L16 Flashcards
(26 cards)
examples of self tolerance
- central tolerance
- antigen segregation
- peripheral anergy
- Tregs
- functional deviation
- activation-induced cell death
what is ai disease caused by
failure of self tolerance
- mut AIRE (usually deletes strongly self reactive T cells)
- mut in FoxP3 (usually involved in development of Tregs)
what are mutations in FoxP3 linked to
IPEX
immunological polyendocrinopathy X-linked disease
features of IPEX
immunodysregulation, polyendocrinopathy, enteropathy
- presents as diarrhoea, endocrinopathy and eczematous dermatitis
- treated with bone marrow transplant and immunosuppression
organ specific AI examples
multiple sclerosis (myelin sheaths)
type 1 diabetes (beta cells of pancreas)
systemic AI exampes
systemic lupus erythmatosis
rheumatoid arthiritis
prim and secondary pathology exampls
hashimotos thyroiditis
prim = detruction of thyroid tissu
2 = hypothyroidism
2 immunological features of ai diseases
- auto antibodies in serum or in tissues
-cellular infiltrate = lots of t and b cells
ai disease mechanisms that are mediated by t cells
Th17/Th1/Th2 cells
Production of pro-inflammatory cytokines
Damage to epithelial barrier integrity (can involve Tc)
Promote CD8 cytotoxic T cell function
Promote macrophage mediated destruction
Drive the inflammatory response
Promoting antibody responses
typical t cell stuff tbh
experimental autoimmune encephalomyelitis EAE model
Mice injected with Myelin Basic protein (MBP) and adjuvant develop EAE
Disease is mediated by Th1 and Th17 specific for MBP
Disease can be transmitted by transfer of T cells from affected animal
disease mechanisms caused by antibodies
Damage or destruction:
Complement mediated lysis
Opsonisation and phagocytic removal
Alteration of function:
Stimulation of receptors (Agonist)
Inhibition of function
Blockage of Function
Deposition of immune complexes
Auto-antibody mediated damage or destruction example
Complement mediated lysis - lysis of RBCs = AI haemolytic anemia
Opsonisation - phagocytosis of platelets = AI thrombocytopenia
Antibody mediated alteration of function: Stimulation of receptors example
Graves disease - hyper thyroidism
autoimmune b cell makes ABs agains TSH receptor which stimulates thyroid production
= excessive, prevents the regular negative feedback
Antibody mediated alteration of function:
Inhibition of function example
myasthenia gravis
Antagonist to receptor = no signal to muscle
or
Antibody can trigger receptor internalisation/degradation
Antibody mediated alteration of function:
Blocking example
Pernicious Anaemia
blocks receptor ligand interaction (binds to IF, cant bind to B12)
vit B12 deficiency
Antibody mediated deposition of immune complexes: example
Systemic lupus erythematosus (SLE)
Immune complexes deposit in small blood vessel walls (kidney, joints, skin) and initiate inflammatory reaction
symptoms of SLE
Arthritis,
“butterfly” rash
Vasculitis
glomerulonephritis
whats the concordance like in autoimmune diseases
concordance in identical twins > non-identical twins i.e. GENETIC
but concordance in identical twins is <50% i.e. environment cuz not 100
2 types of polymorphism
Structural polymorphism
Non-structural Polymorphism
structural Polymorphism
Different forms of protein are made (if in protein coding gene region) e.g. MHC
Non-structural Polymorphism:
Altered protein activity or protein levels (if in non-protein coding region/promoter/ enhancer region)
what is relative risk RR
The degree to which an allele of a gene increases susceptibility
Susceptibility to autoimmunity is generally due to expression of different gene alleles, i.e. Polymorphisms and not mutations
what accounts for ~50% of genetic risk
MHC genes
especially class II
e.g. HLA-DR2
75% of autoimmune diseases are found in ?
females
Usually arises during child-bearing years
Can vary during pregnancy
