Lecture 25-Tolerance and Autoimmunity II Flashcards
Autoimmunity
Immune response against normal body components
Autoimmune disease
Disease resulting from an attack by an individuals immune system against an individuals own tissues
Does autoimmunity always create disease
No
Autoimmunity and autoimmune disease occurs from loss of
Central or peripheral tolerance
Autoimmunity and autoimmune diseases likely occurs from
Random, cumulative small mutations
Risk to autoimmunity and autoimmune disease affected by
Increasing age, genetics, heritability, sex hormones
What are the two scenarios for autoimmunity and autoimmune disease
- Normal response to unusual antigen
- Abnormal response to normal antigen
What are cryptic antigens and is it a normal or abnormal response
Normal response
Antigens previously hidden by immune system
How are cryptic antigens released and from where
Via tissue trauma
From immune privileged sites, inside cells (heart attack, infection, chronic inflammation)
What is CD233
New epitope forms on CD233 on aging RBC’s and antibody mediated destruction by splenic macrophages occurs
Is CD233 on aging epitopes causing antibody mediated destruction by splenic macrophages an example of physiologic or pathological autoimmunity
Physiologic
CD233 is an example of what type of normal response
Newly formed antigens
What is rheumatoid factor
Autoantibodies to other immunoglobulins
How are rheumatoid factors formed
Occurs when a new epitope forms in the Fc region and Ig antibodies bind it
Rheumatoid factors are most common when
Immune complexes are formed
Rheumatoid factors are present in what diseases
Rheumatoid arthritis and lupus
Rheumatoid factors are what kind of normal response
Newly formed antigens
What are immunoconglutinins
Autoantibodies to complement, new epitope form on activated complement
What type of normal response are immunoconglutinins
Newly formed antigens
An abnormal response is a failure of
Regulatory control
Autoimmune disorders are common in individuals with what types of tumors
Lymphoid
What is the result of a defect in CD95 or CD95 ligand
CD95 is involved in apoptosis of self T cells in thymus so with defect, release self reactive cells
What is microchimerism
Presence of another individuals cells within your own body
What is an example of microchimerism
Mother and fetus exchange of cells
Fetal cells often found in women with what disease
Scleroderma
Maternal cells often found in boys with
Dermatomyositis
What is an example of a virus that can cause multisystemic AD
Reovirus
What is an example of a bacteria that can cause AD uveitis
Leptospira
What is an example of a Protozoa that can cause cardiomyopathy
Tyranosoma cruzi
What are the three mechanisms that could be responsible for an abnormal response: infection induced AD
- Molecular mimicry
- Epitope spreading
- Bystander activation
What is infection induced AD: molecular mimicry
Shared epitopes on infectious agents and self antigens, epitope on self isn’t recognized but one on pathogen is so antibodies are formed
Antibodies then react with self epitope
What is infection induced AD: bystander activation
Infection results in tissue destruction and releases antigens, infection causes massive inflammatory cascade and help is accidentally provided to nearby cells to respond to new antigens
What type of antigen is usually the culprit in mimicry and bystander activation
Viruses
What is infection induced AD: epitope spreading
Reaction initially occurs to specific pathogenic epitope then reaction spreads to additional epitopes some which may be self—> runaway train of autoimmune disease
What type of hypersensitivity is immediate
Type 1
What type of hypersensitivity is cytotoxic
Type II
What type of hypersensitivity has immune complexes
Type III
What type of hypersensitivity is delayed
Type IV
What type of hypersensitivity is the following: milk allergy in cattle, delayed milking forces casein into circulation and anaphylaxis occurs
Type I immediate
What type of hypersensitivity is Lupus
Type III immune complex
What type of hypersensitivity is autoimmune thyroiditis
Type II cytotoxic
What type of hypersensitivity is MS, insulin-dependent DM
Type IV delayed
Immune meditated disease
Immune system attacks the organs and tissues of body
Autoimmune disease
Subset of immune mediated disease, in which specific antigens of the body are known to initiate a response
What are some endocrine targets of autoimmunity
Thyroid gland, parathyroid gland, adrenal gland, pancreas
What is the target of autoimmunity in pancreas
Islet of langerhans—> insulin-dependent DM
What is equine polyneuritis
Cause equina in horses: sacral and coccygeal nerves become damaged as AD disease targets myelin protein
What is canine polyneuritis
Coonhound paralysis
What species does steroid responsive meningitis-arteritis occur in
Dogs
What are the targets of necrotizing meningeoencephalitis and what species does it occur in
Targets- neural or vascular
Species; dogs
What is degenerative myelopathy
Demyelination disorder in dogs
What is the target of cerebellar degeneration
Granular cells
Common in coton du tulear puppies
What is equine recurrent uveitis often associated with
High leptospira titers
What does uveodermatological syndrome affect
Eyes, skin, hair
What is alopecia areata
Hair follicle AD
What are two examples of blistering diseases
Pemphigus vulgaris
Pemphigus folicaceus
What is desmoglein 3 associated with
Pemphigus vulgaris
What is desmocolin 1 associated with
Pemphigus foliaceus
Where is Pemphigus vulgaris located
Deep epidermis
where is Pemphigus foliaceus located
Superficial epidermis
What are 3 examples of basement membrane diseases
Bulbous Pemphigoid
Linear IgA dermatosis
Epidermolysis bullosa
What is type XVII collagen associated with
Bulbous pemphigoid
Where is bullous pemphigoid located
Basement membrane
What are two common AD as a result of targeting blood cells
IMHA and IMTP
What is the target of myasthenia gravis
Acetylcholine receptor
What is primary clinical sign of myasthenia gravis
Muscle weakness
What are some AD caused by targeting muscle
myasthenia gravis, polymyositis, autoimmune masticatory myositis, canine cardiomyopathy, dermatomyositis
What is the pathogenic of SLE
Genetic factors leading to T and B cell abnormalities, resulting in impaired apoptosis via multiple autoantibodies
What symptoms/signs does an animal need to have to diagnose SLE
Two of the following: skin lesions, polyarthritis, IMHA, thrombocytopenia, renal disease/proteinuria, positive ANA or positive LE
What does a positive LE test look like
Neutrophils phagocytosing nuclear components of apoptosis cells
What are some signs of canine RA
Stiffness or joint pain after inactivity, symmetrical swelling in multiple joints, sterile synovial fluid containing neutrophils, positive rheumatoid factor test, erosive polyarthritis
What inflammatory cells/cytokines are released in pathogenesis of RA
anti-IG, IL-17, IL-6, TNF, and neutrophils
What is equine recurrent uveitis
Painful, inflammatory ocular condition
What T cell response mediates equine recurrent uveitis
Th1
what type of hypersensitivity reaction is equine recurrent uveitis
Type IV delayed
What is the target of equine recurrent uveitis
Retinal proteins
What is equine recurrent uveitis a common sequelae to
Leptospira
