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
Which infectious disease could cause secondary immunodeficiency? How?
FIV
* This is a T-lymphotropic retrovirus that infects lymphocytes.
* Affects cats
Parvovirus
* Direct depletion of lymphoid tissue
* Affects dogs and cats
Describe the epidemiology of IMHA
- Most commonly affects young adults and middle-aged dogs
- Primary IMHA is more common in dogs
- Secondary IMHA is more common in cats (often secondary to FIP, Mycoplasma haemofelis, FeLV, chronic bacterial infections)
IMHA in dogs and cats is:
a) an antibody-mediated disease
b) a T-cell mediated disease
a) an antibody-mediated disease
Antibodies and complement attach to the surface of RBCs leading to haemolysis.
What is primary IMHA?
- IMHA with no known causative trigger (60-75% cases in dogs)
- There is a failure of tolerance for no discernable reason
- There is an inherited predisposition in dogs, especially cocker spaniels, springer spaniels, poodles.
Which of the following events could result in IMHA?
a) autoantibody to RBC membrane antigen is produced
b) there is an antibody for an infectious agent that cross-reacts to an RBC
c) there is an antibody against a drug, which ends up adhering to a RBC
d) drug or infection modifies RBC antigen or exposes a hidden antigen
e) alloantibodies enter the body e.g. from a blood transfusion or in neonatal isoerythrolysis
All these can result in IMHA.
IMHA can also be idiopathic.
What is secondary IMHA?
- A trigger e.g. drug or infectious cause results in IMHA
- IMHA has been strongly linked with organisms that infect RBCs e.g. Babesia, Mycoplasma haemofelis
- IMHA has been speculatively linked with FeLV, recent vaccination, neoplasia, medications e.g. TMPS in dogs, and possibly bee stings and snake bites.
Which infectious agent is pictured here? What would you treat the animal with?
Mycoplasma haemofelis
Treat wth doxycycline
What does this image show and what does this finding indicate?
Autoagglutination -> indicates IMHA
What are the two types of haemolysis?
Extravascular and intravascular
Extravascular haemolysis
Antibody-coated RBCs are recognised and phagocytosed by macrophages in organs such as then spleen.
Intravascular haemolysis
Antibody and complement on the RBC surface lead to direct cell lysis within the circulation.
This presents as more acute red/pink plasma ± red/pink urine.
What cell type is indicated by the green arrows? What does it indicate?
Spherocytes
* These are formed when partial phagocytosis of RBCs occurs.
* Phagocytes take a bite out of RBC; it then repairs itself and forms a sphere rather than a nice biconcave shape (hence lack of central pallor in spherocytes)
* They are useful markers of IMHA in peripheral blood smears.
What do Heinz bodies indicate?
Oxidative damage to RBCs
The damage occurs specifically to the components of haemoglobin within these cells
True/false: you can diagnosie IMHA in the dog based on the presence of spherocytes.
True
True/false: spherocytes will be seen in animals that have received transfusions.
True
These RBCs are foreign and get damaged
IMHA produces anaemia. Is this a regenerative or non-regenerative anaemia?
- Usually IMHA produces regenerative anaemia
- However, occasionally auto-immune reactions affect bone marrow, and chronic inflammation also results in functional iron deficiency.
- Therefore, the anaemia could also be minimally-regenerative or non-regenerative.
If you see orange/pink serum, what type of haemolysis are you suspicious of?
Intravascular haemolysis
True/false: animals with intravascular haemolysis can enter renal failure.
True
* Haemoglobin can cause nephropathy
* This means the haemoglobin passing through the kidneys can cause renal failure
Which type of haemolysis can produce jaundice?
Extravascular haemolysis
Haemoglobin is metabolised by the liver -> too much can lead to jaundice
What are some clinical signs of IMHA?
- Pale gums, pallor
- Hepatomegaly (liver reaches last rib on radiograph)
- Jaundice, icterus
Describe the clinical sign of IMHA observed here
Hepatomegaly
What laboratory findings might you see in a dog with IMHA?
- Anaemia: usually regenerative, with polychromasias and reticulocytes (i.e. often see increased MCV, decreased MCHC)
- Blood smear: spherocytes, ghost cells, schistocytes, acanthocytes
- Autoagglutination
- Inflammatory leucogram inc. high neutrophil counts with a left shift (cam occur ± an infectious trigger)
- May see thrombocytopaenia as well (could be consumptive, or due to concurrent IMTP)
- Hyperbilirubinaeia, bilirubinuria
- Haemglobinaemia
- Elevated liver parameters
True/false: spherocytes are easy to identify in cats.
False
Spherocytes are hard to see in cats
How long does it take bone marrow to mount a regenerative response to anaemia? What is the relevance of this?
- It takes 3-5 days for bone marrow to mount a regenerative response
- This means, a dog hit by a car losing blood will be non-regenerative to start with
What other diseases could cause autoagglutination aside from IMHA?
None!
IMHA is the only reason for autoagglutination.
True/false: all animals with IMHA will show autoagglutination.
False
Not all animals with IMHA will show autoagglutination - false negatives are possible due to lack of required number of antibodies.
What does a direct Coombe’s test do?
- Identifies antibody on the surface of the patient’s RBCs (therefore you must submit an EDTA sample)
- This is more sensitive than an indirect Coombe’s test
- It is more sensitive but less specific than saline agglutination test
- Can pick up IMHA that saline agglutination test didn’t
When would you use a Coombe’s test?
- No point doing this if you saline agglutination test was positive!
- Worthwhile in cases that are challenging to diagnose e.g. no autoagglutination, no spherocytes, or potentially a non-regenerative anaemia
Orange/yellow serum=
bilirubinaemia
Red serum=
haemoglobinaemia
True/false: you might see raised liver enzymes in IMHA.
True
This is associated with anaemia and hypoxic liver damage
Which of these is consistent with pre-hepatic jaundice?
a) high PCV with high ALT
b) low PCV with low bilirubin
c) low PCV with high bilirubin
c) low PCV with high bilirubin
