Old exams hard questions Flashcards
For one of the three Th subsets, give one example of a cytokine that would be beneficial to block in a disease setting, and in which disease.
In RA we block TNF-a which infliximab as a monoclonal antibody as it is a pro-inflammatory cytokine that can drive destruction of tissue in this disease setting.
Describe two mechanisms by which IgG immune complexes together with complement may result in harm to tissues.
) IC complexes can activate the complement system which forms C3a which activates inflammation recruits immune cells such as macrophages and neutrophils, release ROS and pro-inflammatory cytokines which results in tissue damage. C5b also forms the MAC complex which results in cell lysis as it disrupts the integral properties of the membrane.
Describe the general mechanism-of-action of JAK inhibitors on a cellular and molecular basis. Which underlying inflammatory mechanisms are inhibited, and which potential detrimental side effects require attention?
JAK/STAT inhibitors block the different JAK associated receptors and inhibit binding. Otherwise cytokines would bind to these receptors and cause phosphorylation which would create a docking site for STAT to bind which would also then become phosphorylated. The complex then translocate to the nucleus where it enhances gene expression of cytokines such as IL-6,12,23 etc which impairs Th cell proliferation, B cell antibody production, decreased inflammatory cytokine secretion which then limits recruitment of innate immune cells. However it causes broad immune suppression in patients, can cause anemia etc.
What are Fc receptors? Which cells typically express them and what are their ligands?
Fc receptors are found on different immune cells and is part of the humoral immunity. The Fc receptors are specific for the antibodies and have different functions. For example FcyR is found on macrophages, neutrophils and dendritic cells and facilitate phagocytosis and antigen presentation. IgE FC receptors facilitate mast cell degranulization.
Give two examples of the functions of Fc receptors and briefly explain their biological role.
Opsonization because phagocytic receptors found on example macrophages are dependent on opsonization to perform phagocytosis. It can also activate the complement system through the classical pathway. Phagocytosis is important for the immune system to eridicate intracellular pathogens and apoptopic bodies etc. The complement system has three major functions, C3a causes inflammation. C3b opsonizies pathogens for phagocytosis and C5a forms the MAC complex which causes cell lysis by creating perforin holes in membrane where granzymes can enter.
Give one example of an immune-mediated disease where Fc receptors play a role. How
are they involved in the pathogenesis of the disease?
For example allergies where the FC receptors on the IgE antibodies activate mast cells to release histamine which causes an allergic reaction in patients. There are also cases of RA that it autoantibody driven where FC receptors bind to immune cells and cause destruction of bodies own tissue.
Describe briefly 1) the presumed main mechanism, 2) why these drugs lead to improvement
and 3) one principal side-effect for the following biological drugs:
a) Rituximab (monoclonal antibody directed against CD20) (3p)
b) Anakinra (IL-1 receptor antagonist) (3p)
Rituximab causes B cell depletion since it blocks CD20 which is a receptor on the B cell which is vital for their activation of antibody production and in cases of autoantibody driven RA for example it can be very helpful. However it causes sensitivity to infections. IL-1 antagonist blicks the binding site to the receptor for IL-1 to bind so it can activate the inflammatory cascade.
