7. Immunity and Disease Flashcards
Define an immune deficiency
Impairment in parts, or the function of specific parts, of the immune system that, in having this impairment, causes the animal to be susceptible to infectious disease.
What is a primary immune deficiency
Inherited or congenital
Occurs when there is a mutation in a gene that is associated with the immune response
What is a secondary immune deficiency and what are the common causes
Normal immune system until a physiological or pathological change occurs within the immune system
Causes - age, chronic disease, infection, therapeutics
Give 2 examples of primary immune deficiency diseases
SCID - severe combined immunodeficiency
CLAD - Canine leukocytic adhesion deficiency
What 2 dog breeds and one horse breed get SCID, and what does the mutation affect
Basset Hound - mutation for key cytokines
Jack Russel Terrier - mutation for lymphocyte formation
Arabian horse - Mutation impacts T and B cell receptor
which dog breed is CLAD common in
Irish setters
What does CLAD do to the body
Abnormal blood clotting and impair immune system
Prevents white blood cells adhering/eliminating pathogens
Give 4 examples of secondary immune deficiencies
Age-related decline - decline in CD4+
Specific infections disease - e.g. FIV
Chronic stress
Malnutrition
Why does chronic stress cause secondary immune deficiency
Glucocorticoids suppress the immune system
Why does malnutrition cause secondary immune deficiencies
reduced leptin => reduced T lymphocyte function
what is type I hypersensitivity
Immediate hypersensitivity reaction
IgE antibodies bound to mast cells
Phase 1 - sensitisation phase
Phase 2 - re-exposure phase
Explain sensitisation phase of type 1 hypersensitivity
Allergen exposure
Antigen-presenting cells capture antigens
Naive helper cells differentiate to T helper 2
Release cytokines
B cell proliferation
IgE binds to mast cells
Relocate to where allergen was first encountered
Explain re-exposure phase of type 1 hypersensitivity
Same allergen encountered
Primed IgE coated mast cells bind to antigen of allergen
Release of cytoplasmic granules
Breakdown of mast cells
Immediate hypersensitivity
Give 2 examples of type 1 hypersensitivity
Anaphylaxis
Atopic dermatitis
What is type 2 hypersensitivity
Antibody-mediated cytotoxicity
Mediated by antibodies, activates classical complement pathway
IgG antibodies travelling in the blood
Give an example of type 2 hypersensitivity
Myasthenia Gravis
What is type 3 hypersensitivity
Immune complex hypersensitivity
Formation of immune complexes and activation of the complement system
What are the two subtypes of type 3 hypersensitivities
Antibody excess (lots of IgG)
Antigen excess (less IgG but lots of antigens)
Give 2 examples of type 3 hypersensitivity
Equine recurrent airway obstruction
Canine blue eye
What is type 4 hypersensitivity
Cell-mediated, not antibody
Prolonged onset
Sensitisation and re-exposure phases
Interferon gamma and chemokine to site of presentation, recruitment of macrophages, CD4+/8+ and granulocytes
Give an example of type 4 hypersensitivity
TB skin test in cows
What lab tests are used to detect viruses
Immunodiagnostics e.g. ELISA
Culture
PCR
What lab tests are used to detect bacteria
Culture
PCR
name 2 animal side tests which are used to detect pathogens
Lateral flow
Latex agglutination tests
What test is used to detect antibodies
Indirect and sandwich ELISA
Name 3 specialised blood tests to detect antibodies
Agglutination/haemagglutination inhibition
Single radial haemolysis
Complement fixation
Name 3 inflammatory markers which can be tested for
Fibrinogen
C reactive protein (CRP)
Serum amyloid A (SAA)
Ways a pathogen can evade the immune system
Virokines/viroceptors
Bacterial capsules
Viral latency
Infect immunoprivilaged tissues
Antigenic variation
Antigenic drift vs antigenic shift
Drift = RNA cycle mistakes are made during replication => surface protein change
Shift = 2 viruses join inside a cell, surface proteins of the new virus are encoded by both parent proteins
how viruses actively attack the immune system
infect and kill immune cells
Down regulate/ inhibit immune effector molecules
Inhibit cell signalling pathways
what type of virus is FIV
T lymphocytic retrovirus
explain the effect of FIV of CD4+ and CD8+
Pathogen directly infects and replicates within the CD4+ T cells
Progressive decline of CD4+ cells in blood, virus is causing a cytopathic effect on the CD4+ cells
Prefers CD4+ over CD8+ cells due to a specific binding receptor
Innate immunity in the male definition
Immunity maintains the balance of commensal bacteria and pathogens
Innate immunity in the female definition
Immunity maintains the balance of commensal bacteria, pathogens and any introduced bacteria, allogenic* sperm, and the immunologically distinct fetus
what is a reproductive pathogen
