List some inflammatory neurological diseases:
- Kreuzfeld-Jakob
- multiple sclerosis
- neuromyelitis optical
- Stiff-person’s disease
General features of myasthenia gravis:
- prevalence: 20/100 000
- fluctuating, asymmetric ptosis (drooping eyelid)
- weakness in eye muscles with double vision
- possible: respiratory crisis, respiratory tract infections
- treatment complications are common
- some treatment resistant patients
Myastenia gravis: symptoms & cause:
Symptom: weakness of skeletal muscle
- muscles in the eye & face
- NOT in other muscle types (heart, blood vessels, etc.)
Cause: antibodies against
- muscle AChR
- MuSK
- LRP4 (low density lipoprotein receptor-related protein 4)
Link between myasthenia gravis and thymoma
- approx. 15% of MG patients have a thymoma
- thymectomy causes and improvement in 30-40% of patients
Autoantibody effector mechanisms in AchR-MG
Functional AChR inhibition: - curare or slow channel effect - loss of AChR - loss of AchR-associated proteins Complement activation: - formation of membrane attack complex - calcium influx - depolarization - antigenic modulation (AChR crosslinking)
Immune pathogenesis of multiple sclerosis
- T & B cells recognize myelin fragments:
- proteolipid protein
- myelin-basic protein
- myelin-oligodendrocyte glycoprotein
Animal models for myasthenia gravis
- source of alpha-bungarotoxin (Banded Krait)
- cobratoxin (Indian cobra - Naja Naja)
- AChR resistant to cobratoxin (mongoose)
- AChR in electric organ (Torpedo marmorata)
Experimental therapies in myasthenia gravis animal models:
- proteasome inhibitors
- immunosupressive drugs
- competitor antibodies
- therapeutic antibodies
Immunization for AD
Active immunization:
- injection with full or partial Aβ together with adjuvant
- B cells will produce antibody against Aβ
Passive immunization:
- Injection with full antibody against Aβ
Effector mechanisms of AD immunotherapy
- catalytic dissolution (Aβ plaques dissolve)
- Fc-receptor-mediated phagocytosis
- peripheral sink (Aβ dissolves intro the periphery and is acted upon by the immune system there)
IgG1 vs IgG4 effector mechanisms:
IgG1 (IgG2a in mice): - strong FcR binding - complement activation IgG4 (IgG1 in mice): - weak FcR binding - no complement activation
The HLA gene family
The human leukocyte antigen family (HLA). The HLA complex helps the immune system to distinguish own from foreign Major histocompatibility complex (MHC)
More than 100 diseases have been associated with different alleles of HLA genes, however it is often unclear what role HLA genes play in the risk of developing these diseases
Anti-inflammatory effects of corticosteroid therapy
Effect on:
- reduced IL-1,3,4,5,8, TNF-alpha - reduced inflammation caused by cytokines
- reduced Phospholipase A2, COX-2, Lipocortin-1 - fewer prostaglandins and leukotrienes
- fewer adhesion molecules - reduced emigration of leukocytes from vessels
- increased endonucleases - induction of apoptosis in lymphocytes and eosinophils