Antibody Opsonization
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Antibody opsonization is a process by which a pathogen is marked for
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
through coating of a target cell with antibodies. Immunoglobulins participate in molecular tagging of pathogens which display antigens recognised by their specific paratope. The binding of antibodies enhances pathogen identification and recruitment of immune effector cells, ultimately accelerating microbial clearance through phagocytic destruction or
antibody-dependent cellular cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system kills a target cell, whose membrane-s ...
.


Principles

Antibody-mediated opsonisation (marking) of pathogens depends on high affinity paratope-epitope interactions. Immunoglobulins are highly effective opsonins, with the IgG subclasses IgG1 and IgG3 being recognised as the most efficacious opsonins in humans. Antibodies structurally contain two important domains # Fab domain - the region of the antibody which displays the paratope capable of binding to antigenic epitopes # Fc fragment - the 'tail' region of the Y-shaped immunoglobulin which provides a binding site for endogenous
Fc receptors In immunology, an Fc receptor is a protein found on the Cell membrane, surface of certain Cell (biology), cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophi ...
(FcRs) displayed on immune cell surfaces This Fc domain allows antibodies to engage with various effector
leukocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
, enhancing the detection and elimination of encountered pathogens. The interaction with leukocytes is largely driven by the predominant antibody isotype as well as the presence and concentration of immune cells recruited to the local environment. The resulting immune cell recruitment may result in phagocytosis if monocytes, macrophages, or neutrophils are the primary cells recruited, release of granzymes and other killing factors if NK cells or neutrophils are recruited, and release of pro-inflammatory cytokines in nearly all cases.


Recruitment and clearance


Antibody-stimulated phagocytosis

Mononuclear
phagocytes Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...
and
neutrophils Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...
express FcRs that bind strongly to the Fc regions of particular antibody isotypes. During a normal inflammatory response, microbial pathogen-associated molecular patterns (PAMPs) bind with
phagocytic Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
pattern recognition receptors Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of th ...
(PRRs), triggering sequential intracellular signalling cascades culminating in phagocytotic clearance. Co-expression of
opsonin Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...
receptors such as FcRs enhances their ability to detect microbes which have been tagged by as pathogenic. These interactions result in envelopment of the particle by the cytoplasmic membrane of the phagocytic cell, until the particle is contained in a membrane-bound vacuole (phagosome) within the cell. The pathogen is subsequently destroyed following intracellular vesicle fusion with lytic vessels.


Antibody-dependent cell-mediated cytotoxicity

In antibody-dependent cell-mediated cytotoxicity, the pathogen does not need to be internalised to be destroyed. ADCC requires an effector cell with the ability to eliminate pathogens through release of cytotoxic agents, most notably
natural killer cell Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells ...
s. However,
macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
,
neutrophils Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...
and
eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...
are sometimes implicated. During this process, the pathogen is opsonized and bound with the antibody IgG via its Fab domain. Cells with cyotoxic function (e.g. NK cells) expresses Fcγ receptors which recognize and bind to the reciprocal Fc portion of an
antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
. This receptor conjugation triggers degranulation and release of cytotoxic granules containing perforin and granzymes to kill antibody-sensitized target cells.


References

{{DEFAULTSORT:Antibody Opsonization Immune system