B.22 Autoimmune Disease

Question 1

Guillan Barre Syndrome- Clinical

Answer 1

• muscle weakness
• begins in feet and hands
• resolves after weeks
• does not tend to reoccur
• occurs post infection with upper respiratory viruses , vaccination or gastro intestinal infection

Question 2

Guillan Barre Syndrome - Pathology

Answer 2

• de-myelination, but Axons are spared
• nerves are infiltrated with leucocytes and macrophages -> disruption of the blood nerve barrier)
• T-cells react against Schwann Cells (peripheral nerves)
• cross reactive gangliosides
• certain haplotypes of MHC are weakly associated with it (major histocompatibility complex) which indicates importance of immune system
• (MHC present antigen Fragments to T cell which recognised by T cell receptor which activates it)

Question 3

Guillain Barre Syndrome- Types

Answer 3

-several subtypes
-geographical association
symptoms of demyelination of different verse-different symptoms
-associated with different types of immune reactions

Question 4

Guillain Barre Syndrome- Immunological features

Answer 4

• acute inflammatory demyelination polyneuropathy
• anti ganglioside antibodies in AMAN (acute motor axonal neuropathy)
• associations to variants of CD1 (CD1 presents lipid antigens and glycolipid antigens, its structure is similar to MHC and can stimulate T cell)

Question 5

Immune System

Answer 5

• set up to recognise self- belonging components and distinguish from non-self components (like bacteria, pathogens, viruses and parasites) and produce appropriate reaction against them
• should be able to recognise and tolerate own tissue -> when this breaks down AUTOIMMUNE DISEASES occur

Question 6

Mechanism Of self tolerance

Answer 6

• T cells come from Thymus
• supposed to recognise material in cells
• most self reactive t-cells will be deleted through thyme education, some however emerge during development
• central selection eliminates T or B cells that are self reactive

Question 7

Central Tolerance

Answer 7

deletion of self reactive cells

Question 8

Co- Stimulation

Answer 8

• is needed to generate auto-antigen
• provided by bacterial products and inflammatory cytokines
• recognised by receptors and induce co stimulating molecules on antigen presenting cell

Question 9

Cross Reactivity (B-Cells)

Molecular Mimicry

Answer 9

-> leading to autoimmunity via B-Cells

• a foreign molecule appears similar to a self molecule to B/T cell receptor
• normally B cell processes this and presents foreign molecule which then can be recognised by T-cell which is not tolerant to it
• > T cell would present help to B-Cell which produces antibodies to foreign/ self molecules !!!! antibodies against own mimicked molecule!!!
• > basis of autoimmunity

Question 10

Cross- Reactivity (T-Cells)

Answer 10

• T-Cell receives through receptor presented on MHC or CD1 Molecule
• Co-Stimulatory signal from CD28
• these 2 signals trigger autoimmune reactivity
• non self molecule enter fragment of antigen processed by APC presented on MHC molecule can look like self-molecule to T-CELL

Question 11

Narcolepsy -Immunological Features

Answer 11

• low levels of orexin
  which is important for maintenance of alertness and produced by subset of neurons near hypothalamus
  -destruction of these neurons orexin producing neurons (up to 95percent)
  -melanine producing neurons are spared which makes general inflammation unlikely
  -MHC disease association is strong, however not antibodies or T-Cell detected
  CATAPLEXY: loss of muscle tone, these cases show higher decrease of orexin

Question 12

Narcolepsy - Cause

Answer 12

• unclear
• evidence toward T-cell activation triggered in individuals through influenca or influenca vaccination
• > increased incidents of narcolepsy after H1N1 contraction or vaccination
• gene linked to sleep control could be relevant too

Question 13

Myasthenia Gravis

Answer 13

-number of different conditions
-defect in thymus (thymoma) = presents a variety of antigens to passing T-Cells and educates them might be randomly presenting wrong antibodies
-acetylcholine receptor becomes target of autoantibodies
-severe muscle weakness
-impaired musclier transmission
-can be improved by acetylcholinesterase inhibitors for better nerve to muscle transmission
-different subgroups related to age, sex and MHC haplotypes or even antibody negative group
Anti- receptor antibodies recruit damaging immune response around muscle fibre / nerve terminal
• High level of antibodies in MG against receptors