Immune Mediated Diseases Flashcards
What is an immune mediated disease?
Failure of ‘self tolerance’ mechanisms
○ An immune response can then be targeted against the body’s own healthy cells and organs
○ Failure of innate and/or adaptive immune system
Examples of IMD in dogs
- Immune mediated haemolytic anaemia (IMHA)
- Immune mediated thrombocytopenia (IMT)
- Immune mediated polyarthritis (IMPA)
IM destruction can also cause irreversible disease
○ Addison’s/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 reversible IMD
Treatment is aimed at reducing or controlling abnormal immune repose to improve clinical signs
Management of irreversible IMD
When organ damage is severe
Treatment is aimed at restoring lost function (supplementation
Addison’s - glucocorticoids/mineralocorticoids
Diabetes - injectable insulin
Hypothyroidism - oral thyroxine
EPI - pancreatic digestive enzymes
Type 2 Hypersensitivity IMDs
Antibody mediated cytotoxicity
* IMHA
* Myasthenia gravis
IMHA
Immune Mediated Haemolytic Anaemia
* Red blood cell destruction is mediated by autoantibody and complement activation
Myasthenia gravis
Autoantibody targeted against ACh receptors at neuromuscular junctions
* Blocks or permanently destroys receptors
Type 3 hypersensitivity IMDs
Immune complexes
○ Circulating immune complexes deposit in wall of small capillaries such as:
Renal glomerulus - glomerulonephritis
Synovium - polyarthritis
Uveal tract - uveitis
Type 4 hypersensitivity IMDs
Hypothyroidism from destruction of thyroid tissued by cytotoxic T cells
Multi-systemic Immune Mediated Disease
Most IMDs are organ or cell target specific
*Multi-systemic IMD occurs if immune response targets more than one organ
Why are mid-older dogs more likely to get IMD?
- Reduction in cell mediated immunity
○ Shift in CD4+:CD8+ ratio
○ Increased CD8+, decreased CD4+
○ Fewer natural T regulatory cells - loss of immune tolerance?
Triggers of IMDs
Primary or idiopathic IMD
○ Spontaneous loss of immune tolerance in a genetically susceptible individual
○ No trigger factor
Secondary IMD
○ Triggered by a distinct factor
○ Need to identify trigger in order to plan treatment
Examples of IMD triggers
Infection
Drugs
Neoplastic disease
Inflammation
Vaccinations
Infection triggers
○ Often hard to identify - not easy to culture, can be sequestered
○ Infection might have occurred weeks prior to onset of IM clinical signs
Drug triggers
○ Trimethoprim sulphonamides (antibiotic) act as hapten and bind to blood cells triggering a targeted immune response
○ Carbimazole and methimazole can trigger secondary IMD (IMHA, IMT)
Used to treat hyperthyroidism in cats
Neoplastic disease triggers
Lymphomas and splenic haemangiosarcomas are associated with IM cytopenia (IMHA, IMT)
Inflammation triggers
○ Chronic pancreatitis/enteropathy is associated with IM cytopenias (IMHA, IMT)
○ Acute enteritis associated with type 3 IMPA
Vaccination tiggers
Poor evidence to suggest link with IMD
Pathophysiology of Immune Mediated Polyarthritis (IMPA)
Type 3 hypersensitivity - Immune complexes
* Immune complex deposition in synovial basement membrane
* Complement cascade activation - recruitment of neutrophils and macrophages
* Release of NO, free radicals and proteases
Leads to tissue damage
If trigger antigen can be found treat this
* Avoid use of immunosuppressive drugs
Types of IMPA - Categorised by triggers
Type I: Idiopathic IMPA
Type II: Infection remote from joints
Type III: Inflammatory GI disease
Type IV: Neoplastic disease
IMPA can be part of a multi-systemic immune mediate disease
Type I: Idiopathic IMPA
Most common
No trigger identified
Type II: Infection remote from joints
~25% of cases
Lyme disease
Leishmaniasis
Other focal infection
Type III: Inflammatory GI disease
~15% of cases
Type IV: Neoplastic disease
Rare