A pathogen that affects the reproductive tract
How can reproductive pathogens be transmitted
Via semen or vaginial secretions => venereal
Via other routes e.g. respiratory (non venereal)
When is uterine contamination common
Post partum in all species as cervix is open
Post mating in mare, sow and bitch as ejaculation occur directly into the uterus
How does post partum uterine contamination occur and progress
Commensal organisms most common
Damage to endometrium from placental detachment
Commensals can penetrate the myometrium => metritis
if more superficial just endometritis
How does post mating uterine contamination occur and progress
Commensals enter the uterus of the mare, bitch and sow
Normal response is the bacteria are cleared
If poor uterine response => endometritis
Name pathogen which can cause endometritis in the mare
Taylorella
Name pathogen which can cause endometritis in the cow
Bovine venereal camplylobacteriosis
Give an example of a reproductive pathogen which enters via respiratory tract
Herpes virus
Name the common herpes virus in each species which are transmitted via respiratory system
Equine - EHV1 => cause abortion
Bovine - BoHV1 => causes abortion
Canine - CaHV1 => abortion
Feline - FeHV1 => Rarely causes abortion
Which herpes viruses are transmitted venereally for each species
Equine - EHV3
Canine - CaHV1
Bovine - BoHV1
What routine reproductive screening takes place in mares
Clitoral swabs for bacterial venereal pathogens Taylorella, Klebsiella and Pseudomonas
What routine reproductive screening takes place in stallions
Penile swabs for bacterial venereal pathogens Taylorella, Klebsiella and Pseudomonas
What routine reproductive screening takes place in bitches and dogs
None
What routine reproductive screening takes place in toms and queens
FeLV and FIV serology
What routine reproductive screening takes place in bulls
Screen for campylobacter and sometimes Trichomonas
What routine reproductive screening takes place in cows
none
What routine reproductive screening takes place in rams
Boarder disease
What routine reproductive screening takes place in ewes
None
Empty or aborted ewes tested for toxoplasma and EAE (enzoonotic abortion in ewes)
What routine reproductive screening takes place in boars
serology for PRRS, Aujzeskys, Brucella and Classical swine fever
What routine reproductive screening takes place in sows
none
When in her lactation cycle is a cow most susceptible for mastitis
Just before she calves
Name innate immunity against mastitis in a cow
Anatomy of the teat and teat end
Lactoferrin
Macrophages, neutrophils and somatic cells
Give an example of an environmental pathogen causing mastitis
S. uberis
Give an example of a contagious pathogen causing mastitis
Staphylococcus aureus
Give example control measures to reduce infection on the dry cow envrionment
Increase frequency of cleaning bedding material in loose yards
Give example control measures to reduce infection in the milking parlour
Implement full pre-milking teat disinfection routine, to include 30 second contact time with disinfectant and wipe dry
Give 3 functions of colostrum
Provides energy and fluids
Transfer of passive immunity
Development of the early GI microbiota
Which antibodies are present in colostrum
IgG, IgA and IgM - majority IgG
what is the most important management factor in determining calf health and survival
Colostrum management
why we vaccinate
Most vaccines are given to prevent (infectious) disease in the individual and/or their offspring and/or the population = Prophylactic vaccine
Apart from prophylactic vaccines, name 2 other types
Therapeutic vaccines - e.g. melanoma vaccine for dogs
Immunocontraceptive vaccines e.g. GnRH/zona pellucida targeting vaccines
Give the qualities of a perfect vaccine
Safe, cheap, easy to administer
Immune response that is strong, lifelong, and gives an appropriate immune response
Give 6 different types of vaccines
Split inactivated
Live attenuated
Recombinant DNA
Virus Vectored
DNA vaccines
mRNA vaccines
Pros and cons of inactivated vaccines
Pros - can be made rapidly
Cons - expensive if high level containment needed, short duration of immunity
Con of a subunit vaccine
Poor immune response
Pros and cons of a live attenuated vaccine
Pros - good at inducing an immune response
Cons - Potential for reversion to virulence
Pros and cons of vectored vaccines
Pros - good immune response
Cons - can get immunity to the vector
pros and cons of DNA vaccines
Pros - good T cell mediated immunity
Cons - Difficult to get strong antibody response
5 Common components of vaccines
Active ingredients
Adjuvant
Stabilisers
Preservatives
Trace components
What do adjuvants in vaccines do
Enhance immunogenicity - help make sure the vaccine isn’t just ‘swept away’
What is parenteral administration
Administered or occurring elsewhere in the body than the mouth and alimentary canal.
