Lecture 25: Tolerance and Autoimmunity II Flashcards
does autoimmunity always create disease?
no
autoimmunity / autoimmune disease occurs upon loss of ______or_______tolerance
central or peripheral
risk for autoimmunity/autoimmune disease may be effected by…
- increasing age
- genetics+heritability
- sex hormones
cryptic antigens
antigens previously hidden from immune system
released by tissue trauma from immune privileged sites (heart attack, infection, chronic inflammation)
receptor editing and molecular modifications generate new ____
epitopes
CD233 is an epitope that forms on aging RBCs and causes antibody-mediated destruction of RBCs by macrophages, what kind of autoimmunity is this
physiologic
what are rheumatoid factors? when do they occur?
- autoantibodies to other immunoglobulins
- occur when a new epitope forms in the Fc region
- most common when immune complexes are formed
*lupus, rheumatoid arthritis
autoantibodies to complement
immunoconglutinins C3, C2, C4
new epitopes formed on activated complement that reflect the degree of antigenic stimulation in an individual
immunoconglutinins
a persistent _____ response in required for disease to develop
autoimmune
Autoimmune diseases are common in individuals with ______tumors
lymphoid
CD95 is involved in what
apoptosis of “self” T cells in thymus
A defect in CD95 results in…
release of self reactive T cells from the thymus
what is mircrochimerism
- During pregnancy, cells travel between the mother and fetus
- can sometimes triggen autoimmune dz
viruses can induce ______AD
Multisystemic
Reovirus
Bacteria can induce ______AD
uveitis (inflammation inside eye)
common in horses, Leptospira
Protozoa can induce _____AD
cardiomyopathy
Trypanosoma cruzi
3 proposed mechanisms by which infection induces AD
- Molecular mimicry
- Epitope spreading
- bystander activation
molecular mimicry and bystander activation is most commonly seen with
viruses
how does molecular mimicry induced AD occur
- shared epitopes on infectious agent and self antigen
- epitope isn’t recognized on self but is recognized on pathogen and antibodies form
- antibodies then react w/ self epitope
How does bystander activation caused by infection induced AD occur
infection causes tissue destruction and massive inflammatory cascade that ‘accidentally’ causes nearby resting T cells to active and respond to new antigen
how does epitode spreading occur
- reaction initially occurs to specific pathoenic epitope
- rxn then spreads to additional epitopes, some of which may be self
- causes ‘runaway train’ of autoimmune disease
milk allergy in cattle is an example of type___hypersensitivity
1, immediate
delayed milking causes casein into circulation –> anaphylaxis occurs
autoimmune thyroiditis is a type____hypersensitivity
II, cytotoxic
Lupus is a type____hypersensitivity
III immune complex
MS and insulin dependent diabetes are type ____Hypersensitivities
IV, delayed
in __________disease, the immune system attacks organs and tissues of the body
immune mediated
______ is a subset of immune mediated disease in which specific antigens of the body inititate the immune response
autoimmune disease
autoimmune thyroiditis is an example of what kind of AD
Specific to a single cell type or organ
Example of multisystemic AD
lupus
Autoimmunity against pancreas islets of Langerhans causes
insulin dependent DM
endocrine target
cauda equina is…
- autoimmunity against sacral and coccygeal nerves
- target is myelin protein
Coohound paralysis in dogs
canine version of cauda equina
Coonhound paralysis (similar to Guillain Barre in humans)
examples of diseases in canines in which neural tissue is the target of autoimmunity
- coonhound paralysis
- steroid responsive meiningitis arteritis
- necrotizing meningoencephalitis
- degenerative myelopathy
- cerebellar degeneration
Equine recurrent uveitis is …
Autoimmunity targeted against ocular tissue
- often associated w/ high Leptospira titers (bacterial)
Uveodermatological syndrome in canine
autoimmunity targets ocular tissue, affects eyes, skin and hair
blistering diseases caused by autoimmunity targeting the skin (3)
pemphigus foliaceus (superficial epidermis): desmocollin 1
Pemphigus vulgaris (deep epidermis): desmoglein 3
bullous pemphigoid (basement membrane) type XVII collagen
alopecia areata is an AD where ____ is the target
skin
Bullous pemphigoid (type XVII collagen) is an AD where ____ is the target
basement membrane
examples of diseases in which blood cells are the target of autoimmunity
- immune mediated hemolytic anemia
- autoimmune thrombocytopenia
AD in which acetylcholine receptor is the target & muscle weakness is the primary clinical sign
myasthenia gravis
Systemic lupus erythematosus (SLE) pathogenesis
- genetic factors
- T & B cell abnomalities
- impaired apoptosis
- multiple autoantibodies
canine rheumatoid arthritis causes….
erosion of articular cartilage
equine recurrent uveitis is ___cell mediated and an example of _____hypersensitivity
T cell mediated (Th1)
delayed (type IV)
type of blistering disease in the superficial epidermis, desmocollin 1
pemphigus foliaceus
type of blistering disease in the basement membrane, type XVII collagen
Bullous pemphigoid
type of blistering disease in the deep epidermis, desmoglein 3
Pemphigus vulgaris
Diabetes Mellitus and Myasthenia gravis are both what types of hypersensitivities
Type IV (delayed)
autoimmune thyroiditis is what type of hypersensitivity
Type II (Cytotoxic)
