Lecture 25: Tolerance and Autoimmunity II

Question 1

does autoimmunity always create disease?

Answer 1

no

Question 2

autoimmunity / autoimmune disease occurs upon loss of ______or_______tolerance

Answer 2

central or peripheral

Question 3

risk for autoimmunity/autoimmune disease may be effected by…

Answer 3

• increasing age
• genetics+heritability
• sex hormones

Question 4

cryptic antigens

Answer 4

antigens previously hidden from immune system
released by tissue trauma from immune privileged sites (heart attack, infection, chronic inflammation)

Question 5

receptor editing and molecular modifications generate new ____

Answer 5

epitopes

Question 6

CD233 is an epitope that forms on aging RBCs and causes antibody-mediated destruction of RBCs by macrophages, what kind of autoimmunity is this

Answer 6

physiologic

Question 7

what are rheumatoid factors? when do they occur?

Answer 7

• autoantibodies to other immunoglobulins
• occur when a new epitope forms in the Fc region
• most common when immune complexes are formed

*lupus, rheumatoid arthritis

Question 8

autoantibodies to complement

Answer 8

immunoconglutinins C3, C2, C4

Question 9

new epitopes formed on activated complement that reflect the degree of antigenic stimulation in an individual

Answer 9

immunoconglutinins

Question 10

a persistent _____ response in required for disease to develop

Answer 10

autoimmune

Question 11

Autoimmune diseases are common in individuals with ______tumors

Answer 11

lymphoid

Question 12

CD95 is involved in what

Answer 12

apoptosis of “self” T cells in thymus

Question 13

A defect in CD95 results in…

Answer 13

release of self reactive T cells from the thymus

Question 14

what is mircrochimerism

Answer 14

• During pregnancy, cells travel between the mother and fetus
• can sometimes triggen autoimmune dz

Question 15

viruses can induce ______AD

Answer 15

Multisystemic

Reovirus

Question 16

Bacteria can induce ______AD

Answer 16

uveitis (inflammation inside eye)

common in horses, Leptospira

Question 17

Protozoa can induce _____AD

Answer 17

cardiomyopathy

Trypanosoma cruzi

Question 18

3 proposed mechanisms by which infection induces AD

Answer 18

• Molecular mimicry
• Epitope spreading
• bystander activation

Question 19

molecular mimicry and bystander activation is most commonly seen with

Answer 19

viruses

Question 20

how does molecular mimicry induced AD occur

Answer 20

• 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

Question 21

How does bystander activation caused by infection induced AD occur

Answer 21

infection causes tissue destruction and massive inflammatory cascade that ‘accidentally’ causes nearby resting T cells to active and respond to new antigen

Question 22

how does epitode spreading occur

Answer 22

• 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

Question 23

milk allergy in cattle is an example of type___hypersensitivity

Answer 23

1, immediate
delayed milking causes casein into circulation –> anaphylaxis occurs

Question 24

autoimmune thyroiditis is a type____hypersensitivity

Answer 24

II, cytotoxic

Question 25

Lupus is a type____hypersensitivity

Answer 25

III immune complex

Question 26

MS and insulin dependent diabetes are type ____Hypersensitivities

Answer 26

IV, delayed

Question 27

in __________disease, the immune system attacks organs and tissues of the body

Answer 27

immune mediated

Question 28

______ is a subset of immune mediated disease in which specific antigens of the body inititate the immune response

Answer 28

autoimmune disease

Question 29

autoimmune thyroiditis is an example of what kind of AD

Answer 29

Specific to a single cell type or organ

Question 30

Example of multisystemic AD

Answer 30

lupus

Question 31

Autoimmunity against pancreas islets of Langerhans causes

Answer 31

insulin dependent DM | endocrine target

Question 32

cauda equina is...

Answer 32

* autoimmunity against sacral and coccygeal nerves * target is myelin protein | Coohound paralysis in dogs

Question 33

canine version of cauda equina

Answer 33

Coonhound paralysis (similar to Guillain Barre in humans)

Question 34

examples of diseases in canines in which neural tissue is the target of autoimmunity

Answer 34

* coonhound paralysis * steroid responsive meiningitis arteritis * necrotizing meningoencephalitis * degenerative myelopathy * cerebellar degeneration

Question 35

Equine recurrent uveitis is ...

Answer 35

Autoimmunity targeted against ocular tissue - often associated w/ **high Leptospira titers (bacterial)**

Question 36

Uveodermatological syndrome in canine

Answer 36

autoimmunity targets ocular tissue, affects eyes, skin and hair

Question 37

blistering diseases caused by autoimmunity targeting the skin (3)

Answer 37

pemphigus **foliaceus** (superficial epidermis): **desmocollin 1** Pemphigus **vulgaris** (deep epidermis): **desmoglein 3** **bullous** pemphigoid (basement membrane) **type XVII collagen**

Question 38

alopecia areata is an AD where ____ is the target

Answer 38

skin

Question 39

Bullous pemphigoid (type XVII collagen) is an AD where ____ is the target

Answer 39

basement membrane

Question 40

examples of diseases in which blood cells are the target of autoimmunity

Answer 40

* immune mediated hemolytic anemia * autoimmune thrombocytopenia

Question 41

AD in which acetylcholine receptor is the target & muscle weakness is the primary clinical sign

Answer 41

myasthenia gravis

Question 42

Systemic lupus erythematosus (SLE) pathogenesis

Answer 42

* genetic factors * T & B cell abnomalities * impaired apoptosis * **multiple autoantibodies**

Question 43

canine rheumatoid arthritis causes....

Answer 43

erosion of articular cartilage

Question 44

equine recurrent uveitis is ___cell mediated and an example of _____hypersensitivity

Answer 44

T cell mediated (Th1) delayed (type IV)

Question 45

type of blistering disease in the superficial epidermis, desmocollin 1

Answer 45

pemphigus foliaceus

Question 46

type of blistering disease in the basement membrane, type XVII collagen

Answer 46

Bullous pemphigoid

Question 47

type of blistering disease in the deep epidermis, desmoglein 3

Answer 47

Pemphigus vulgaris

Question 48

Diabetes Mellitus and Myasthenia gravis are both what types of hypersensitivities

Answer 48

Type IV (delayed)

Question 49

autoimmune thyroiditis is what type of hypersensitivity

Answer 49

Type II (Cytotoxic)