5 Examples of parenteral administrationn routes for vaccines
- Intramuscular
- Intranasal
- Submucosal
- Intradermal
- Subcutaneous
Disadvantages of parenteral vaccines
Have to do it in one administration
Not good for mass vaccinating
Which routes are best for mass vaccination
Oral - water or bait
Immersion - fish
Spray - poultry
Name the 4 core vaccines for dogs according to BSAVA
Canine distemper virus
Canine adenovirus type 2
Canine parvovirus type 2
Leptospira interogans
Name the 3 core vaccines for cats according to BSAVA
Feline parvovirus
feline herpesvirus type 1
feline calicivirus
Name the 2 core vaccines for rabbits
Myxomatosis
Rabbit haemorrhage disease virus 1 and 2 (RHDV1 and 2)
Name the 2 core vaccines for ferrets
Canine distemper virus
Rabies (if travelling)
Name some vaccines which may be required for horses
Equine influenza - may be compulsory for competition animals
Equine arteritis for breeding stock
Equine herpesvirus
Strangles
What does DIVA stand for
Differentiation of Infected from Vaccinated Animals
what groups of animals shouldn’t be vaccinated
Old animals - don’t respond well to vaccination
Immunosuppressed - be careful with live attenuated vaccines as can become pathogenic
Pregnant - immunosuppressed to an extent, vaccination can cause adverse effects on the foetus e.g. pyrexia
How many times should you give a vaccine to an animal
Second and third immunisations increase IgG response a lot
What is the “immunity gap” in young animals
The gap between decrease in maternally derived antibodies and increase in antibodies produced by the offspring
What is the equine influenza vaccination protocol
First vaccine at 5-6 months old
Second vaccine 4 weeks later
Third vaccination given 6 months later
Booster must be given within a 365 day period otherwise vaccinations must be restarted
If a horse is competing under FEI, how often is the equine influenza booster required
Every 6 months
What 3 aspects are tested in the pre-licensing testing of vaccines
Safety
Efficacy - how well it works under controlled conditions
Effectiveness - how well it works in the field
Name 4 aspects of adverse effects of vaccines
Vaccine induced effects
Vaccine potentiated effects
Programatic error
Coincident effects
Give examples of adverse events from vaccines
Heat, swelling, redness at vaccine site
Lethargy, loss of appetite, fever (can lead to pregnancy loss)
Severe allergic reactions
Feline injection site sarcoma
What type of reaction are adverse effects from vaccines commonly
Hypersensitivity reactions
Where do you report adverse event from a vaccine
Veterinary Medicines Directorate Pharmacovigilance Team
What 3 things do you visually assess when looking at synovial fluid
Colour
Turbidity
Viscosity
what 3 parameters do you assess using cytology on synovial fluid
Total leukocytes
Neutrophil percentage
Total proteins
What 3 structures are affected by inflammatory joint disease
Joints
Tendons
Bursae
Name 3 possible causes of inflammatory joint disease
Developmental
Degenerative
Iatrogenic
Name the acute and chronic aetiologies of joint inflammation
Acute - intra-articular fracture, joint injection, arthroscopy
Chronic - Bone fatigue, osteoarthritis
Give 2 methods to diagnose joint disease
Imaging
Lameness exam
Give 2 examples of medications that can be used to treat joint disease
Anti-inflammatories
Biological therapies - injecting hyaluronic acid
Give 3 examples of surgical treatments for joint disease
Arthroscopy
Tenoscopy
Bursoscopy
Give 3 examples of aeitopathologies of joint sepsis
Traumatic
Iatrogenic
Haematogenous
What is an overactive immune system
When there is inappropriate or extreme triggering of the immune system leading to generation of antibodies and/or T cells directed against self antigens
How can an overactive immune system progress
Marked local or systemic inflammatory response
=> tissue destruction
=> clinical disease which can be life threatening
What is an immunomodulatory drug
Substance that stimulated or supresses the immune system OR
A drug which is used to modify the immune response
What is a ‘specific’ immunomodulatory drug
a drug targeted against a specific component of the immune system
How is the specificity of a specific immunomodulatory drug determined
Ability to bind to:
An immune protein to prevent interactions with a receptor
A receptor without activating it (blocking the receptor)
Ability to specifically inhibit inflammatory cytokines
What is an immunosuppressive drug
High dose glucocorticoids are the first line treatment for immune suppression
What is the most common immunosuppressive drug class and give an example
Glucocorticoids e.g. prednisolone
How are glucocorticoids a dose dependant drug
Anti inflammatory dose
Immune suppressive dose
How do glucocorticoids achieve an immune suppressive dose
Target macrophage function
