TBL 1 Flashcards
How can antibodies specific for cell and tissue antigens cause injury?
They may deposit in tissues and cause injury by local inflammation, or promotion of destruction of cells, or interfere with normal cellular functions
How do antibodies against tissue antigens and immune complexes cause inflammation?
By attracting and activating leukocytes
What antibodies activate inflammation complexes?
IgG: IgG1 and IgG3
How do IgG1 and IgG3 cause activate inflammation complexes?
By binding to neutrophil and macrophage Fc receptors and activate the leukocytes
How is complement used in AB auto-reactivity?
IgG1, IgG3, IgM can activate complement (classical pathway) to cause inflammation via leukocytes
How can antibody deposition cause adjacent cell damage?
Activation of leukocytes at sites of antibody deposition these cells release ROS and lysosomal enzymes that damage adjacent tissues
What happens if AB bind to erythrocytes or platelets?
They are opsonized leading to phagocytosis
What are two ways AB can interfere with normal cellular functions?
AB stimulate receptors without the hormone present (Graves’ disease)
AB inhibit binding of neurotransmitter to receptor (Myasthenia gravis)
How does plasmapheresis work?
Reduces levels of circulating AB’s or immune complexes
How can B cells be targeted and depleted?
AB specific for CD20 can be introduced to the patient to attack B cells
How is T cell-dependent B cell activation inhibited?
AB specific for CD40L blocks the CD40L site on T cells not allowing B cells to be activated
How are AB used against cytokines?
Specific for cytokines that are necessary for B cell and plasma cell survival
What are two diseases that can be caused by staphylococcal infections?
Anti-streptococcal AB can cross-react with heart tissues in rheumatic fever
Anti-streptococcal AB can deposit in the kidney glomeruli causing post-streptococcal glomerulonephritis
What are three postsynaptic proteins that can be targeted in Myasthenia Gravis?
Nicotinic acetylcholine receptors
Muscle-specific tyrosine kinase
Low-density lipoprotein receptor-related protein 4
What happens when anti-AChR antibodies bind to AChR?
Increased endocytosis and degradation of AChR by the muscle
What occurs when anti-AChR bind complement factors at the post-synaptic membrane?
It leads to focal lysis of postsynaptic folds at the NMJ by MAC
How do anti-AChR binding to complement factors affect AChR associated proteins?
Destruction of utrophin (cytoskeleton), rapsyn (anchoring site), and voltage-gated sodium channels which impairs NMJ transmission
In mild MG what is the possible only symptom?
Neck muscle weakness
General symptoms of MG?
Eye droopy
Expressionless face or snarl when smiling
General clinical characteristics of LE syndrome?
Muscle weakness Depressed tendon reflexes Achy tender muscles Dry mouth Male impotency Chewing, speech and swallowing difficulties
What are general clinical biomarkers of LE syndrome?
Discovering malignancy
Voltage gated calcium channel AB’s
What imaging techniques would be used for MG?
CT or MRI of the thorax to screen for thymomas or thymic hyperplasia
What imaging techniques would be used for LE?
CT or MRI of the chest to include chest malignancy
What is the ice pack test used for?
MG screening
How is the ice pack test used?
Ice cube is placed over the drooping eyelid for 2 minutes and if there is improvement in ptosis, then there is a neuromuscular transmission disorder
How to test for MG with AB?
Anti-AChR antibody test, if negative, run anti-Musk AB test
How does a endrophonium test for MG work?
Administer endrophonium chloride which inhibits AChesterase inhibitors. It aims to demonstrate reversibility of muscle weakness
What are the physiological roles of the thymus?
Main site of auto-sensitization
AChR expression by myeloid cells in thymus, in presence of inflammation it leads to the induction and maintenance of anti-AChR autoimmune responses in MG
What is unique about people when anti-Musk ABs and anti-LRP4 AB titers are positive?
They do not have issues with their thymus
Why is a thymectomy performed?
MG in thymamatous patients are usually more severe than in non-thymamatous patients
How to differentiate between MG and LES?
Run a antibody test looking for antibodies specific for Ca antibodies
