Immunology 3 Flashcards
Outline the importance of vaccination?
- Individual and herd welfare
- Disease control
- Disease eradication
- Altruism (protect those that cannot be vaccinated)
List animal factors to consider regarding vaccination
- Pathogen and protective immune response required
- Age of animal/colostral Ab decline/immunosenescence
- Health
- Management
- Timing of vaccination
- Previous disease/vaccination history
- Pregnancy status
List vaccine factors to consider regarding vaccination
- Content of vaccine (strains, adjuvants)
- Types of vaccine available
- Route of vaccination
- course of vaccination
- Efficacy
- Registration license
- Adverse effects/risks
What does DIVA stand for?
Differentiating Infected from Vaccinated Animals
Give examples of passive immunisation methods
- Colostrum
- Serum or purified Ig
Describe the features of passive immunisation
- Preformed antibodies
- Rapid protect but short-term (days)
What protection does colostrum provide?
- Passive immunisation
- Protection against local pathogens that the dam has been exposed to
Describe serum or purified Ig used for immunisation
- Donor animals hyper-immunised against specific pathogen
- Serum collected/Ig purified
- Administered to deficient animals
What are the risks of using antibody-rich serum for immunisation of animals?
- Serum sickness
- Immune complex disease (hypersensitivity)
- Immune responses against donor Igs
- Inadvertent disease transfer
Outline the features of active immunisation
- Vaccine antigen
- Commonly with adjuvants
- Induces long-term protective immunity
- Memory cells formed
- Protects animal when exposed to pathogen in infectious form
- Multiple routes of adminstration
Via what routes can vaccines be administered?
- Systemic (IM, subcut, ID)
- Mucosal (oral, aerosol, intranasal)
- Water (form of mucosal used for fish)
Outline the key features of mucosal vaccines
- Local to site of pathogens invasion
- Immunity generally short-lived (weeks)
- Require frequent boosters
Give examples of vaccine adjuvatns
- Aluminium and calcium salts (aka alum, safe)
- Microbial products (bacterial cell wall extracts/fragments aka Freunds)
- Synthetic agents (Carbopol, ISCOMs)
- Exogenous cytokines (IL-2 in tetanus vaccine)
How do vaccine adjuvants function?
- Enable slow release of vaccine antigens into body to enhance immune recognition and response
- Stimulate immune response non-specifically (Th2)
In what types of vaccines are adjuvants commonly used?
Non-living/inactivated
What is meant by “correlate of immunity”?
Where the details of protective immunity following infection has been characterised in the host animal
Why is the “correlate of immunity” important?
Want vaccine to generate immune response as similar as possible to the natural response i.e. if pathogen is rarely found outside of cell, then stimulating high levels of antibody is not so useful
What are the preferred responses to vaccination?
- Generate protective immune response
- Ling term immunity
- Stimulation of long-lived memory
- Rapid secondary response if re-exposed
- Ideally combination of all of above
List the different types of vaccine
- Live (attenuated)
- Marker/gene deletion mutants
- Subunit
- Multivalent
- recombinant protein
- Naked DNA
How are inactivated vaccines killed?
Heat, sometimes chemicals
What is a subunit vaccine?
Selected proteins or peptides of pathogen, only used where immune response is well characterised and know what subunit will lead to response on re-exposure
What is a multivalent vaccine?
Multiple pathogens in one administration
What is a recombinant protein vaccine?
One where the desired gene has been expressed in vitro and the protein purified
What is a naked DNA vaccine?
One where you transfect in vivo host cells, stimulating immune response as host cell produces the immunogenic protein
What is a benefit of a whole, attenuated pathogen vaccine?
Mutants selected in vitro to have reduced virulence but retain antigenicity, therefore are safe but will get response to virulent strains
What are benefits of deletion mutant, and live vectored vaccines?
DIVA potential, correct CMI or Ab response
What is a disadvantage of deletion mutant and live vectored vaccines?
Potential reversion to virulence (e..g by recombination with field strain), may cause disease in the individual and spread to others that have not be vaccinated
What are the outcomes of cell mediated immunity (CMI) to live attenuated vaccines?
- Vaccines infect host cells to a limited degree
- Endogenous processing of antigens and presentation by APC, MHC class II
- Infection of target cells and presentaiton by MHC class I in vivo follows
- Results in CTL recognition of virus and memory cells established (Th1 to enhance CTL)
- Humoral immunity also generated
- Re-exposure of vaccinated host to pathogen results in anamnestic response
Give an example of a gene deletion mutant vaccine
Infectious Bovine Rhinotracheitis (BHV-1) vaccine
Describe inactivated vaccines
- Killed whole/part organisms
- Cannot replicate so no clinical disease
- Retain some antigenicity
- Ag presentation to Th1 and Th2 results in promotion of B cells (antibody), likely to stimualte more Ab and less CTL
What is an advantage of inactivated vaccines?
