28 Autoimmunity Flashcards
what is the immunological responses
regulated response
exaggerated response
what does the regulated response lead to
protection
what does the exaggerated response lead to
tissue protection
what leads to autoimmune response
If self-responding to and self being damaged
examples of organ-specific autoimmune diseases
type 1 diabetes mellitus
Crohn’s syndrome
grave’s disease
examples of systemic autoimmune diseases
rheumatoid arthritis
Scleroderma
polymyositis
examples of organ specific diseases
multiple sclerosis -myelin sheath of nerve fibres
what are organ specific diseases
antigens (self-proteins/components) recognised – immune responses are organ specific, only in a particular area
examples of systemic diseases
systemic lupus erythematosus – ds (native) DNA, histones, ribonucleoprotein
what are systemic diseases
not one area, affects different
how many types of hypersensitivity are there
4
what is type 1 hypersensitivity
allergy
what is type 2 hypersensitivity
hypersensitivity reaction / autoimmunity – binding of auto antibody to self can trigger immune response = destruction
what is the type 3 hypersensitivity
immune complex disease
what is the type 4 hypersensitivity
delayed hypersensitivity – takes time to develop, cell-mediated response, cell has to have T cell on by APC, can trigger macrophages – macrophages damage as well as T cell related damage
what are autoimmune diseases
complex/multifactorial diseases
what effects the autoimmune diseases
Genetics effects how likely to get autoimmune disease, particular variants in genes, can give decrease or increased risk in developing an autoimmune disease
Infections and environmental factors effect too
Smoking is a risk factor for increasing risk
Lead to immune dysregulation and can lead to triggering of immune response
what mechanism is controlled for central tolerance
deletion
editing
where is the site of action of central tolerance
thymus (T cells) bone marrow (B cells)
what mechanism is controlled for antigen segregation
physical barrier to self-antigen access to lymphoid system
where is the site of action of antigen segregation
peripheral organs
what mechanism is controlled for peripheral anergy
cellular inactivation by weak signalling without co-stimulus
where is the site of action for periphery anergy
secondary lymphoid tissue
what mechanism is controlled for regulatory T cells
suppression by cytokines, intracellular signals
where is the site of action for regulatory T cells
secondary lymphoid tissue and sites of inflammation, multiple tissues in steady state
what mechanism is controlled for functional deviation
differentiation of regulatory T cells that limit inflammatory cytokine secretion
where is the site of action for functional deviation
secondary lymphoid tissue and sites of inflammation
what is mechanism of activation induced cell death
apoptosis
where is the site of action for activation induced cell death
secondary lymphoid tissue and sites of inflammation
examples of Graves disease causes - Hyperthyroidism
Weight loss Twitching Palpitations Restlessness Heat sensitive
what do autoantibodies do in grave’s disease
Autoantibodies that stimulate TSH receptors
- Hyperthyroidism
- Type II HS
what does the pituitary gland secrete
thyroid-stimulating hormone which acts on thyroid to induce release of thyroid hormones
what do thyroid hormones do following pituitary gland secretion
act on pituitary to shut down production of TSH, suppressing further thyroid hormone synthesis
what does autoimmune B cell make
antibodies toTSH receptor that also stimulate thyroid hormone production
what does the thyroid hormone shut down
TSH production
what AB do grave’s diseases patients make
anti-TSHR
can newborns get grave’s disease
transfer anti-TSHR AB across placenta to fetus
newborn suffers disease
what removes anti-TSHR AB
plasmapheresis
what is Graves’ opthalmopathy
eyeballs protrude slightly – increased deposition of fat, pushes eyes out
what is Hashimoto’s thyroiditis
Almost exact opposite to graves’
examples of Hashimoto’s thyroiditis
causes - Hypothyroidism
Low BMR Weight gain Pain, numbness Slow responses Goitre Cold sensitive
what are grave’s disease autoantibodies like
not thought to be part of the pathology of Graves disease, but are pathological in HT
what do the autoantibodies do in myasthenia gravis
inhibit acetylcholine receptors
Progressive loss of motor function
Block or cause degradation of the receptor
what does Goodpasture’s disease cause
Kidney damage due to antibody stimulated immune cell activation and complement fixation
what do autoantibodies do in goodpastures disease
bind directly to glomerular basement membranes giving a ‘smooth’ staining pattern
what happens due to Autoimmune haemolytic anaemia
Autoantibodies to RBC
Activation of phagocytosis
Activation of complement
what HS type is Autoimmune haemolytic anaemia
III
what HS type is Goodpasture’s disease
II
what HS type is Myasthenia gravis
II
what HS type is Systemic lupus erythematosus
III
what causes an irregular staining pattern in Systemic lupus erythematosus (SLE or ‘lupus’)
Immune complexes of DNA/anti-DNA in the blood are deposited in the glomeruli
what does SLE cause
‘butterfly’ rash
what happens in the failure of clearance of immune complexes
- Components released by dead and dying cells
- Continuous generation of small immune complexes
- Deposition on vessel walls, glomeruli, skin, organs
- Trigger activation of phagocytosis via Fc receptors
- Destruction of cells leads to more immune complexes
5 –> 1
what leads to tissue damage in SLE
T cells support the generation of autoantibodies, may contribute directly to tissue damage
what do the Islets of Langerhan cells express
different tissue-specific proteins
what does the effectorT cell recognise in insulin-dependent diabetes
recognises peptides from a beta cell-specific protein and kills beta cell
what do alpha and sigma cells make
Glucagon and somatostatin
what cant alpha and sigma cells make
insulin
what do B cell specific T cells recognise
peptides from insulin or glutamic acid decarboxylase
what increases the risk of Rheumatoid arthritis
Obesity, smoking increase risk
what is the first stage that causes Rheumatoid arthritis
- Unknown trigger sets up initial focus of inflammation in synovial membrane, attracting leukocytes into tissue
what is the second stage that causes Rheumatoid arthritis
- Autoreactive CD4 T cells activate macrophages = pro -inflammatory cytokines made and sustained inflammation
what is the third stage that causes Rheumatoid arthritis
- Cytokines induce production of MMP and RANK ligands by fibroblasts
what is the last stage that causes Rheumatoid arthritis
- MMPs attack tissues. Activation of bone-destroying osteoclasts by RANK ligand results in joint destruction
what is needed for the Rheumatoid arthritis disease pathology
both B and T cells are required for disease pathology
what are the proposed antigens for Rheumatoid arthritis
collagens, heat-shock proteins, citrullinated derivatives of proteins
what contributes to tissue and bone destruction in Rheumatoid arthritis
MMPs and RANKL
what causes Synovitis in rheumatoid arthritis
accumulation of cells includes CD4+ T cells, B cells and macrophages
