Effector Mechanisms of Humoral Immunity Flashcards
The Fc regions on the different isotypes of antibodies contain the binding sites for Fc receptors on phagocytes and for complement proteins. However, these interactions only occur when [] have bound to the microbe or toxin, ensuring that they only activate effector mechanisms when warranted – when there is truly a threat to the host.
The Fc regions on the different isotypes of antibodies contain the binding sites for Fc receptors on phagocytes and for complement proteins. However, these interactions only occur when multiple antibodies have bound to the microbe or toxin, ensuring that they only activate effector mechanisms when warranted – when there is truly a threat to the host.
Abs and neonatal immunity: [] contributes to the long half-life of IgG
Abs and neonatal immunity: Neonatal Fc receptor (FcRn) contributes to the long half-life of IgG.
- Circulating IgG is ingested by endothelial cells and binds the FcRn in the acidic environment of endosomes.
- In endothelial cells, FcRn sequesters IgG molecules in endosomal vesicles (pH ~4).
- The FcRn-IgG complexes recycle back to the cell surface, where they are exposed to the neutral pH (~7) of the blood, releasing the bound IgG back into the circulation.
Antibodies – particularly [] – are able to bind to and block (neutralize) microbes and toxins.
Antibodies – particularly IgG and IgA – are able to bind to and block (neutralize) microbes and toxins.
•Many pathogens use molecules within their cell walls or envelopes to bind to and gain access into host cells. Antibody binding to the pathogen surface is able to prevent this proces
The most effective vaccines we possess (including these against miocrobial toxins) generate neutralizing Ab responses. At mucosal surfaces, these neutralizing antibodies are of the [] isotype, while in the circulation/tissues they are [].
The most effective vaccines we possess (including these against miocrobial toxins) generate neutralizing Ab responses. At mucosal surfaces, these neutralizing antibodies are of the IgA isotype, while in the circulation/tissues they are IgG.
Antibodies to toxins are able to prevent the toxin from [], thus blocking the toxin’s damaging effects.
Antibodies to toxins are able to prevent the toxin from binding to the host cell, thus blocking the toxin’s damaging effects.
[] antibodies that coat pathogens are highly efficient at targeting that microbe for opsonization and destruction by professional phagocytic cells (macrophages, neutrophils).
IgG antibodies that coat pathogens are highly efficient at targeting that microbe for opsonization and destruction by professional phagocytic cells (macrophages, neutrophils
• Multiple different types of Fc receptors, expressed on different immune cell populations, exhibit different functions
[] is a negative regulator of antibody production and inflammation. It is primarily expressed on activated B cells, where binding of antibody to this low affinity receptor signals to the B cells that enough antibody has been made, and shuts down the response.
FcRγIIB is a negative regulator of antibody production and inflammation. It is primarily expressed on activated B cells, where binding of antibody to this low affinity receptor signals to the B cells that enough antibody has been made, and shuts down the response.
Binding of pathogens coated with IgG to the high-affinity [] leads to phagocytosis of the “opsonized” microbe.
Binding of pathogens coated with IgG to the high-affinity FcgRI leads to phagocytosis of the “opsonized” microbe.
•FcgRI binding also leads to a signaling cascade within the phagocyte, activating the cell to increase expression of reactive oxygen species and proteolytic enzymes within its’ lysosomes, effectively making the phagocyte a better killer. This is a major strategy of combatting infection with encapsulated bacteria such as pneumococci.
Natural killer (NK) cells can recognize IgG antibody coated cells through their expression of the low-affinity [] receptor.
Natural killer (NK) cells can recognize IgG antibody coated cells through their expression of the low-affinity FcgRIII (CD16) receptor.
•Such recognition leads to degranulation of the NK cell onto the target cells, a process termed antibody-dependent cellular cytotoxicity.
ADCC
- This process is utilized to clear virally infected host cells, which often express viral glycoproteins on the host cell surface (where they can be bound by antibodies) as a consequence of the viral replication occurring inside the cell.
- This effector function has been therapeutically utilized to develop antibodies that recognize tumor cells, thus rendering the tumor susceptible to attack by NK cells.
[] antibodies activate mast cells and eosinophils to provide protections against helminth parasites, and are also involved in hypersensitivity allergic reactions.
IgE antibodies activate mast cells and eosinophils to provide protections against helminth parasites, and are also involved in hypersensitivity allergic reactions.
•Helminths are typically too large to be phagocytosed, so the immune strategy for defense is to target them for extracellular destruction by the release of toxic granules from eosinophils.
After IgE antibodies bind to the parasite, the Fc portion of the IgE is recognized by high-affinity [] expressed by eosinophils and mast cells.
After IgE antibodies bind to the parasite, the Fc portion of the IgE is recognized by high-affinity FceRI expressed by eosinophils and mast cells.
The presence of TH2 CD4 T cells secreting [], aids the recruitment of eosinophils to the site of infection to release their granules (that contain multiple proteins and other mediators that are toxic to the parasite).
The presence of TH2 CD4 T cells secreting IL-5, aids the recruitment of eosinophils to the site of infection to release their granules (that contain multiple proteins and other mediators that are toxic to the parasite).
Classical Complement Pathway and IgM (and certain subclasses of IgG)
- Binding of multiple antigenbinding sites of the IgM pentamer reveals the Fc portions of the antibodies that contain complementbinding sites.
- The Fc portions are now available for the C1 complex (C1qrs; Fig. 10-8) to bind. The binding of C1qrs induces a conformational change that activates the proteases (subunit C1s).
- Active C1qrs now begins the proteolytic cleavage cascade on the surface of the pathogen:
IgA and Mucosal Immunity
- IgA is produced in mucosal lymphoid tissues, and then is transported across the epithelial layer to provide protection within the lumen of mucosal organs.
- Microbes often gain access into the body by ingestion and inhalation, and IgA is positioned at those surfaces to protect against pathogen colonization of these epithelia, and to prevent microbial breach to gain access to the body.
B cells in mucosal tissues (such as the lamina propria in the gut) are easily polarized to become IgA-producers as there is a high level of [] produced in mucosal tissues (which drives the istoype switch to IgA).
B cells in mucosal tissues (such as the lamina propria in the gut) are easily polarized to become IgA-producers as there is a high level of TGFb produced in mucosal tissues (which drives the istoype switch to IgA).
Secreted IgA is actively transported across the epithelial layer by a specialized Fc receptor called the [], which is expressed on the basal layer of the epithelium.
Secreted IgA is actively transported across the epithelial layer by a specialized Fc receptor called the poly-Ig receptor, which is expressed on the basal layer of the epithelium.
•Upon binding of IgA, the poly-Ig receptor is endocytosed, and transported to the luminal surface of the epithelium. Proteolytic cleavage releases the IgA into the lumen, with a small portion of the poly-Ig receptor remaining attached, providing protection against degradation by the proteases in the gut.
IgA1
•has a flexible hinge region that allows more adaptation in binding to antigen, and it dominates in the small intestine, that has a relatively lower concentration of bacteria.