No danger of reversion to virulence
What is a disadvantage of inactivated vaccines
Only structural proteins present, need an adjuvant as are less immunogenic
Describe the outcomes of inactivated vaccines
- Antibody production primarily
- Taken up by APC, proteins processed exogenously
- Processing and presentation by MHC II
- Leads to Th2 response, cytokines enhance differentiation of B cells to plasma cells, specific Ab secreted
- Memory cells established
- Some (less efficient) CMI
- Re-exposure leads to anamnestic response
Give examples of inactivated vaccine types
- Whole pathogen
- Inactivated toxins
- Subunit vaccines (e.g. flu haemaglutinin)
- Subcellular fragments (e.g. cell wall extracts, require adjuvant)
- Specific recombinant gene products
- Naked DNA
Outline the vaccine type and vaccination protocol for Feligen RCP
- Multivalent containing feline FIE (parvovirus), Rhinotracheitis virus, Calicivirus
- 1ml SC >9 wks (V1)
- 3-4 weeks later V2
- Maternal Ab suspected, V3 at >15 wks
- Revaccination 1x annually
Outline the vaccine type and vaccination protocol for Infectious Bovine Rhinotracheitis
- Live deletion mutant, marker
- V1: 2ml IM neck, >3mo
- 3 weeks later V2
- revaccination 2x annually
Outline the vaccination protocol of avian rhinotracheitis
- Mucosal: eye or nose drop, or corase spray at 30-40cm
- > 1d old
- V1 in broilers, future layers, breeders
- Future layers and breeders before lay onset V2 with inactivated vaccine
Compare hypoimmunisation and vaccination
- Vaccination aims to increase immune response to an antigen/pathogen
- Hypoimmunisation aims to reduce response (and so decrease clinical signs)
How does hypoimmunisation work?
- Identify allergen
- Administer allergen to bias immune response away from IgE and towards IgG
- Reduces the clinical signs
What are the benefits of vaccination?
- Protection of the individual
- Protection of the herd
- Reduction of clinical signs in infection
What are the drawbacks of vaccination?
- Unable to distinguish infected and vaccinated
- May cause adverse reactions
- Difficult to keep up with mutations in pathogens
List the key chicken vaccines
- Coronavirus (infectious bronchitis0
- Birynavirus (Gumboro disease)
- Herpesvirus (Marek’s disease)
List the key sheep vaccines
- D nodosus (footrot)
- Chlamydia abortus (Enzovax)
- Clostridia (HeptavacP)
List the key pig vaccines
- Erhysipelothrix rhusiopathiae
- Parvovirus (SMEDI)
- Mycoplasma hypopneumoniae
- Porcine reproductive and respiratory syndrome (PRRS)
- Porcine circovirus (post-weaning mutli-systemic wasting syndrome)
List the key horse vaccines
- Equine influenza virus (all)
- Equine herpesvirus1/4 (normally bloodstock only)
- Streptococcus equi (strangles, dependent on risk)
List the key cattle vaccines
- Bovine viral diarrhoea virus
- Leptospirosis
- Bovine herpesvirus 1 (IBR)
- Bovine respiratory syncytial cirus (BRSV, calves)
- Parainfluenza virus-3
- Dictyocaulus viviparus 3rd stage irradiated larvae
List the core dog vaccine
- Canine distemper virus
- Canine adnovirus type-2 (infectious Heptatitis)
- Canine Parvovirus (parvovirus) (often combined as DHP)
- Leptospira interrogans (L4)
List the non-core dog vaccines
- Bordatella bronchoseptica (canine parainfluenza virus, kennel cough)
- Borellia burgdorferi (Lyme disease)
List the exotic disease vaccines for dogs
- Rabies
- Leishmania vaccine
List the core cat vaccines
- Feline herpesvirus
- Feline calicivirus
- Feline panleukopaenia (aka parvo, infectious enteririts/FIE)
Give examples of diseases eradicated by vaccine
- Classical swine fever
- Aujesky’s disease in Netherlands
What are the licensing requirements for veterinary vaccines?
- Target species identified
- Safe
- Efficacious
- Route of administration stated
- Pregnancy status may also be included
How is vaccine safety demonstrated?
