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72 Cards in this Set

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What is the definition of autoimmune?
An immune system that no longer recognizes "self" and forms antibodies against "self" antigens
What is the definition of an immune mediated response?
It is when the immune system is stimulated by foreign antigens that act as haptens, adhering to or altering cell surface antigens.
What are the components of the immune system?
B lymphocytes (humoral immunity)
T lymphocytes (cell mediated immunity)
Macrophages/neutrophils
Complement
Describe Type 1 immune mediated tissue injury
It is a IgE mediated reaction, where mast cells or basophils bind IgE, which leads to cell degranulation, which causes a release of vasoactive substances, such as histamine and heparin. This causes local tissue injury
What are the clinical signs of Type 1 immune mediated tissue injury in dogs?
GI signs - vomiting, dirrhea
Derm signs - erythema, edema, pruritus
What are the clinical signs of Type 1 immune mediated tissue injury in cats?
Respiratory signs - pulmonary edema, laryngeal spasms, bronchial constriction
What are examples of Type 1 immune mediated tissue injury?
Anaphylactic reaction and atopy
Describe Type 2 immune mediated tissue injury
Antibodies and complement bind to cell surface antigens, which causes destruction of the cell by the mononuclear phagocytic system
What are examples of Type 2 immune mediated tissue injury?
IMHA, ITP, pemphigus skin diseases
Describe Type 3 immune mediated tissue injury
Antigen, antibody and complement get deposited in the walls of the blood vessels, which results in tissue and organ dysfunction secondary to the associated inflammatory response
What are examples of Type 3 immune mediated tissue injury?
Glomerulonephropathy, rheumatoid arthritis and immune mediated uveitis
Describe Type 4 immune mediated tissue injury
Sensitized T lymphocytes react with antigens that results in a delayed reaction, peaking at 24 hours
What are examples of Type 4 immune mediated tissue injury?
lymphocytic thyroiditis and the tuberculin reaction
What are the two groups of immune mediated/autoimmune diseases?
1. immune system recognizes body tissues as foreign and directs a humoral and/or cellular response against specific target organs or tissues
2. immune system produces antibody that complexes with antigen. These complexes get deposited in tissues or organs. Once deposited the complexes activate the compliment cascade, which causes tissue damage
What is the etiology of immune mediated disease?
It is multifactorial. Caused by genetics (predisposed breeds) and environment (infections, vaccines, drugs) and immune dysregulation
What is the difference between primary and secondary immune mediated disease?
Primary is idiopathic, where as secondary immune disease is caused by some other antigenic stimulus such as infection, neoplasia, drugs or vaccines
What are some infectious causes of secondary immune disease?
Babesia, Ehrlichia, Anaplasma, Neorickettsia, Rickettsia, Wolbachia, Borrelia, Leptospirosis, Mycoplasma, Bartonella vinsonii, Dirofilaria, FeLV, FIV, blastomyces, histoplasma
What are some neoplastic causes of secondary immune disease?
Lymphosarcoma and hemangiosarcoma
What are some drugs that can cause secondary immune disease?
Cephalosporins, sulfonamides, penicillins, methimazole in cats, chlorpromazine, vaccines
What does the diagnostic workup for an immune mediated problem include?
History (focus on drugs and vaccine history)
Infectious disease panel
Cancer hunt (imaging)
What are some examples of immune dysregulation?
failure to eliminate autoreactive lymphocytes
Failure to clearimmune complexes
cytokine defects
defects in apoptosis
What is the name of a common autoimmune disease that affects red blood cells, and what is the proposed mechanism of inflammation?
Immune mediated hemolytic anemia (IMHA)
Antibody attaches to RBC membranes and triggers destruction by either complement fixation (intravascular) or destruction by tissue macrophages (extravascular). Humoral and/or cell mediated
What is the name of a common autoimmune disease that affects erythroid precursors in the bone marrow, and what is the proposed mechanism of inflammation?
Pure red cell aplasia
Humoral and/or cell mediated
What is the name of a common autoimmune disease that affects platelets, and what is the proposed mechanism of inflammation?
