen can be instead in to a bioreactor and later purified for incision in a vaccine
the gene coding the antigen protein can be inserted into a vector, which is then delivered to the vaccine recipient
Advantages of vector approach
- it could replace costly and labour intensive parental antigen delivery strategies
- it could alleviate the need for booster immunizations because the immune system is under constant stimulation with antigen
- it could help stabilize antigen –> pass through the stomach before being broken down so it can be absorbed by SI
Conjugate Vaccines
these vaccines contain poorly immunogenic but important bacterial membrane target antigens; immunogenicity can be increased by chemically linking these antigens to a carrier protein
Toxoids
some bacteria release harmful toxins that cause illness in infected animals
toxoid vaccines contain antigenic toxins that have been chemically inactivated
immunization with the immunogenic toxoid induces an acquired immune response, without causing toxicity
Active Immunization
a microbial antigen is administered to an animal in a vaccine to elicit an acquired immune response.
re-immunization with the antigen results in enhanced and long-lasting immunity provided by memory T- and B-cells that were generated during the primary immune response
Passive Immunization
antigen-specific antibodies are trasnferred from a “resistant donor” animal to a “susceptible recipient” animal. this provides immediate but temporary immunity
passive immunization is most effective against toxin -producing organisms
Adverse Immune Reaction to Passive Immunization
an adverse immune reaction can occur if the recipient animals immune system recognizes and mounts an immune response against the “non-self” donor antibodies
if donor antibodies are still present during the recipients immune response, it can cause serum sickness
if dose is repeated anaphylaxis can occur
both of these can be minimized by ensuring a single donor antibody treatment for a short duration of time
Maternal- neonatal Passive Immunity
transfer of maternal antibodies to offspring via colostrum
ruminants and piglets rely very heavily on colostrum for passive immunity
administrations of vaccine
most vaccine are administered by parenteral delivery (injection) and they elicit a systemic immune response
in the case of birds: aerosol, water or food is preferred
for fish, immersion and food is preferred
Duration of Immunity
not all vaccines provide long-term immunity, it has bee common practice to administer an annual booster for these vaccines
an alternative is to measure serum antibody tigers by ELISA to determine if a booster immunization is required
titer
a measurement of how much antibody is produced without actually having to measure the antibody concentration
Proactive Vaccination
it may not be necessary to vaccinate all animals to prevent disease transmission within a population; this depends on the disease
ideally this is done with higher risk individuals
Reactive Vaccination
it may not be feasible to vaccinate all animals during a disease outbreak. thus a ring vaccination strategy can be employed to contain the disease, and proactive vaccination can be carried out on high risk individuals that are most likely to contribute to the future spread of disease
most common causes of failure to respond to vaccination
- improper storage of live vaccine
- use of antibodies during administration of a live vaccine
- poor distribution of an aerosol vaccine
- poor quality vaccines
- inappropriate vaccination protocol
- failure to follow manufacturer’s immunization protocol
- immunocompromised animal
- inappropriate antigen in vaccine in the case of the flu vaccine
adverse risks of vaccination
- residual virulence of live attenuated vaccines can lead to disease in immunocompromised individuals
- local or systemic inflammatory reaction
- hypersensitivity reactions
- congenital defects to fetus
- febrile seizures in children
- autoimmune disease
- immune thrombocytopenia purport following MMR vaccination
- arthritis
9, encephalitis following measles and mumps vaccine
