4.3.3: Immune mediated disease 1 Flashcards
Autoimmunity
A failure of self-tolerace; self-reactive T and B lymphocytes become active and may cause tissue damage and clinical autoimmune disease
What are some factors that predispose animals to autoimmune disease?
- Age: more common in middle aged-older (immunosenscene)
- Sex and neutering status: evidence suggests no sex predisposition but neutered animals more likely to die from autoimmune dz than entire ones.
- Lifestyle
- Diet
- Environmental factors: vaccination, drugs, infectious disease
- Genetics e.g. Cocker Spaniels and autoimmune cytopaenia e.g. IMHA and IMTP
Immunological imbalance occurs when the normal self-tolerance mechanism goes wrong. What T cells are involved and how?
- T regulatory cells don’t do their job
- Autoreactive T cells are generated
How can we subdivide immune-mediated diseases?
Attacking the body vs attacking something else
* Hypersensitivity (allergic) disorders - attacking something else
* Autoimmune disorders - attacking the body
* Immune system neoplasia
* Immunodeficiency disorders - failure to attack anything well
Remember - these can overlap. i.e. hypersensitivity reactions can form part of autoimmune disease.
Which breed of dog is suspectible to autoimmune cytopaenias (IMHA, IMTP)?
Cocker Spaniels
What is immunosenescence?
age-related deterioration in immune system function.
(Immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumours).
Which species are autoimmune diseases most prevalent in within veterinary medicine?
Dogs
What are some examples of canine autoimmune diseases?
- Immune-mediated haemolytic anaemia (IMHA)
- Immune-mediated thrombocytopaenia (IMTP)
- Immune-mediated neutropaenia (IMNP)
- Pemphigus disorders
- Cutaneous lupus erythematosus (CLE)
- Systemic lupus erythematosus (SLE)
- Autoimmune polyarthritis e.g. rheumatoid arthritis
- Myasthenia gravis
- Lymphocytic thyroiditis (the underlying mechanism of canine hypothyroidism)
- Diabetes mellitus
- Exocrine pancreas insufficiency (EPI)
What are other names for the following diseases?
* Autoimmune haemolytic anaemia
* Autoimmune thrombocytopaenia
* Autoimmune neutropaenia
- Autoimmune haemolytic anaemia = IMHA
- Autoimmune thrombocytopaenia = IMTP
- Autoimmune neutropaenia = IMNP
True/false: a number of different immunopathological mechanisms may be involved in canine autoimmune diseases. For example, hypersensitivity reactions can be part of the process in autoimmune disease.
True
e.g. IMHA involves a Type II hypersensitivity reaction
* IgG or IgM autoantibody destroy RBCs
e.g. lymphocytic thryoiditis involves a Type IV hypersensitivity reaction
* Cytotoxic T lymphocytes destroy the thyroid follicular epithelium
Differentiate between primary and secondary autoimmune disease
- Primary idiopathic autoimmune disease: arises in a genetically susceptible individual in the absence of a known trigger.
- Secondary autoimmune disease: occurs due to a recognised trigger.
True/false: triggers to autoimmune disease have been identified. If an animal is exposed to one of these triggers, they will develop autoimmune disease.
False
Triggers do not cause autoimmune disease in all animals - only some of those who come into contact with these triggers will then develop autoimmune disease.
What are some possible triggers for (secondary) autoimmune disease?
If autoimmune disease is caused by a trigger, it is by definition secondary (see Card 11)
- Neoplasia e.g. lymphoma, splenic haemangiosarcoma can cause IMHA, IMTP
- Chronic disease
- Environmental triggers e.g. lifestyle, stress, diet, UV exposure
- Drugs e.g. TMPS can trigger IMHA/IMTP/IMNP (dogs), methimazole can trigger IMHA/IMTP in cats
- Vaccines - contentious issue
- Infection - this is the most significant trigger for autoimmunity. There may be a long lag period
What disease are these lesions consistent with?
Systemic lupus erythematosus (SLE)
What is this?
This two-lobed intracellular parasite is Babesia.
What is shown here and how does it link to autoimmunity?
This intracellular parasite is Babesia.
* Canine babesiosis can cause secondary IMHA
* Exact mechanism not 100% clear; it is possible that Babesia antigen carries an epitope that is a molecular mimic for an RBC eptiope
Epitope: (a.k.a. antigenic determinants) regions of proteins that can trigger a cellular immune response mediated by T or B cells.
What are the key points to remember regarding immunodeficiency syndromes?
Immunodeficiency: a functional problem with the immune system.
* 2 types: primary and secondary
* ** Primary immunodeficiency**- rare, seen in young puppies and kittens that are repeatedly not right. May be breed specific. Rule out possible common causes, then ask an expert/get a textbook.
* Secondary immunodeficiency- comparatively common, can affect animals of any breed. Some form of physiological/pathological change affects an aimal that previously had normal immune function.
What is SCID? Which animals and breeds is it seen in?
SCID: severe combined immunodeficiency.
* Seen in JRTs, Arab foals and others.
* Autosomal recessive condition (at least in foals)
* Foals have no functional B or T lymphocytes (no adaptive immunity).
* The animal suffers recurrent opportunistic infections.
* This disease is fatal.
What condition is pictured here?
Lethal acrodermatitis in a Bull Terrier
This is an autosomal recessive disease
What are primary immunodeficiency disorders and how are they recognised?
Primary immunodeficiency disorders: congenital deect affecting formation or function of cells/proteins of the innate/adaptive/both immune system.
Might see:
* Repeated infections in a young animal post-weaning/after the loss of maternal antibody.
* Purebred puppy or several puppies from a litter experiencing problems.
What factors could cause secondary immunodeficiency?
- Immunosenescence: normal age-related decline in immune function.
- Medical immunosuppression
- Specific infections