Organ-specific autoimmunity

Question 1

Describe the difference between organ-specific autoimmunity and non-specific autoimmunity

Answer 1

organ-specific = endocrine glands, antigen expressed by glands

non-specific = multiple organs, self-antigen expressed in a lot of different tissues, connective tissue diseases

Question 2

What immunoglobulin is normally involved in autoimmune reactions involving antibodies?

Answer 2

IgG

Question 3

What immunoglobulin does allergies involve?

Answer 3

IgE

Question 4

Fab and Fc parts of antibodies functions

Answer 4

Fab = antigen recognition
Fc = effector function - binds proteins

Question 5

What is opsonisation?

Answer 5

Fc binding to Fc receptors on macrophages
marks them for phagocytosis

Question 6

What is antibody-dependent cell-mediated cytotoxicity?

Answer 6

Fc binding to Fc receptors on NK cells leads to release of cytotoxic granules onto pathogen

Question 7

Describe antibody-mediated type 2 hypersensitivity

Answer 7

antibodies (IgG, IgM) bind self antigen on tissue
Fc domains activate complement and recruit NK cells, macrophages, neutrophils etc leading to tissue damage and inflammation

Question 8

What diseases are caused by type 2 hypersensitivity reactions?

Answer 8

haemolytic anaemia
thrombocytopaenia
Goodpasture’s syndrome
Pemphigus vulgaris
acute rheumatic fever
Guillain-Barre syndrome
Grave’s disease
Myasthenia gravis
rheumatoid arthritis

Question 9

Describe antibody-mediated damage (type 3 hypersensitivity) immune complex disease

Answer 9

antibodies bind soluble self antigen and form immune complexes
immune complexes get stuck in small blood vessels
Fc domains activate complement and recruit NK cells, neutrophils etc leading to cell damage and inflammation

Question 10

Name some diseases caused by type 3 hypersensitivity reactions

Answer 10

SLE
RA
post-strep glomerulonephritis
polyarteritis nodosa
reactive arthritis
serum sickness
arthus reaction
farmer’s lung
henoch-schonlein purpura

Question 11

Describe cell-mediated type 4 hypersensitivity

Answer 11

activated autoreactive cytotoxic T cells release cytotoxic cytokines (TNF) and perforins and kill cells

Question 12

Name some diseases caused by type 4 hypersensitivity

Answer 12

T1DM
RA
MS

Question 13

What causes type 1 hypersensitivity reactions?

Answer 13

allergy
IgE secreted by B cells into the blood supply and binds IgE receptors on mast cells and eosinophils
allergens recognised by IgE cause histamine release from mast cells leading to local inflammation

Question 14

Describe the autoimmunity of anti-GBM disease

Answer 14

type 2 hypersensitivity
autoantibodies bind collagen in glomerular basement membrane
often follows damage to lungs (smoking) which reveals cryptic antigens

cryptic antigens = antigens that are not normally present

Question 15

Describe the autoimmunity of Goodpasture syndrome

Answer 15

autoantibodies bind collagen in the kidney and lungs
kidney and lung damage - haemorrhage

Question 16

Describe the autoimmunity of T1DM

Answer 16

delayed type 4 hypersensitivity
cytotoxic T cells recognising beta islet cell proteins contribute to T1DM
activated cytotoxic T cells release perforins and kill islet cells

Question 17

Describe the autoimmunity of SLE

Answer 17

antibodies against DNA form immune complexes that deposit in small blood vessels
the complexes bind complement, induce recruitment of neutrophils leading to inflammation

Question 18

Describe the immune processes in post-streptococcal glomerulonephritis

Answer 18

immune complexes lodge in kidney capillaries
the complexes bind complement, induce recruitment of neutrophils and inflammation

Question 19

When is IgA made?

Answer 19

made by B cells in response to infection of mucosal surfaces

Question 20

Cause of IgA nephropathy

Answer 20

patients make an IgA with unusual sugars that are antigenic
infection increases IgA production
IgA is recognised by autoantibodies and incorporated into immune complexes that lodge in the glomerulus

Question 21

What is central tolerance?

Answer 21

T cells that recognise self antigens are killed in the thymus
immature T cells that have strong binding for MHC self-peptide they die - negative selection

Question 22

Where do T cells differentiate?

Answer 22

in the thymus

Question 23

How does the thymus educate T cells?

Answer 23

thymic medulla cells use MHC to educate T cells by presenting self proteins to immature T cells

Question 24

What goes wrong in the thymus in autoimmunity?

Answer 24

some self reactive T cells survive and generate helper T cells that recognise self antigens

Question 25

HLA gene for ankylosing spondylitis

Answer 25

HLA-B27

Question 26

HLA gene for Crohn’s disease

Answer 26

HLA-DRB1

Question 27

HLA gene for Goodpasture’s syndrome

Answer 27

HLA-DR2

Question 28

HLA gene for Grave’s disease

Answer 28

HLA-DR3

Question 29

HLA gene for MS

Answer 29

HLA-DR2

Question 30

HLA gene for RA

Answer 30

HLA-DR3

Question 31

HLA gene for Sjogren’s syndrome

Answer 31

HLA-DR3

Question 32

HLA gene for T1DM

Answer 32

HLA-DR3, DR4, DQ2, DQ8

Question 33

How can infections trigger autoimmunity?

Answer 33

cytokines generated during infection can stimulate low numbers of self-reactive T-cells
these provide help to self-reactive B-cells

Question 34

Treatment of autoimmune disease

Answer 34

remove antibody by plasmapheresis or IgG therapy:
- GBS
- MG
- TTP

anti-inflammatory drugs (NSAIDs, steroids, biologics):
- RA

immunosuppressive drugs

restore/reverse specific damage:
- T1DM - insulin
- Grave’s - carbimazole
- Hashimoto’s - thyroxine

DMARDs