- Experimental/field trials
- Multiple immunisations in target species
- 5-10 times antigenic payload
- Responses in pregnant animals if needed
- Possibility of reversion to virulence included
- Shedding of vaccine to cohorts
How is vaccine efficacy tested?
Challenge infection following vaccine administration
What authority regulates vaccines?
Veterinary Medicine Directorate (VMD)
What is the role of the VMD regarding vaccines?
- Vaccine monitoring
- Vaccine registration
- Antibiotic resistance
- Monitoring of adverse reactions
- Monitoring of residue problems
Why might vaccines be inactive in neonatal mammals?
- Immunologically naive
- Immature immune systems (inefficient T cell production of IFNy)
- Colostral antibody interferes with vaccine response until wanted
Why might vaccines be ineffective in aged animals?
- Immunosenescence
- Compromised immunity
List the common types of adverse reactions that may occur as a result of vaccination
- Inflammation at site of injection
- Feline injection site sarcoma
- Hypersensitivity responses
- Lack of efficacy
List the very rare adverse reactions that may occur as a result of vaccination
- Fever
- Stiffness
- Sore joints and abdominal tenderness
- Susceptibility to infections
- Neurological disorders and encephalitis
- Collapse with auto-agglutinated red blood cells and icterus (Autoimmune haemolytic anaemia AIHA)
- Generalised petechiae, other haemorrhage types
- Reversion to virulence
Describe inflammation at vaccination injection site
- Good, recruits macrophages etc to present antigen
- Bad if excessive
- Warm, oedematous, firm
- May be painful
- Can appear 1 day post vaccine up to 7 days
- Rare in dogs ad cats
Describe feline injection site sarcoma
- FISS
- Adjuvanted DeLC and rabies vaccine
- Injection into neck can lead to sarcoma
- Inject in distal limb to overcome this
What governing body monitors the adverse reactions to vaccines in the field?
Marketing Authorisation Veterinary Information Service (MAVIS)
What is the result of partial vaccination?
- Did not complete schedule
- May lead to modulation of typical clinical signs
What is the purpose of continued vaccine monitoring in the field?
- Epidemiological investigations
- Pathogen resistance (selection pressure of vaccination leading to increased mutation frequency)
- Evidence for vaccine breakdown
- Update strains in vaccine
- Adverse reaction monitoring
- Feedback to the manufacturer
What are marker vaccines?
A vaccine that allows differentiation between animals that have been infected and those that have been vaccinated, by the deletion of a novel component
What would be the consequence of adding a novel component to a vaccine virus?
Would not be able to differentiate between animals that have been infected AND vaccinated
What is the importance of IgG in secondary infection and vaccination?
IgG increases due to seroconversion following repeated exposure to an antigen
Compare the use of latex agglutination assays and ELISAs in determining immune response via IgG
- Latex agglutination gives a positive/negative result, allows determining whether or not an immune response has been mounted (cheap)
- ELISA allows determination of degree of immune response (but more expensive)
Outline the procedure of the Zinc sulphate turbidity colostrum test
- Add 100ul of serum from calf to tube containing 6ml ZnSo4, immediately cap
- Mix contents, incubate at room temp for 30 mins
- Record data using +/- as indicators of results
- Carry out spectrophotometer test, compare to reference values of optical density
What is the effect of CO2 on the zinc sulphate test?
Causes precipitation and therefore a false positive
What field tests are available to assess colostrum?
- DVM rapid test (Ab based, turbidity measured by turbidimitry, equipment needed)
- SNAP test (rapid ELISA)
- Foal check Latex Agglutination
Outline the importance of colostrum testing
- Neonate needs sufficient colostrum within 12h of birth
- Needs sufficient Abs from that colostrum and so need to determine is colostrum contains enough or if supplementation is needed
- Determine degree of Ab transfer into the neonate
What is meant by immune tolerance?
The failure of the adaptive immune system to respond to an antigen
What is the function of immune tolerance?
