L16

Question 1

examples of self tolerance

Answer 1

• central tolerance
• antigen segregation
• peripheral anergy
• Tregs
• functional deviation
• activation-induced cell death

Question 2

what is ai disease caused by

Answer 2

failure of self tolerance
- mut AIRE (usually deletes strongly self reactive T cells)
- mut in FoxP3 (usually involved in development of Tregs)

Question 3

what are mutations in FoxP3 linked to

Answer 3

IPEX
immunological polyendocrinopathy X-linked disease

Question 4

features of IPEX

Answer 4

immunodysregulation, polyendocrinopathy, enteropathy

• presents as diarrhoea, endocrinopathy and eczematous dermatitis
• treated with bone marrow transplant and immunosuppression

Question 5

organ specific AI examples

Answer 5

multiple sclerosis (myelin sheaths)
type 1 diabetes (beta cells of pancreas)

Question 6

systemic AI exampes

Answer 6

systemic lupus erythmatosis
rheumatoid arthiritis

Question 7

prim and secondary pathology exampls

Answer 7

hashimotos thyroiditis
prim = detruction of thyroid tissu
2 = hypothyroidism

Question 8

2 immunological features of ai diseases

Answer 8

• auto antibodies in serum or in tissues
  -cellular infiltrate = lots of t and b cells

Question 9

ai disease mechanisms that are mediated by t cells

Answer 9

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

Question 10

experimental autoimmune encephalomyelitis EAE model

Answer 10

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

Question 11

disease mechanisms caused by antibodies

Answer 11

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

Question 12

Auto-antibody mediated damage or destruction example

Answer 12

Complement mediated lysis - lysis of RBCs = AI haemolytic anemia

Opsonisation - phagocytosis of platelets = AI thrombocytopenia

Question 13

Antibody mediated alteration of function: Stimulation of receptors example

Answer 13

Graves disease - hyper thyroidism
autoimmune b cell makes ABs agains TSH receptor which stimulates thyroid production
= excessive, prevents the regular negative feedback

Question 14

Antibody mediated alteration of function:
Inhibition of function example

Answer 14

myasthenia gravis
Antagonist to receptor = no signal to muscle
or
Antibody can trigger receptor internalisation/degradation

Question 15

Antibody mediated alteration of function:
Blocking example

Answer 15

Pernicious Anaemia
blocks receptor ligand interaction (binds to IF, cant bind to B12)
vit B12 deficiency

Question 16

Antibody mediated deposition of immune complexes: example

Answer 16

Systemic lupus erythematosus (SLE)
Immune complexes deposit in small blood vessel walls (kidney, joints, skin) and initiate inflammatory reaction

Question 17

symptoms of SLE

Answer 17

Arthritis,
“butterfly” rash
Vasculitis
glomerulonephritis

Question 18

whats the concordance like in autoimmune diseases

Answer 18

concordance in identical twins > non-identical twins i.e. GENETIC

but concordance in identical twins is <50% i.e. environment cuz not 100

Question 19

2 types of polymorphism

Answer 19

Structural polymorphism
Non-structural Polymorphism

Question 20

structural Polymorphism

Answer 20

Different forms of protein are made (if in protein coding gene region) e.g. MHC

Question 21

Non-structural Polymorphism:

Answer 21

Altered protein activity or protein levels (if in non-protein coding region/promoter/ enhancer region)

Question 22

what is relative risk RR

Answer 22

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

Question 23

what accounts for ~50% of genetic risk

Answer 23

MHC genes
especially class II
e.g. HLA-DR2

Question 24

75% of autoimmune diseases are found in ?

Answer 24

females
Usually arises during child-bearing years

Can vary during pregnancy

Question 25

Environment and Autoimmune Disease

Answer 25

Rapid increase in incidence over the last 40-50 years
too quick to be explained by genetics alone

Question 26

Environmental influences

Answer 26

Vitamin D
- Active form of Vitamin D may suppress Th17 development
Drugs
-drugs or metabolites may bind to self-Ag and then Ag appears foreign
Toxins
–pollutants, UV, pesticides, smoking
-Cause damage and expose areas for autoantibody mediated damage