Autoimmune Diseases L6-7 Flashcards
Define an autoimmune response.
An immune response specific for “self”.
Define an autoimmune disease.
An autoimmune response central to pathogenesis.
What are the 2 types of autoimmune disease?
- Organ-specific
- Non-organ-specific (systemic)
Name some organ-specific autoimmune diseases.
- Type 1 diabetes mellitus
- Goodpasture’s syndrome
- MS
- Grave’s disease
- Myasthenia gravis
- Hashimoto’s thyroiditis
- Autoimmune pernicious anemia
- Autoimmune Addison’s disease
- Vitiligo
Name some non-organ-specific autoimmune diseases.
- Rheumatoid arthritis
- Scleroderma
- Systemic lupus erythematosus
- Polymyositis
- Primary Sjogren’s syndrome
Describe autoantibodies.
4
- Often >1 autoantibody
- May be primary or secondary
- Overlap between organ-specific diseases
- Also between non-organ-specific diseases
Autoimmune disease may be antibody or ___ ___ -mediated.
T cell
Describe the role of autoantibodies in Pernicious anemia.
Ab to intrinsic factor in pernicious anaemia, preventing absorption of vitamin B12.
Describe the role of autoantibodies in Myasthenia gravis.
Ab to acetyl choline receptor in myasthaenia gravis that binds to receptor causing its removal from the muscle surface.
Describe the role of autoantibodies in Grave’s disease.
Ab to TSH receptor in Graves’ disease which mimics the effect of TSH causing excessive secretion of thyroid hormones.
Describe the role of autoantibodies in autoimmune haemolytic anemia.
Autoantibodies mediate the destruction of red blood cells.
Describe the role of autoantibodies in immune thrombocytopenic purpura.
Autoantibodies mediate the destruction of platelets.
Name the 3 pathogenic effects of autoantibodies.
- Interference with molecular function
- Mediation of cell desctruction (Type 2 hypersensitivity)
- Immune complex mediated reactions (Type 3 hypersensitivity)
Describe the role of autoantibodies in systemic lupus erythematosus.
Autoantibodies to DNA form complexes which are deposited at susceptible sites leading to symptoms of disease (skin, kidneys, joints).
Which type of hypersensitivity causes T-cell-mediated pathogenesis.
Type 4.
The best evidence of T-cell-mediated pathogenesis comes from where?
Animal models.
Which disease is the animal model for MS?
EAE (Experimental allergic encephalitis).
Describe Rheumatoid arthritis and the role of synovial fibroblasts.
Joints are infiltrated by CD4 T cells that activate macrophages to secrete inflammatory cytokines.
Role of synovial fibroblasts
- Secrete matrix metalloproteases: damage tissue
- Express RANK ligand: activate osteoclasts to break down bone
True or false? Single gene defects causing autoimmune disease are common.
False. They are rare.
In mice which genes can be knocked out to give rise to an autoimmune disease?
- CTLA4
- IL-2
- IL-10
Name the 4 genetic factors in diabetes.
- HLA
- Insulin gene
- CTLA-4
- PTPN22
Autoreactive T-helper cells are normally unresponsive due to what 4 mechanisms?
How does a full autoimmune response occur?
- Clonal deletion
- Clonal anergy
- Suppression (by Treg)
- Inadequate autoantigen presentation
A full autoimmune response requires these mechanisms to be bypassed or subverted
Name the 5 ways in which autoimmune disease could arise.
- Molecular mimicry
- Microbes provide ‘danger signals’
- Autoantigens act as ligands for TLRs, so interpreted as foreign by immune system
- Release of “sequestered” antigen
- Abnormal expression of autoantigens to which there is no tolerance
Describe molecular mimicry in the development of an autoimmune disease.
Microbial antigen is similar to an autoantigen and induces a cross-reactive immune response.
What do microbe released ‘danger signals’ do in the development of an autoimmune disease?
- Upreguate costimulator molecules
- Induce inflammatory cytokines
Give an example of how the release of “sequestered” antigen could play a role in the development of an autoimmune disease.
Traumatic damage to one eye can lead to an autoimmune response affecting the other eye.
Describe Narcolepsy.
- Narcolepsy is a sleep disorder causing daytime sleepiness
- Associated with deficiencies in the wakefulness hormone hypocretin
- Neurones that produce hypocretin are deficient in narcoleptic brains
- Thought to be an autoimmune disease because of very strong HLA-association (HLA-DQB1*0602)
Gut microbes have been shown to influence the development of type 1 diabetes in a mouse model.
The incidence is higher in females, why is this?
Due to protective effect of microbes in males since male mice in germ-free conditions show a similar incidence of disease to females.
Microbes in male mice induced increased production of testosterone and protected against the development of diabetes.
List the treatments of autoimmune diseases.
Give examples.
- Metabolic control
e. g. insulin in diabetes - Anti-inflammatory drugs
e. g. steroids in SLE - Immunosuppressive drugs
e. g. cyclosporin A, anti-mitotics