Decreases antigen processing
Give 3 examples of adverse effects of glucocorticoids
Immune suppression increases risk of bacterial infections
Increased risk of thrombosis and thromboembolic disease
Iatrogenic hyperadrenocorticism
(can get iatrogenic hypoadrenocorticism if treatment is suddenly removed)
What is the “steroid sparing” concept when treating immune mediated disease
Using additional immune suppressive agents to enable reductions in prednisolone dose
Give 5 examples of steroid sparing drugs
Ciclosporin
Azathioprine (NEVER in cats)
Chlorambucil
Mycophenolate
Leflunomide
Name 4 naturally occurring supplements for the immune system
Vitamin D
Omega 3 fatty acids
Glutamine
Arginine
Name 3 clinical presentations which would call for specific management (joint diseases)
Osteoarthritis
Sepsis
Autoimmune disease
Name 3 systemic options for treating osteoarthritis
NSAIDS
Bisphosphonates (equine)
Glycosaminoglycan derivatives
Name 4 intra-articular options for treating osteoarthritis
Corticosteroids
Glycosaminoglycan derivatives
Synthetic hydrogels
Biological products e.g. stem cells, IRAP, PRP
Name 2 systemic options for management of joint sepsis
Antibiotics
NSAIDs
Name 2 intra articular options for management of joint sepsis
Antibiotics
(Opioids)
What does IVRP stand for when talking about joint disease treatment
Intravenous regional limb perfusion
Name 2 systemic options for treating immune mediated disease
Corticosteroids
Immunomodulators
What are the broad therapeutic considerations for pregnancy
What is the effect on the pregnancy
What is the effect on the foetus
What are the broad therapeutic considerations for lactation
What could the effect of the neonate be
Is there any affect on lactation
Milk withdrawal times for dairy producing animals
Name 6 things to consider regarding pregnancy and drugs used
Absorption
Distribution
Metabolism
Excretion
Transplacental tranfer of drug
Ion trapping of drugs in the foetus
What are the pharmacokinetic considerations in lactation
Lactation = new route of elimination
Drugs which are lipid soluble, basic, non ionised, lower plasma protein binding are most likely to be eliminated via lactation
Some drugs are inactivated by milk
What does an immune mediated disease mean
In immune mediated disease there is a failure of the mechanisms that underpin “self tolerance”
Give 3 examples of immune mediated disease in dogs
Immune mediated haemolytic anaemia
Immune mediated thrombocytopenia
Immune mediated polyarthritis
Give 4 examples of irreversible diseases that can be caused by immune mediated destruction
Hypoadrenocorticism
Type I diabetes
Hypothyroidism
Exocrine pancreatic insufficiency
What is treatment aimed at in reversible immune mediated disease
Aimed at reducing or controlling the abnormal immune responses
Improve clinical signs of disease
What is treatment aimed at in irreversible immune mediated disease
Treatment aimed at restoring lost function
Supplementation e.g. injecting hormones or substances to make up for the lost function
Which hypersensitivities underly immune mediated disease
Type II
Type III
Type IV
Give examples of type II hypersensitivities which underly immune mediated diseases
IMHA - RBC destruction
Myasthenia gravis
Give examples of type III hypersensitivities which underly immune mediated diseases
Circulating immune complexes deposit in wall of small capillaries causing: glomerulonephritis, poly arthritis, uveitis
Give examples of type IV hypersensitivities which underly immune mediated diseases
Hypothyroidism results from destruction of thyroid tissue by cytotoxic T cells
What is multi systemic immune mediated disease
Multisystemic immune mediated disease occurs if the immune response targets more than one organ
Give an example of multi systemic immune mediated disease
Systemic lupus erythematosus (SLE) in people
What immune mediated diseases are cocker spaniels at increased risk of
IMHA and IMT
Hypothyroidism
Keratoconjunctivitis sicca
Immune mediated pancreatitis
Why are older dogs more likely to get immune mediated disease
Reduction in cell mediated immunity
e.g. increased CD8+ and reduce CD4+ cells
Name 5 triggers for secondary immune mediated disease
Infection
Drugs
Neoplastic disease
Inflammation
Vaccine? poor links
What is the pathophysiology of immune mediated poly arthritis
Type III hypersensitivity
Immune complex deposition in synovial basement membrane
Complement cascade activation
Recruitment of inflammatory cells (neutrophils & macrophages)
End result = release of nitric oxide, free radicals and proteases => tissue damage
What are the 4 trigger factors for immune mediated polyarthritis
Type I - idiopathic IMPA
Type II - associated with infection remote from joints
Type III - associated with inflammatory GI disease
Type IV - associated with neoplastic disease
