Immune-mediated disorders Flashcards
How does the immune system recognize itself
While the fetus is in utero the developing thymus “teaches” the body’s earliest T-lymphocytes within the thymic cortex to ignore its own antigens
- the thymic cortex contains epithelial cells that express a wide range of host tissue antigens and major histocompatibility (MHC) antigens classes I and II
The immature T-cells are tested to see whether they can bind to the MHC antigens
- those that fail to bind at all or bind too strongly are eliminated
- other cells are retained and eventually become CD4+ cells (that can bind to MHC class II antigens) and CD8+ T cells (that bind to MHC class I)
All of these thymic lymphocytes have a T-cell receptor (TCR) which is normally specific for a foreign antigen
- the immature thymic lymphocytes are also screened for any binding of their TCR to the tissue antigens expressed by the epithelial cells within the thymic cortex
- any affinity prompts apoptosis of the offending lymphocyte
Once they are screened against self-MHC and self-tissue antigens the new T-cells are released into the fetal circulation to populate the secondary lymphoid organs
Explain why, even if B-lymphocytes are not as tightly screened in the fetus as T-lymphocytes (i.e., some are able of recognizing some self-antigens), this is of little consequence normally
The immune response cannot progress without the secondary help of specific T-cells which have normally already been weeded out by the thymus
If the selection of T-cells is so specific, how then, does autoimmune disease arise
In some cases the reason an autoimmune reaction arises remains unknown
Some mechanisms have been discovered:
- access to tissues in privileged sites that contain antigens that were not screened in the thymus (e.g., CNS, lens of the eye)
- shared antigenic epitopes between the host and a pathogen (e.g., group A Strep) - loss of regulatory T-cell function - up-regulation of T-helper 17 cell function which secreteq IL-17, a pro-inflammatory cytokine
What are the main pathomechanism of systemic lupus erythematosus
The principal pathogenic immunological mechanism in SLE is a Type III hypersensitivity reaction, in which antigen-antibody complexes are inadequately cleared from the body and become deposited in vessel walls (especially of the synovium, glomerulus and choroid plexus)
Type II hypersensitivity may also be responsible for producing the hematological changes sometimes seen with the disease (IMHA and/or IMT) and autoantibodies may also be directed at cellular nuclei
What is the typical signalment for SLE
Young to middle-aged purebreds tend to be the most commonly affected
- unlike people, there appears to be no sex predilection
What are the clinical signs of SLE
Clinical signs depend on the body system affected and are due to inflammation of this body part
- typically, the synovial joints, glomeruli, skin, blood cells and CNS are affected in cats
Many affected cats experience several of the following signs:
- fever
- muscle pain, joint pain, lameness
- lymphadenopathy
- oral and/or skin lesions (e.g., ulceration, crust, erythema, depigmentation)
- signs attributable to anemia
- CNS signs (e.g., alterations in behavior and/or mentation, seizures)
Signs may be exacerbated by ultraviolet radiation from the sun or concurrent infection
Which aspect of the clinical signs make a diagnosis of SLE difficult to reach
The clinical signs can often be waxing and waning and they mimic many different infectious and neoplastic diseases
When can you make a presumptive diagnosis of SLE
The disease should be suspected when two or more immune-mediated conditions occur concurrently
These include, but are not limited to:
- IMHA
- IMT
- immune-mediated skin disease (i.e., vesicobullous dermatitis)
- glomerulonephritis
- nonerosive immune-mediated polyarthritis
- CNS signs (e.g., seizures, dementia, coma)
How can you reach a diagnosis of SLE
No single test is available to diagnose SLE
- to make a diagnosis, infections and neoplastic causes must be eliminated as possible explanation for the cat’s clinical signs
If there is evidence of regenerative anemia, FeLV and FIV tests as well as a Coombs’test and a PCR test for hemotropic Mycoplasma spp should be performed
If there is joint pain or effusion, synovial fluid should be obtained for cytology
- the synovial neutrophils should be well preserved
Cats with azotemia and proteinuria should have a urine protein-to-creatinine ratio measured
Skin lesions should be biopsied
The presence of a positive anti-nuclear antibody test is supportive, but does not confirm the disease
- many false-positive and false-negative tests occur
- a high ANA titer is more consistent with SLE than a low titer
What are the classical criteria retained to reacha diagnosis of SLE
Various criteria have been proposed for the diagnosis of SLE based on those used in people
Evidence for autoimmune injury to at least two organ systems, along with a positive ANA titer
Or, three affected organ systems with a negative ANA titer
What are the goals of therapy for SLE
Controlling tissue inflammation and addressing organ failure are the goals of therapy for SLE
Immunosuppressive doses of glucocorticoids should be started
- oral prednisolone (2-4 mg/kg, q24h)
- if there is no improvement in 1 week, consider adding chlorambucil (0.25-0.5 mg/kg, PO, q48h)
Once remission has been achieved, a reduction in drug dose can begin
- if combination therapy has been used, the chlorambucil should be reduced first by 50% for 4 weeks
UV light can be a trigger for some cats with SLE, they should be kept out of the sun
Give a definition of systemic anaphylaxis
Systemic anaphylaxis is a life-threatening allergic event resulting in massive, generalized mast cell degranulation
The inflammatory mediators released by mast cells result in grave consequences if not treated promptly
What is the pathomechanism of anaphylaxis
Immunologic anaphylaxis is mediated by interactions among antigens, IgE antibodies, and mast cells
- this type I hypersensitivity reaction requires previous exposure to an antigen and production of IgE against that antigen
Degranulation of mast cells results in the release of preformed mediators of inflammation
- this occurs rapidly, with effects appearing within seconds to minutes of exposure to the antigen
Nonimmunologic anaphylaxis is the result of mast cell degranulation without an immune component
- IgE is not involved
- previous exposure to the antigen is not required
What are the clinical signs of anaphylaxis
Immunologic and noninmmunologic reactions have the same clinical signs that can be divided into four categories:
- cutaneous (i.e., generalized erythema, urticaria, pruritus, angioedema)
- respiratory (i.e., dyspnea, bronchospasm, stridor, cough, open mouth breathing) - cardiovascular (i.e., pale mucous membranes, prolonged CRT, poor pulse quality, hypotension) - GI (i.e., nausea, vomiting, diarrhea)
The major shock organ in the cat is the lung, with the intestinal tract involved to a lesser degree
- respiratory distress is the major sign of anaphylactic shock in cats
What is the treatment for systemic anaphylaxis
Once anaphylaxis is recognized, rapid and aggressive treatment may be lifesaving
For mild reactions, treatment with the H1 antihistamine diphenhydramine (0.5-1.0 mg/kg, IM or PO, q12h) may be sufficient
Epinephrine is the recommended first-line treatment for severe reactions
- dose 0.01 mg/kg, slow IV or IM, q 5-15min as needed
IV access should be established as soon as possible for drug administration and correction of hypovolemia (i.e., aggressive fluid therapy)
Explain why glucocorticoids are not useful for the acute treatment of anaphylaxis
Glucocorticoids are not useful for the acute treatment of anaphylaxis because they cause vasodilation and decrease cardiac contractility
Once the life-threatening crisis has resolved, dexamethasone sodium phosphate (0.1 - 0.5 mg/kg, IV) may be beneficial by enhancing beta-receptor sensitivity and decreasing phospholipase A2 activity
