Autoimmune Diseases 1

Question 1

What is tolerance?

Answer 1

A state of immunological non-reactivity to an antigen

Question 2

Why is sarcoidosis and IBS not autoimmune?

Answer 2

The adaptive system does not react to self antigens

Question 3

What is negative selection?

Answer 3

Too strong interaction between T cells and antigen presenting cells with peptide

Question 4

Type 2 hypersensitivity is ?

Answer 4

Pathogenic autoantibodies

Question 5

Autoimmune cytopenias?

Answer 5

Antibodies stuck to antigens on red cells, macrophages with fcr receptors will phagocytose or complement activation

Question 6

What happens in graves thyroiditis?

Answer 6

Antibody against TSH receptor stimulating thyroid hormone release, so TSH levels go down

Question 7

Signs of myasthenia gravis?

Answer 7

Ptosis at rest
Muscle weakness
Facial muscles talking and swallowing affected

Question 8

Bells syndrome is?

Answer 8

Eyes turn inwards and upwards

Question 9

What happens in myasthenia gravis molecular level?

Answer 9

Acetylcholine receptors degraded and internalised

Question 10

Spontaneous urticaria is caused by?

Answer 10

IgG FcER1 antibody cross links mast cel receptor causing degranulation
Presents with hives and swelling

Question 11

Type 4 hypersensitivity is caused by?

Answer 11

T cell dependent mechanisms because they activate other elements of innate immunity or damage tissue

Question 12

T cell mediated autoimmune diseases?

Answer 12

Coeliac
Type 1 diabetes
Multiple sclerosis

Question 13

Autoimmune polyglandular syndrome candiasis and ectodermal dystrophy?

Answer 13

AIRE gene regulates ectopic expression of tissue specific antigens in thymus,

AIRE mutations result in failure of negative selection

Question 14

Why candiasis?

Answer 14

Prone to developing antibodies against IL 17, which is important for fungal defence

Question 15

DiGeorge syndrome is due to?

Answer 15

Failure migration 3/4 brachial arches

Microdeletion of chromosome 22

Question 16

A permissive negative selection?

Answer 16

Broad repertoire
Low risk of infection
High risk of autoimmunity

Question 17

Pemphigus?

Answer 17

Organ specific autoimmune disease with blisters and sores on skin or mucous membranes

Question 18

For coeliac which antibody would you check for?

Answer 18

Tissue transglutaminase antibody

Question 19

APACED is associated with organ specific diseases such as?

Answer 19

Type 1 diabetes, vitiligo, alopecia, autoimmune adrenal disease

Question 20

Phenotype of DiGeorge syndrome?

Answer 20

Absent parathyroids( low Ca, tetany),
Cleft palate
Congenital heart defects
Thymus aplasia

Question 21

IPEX, immune dysregulation, polyendocrinopathy, enteropathic, x linked?

Answer 21

FOXP3 gene

Question 22

Key features of IPEX?

Answer 22

IBD
Dermatitis
Organ specific autoimmunity

Question 23

HLA encoded on?

Answer 23

Chromosome 6

Question 24

HLA system

Answer 24

Class I: A,B C

Class II: DR, DP, DQ

Question 25

Coeliac prevalence?

Answer 25

1% in UK

Question 26

Sign of coeliac?

Answer 26

``` Loose stool Weight loss Vit deficiency Anaemia Poor growth in children ```

Question 27

Coeliac disease microscope

Answer 27

Total villus atrophy Crypt hyperplasia Lymphocyte infiltration

Question 28

Coeliac patient express either or both?

Answer 28

HLA DQ2 | HLA DQ8

Question 29

What happens in coeliac?

Answer 29

Gliadin is degraded by transgluatmine 2 enzyme to form gliadin peptides. HLA DQ2/8 molecules can present gliadin peptides to T cells

Question 30

What percent of Europeans have HLA DQ2/8?

Answer 30

30-50%

Question 31

What are the peripheral tolerance mechanisms?

Answer 31

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

Question 32

AID organ specific?

Answer 32

``` Type 1 diabetes Pemphigus Graves Hashmitos Autoimmune cytopenia etc ```

Question 33

Multi system AID?

Answer 33

Lupus Rheumatoid arthritis Sjogrens

Question 34

Criteria for type 2 hypersensitivity?

Answer 34

Pathogenic antibody is identified Removal of antibody by plasmapheresis is beneficial Diseases can be transferred between experimental animal/gestation

Question 35

Type 2 hypersensitivity, antibody mediated?

Answer 35

``` Graves Autoimmune thrombolysis Autoimmune haemolytic anaemia Myasthenia gravis (ptosis) Spontaneous urticaria ```

Question 36

Why is it hard to check for T cell mediated conditions?

Answer 36

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

Question 37

T cell mediated conditions?

Answer 37

Hashimotos Type 1 diabetes Coeliac

Question 38

IPEX cause?

Answer 38

Foxp3 mutation Abrogates production of CD4 cd25 and foxp3 reg T cells Key features: IBD dermatitis organ specific autoimmunity

Question 39

Which are the monogenic autoimmunity conditions?

Answer 39

IPEX DiGeorge APACED