Autoimmunity Flashcards
Autoimmunity Definition
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
Autoimmune disease
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
Induction of autoimmunity
Normal response to an unusual or abnormal antigen abnormal response to a normal antigen
also are genetic predisposition and hormonal influences
Autoimmunity
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
Infection induced autoimmunity
Molecular mimicry
Epitope spreading
Bystander activation
Cryptic antigens
Molecular Mimicry
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.
Epitope spreading
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.
Bystander activation
Rupture of tolerance induced by the presence of cytokines and chemokines
costimulation activated normally supressed self-reactive cell due to increased self-antigen presentation
Cryptic antigens
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
Autoimmunity Predisposing factors
Genetic predisposition: breed related autoimmunity
Intestinal microbiota
Autoimmune thyroiditis
T3 and T4 autoantibodies
Type II hypersensitivity mechanism (also type IV)
Insulin dependent diabetes mellitus
Glutamic acid decarboxylase (humans)
Dogs: autoantibodies against B cells. CTLs also play a role
Hyperthyroidism
Thyroid peroxidase autoantibodies (1/3 of the cases) Lymphocytic infiltrate (1/3 of the cases)
Lymphocytic pancreatitis
Lymphocytic infiltration
Lymphocyte mediated destruction of the adrenal cortex
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Autoimmune eye diseases
Equine recurrent uveitis
Uveodermatological syndrome
Equine recurrent uveitis
(periodic ophthalmia)
Molecular mimicry
Interphotoreceptor retinoid-binding protein
Leptospira interrogans
Uveodermatological syndrome
Uveitis and dispigmentation of the hair (poliosis) and skin (vitiligo)
In humans: Vogt-koyanagi-harada syndrome
-autoimmune response against melanocytes
Skin Autoimmunity
Blistering diseases
Basement membrane
Blistering diseases
Pemphigus complex
- pemphigus vulgaris- Desmoglein 3
- pemphigus foliaceus- desmoglein 1. Pemphigus erythematosus, pemphigus vegetans
- paraneoplastic pemphigus- multiple autoantibodies against skin Ag
Basement membrane
Bullous pemphigoid- type XVII collagen
Linear immunoglobulin A dermatosis- extracellular form of collagen XVII
Epidermolysis Bullosa Acquisita- Type VII collagen
Hematologic autoimmune diseases
Immune mediated hemolytic anemia
Immune mediated thrombocytopenia
Immune mediated neutropenia
Autoimmune muscle disease
Myasthenia gravis
Polymyositis
Myasthenia gravis
Impaired neuromuscular transmission
Autoantibodies agains the NMJ
-acetylcholine receptor (AChR)
-Muscle specific kinase (MUSK)
Polymyositis
Systemic immune-mediated inflammatory disorder
German shepherds, quarter horses
Muscle damage
Autoimmune neurological disease
Canine polyneuritis
Canine polyneuritis
Coonhound paralysis
Raccoon saliva
Autoantibodies against peripheral nerve glycolipids
Vaccine polyneuritis
Resembles Guillain Barre syndrome in humans
Equine polyneuritis
Rare
Antibodies to peripheral myelin protein called P2
Steroid-responsive meningitis-arteritis (SRMA)
Autoimmune neurological disease
Sterile inflammation of the meningeal arteries and cervical meningitis
Acute and chronic forms
Canine necrotizing meningoencephalitis (NME)
Autoimmune neurological disease
Pugs, maltese, terriers, pekinese, and chihuahuas
Necrotizing leukoencephalitis (NLE)
Granulomatous meningoencephalitis
Systemic autoimmune diseases
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
Sjogren’s syndrome
Autoimmune attack on salivary and lacrimal glands- keratoconjunctivitis sicca and mouth dryness (xerostomia)
Often associated with rheumatoid arthritis, systemic lupus, polymyositis and autoimmune thyroiditis
Systemic Lupus Erythematosus
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
Autoimmune Polyarthritis
Erosive polyarthritis
Non-erosive polyarthritis
Erosive polyarthritis
Rheumatoid arthritis
-rheumatoid factor
Anti-IgG leads to neutrophil accumulation and synovitis. Leads to protease secretion and cartilage and bone erosion
Non-erosive polyarthritis
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)