Immune mediated thrombocytopenia
Humoral and/or cell mediated
What is the name of a common autoimmune disease that affects neutrophils, and what is the proposed mechanism of inflammation?
immune mediated neutropenia
Humoral and/or cell mediated
What are the names of the common autoimmune diseases that affect synovium, and what is the proposed mechanism of inflammation?
Polyarthritis and rheumatoid arthritis
Immune complexes get deposited in the synovial membrane
What is the name of a common autoimmune disease that affects glomeruli, and what is the proposed mechanism of inflammation?
Glomerulonephritis
Immune complexes get deposited in the glomerulus
What is the name of a common autoimmune disease that affects the eye, and what is the proposed mechanism of inflammation?
Anterior uveitis
Immune complexes get deposited in the uvea
What are the names of common autoimmune diseases that affect skin, and what is the proposed mechanism of inflammation?
Discoid lupus erythematosis and pemphigus
humoral and/or cell mediated
What is the name of a common autoimmune disease that affects blood vessels, and what is the proposed mechanism of inflammation?
vasculitis
immune complexes get deposited in the blood vessel walls
What is the name of a common autoimmune disease that affects muscle, and what is the proposed mechanism of inflammation?
polymyositis and masticatory myositis
humoral and/or cell mediated
What is the name of a common autoimmune disease that affects the meninges, and what is the proposed mechanism of inflammation?
steroid responsive meningitis
humoral and/or cell mediated
What is the name of a common autoimmune disease that affects nerve end plates, and what is the proposed mechanism of inflammation?
myasthenia gravis
antibodies develop against the acetylcholine receptors in the nerve end plate
humoral and/or cell mediated
What is the definition of Systemic Lupus Erythmatosis (SLE)?
SLE is an idiopathic autoimmune disease, where the immune system loses self tolerance towards body proteins (autoantigens) and starts attacking target tissues. Both humoral immunity and immunoglobulin complexes may be involved
What are the characteristics of SLE?
Numerous clinical manifestations
Waxing and waning clinical signs
No pathognomonic abnormalities
Basically, you will never recognize it.
It is a multiorgan autoimmune disease
Dogs with SLE will have one or more of the following disorders:
IMHA, pure red cell aplasia, immune mediated thrombocytopenia, immune mediated neutropenia, myasthenia gravis, nonerosive polyarthritis, glomerulonephritis, dermatitis, polyneuritis, polymyositis, vasculitis
What is the incidence of SLE?
It is an uncommon disease of dogs, and rare in the cats.
What are the genetic predisposing factors for SLE?
familial associations and breed predispositions
German shepherds, collies, shelties and cocker spaniels
What are the infectious predisposing factors for SLE?
infections with an unidentified organism may cause the disease
How does a deficiency of IgA predispose a dog to SLE?
Inefficent mucosal immune defenses can allow microbes to colonize that trigger the process that leads to the loss of self tolerance
What are the major clinical signs of SLE?
polyarthritis, PLN, IMHA, marked ITP, leukopenia, skin lesions and polymyositis
What are the minor clinical signs of SLE?
Fever, lymphadenopathy, oral ulceration, CNS signs, pericarditis, pleuritis
What are the serological signs of SLE?
antinuclear antibodies are greater than 1:160
LE cells (+sig, macrophage)
If you have a high ANA titer without evidence of an immune mediated disease, does this diagnose SLE?
No
High titers characterize autoimmune disorders but you need more to diagnose
What are antinuclear antibodies (ANA)
antibodies that are specific for the nucleus
ANA may be present in the serum of animals with any chronic inflammatory, infectious or neoplastic disease, but in these situations the ANA titers are usually low
When should you consider ANA titer assays?
If there are 2 major signs present, there is a good chance that the ANA will be positive, and the dog will have an immune mediated disease.
Limit ANA assays to dogs that have at least 1 major SLE sign
What is required to diagnose SLE in a dog?
