Immune Mediated Diseases

Question 1

What is an immune mediated disease?

Answer 1

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

Question 2

Examples of IMD in dogs

Answer 2

• Immune mediated haemolytic anaemia (IMHA)
• Immune mediated thrombocytopenia (IMT)
• Immune mediated polyarthritis (IMPA)

Question 3

IM destruction can also cause irreversible disease

Answer 3

○ 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

Question 4

Management of reversible IMD

Answer 4

Treatment is aimed at reducing or controlling abnormal immune repose to improve clinical signs

Question 5

Management of irreversible IMD

Answer 5

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

Question 6

Type 2 Hypersensitivity IMDs

Answer 6

Antibody mediated cytotoxicity
* IMHA
* Myasthenia gravis

Question 7

IMHA

Answer 7

Immune Mediated Haemolytic Anaemia
* Red blood cell destruction is mediated by autoantibody and complement activation

Question 8

Myasthenia gravis

Answer 8

Autoantibody targeted against ACh receptors at neuromuscular junctions
* Blocks or permanently destroys receptors

Question 9

Type 3 hypersensitivity IMDs

Answer 9

Immune complexes
○ Circulating immune complexes deposit in wall of small capillaries such as:
Renal glomerulus - glomerulonephritis
Synovium - polyarthritis
Uveal tract - uveitis

Question 10

Type 4 hypersensitivity IMDs

Answer 10

Hypothyroidism from destruction of thyroid tissued by cytotoxic T cells

Question 11

Multi-systemic Immune Mediated Disease

Answer 11

Most IMDs are organ or cell target specific
*Multi-systemic IMD occurs if immune response targets more than one organ

Question 12

Why are mid-older dogs more likely to get IMD?

Answer 12

• Reduction in cell mediated immunity
  ○ Shift in CD4+:CD8+ ratio
  ○ Increased CD8+, decreased CD4+
  ○ Fewer natural T regulatory cells - loss of immune tolerance?

Question 13

Triggers of IMDs

Answer 13

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

Question 14

Examples of IMD triggers

Answer 14

Infection
Drugs
Neoplastic disease
Inflammation
Vaccinations

Question 15

Infection triggers

Answer 15

○ Often hard to identify - not easy to culture, can be sequestered
○ Infection might have occurred weeks prior to onset of IM clinical signs

Question 16

Drug triggers

Answer 16

○ 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

Question 17

Neoplastic disease triggers

Answer 17

Lymphomas and splenic haemangiosarcomas are associated with IM cytopenia (IMHA, IMT)

Question 18

Inflammation triggers

Answer 18

○ Chronic pancreatitis/enteropathy is associated with IM cytopenias (IMHA, IMT)
○ Acute enteritis associated with type 3 IMPA

Question 19

Vaccination tiggers

Answer 19

Poor evidence to suggest link with IMD

Question 20

Pathophysiology of Immune Mediated Polyarthritis (IMPA)

Answer 20

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

Question 21

Types of IMPA - Categorised by triggers

Answer 21

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

Question 22

Type I: Idiopathic IMPA

Answer 22

Most common
No trigger identified

Question 23

Type II: Infection remote from joints

Answer 23

~25% of cases
Lyme disease
Leishmaniasis
Other focal infection

Question 24

Type III: Inflammatory GI disease

Answer 24

~15% of cases

Question 25

Type IV: Neoplastic disease

Answer 25

Rare