Immune Mediated Disease Flashcards
What is immune-mediated disease
An immune response is generally a beneficial response targeted against infectious organisms (viral, bacterial, protozoal, parasitic) and other diseased cells
In immune-mediated disease there is a failure of the mechanisms that underpin “self-tolerance”
an immune response can then be targeted against the body’s own healthy cells and organs
failure of innate and/or adaptive immune system
Immune mediated disease and auto immune disease- same thing
3 Examples of immune-mediated diseases in dogs
Auto-immune or immune-mediated haemolytic anaemia (IMHA)
Immune-mediated thrombocytopenia (IMT)
Immune-mediated polyarthritis (IMPA)
(rheumatoid arthritis is just one type of immune-mediated polyarthritis; very rare in dogs but relatively common in people)
Examples of immune-mediated disease causing irreversible disease (4)
Addison’s disease or hypoadrenocorticism (destruction of adrenal glands)
Type I diabetes (destruction of pancreatic islet cells)
Hypothyroidism (destruction of thyroid follicular epithelium)
Exocrine pancreatic insufficiency (destruction of pancreatic exocrine glands)
Management of a reversible immune mediated disease
treatment is aimed at reducing or controlling the abnormal or aberrant immune response to improve clinical signs of disease: more in separate presentation (Therapeutics)
Management of irreversible disease
where organ damage is severe, treatment is aimed at restoring lost function eg supplementation:
of adrenal cortex hormones to treat Addison’s (glucocorticoids and mineralocorticoids)
with injectable insulin to help manage blood glucose in diabetes
with oral thyroxine to manage hypothyroidism
of pancreatic digestive enzymes to improve clinical signs associated with EPI: exocrine pancreatic insufficiency
Types of hypersensitivity underlying IMHA and Myasthenia Gravis
Type 2
IMHA: red blood cell destruction (dogs > cats) is mediated by autoantibody (IgG or IgM) +/- complement pathway activation
Myasthenia gravis: (dogs and cats) autoantibody targeted against acetyl choline receptors at the neuromuscular junction -> blocks or permanently destroys the receptors
IMD are caused Type III hypersensitivity: immune complex hypersensitivity
Circulating immune complexes deposit in the wall of small capillaries such as:
renal glomerulus causing glomerulonephritis
synovium causing polyarthritis
uveal tract causing uveitis
What type of hypersensitivity underlies hypothyroidism
Type IV hypersensitivity: cell-mediated immunity
Hypothyroidism results from the destruction of thyroid tissue by cytotoxic T cells
What is a multisystemic immune-mediated disease
Most immune-mediated diseases are organ or cell target specific ie as a result of the reaction to a single autoantigen
Multisystemic immune-mediated disease occurs if the immune response targets more than one organ eg:
systemic lupus erythematosus (SLE) in people
SLE-like syndromes in dogs: it is rare for disease in dogs to fulfil all the specific diagnostic criteria for SLE but they do get less well-defined multisystemic diseases
Recognised genetic predisposition to immune-mediated diseases in dogs
Cocker Spaniel: at increased risk of
IMHA and IMT
hypothyroidism
keratoconjunctivitis sicca
immune mediated pancreatitis- similar to immune mediated disease in people but different to most forms of pancreatitis in the dog
think about the possibility of multi system involvement in Cockers- if they have pancreatitis, could they also be hypothyroid and/or have dry eye?
Why are mid to older age dogs more likely to get an IMD
Age related changes to the immune system include:
Reduction in cell mediated immunity
Shift in balance of circulating T cells:
increased CD8+cells and reduced CD4+ cells
-> possibly fewer natural T regulatory cells resulting in loss of immune tolerance?
Humoral immunity tends to be preserved
What triggers primary or idiopathic immune-mediated disease
Spontaneous loss of immune tolerance in a genetically susceptible individual
No trigger factor identified
What triggers secondary immune-mediated disease
Aberrant immune response is triggered by a distinct factor
Identifying a trigger (ie diagnosing secondary immune-mediated disease) means treatment is aimed at the trigger factor rather than necessarily opting for immune suppression
Infection:
Drugs…examples include:
trimethoprim sulphonamides (antibiotic) act as a hapten (a smallmoleculewhich, when combined with a larger carrier such as a protein, canelicitthe production ofantibodieswhichbindspecifically to it) and bind to cells (red blood cells, platelets or white cells) triggering a targeted immune response
carbimazole and methimazole (used to treat hyperthyroid cats) can trigger 2ry immune mediated disease (IMHA, IMT)
Neoplastic disease
recognised triggers for immune mediated cytopenias (IMHA; IMT) include lymphoma and splenic haemangiosarcoma
Inflammation
chronic pancreatitis/enteropathy is associated with immune mediated cytopenias
acute enteritis associated with type III IMPA
Vaccine?
still poor evidence to suggest a clear link with immune mediated disease
How does infection lead to secondary immune-mediated disease
+ 3 examples
Infectious agents are often hard to identify
Not easy to culture +/or sequestered eg
babesia, leishmania, ehrlichia
Improved diagnostic methods might find more links in future
Infection might have occurred weeks prior to onset of immune mediated disease signs
Various mechanisms are proposed for infection triggering auto immunity- not always well understood
Recognising infection as a link is important (if possible) because treatment can then be aimed at managing the infection
Pathophysiology of IMPA (poly-arthritis)
Type III hypersensitivity reaction
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
prompt treatment is therefore important!
If a trigger antigen is found and/or an underlying cause can be treated this could avoid use of immune suppressive drugs
these drugs always have a risk of side effects
