Autoimmune disease Flashcards
What is central tolerance (2)
Thymic education
Happens early in life
What is peripheral tolerance? (2)
T regs suppress self-reactive immune responses in tissues
What are the 2 types of autoimmune disease? (2)
Organ-specific
Non-organ specific (systemic)
What are the causes of autoimmune disease? (2)
Combination of genetic and environmental factors and infections
Give an example of a genetic factor causing autoimmune disease (3)
Loss of function single-gene Foxp3 (transcription factor) - decreased function of CD4 CD25 regulatory T cells
Pemphigus vulgaris (4)
Autoantibodies (IgG) attack desmosomes → Loss of epithelial cell adhesion → Skin blisters.
Often begins with erosions of the oral mucosa
Describe the histology of Pemphigus vulgaris (2)
Loss of normal epithelial cell adhesion and detachement of cells within the epidermis
(suprabasal acantholysis)
How to detect Pemphigus vulgaris (3)
Direct - Deposition of complement components and immunoglobulin molecules in skin lesions
Find desmosomes
Indirect - Circulating autoantibodies
can be detected by indirect
immunofluorescense
What is molecular mimicry? (2)
By detecting a pathogen, immune system starts to recognise antigen of own body
Body exposed to pathogens and response to own antigen becomes stronger
Therapy for Pemphigus vulgaris (2)
Steroids
Steroids in combination with
Immunosuppressive drugs
Rituximab (3)
Monoclonal antibody injected into patient
Takes out circulating B cells (which form antibodies)
Takes out cells which have CD20 on surface
Systemic Lupus erythematosus (3)
Multisystem disorder
Typically affects young women
Autoantibodies attack nuclear antigens leading to multisystem damage
Trigger Factors for chronic-discoid LE (4)
UV-Light!
Infection
Exposure to Cold
Stress
Neonatal lupus erythematosus (4)
Transplacentally acquire autoimmune disorder
Clinical manifestations:
* skin rash
* congenital atrioventricular block
* thrombocytopenia
* leukopenia
* anemia
The skin as target organ in LE (3)
Apoptotic cells are not cleared properly.
Autoantigens become “accessible” to the immune system.
This is called the “Clearance” Hypothesis
Apoptosis in LE (2)
IL-18 induces apoptosis in LE HPK
HPK from LE-patients produce TNFalpha upon stimulation
with IL-18
Therapy for LE (6)
No therapy which treat the “cause” of the disease available yet
* Protection from UV-Light
* Chloroquin
* Immunosuppression
* Anti B cell therapy
* Anti IFN therapy
