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Immunology > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

Autoimmunity Definition

A

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

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2
Q

Autoimmune disease

A

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

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3
Q

Induction of autoimmunity

A

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

also are genetic predisposition and hormonal influences

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4
Q

Autoimmunity

A

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

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5
Q

Infection induced autoimmunity

A

Molecular mimicry
Epitope spreading
Bystander activation
Cryptic antigens

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6
Q

Molecular Mimicry

A

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.

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7
Q

Epitope spreading

A

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.

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8
Q

Bystander activation

A

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

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9
Q

Cryptic antigens

A

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

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10
Q

Autoimmunity Predisposing factors

A

Genetic predisposition: breed related autoimmunity

Intestinal microbiota

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11
Q

Autoimmune thyroiditis

A

T3 and T4 autoantibodies

Type II hypersensitivity mechanism (also type IV)

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12
Q

Insulin dependent diabetes mellitus

A

Glutamic acid decarboxylase (humans)

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

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13
Q

Hyperthyroidism

A 
Thyroid peroxidase autoantibodies (1/3 of the cases)
Lymphocytic infiltrate (1/3 of the cases)
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14
Q

Lymphocytic pancreatitis

A

Lymphocytic infiltration

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15
Q

Lymphocyte mediated destruction of the adrenal cortex

A

.

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16
Q

Autoimmune eye diseases

A

Equine recurrent uveitis

Uveodermatological syndrome

17
Q

Equine recurrent uveitis

A

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

18
Q

Uveodermatological syndrome

A

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

19
Q

Skin Autoimmunity

A

Blistering diseases

Basement membrane

20
Q

Blistering diseases

A

Pemphigus complex

  • pemphigus vulgaris- Desmoglein 3
  • pemphigus foliaceus- desmoglein 1. Pemphigus erythematosus, pemphigus vegetans
  • paraneoplastic pemphigus- multiple autoantibodies against skin Ag
21
Q

Basement membrane

A

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

22
Q

Hematologic autoimmune diseases

A

Immune mediated hemolytic anemia
Immune mediated thrombocytopenia
Immune mediated neutropenia

23
Q

Autoimmune muscle disease

A

Myasthenia gravis

Polymyositis

24
Q

Myasthenia gravis

A

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

25
Q

Polymyositis

A

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

26
Q

Autoimmune neurological disease

A

Canine polyneuritis

27
Q

Canine polyneuritis

A

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

28
Q

Equine polyneuritis

A

Rare

Antibodies to peripheral myelin protein called P2

29
Q

Steroid-responsive meningitis-arteritis (SRMA)

A

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

30
Q

Canine necrotizing meningoencephalitis (NME)

A

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

31
Q

Systemic autoimmune diseases

A

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

32
Q

Sjogren’s syndrome

A

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

33
Q

Systemic Lupus Erythematosus

A

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

34
Q

Autoimmune Polyarthritis

A

Erosive polyarthritis

Non-erosive polyarthritis

35
Q

Erosive polyarthritis

A

Rheumatoid arthritis
-rheumatoid factor

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

36
Q

Non-erosive polyarthritis

A 
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)

Immunology (18 decks)

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