Prevent auto-immunity where the immune system attacks self cells
Describe central tolerance
- Selection of T and B cells which only react with “non-self” antigens in thymus and bone marrow respectively
- Requires “education”
- Large numbers of lymphocytes eliminated by apoptosis in these organs
- Once educated, migrate to secondary lymphoid tissue
- Oscurs in utero and until regression of thymus
Describe peripheral tolerance
- T and B cells in secondary lymphoid tissues require further education and regulation
- Ignore normally common environmental antigens e.g. food, saliva from biting insects
- If fails, get hypersensitivity reactions
- Can be induced (Tregs)
Describe neonatal tolerance
- Occurs in foetus or neonate
- If foetal thymus exposed to non-self antigen before it is mature, then animal becomes tolerant to those antigens
- E.g. persistent infection with BVDV
Describe oral peripheral tolerance
- Prevents response to dietary proteins/gut microflora while preserving protective immune responses to GI pathogens
- Failure results in hypersensitivity disease (food allergy, IBD)
Describe the process of central tolerance in the thymus
- First filtered in subcapsular region in cortex by dendritic cells, become TCR positive (double positive)
- Then single positive
- APCs present pathogenic peptides to T cells in context of MHC molecules
- Move into corticomedullary junction
- Any reaction that is on-MHC but against cells with self antigens are deleted
Describe the process of central tolerance development in the bone marrow (B cells)
- Induced in bone marrow, stromal cells support B cell development and B cell receptor Ig acquired
- BCR+ cells interacting with self antigens on stromal cells are deleted by apoptosis
- Mature “educated” B lymphocytes move to populate secondary lymphoid organs, ready for clonal expansion
What are the mechanisms by which T cells become tolerant in the periphery?
- Anergy
- Immunological ignorance
- Antigen presenting cell failure
- T regulatory cells
Explain anergy
- T cells fail to receive appropriate co-stimulatory signals for activation
- Leads to cytokine deficiency, so B cells become anergic
Explain immunological ignorance
- Aka immune privileged sites (testis, brain, eye, kidney etc)
- Some response, but poor, so are predominantly tolerant
Explain antigen presenting failure
- Processes “self” antigen but fails to present
What are the different types of Tregs?
- Natural Tregs (nTregs)
- Tregulatory cells subset 1 (Treg 1)
- T helper 3 cells (Th3)
What is the function of Tregs?
Towards end of immune response, Tregs dampen to limit collateral damage
How do nTregs carryout their function?
- Production of IL-10
- Immunosuppressant properties on Th1 and Th2 cells
- Inhibition of Th2 cells inhibits B cell activity and so antibody production
- Cell-cell contact with APCs, upregulates CTLA-4, ligates B7 but does not cause activation
What cytokine expands nTreg populations?
TGF-beta, produced by APCs
Why is peripheral tolerance important?
- Some antigens may not be presented to T cells in the thymus e.g. certain food proteins, dust mite faeces, flea saliva etc
- Some self reacting T cells may escape thymus by accident
- Allergic responses occur where peripheral tolerance fails
- Autoimmune disease if fails
What is important to consider when carrying out hyposensitisation protocols?
Route of administration and method is based on the way the allergen has its effect
Why is a developing conceptus not destroyed by the maternal immune response?
- Foetoplacental unit is semi-allogeneic
- Pregnant females must still respond to infectious pathogens/vaccinations
- Local immunosuppression (Tregs and split immunological tolerance)
List natural immunosuppressive factors
- Regulatory T cells
- Antibodies
- Specific cytokines (e.g. IL-10)
- HPA axis
Explain the immunosuppressive function of the HPA axis
- Neurological stress stimulates the adrenal cortex to release endogenous glucocorticoids
- These have an immunosupperssive function
Explain how glucocorticoids have an immunosuppressive function
- Bind to receptor and become internalised
- Enter nucleus and bind to promotor sequence of anti-inflammatory cytokine genes
- Production of anti-inflam cytokines e.g. IL-10
- OR by binding to transcription factors such as NFkB to prevent these entering the nucleus so inflammatory cytokines are not transcribed
Compare broad and specific immunomodulators/immunosuppressives
- Broad are general, effects onmnay aspects of inflammation e.g. glucocorticoids, Nsaids
- Specific are targeted
Give some examples of specific immunomodulators or immunosuppressives
- Targeted e.g. cytokine inhibitors (IL-1 receptor antagonist)
- Binds to immune protein preventing it from interacting with receptor (steric hindrance)
- Inhibiting inflammatory cytokines e.g. IL-1 and TNFalpha
Give examples of common immune medaited diseases
- Immune mediated haemolytic anaemia (common)
- Atopy
- Inflammatory boowel disease
- Chronic osteoarthritis
What is the aim of using corticosteroids?
Halt ongoing damage and allow recovery
Describe the mechanism of glucocorticoid action
- Absorbed through cell membrane
- Bind to intracytolasmic receptors, forming complex
- Results in reductin of pro-inflam proteins, increase in anti-inflam proteins
Outline some additional effects of glucocorticoids
- Stabilise cell membrane o macrophages, neutrophils and mast cells (inhibiting inflam mediators and pro-inflam cytokines IL-1, IL-6, TNFa release)
- Inhibit complement formation
- Down regulate FcRs on phagocytic less, so no opsonisation and Igs less effective
