Inflammation and Immunopathology module 4- Fc receptors and antibodies Flashcards
What is the Fc receptor?
The Fc receptor is found on the surface of effector cells in the immune system, like the NK cells, macrophages, eosinophils, leukocytes and lymphocytes.
How does the Fc receptor work?
- Antibodies are produced by the b-cells in response to the presence of a pathogenic antigen in the body. 2. These antibodies then bind to the antigen. 3. The antibody takes the antigen with it and binds to the Fc receptor on the surface of the immune effector cell. 4. The Fc receptor checks for the presence of the antigen and then it starts a signalling cascade to activate the effector cell.
Can any antibody bind to any Fc receptor it wants?
No. There are Fc receptors for each antibody class, thus the antibody must bind to its corresponding receptor type.
Do all the Fc receptors have the same affinity for their antibody?
No. The Fc receptors have varying affinities to the antibodies.
What is the biochemical signalling pathway that takes place once the anitbody binds to the Fc receptor?
The Fc receptor once bound to the antibody and antigen, then activates the leukocytes via the ITAM pathway.
What occurs during the activation of the ITAM pathway by Fc receptors?
The ITAM pathway stands for the immunoreceptor tyrosine activation motif. Here, the src tyrosine kinsases phosphorylate the ITAM motif and also recruit the syk (spleen) tyrosine kinase.
There is one Fc receptor type which inhibits leukocyte when the antibody binds to it. How does it do this?
This Fc receptor type inhibits leukocytes via the ITIM pathway. ITIM stands for the Immunoreceptor Tyrosine Inhibition Motif. Here, see normal phosphorylation by the src tyrosine kinases and recruitment of tyrosine phosphatases.
The Fc receptors can be split into two types of receptors-what are these two classes?
The Fc receptors are either activating receptors and inhibitory receptors. The activating receptors induce the cellular response. The inhibitory receptor works by inhibiting the other receptors so that they can’t be activated.
Describe the structure of the activating Fc receptors.
The activating Fc receptors contain 2-3 antibody binding domains outside the cell (extracellular).
Then there is the transmembrane region (the zig-zag bit), which leads to the signalling dimer which contains the ITAM within it.
It is here at the ITAM that the src and syk tyrosine kinases will bind and phosphorylate it.
Describe the structure of the inhibitory Fc receptor.
The inhibitory Fc receptor is identical to the activating Fc receptor, except that it has a cytoplasmic tail which contains the ITIM.
Describe the FC-epsilon 1 receptor.
Antibody: IgE
Affinity: very high
Found on: Mast cells and eosinophils
Results in: Type 1 hypersensitivity responses, or allergies. causes mast cell degranulation which causes allergic rhinitis and asthma etc.
Describe the Fc gamma 1 receptor
Antibody: IgG,1, 3 and 4.
Affinity: very high
Found on: macrophages and neutrophils
Results in: It is induced by the cytokine interferon-gamma, and it causes the immune complex uptake into the cell for antigen presentation.
Describe the Fc gamma 3a receptor.
Antibody: IgG1, IgG3
Affinity: moderate
Found on: NK cells, macrophages
Results in: Macrophage uptake of immune complexes and the NK killing of antibody coated targets.
Describe the Fc gamma 2a receptor.
Antibody: IgG 1-3 (4, but only weakly).
Affinity: low
Found on: Most leukocytes except NK cells and lymphocytes.
Results in: Cytokine release. This is the most common Fc receptor type in the body. It is also unique to humans.
Describe the inhibitory Fc gamma 2b receptor.
Antibody: IgG 1-3.
Affinity: low affinity
Found on: all leukocytes except platelets and T-cells
Results in: Down regulation of activating FcR receptors.
Why does the IgG antibody have a higher affinity for the inhibitory Fc gamma 2b receptor than the inhibitory receptor?
This ensures that activation of the receptors happens first to induce the cellular response, and the inhibitory response occurs later.
