Autoimmune Diseases 1 Flashcards
What is tolerance?
A state of immunological non-reactivity to an antigen
Why is sarcoidosis and IBS not autoimmune?
The adaptive system does not react to self antigens
What is negative selection?
Too strong interaction between T cells and antigen presenting cells with peptide
Type 2 hypersensitivity is ?
Pathogenic autoantibodies
Autoimmune cytopenias?
Antibodies stuck to antigens on red cells, macrophages with fcr receptors will phagocytose or complement activation
What happens in graves thyroiditis?
Antibody against TSH receptor stimulating thyroid hormone release, so TSH levels go down
Signs of myasthenia gravis?
Ptosis at rest
Muscle weakness
Facial muscles talking and swallowing affected
Bells syndrome is?
Eyes turn inwards and upwards
What happens in myasthenia gravis molecular level?
Acetylcholine receptors degraded and internalised
Spontaneous urticaria is caused by?
IgG FcER1 antibody cross links mast cel receptor causing degranulation
Presents with hives and swelling
Type 4 hypersensitivity is caused by?
T cell dependent mechanisms because they activate other elements of innate immunity or damage tissue
T cell mediated autoimmune diseases?
Coeliac
Type 1 diabetes
Multiple sclerosis
Autoimmune polyglandular syndrome candiasis and ectodermal dystrophy?
AIRE gene regulates ectopic expression of tissue specific antigens in thymus,
AIRE mutations result in failure of negative selection
Why candiasis?
Prone to developing antibodies against IL 17, which is important for fungal defence
DiGeorge syndrome is due to?
Failure migration 3/4 brachial arches
Microdeletion of chromosome 22
A permissive negative selection?
Broad repertoire
Low risk of infection
High risk of autoimmunity
Pemphigus?
Organ specific autoimmune disease with blisters and sores on skin or mucous membranes
For coeliac which antibody would you check for?
Tissue transglutaminase antibody
APACED is associated with organ specific diseases such as?
Type 1 diabetes, vitiligo, alopecia, autoimmune adrenal disease
Phenotype of DiGeorge syndrome?
Absent parathyroids( low Ca, tetany),
Cleft palate
Congenital heart defects
Thymus aplasia
IPEX, immune dysregulation, polyendocrinopathy, enteropathic, x linked?
FOXP3 gene
Key features of IPEX?
IBD
Dermatitis
Organ specific autoimmunity
HLA encoded on?
Chromosome 6
HLA system
Class I: A,B C
Class II: DR, DP, DQ
Coeliac prevalence?
1% in UK
Sign of coeliac?
Loose stool Weight loss Vit deficiency Anaemia Poor growth in children
Coeliac disease microscope
Total villus atrophy
Crypt hyperplasia
Lymphocyte infiltration
Coeliac patient express either or both?
HLA DQ2
HLA DQ8
What happens in coeliac?
Gliadin is degraded by transgluatmine 2 enzyme to form gliadin peptides.
HLA DQ2/8 molecules can present gliadin peptides to T cells
What percent of Europeans have HLA DQ2/8?
30-50%
What are the peripheral tolerance mechanisms?
Immunological heirachy- CD4 T cell wont be activated unless antigen in presented in an inflammatory context with TLR ligation
Antigen segregation
Peripheral anergy- weak signalling APC/CD4 T cell with costimulation causes T cells to become unresponsive
Regulatory T cells- cd25/foxp3
Cytokine deviation- change in phenotype from th1 to TH2
Clonal exhaustion- apoptosis post activation by activation induced cell death
AID organ specific?
Type 1 diabetes Pemphigus Graves Hashmitos Autoimmune cytopenia etc
Multi system AID?
Lupus
Rheumatoid arthritis
Sjogrens
Criteria for type 2 hypersensitivity?
Pathogenic antibody is identified
Removal of antibody by plasmapheresis is beneficial
Diseases can be transferred between experimental animal/gestation
Type 2 hypersensitivity, antibody mediated?
Graves Autoimmune thrombolysis Autoimmune haemolytic anaemia Myasthenia gravis (ptosis) Spontaneous urticaria
Why is it hard to check for T cell mediated conditions?
More difficult to demonstrate auto reactive T cells in vitro than it is to demonstrate antibody
Experimental models rely on genetically susceptible animals that are sensitised, often by exposure to a self antigen with an adjuvant
T cell mediated conditions?
Hashimotos
Type 1 diabetes
Coeliac
IPEX cause?
Foxp3 mutation
Abrogates production of CD4 cd25 and foxp3 reg T cells
Key features:
IBD dermatitis organ specific autoimmunity
Which are the monogenic autoimmunity conditions?
IPEX
DiGeorge
APACED