Multiple manifestations of autoimmunity, along with a high ANA titer
Definitive diagnosis for SLE
ANA titer >1:160 and 2 or more major signs
ANA titer >1:160, 1 major sign and 2 or more minor signs
Probably diagnosis for SLE
ANA titer >1:160, 1 major sign, and 1 or no minor signs
ANA titer <1:160, 2 major signs and at least 1 minor sign
What do you have to do when starting immunosuppressive therapy?
You need to identify possible infectious causes of immune mediated disease, and provide treatment for them
What are the immunosuppressive drugs that are most commonly used in vet med?
Corticosteroids (pred, dex)
Azathioprine
Cyclosporine
Cyclophosphamide
When are corticosteroids good to use for immune suppression?
For induction and maintenance
it is often necessary to initiate immunosuppression to control the disease
What are the 3 major mechanisms of action of corticosteroids?
Suppress mononuclear phagocytic activity (immediate effect)
Removal of antibody from the surface of target cells (immediate effect)
suppress the production of immunoglobulins (delayed effect)
What are the adverse effects of corticosteroids?
Iatrogenic hyperadrenocorticism
GI ulcers
UTIs
Pancreatitis
Diabetes Mellitus
PU/PD
Polyphagia
Panting
What are the doses for prednisone?
Physiologic: 0.1-0.2 mg/kg/day
Anti inflammatory: 0.5-1.0 mg/kg/day
Immunosuppressive: 2 - 4 mg/kg/day
For large dogs, use the low end of the dose range - they are sensitive to the effects.
Use the high end of the dose ranges for cats
Which is more potent, dexamethasone or prednisone?
Dexamethasone is 7 times more potent than prednisone
A dose of dex = the dose of pred divided by 7
When should you use dex instead of pred?
Dex causes less sodium retention, so its a better choice for animals that have heart disease, hypertension or effusion.
Dex does not have MC activity, which is why the difference exists.
What are the adverse effects of dex?
It may be associated with increased GI ulceration
How does azathioprine work?
It is a purine analog that creates nonfunctional DNA and RNA.
When should you use azathioprine?
It is used to maintain remission in refractory cases, or in cases where the corticosteroids cause intolerable side effects
How long does it take for azathioprine to work?
It is effective 7-10 days after meds are started, maybe longer.
What are the adverse effects of azathioprine?
Pancreatitis
Hepatitis
GI distress
reversible myelosuppresion in dogs and cats
don't use in cats - causes severe myelosuppression
How does cyclosporine work?
It inhibits T cell activation
How is cyclosporine absorbed?
There is wide variability in GI absorption.
Need to monitor trough levels to make sure levels are too high
What is the goal for cyclosporine trough levels?
more than 500 ng/ml and less than 1,000 ng/ml
What is a benefit of cyclosporine?
Cost - more affordable in small/medium dogs and cats
How can cyclosporine metabolism be inhibited?
The antifungal medication ketoconazole inhibits cytochrome P450 enzymes, slowing the metabolism. Using ketoconazole with cyclosporine can reduce the dose of cyclosporine needed.
What is a concern of using ketoconazole with cyclosporine?
Ketoconazole can cause hepatotoxicity, so you need to monitor both cyclosporine and liver enzyme levels.
What are the adverse effects of cyclosporine?
Hepatotoxicity
GI distress
Gingival hyperplasia
Some dogs develop cutaneous fungal infections that may not respond to anti fungals
What is cyclophosphamide? (Cytoxan)
It is an alkylating chemotherapy agent that suppresses cell mediated and humoral immunity
What are the adverse effects of cyclophosphamide?
Sterile hemorrhagic cystitis
GI side effects
Myelosuppression
What are the 3 things to monitor for with any animal that is taking a immunosuppressive drug?
Recurrence of the immune mediated disease
Side effects of the drug
- increased liver enzymes with pred, cyclosporine or azathioprine
- Myelosuppression with azathioprine, cyclophosphamide
Secondary infections
- UTIs, respiratory tract infections, cutaneous fungal infection