Autoimmunity

Question 1

Autoimmunity Definition

Answer 1

Self-reactive B cells and self peptide and self MHC reactive T cells, as well as autoantibodies are detectable in the circulation of all individuals
Non-pathological autoimmunity may in fact assist in the removal of worn-out or damaged cells and molecules
Results from a failure of self-tolerance

Question 2

Autoimmune disease

Answer 2

Applied when autoimmunity results in pathology
Estimates in humans suggest that 5-8% of the population develop autoimmune disease
-various degrees of severity
-in most cases these diseases then remain for life

Question 3

Induction of autoimmunity

Answer 3

Normal response to an unusual or abnormal antigen abnormal response to a normal antigen

also are genetic predisposition and hormonal influences

Question 4

Autoimmunity

Answer 4

Antigens hidden in cells or tissues (cryptic antigens)
-CD233 in RBCs

Antigens generated by molecular changes

• Rheumatoid factor- antibodies against Fc portion of IgG
• Immunocoaglutinins- antibodies against complement proteins

Failure of regulation
-central and or peripheral tolerance

Question 5

Infection induced autoimmunity

Answer 5

Molecular mimicry
Epitope spreading
Bystander activation
Cryptic antigens

Question 6

Molecular Mimicry

Answer 6

Cross reactivity between microbial and self-epitopes
Mistaking self-tissue peptides for microbe Ag
Continuation of cytokine production even after Ag has already been cleared because they think its still there
The microbe and self are similar so body gets confused and assumes self is the microbe.

Question 7

Epitope spreading

Answer 7

Diversification of epitope specificity from the dominant to subdominant ones
Damage to host cell -> host cell release peptide which is picked up and presented by APC
Persistent microbial infection increase APC presenting co-stimulation -> peripheral T cell tolerance unable to regulate
In beginning of infection, dominant epitope is invaders, as infection gets outta control, the subdominated self Ag will be targeted.

Question 8

Bystander activation

Answer 8

Rupture of tolerance induced by the presence of cytokines and chemokines
costimulation activated normally supressed self-reactive cell due to increased self-antigen presentation

Question 9

Cryptic antigens

Answer 9

Exposure of antigens that were previously hidden
Damaged cell exposed normally hidden Ag, which is nor previously presented i=to thymocytes during negative selection-> Ag exposed induce immune response

Question 10

Autoimmunity Predisposing factors

Answer 10

Genetic predisposition: breed related autoimmunity

Intestinal microbiota

Question 11

Autoimmune thyroiditis

Answer 11

T3 and T4 autoantibodies

Type II hypersensitivity mechanism (also type IV)

Question 12

Insulin dependent diabetes mellitus

Answer 12

Glutamic acid decarboxylase (humans)

Dogs: autoantibodies against B cells. CTLs also play a role

Question 13

Hyperthyroidism

Answer 13

Thyroid peroxidase autoantibodies (1/3 of the cases)
Lymphocytic infiltrate (1/3 of the cases)

Question 14

Lymphocytic pancreatitis

Answer 14

Lymphocytic infiltration

Question 15

Lymphocyte mediated destruction of the adrenal cortex

Answer 15

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Question 16

Autoimmune eye diseases

Answer 16

Equine recurrent uveitis

Uveodermatological syndrome

Question 17

Equine recurrent uveitis

Answer 17

(periodic ophthalmia)
Molecular mimicry
Interphotoreceptor retinoid-binding protein
Leptospira interrogans

Question 18

Uveodermatological syndrome

Answer 18

Uveitis and dispigmentation of the hair (poliosis) and skin (vitiligo)
In humans: Vogt-koyanagi-harada syndrome
-autoimmune response against melanocytes

Question 19

Skin Autoimmunity

Answer 19

Blistering diseases

Basement membrane

Question 20

Blistering diseases

Answer 20

Pemphigus complex

• pemphigus vulgaris- Desmoglein 3
• pemphigus foliaceus- desmoglein 1. Pemphigus erythematosus, pemphigus vegetans
• paraneoplastic pemphigus- multiple autoantibodies against skin Ag

Question 21

Basement membrane

Answer 21

Bullous pemphigoid- type XVII collagen
Linear immunoglobulin A dermatosis- extracellular form of collagen XVII
Epidermolysis Bullosa Acquisita- Type VII collagen

Question 22

Hematologic autoimmune diseases

Answer 22

Immune mediated hemolytic anemia
Immune mediated thrombocytopenia
Immune mediated neutropenia

Question 23

Autoimmune muscle disease

Answer 23

Myasthenia gravis

Polymyositis

Question 24

Myasthenia gravis

Answer 24

Impaired neuromuscular transmission
Autoantibodies agains the NMJ
-acetylcholine receptor (AChR)
-Muscle specific kinase (MUSK)

Question 25

Polymyositis

Answer 25

Systemic immune-mediated inflammatory disorder German shepherds, quarter horses Muscle damage

Question 26

Autoimmune neurological disease

Answer 26

Canine polyneuritis

Question 27

Canine polyneuritis

Answer 27

Coonhound paralysis Raccoon saliva Autoantibodies against peripheral nerve glycolipids Vaccine polyneuritis Resembles Guillain Barre syndrome in humans

Question 28

Equine polyneuritis

Answer 28

Rare | Antibodies to peripheral myelin protein called P2

Question 29

Steroid-responsive meningitis-arteritis (SRMA)

Answer 29

Autoimmune neurological disease Sterile inflammation of the meningeal arteries and cervical meningitis Acute and chronic forms

Question 30

Canine necrotizing meningoencephalitis (NME)

Answer 30

Autoimmune neurological disease Pugs, maltese, terriers, pekinese, and chihuahuas Necrotizing leukoencephalitis (NLE) Granulomatous meningoencephalitis

Question 31

Systemic autoimmune diseases

Answer 31

Interrelated diseases Overlapping features- difficult to understand how much they are separate and how much they are different aspects of the same issue Extensive and uncontrolled inflammatory responses Difficult to come to a definitive clinical diagnosis

Question 32

Sjogren's syndrome

Answer 32

Autoimmune attack on salivary and lacrimal glands- keratoconjunctivitis sicca and mouth dryness (xerostomia) Often associated with rheumatoid arthritis, systemic lupus, polymyositis and autoimmune thyroiditis

Question 33

Systemic Lupus Erythematosus

Answer 33

Antinuclear antibodies (ANAs) are a very characteristic feature (develop antibodies against several nuclear proteins/components) - nucleic acids - ribonucleoproteins - chromatin - histones Associated with: - increase in IFN-a which is an innate response against viral DNA. - TLR7 and TLR9 (specialized in recognizing microbial DNA) - Bacterial DNA host DNA (hypothesis that there is a mix up of these) - Ultraviolet radiation Other autoantibodies - RBCs - muscle cells - skin basement membrane Horses, dogs, and cats are more affected by SLE

Question 34

Autoimmune Polyarthritis

Answer 34

Erosive polyarthritis | Non-erosive polyarthritis

Question 35

Erosive polyarthritis

Answer 35

Rheumatoid arthritis -rheumatoid factor Anti-IgG leads to neutrophil accumulation and synovitis. Leads to protease secretion and cartilage and bone erosion

Question 36

Non-erosive polyarthritis

Answer 36

``` Equine polyarthritis Canine polyarthritis Feline polyarthritis Lupus polyarthritis polyarthritis with polymyositis Idiopathic polyarthritis Cruciate ligament rupture ``` Type II in dogs: polyarthritis associated with infectious lesions remote from the joints (e.g respiratory or urinary infections)