Organ-specific autoimmunity Flashcards
Describe the difference between organ-specific autoimmunity and non-specific autoimmunity
organ-specific = endocrine glands, antigen expressed by glands
non-specific = multiple organs, self-antigen expressed in a lot of different tissues, connective tissue diseases
What immunoglobulin is normally involved in autoimmune reactions involving antibodies?
IgG
What immunoglobulin does allergies involve?
IgE
Fab and Fc parts of antibodies functions
Fab = antigen recognition
Fc = effector function - binds proteins
What is opsonisation?
Fc binding to Fc receptors on macrophages
marks them for phagocytosis
What is antibody-dependent cell-mediated cytotoxicity?
Fc binding to Fc receptors on NK cells leads to release of cytotoxic granules onto pathogen
Describe antibody-mediated type 2 hypersensitivity
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
What diseases are caused by type 2 hypersensitivity reactions?
haemolytic anaemia
thrombocytopaenia
Goodpasture’s syndrome
Pemphigus vulgaris
acute rheumatic fever
Guillain-Barre syndrome
Grave’s disease
Myasthenia gravis
rheumatoid arthritis
Describe antibody-mediated damage (type 3 hypersensitivity) immune complex disease
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
Name some diseases caused by type 3 hypersensitivity reactions
SLE
RA
post-strep glomerulonephritis
polyarteritis nodosa
reactive arthritis
serum sickness
arthus reaction
farmer’s lung
henoch-schonlein purpura
Describe cell-mediated type 4 hypersensitivity
activated autoreactive cytotoxic T cells release cytotoxic cytokines (TNF) and perforins and kill cells
Name some diseases caused by type 4 hypersensitivity
T1DM
RA
MS
What causes type 1 hypersensitivity reactions?
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
Describe the autoimmunity of anti-GBM disease
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
Describe the autoimmunity of Goodpasture syndrome
autoantibodies bind collagen in the kidney and lungs
kidney and lung damage - haemorrhage
Describe the autoimmunity of T1DM
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
Describe the autoimmunity of SLE
antibodies against DNA form immune complexes that deposit in small blood vessels
the complexes bind complement, induce recruitment of neutrophils leading to inflammation
Describe the immune processes in post-streptococcal glomerulonephritis
immune complexes lodge in kidney capillaries
the complexes bind complement, induce recruitment of neutrophils and inflammation
When is IgA made?
made by B cells in response to infection of mucosal surfaces
Cause of IgA nephropathy
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
What is central tolerance?
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
Where do T cells differentiate?
in the thymus
How does the thymus educate T cells?
thymic medulla cells use MHC to educate T cells by presenting self proteins to immature T cells
What goes wrong in the thymus in autoimmunity?
some self reactive T cells survive and generate helper T cells that recognise self antigens
HLA gene for ankylosing spondylitis
HLA-B27
HLA gene for Crohn’s disease
HLA-DRB1
HLA gene for Goodpasture’s syndrome
HLA-DR2
HLA gene for Grave’s disease
HLA-DR3
HLA gene for MS
HLA-DR2
HLA gene for RA
HLA-DR3
HLA gene for Sjogren’s syndrome
HLA-DR3
HLA gene for T1DM
HLA-DR3, DR4, DQ2, DQ8
How can infections trigger autoimmunity?
cytokines generated during infection can stimulate low numbers of self-reactive T-cells
these provide help to self-reactive B-cells
Treatment of autoimmune disease
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
