Principles of immune mediated disease Flashcards
What is the underlying cause of immune mediated disease?
a failure of the mechanisms that underpin “self-tolerance” – mainly peripheral:
- immune response targeted against body’s own cells
- failure of innate and/or adaptive immune system
Describe central tolerance
deletion of reactive T-cells in the thymus
Describe the components of peripheral tolerance
Anergy – self-antigen recognised by T-cells, but lack of progression of process
Activation - induced cell death of auto-reactive T-cells (FAS-ligand)
Suppression of T-cell response by regulatory T-cells
Give an example of why tolerance is not completely effective => immune mediated disease
Some antigens (termed cryptic) are not expressed in the thymus and immune-mediated disease may occur after damage to the tissues containing these
What is the name of immune mediated damage to RBCs?
immune-mediated haemolytic anaemia (IMHA)
What is the name of immune mediated damage to platelets?
Immune-mediated thrombocytopenia (IMT)
What is the name of immune mediated damage to the joint capsule?
Immune-mediated polyarthritis (IMPA)
What is the name of immune mediated lack of mineralocorticoid or glucocorticoid hormone
Addison’s disease or hypoadrenocorticism (destruction of adrenal glands)
What is the name of immune mediated lack of insulin?
Type I diabetes (destruction of pancreatic islet cells)
What is the name of immune mediated lock of thyroid hormone?
Hypothyroidism (destruction of thyroid follicular epithelium)
What is the name of immune mediated lack of pancreatic digestive enzymes?
Exocrine pancreatic insufficiency (destruction of pancreatic exocrine glands)
Give examples of type II hypersensitivity in immune mediated disease
IMHA: red blood cell destruction (dogs > cats) is mediated by autoantibody (IgG or IgM) +/- complement pathway activation => either opsonises them (taken by macrophages in the liver/spleen) or causes complement binding => lysis of RBCs
Myasthenia gravis: (dogs and cats) autoantibody targeted against acetyl choline receptors at the neuromuscular junction => blocks or permanently destroys the receptors
Describe type III hypersensitivity in immune mediated diseases
Circulating immune complexes deposit in the wall of small capillaries such as:
- renal glomerulus causing glomerulonephritis
- synovium causing polyarthritis
- uveal tract causing uveitis
=> inflammation and lack of blood supply to area
Describe type IV hypersensitivity in immune mediated diseases
cell mediated immunity
e.g., Hypothyroidism results from destruction of thyroid tissue by cytotoxic T cells
Fill in the blanks describing the aetiology behind immune mediated diseases
What is multisystemic immune mediated disease?
the immune response targets more than one organ
What breeds are predisposed to immune mediated diseases?
Cocker Spaniel at increased risk of:
- IMHA and IMT
- hypothyroidism
- keratoconjunctivitis sicca
- immune mediated pancreatitis-
Why are mid to older age dogs more likely to get IMD?
Reduction in cell mediated immunity (immunosenescence)
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
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
e.g., drugs, neoplastic disease, inflammation, vaccines, infection
Give examples of drugs causing secondary immune mediated disease
trimethoprim sulphonamides (antibiotic) act as a hapten 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)
Give examples of how neoplastic disease can trigger secondary immune mediated disease
recognised triggers for immune mediated cytopenias (IMHA; IMT) include lymphoma and splenic haemangiosarcoma
Give examples of how inflammation can trigger secondary immune mediated disease
chronic pancreatitis/enteropathy is associated with immune mediated cytopenias
acute enteritis associated with type III IMPA
What are the clinical signs of immune mediated polyarthritis?
pyrexia
palpable joint effusions
Pain on joint manipulation
What lab tests can be done to test for immune mediated polyarthritis
C-reactive protein
Neutrophilic inflammation + no infectious agents - joint effusion
Describe the pathophysiology of immune mediated polyarthritis
Type III hypersensitivity reaction:
- Immune complex deposition in synovial basement membrane
- Complement cascade activation
- Recruitment of inflammatory cells (neutrophils & macrophages)
- release of nitric oxide, free radicals and proteases -> tissue damage
What are the triggers factors of immune mediated polyarthritis?
Type I: Idiopathic IMPA (most common, no trigger identified)
Type II: Associated with infection remote from joints (Lyme disease, Leishmaniasis, other focal infection)
Type III: associated with inflammatory GI disease
Type IV: associated with neoplastic disease
What is Evan’s syndrome?
IMHA + thrombocytopenia
Clinical signs:
- anaemia
- discoloured urine
- cutaneous bruising
