Multiple Sclerosis (MS) and Guillain-Barré Syndrome (GBS)

00:01 Multiple sclerosis affects the CNS and here we have a image showing the microglia in the CNS and the infiltration of T lymphocytes from the blood vessels into the CNS.

00:19 Now normally there is a blood brain barrier, but in multiple sclerosis and another-- a number of other conditions, this blood brain barrier can become compromised and inflammatory cells can enter the CNS.

00:36 Th1 cells will secrete gamma interferon leading to the activation of macrophages.

00:47 These macrophages can secrete tumor necrosis factor-α.

00:52 Also Th1 cells can help to activate cytotoxic T-lymphocytes.

01:00 And again these cytotoxic T-lymphocytes can attack the myelin sheath of the nerve cells in the CNS.

01:10 Astrocytes which are antigen presenting cells within the CNS which can present peptides to Th2 cells will be involved in this process.

01:21 And the Th2 cells can help B-cells to differentiate into plasma cells and produce autoantibodies.

01:32 The autoantibodies that are produced include anti-myelin basic protein, anti-myelin oligodendrocyte glycoprotein, anti-myelin associated glycoprotein and anti-proteolipid protein.

01:48 In this magnetic resonance image of the brain, from a patient with multiple sclerosis, we can see the typical periventricular demyelination plaques caused by this autoimmune attack.

02:07 Guillain-Barre syndrome occurs following an infection with a variety of different organisms.

02:15 For example, Campylobacter.

02:20 The autoantibodies are against peripheral nerve gangliosides.

02:26 And these are thought to arise due to molecular mimicry.

02:30 There is an acute inflammatory neuropathy with symmetrical weakness of the extremities.

02:37 Complement activation results in neuronal damage.

02:42 And in approximately 25% of patients, there is a respiratory insufficiency that develops.

02:49 So here you can see an antigen presenting cell interacting with Th2 cells.

02:55 Those Th2 cells will help activate B-lymphocytes to develop into plasma cells and produce autoantibodies.

03:04 Those autoantibodies can also then go on and activate complement, leading to the generation of the membrane attack complex, consistent of complement components C5b, C6, C7, C8 and C9.

03:19 And this will cause damage to the Schwann cells.

03:27 In myasthenia gravis, which is characterized by muscle weakness and fatigue, there are autoantibodies against the acetylcholine receptor.

03:38 There is loss or damage to receptors which is caused by complement activation.

03:47 The autoantibodies can also block the binding of acetylcholine to the receptor.