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A phagocyte is a cell of the immune system that is specialized for the engulfment and breakdown of bacteria, foreign particles and other pathogens in the bloodstream; such as a neutrophil, macrophage or dendritic cell. In this essay I am going to describe how a macrophage would phagocytose a pathogen.
A monocyte is the largest cell in the body and it is a precursor to macrophages in the tissue. Initially the cells are derived from the bone marrow of promonocytes, these then differentiate to become circulating blood monocytes, which then emigrate down the blood stream and settle in the tissues as mature macrophages (Roitt & Delves, 2001).Macrophages are very large and long lived cells, found in most connective tissue around the basement membrane of small blood vessels, where their main role is to filter off foreign materials. Their specialty is fighting off bacteria, viruses and protozoa that are capable of living within the host. They are particularly concentrated in the lung (alveolar macrophages), liver (Kupffer cells), the lining of the spleen and lymph nodes (sinus histiocytes) and central nervous system (microglial cells). These constitute the mononuclear phagocyte system (Kumar, Abbas, Fausto, & Mitchell, 2007).
Phagocytosis is a critical process in the immune system where the engulfment and breakdown of infectious agents and senescent cells by phagocytes such as macrophages occurs. It is also necessary for tissue remodelling and repair. Its complexities are due to the diverse number of receptors that are capable of stimulating phagocytosis where most particles are recognised by more than one receptor. The recognition mechanism before phagocytosis can either occur cellularly or humorally (Aderem & Underhill, 1999). There are three main steps that occur for the successful phagocytosis of pathogens.
Attachment of pathogen to phagocyte
Killing and degradation of pathogen
Attachment of pathogen to phagocyte:
Phagocytes are attracted to the area of invasion due to chemical products of the microbe such as phospholipids released by injured mammalian cells or by components of the complement system. Innate immunity does not recognise every single antigen but it does not need to as pathogens have molecular structures that are shared by many other similar pathogens. These molecules are called Pathogen Associated Molecular Patterns (PAMPs), and are normally polysaccharides or polynucleotides that are not found on the host; examples are LPS from e-coli. The receptors that recognise these common PAMPs are called pattern recognition receptors (PRRs) (see figure 1) and are there so as to activate an immediate response against the invading microbe. An example of a PRR is the mannose receptor which binds to the polysaccharide Mannose.
The microbes undergo a process called opsonisation, where they are coated with molecules that alter the structure of the bacteria in order to make them more susceptible to the action of phagocytes, these molecules such as antibody molecules immunoglobulin G (IgG), complement proteins C3b, Mannose binding Lectin. For example if a microbe is opsonised by the antibody IgG. The Fab portion of the IgG will bind to the epitope of the microbe, leaving the Fc region free to bind to the Fc receptor for IgG (called FcÎÂ³RI) on the macrophage (see figure 1); thus binding the pathogen to the macrophage (Kumar, Abbas, Fausto, & Mitchell, 2007).
When the opsonised particle has bound to its specific receptor on the surface of the phagocyte it causes it to undergo a rearrangement in the actin cytoskeleton via polymerization of the actin at the site of ingestion triggering engulfment of the microbe via an actin-based mechanism. Binding induces the actin filaments of the phagocytic cell to send out pseudopods that extend around the microbe and a phagocytic vacuole forms; known as a phagosome (Aderem & Underhill, 1999).
The cytoplasm of the macrophage contains vesicles called lysososmes produced by the golgi apparatus containing digestive enzymes, microbicidal substances and toxic oxygen radical. The membrane of the lysosome fuses with the membrane of the phagosome, and discharge its granule content, forming a phagolysosome (Janeway, Travers, Mark, & Mark, 2001).
There are two killing systems in phagocytosis:
Oxygen dependent system
Oxygen independent system
Oxygen dependent system:
The membrane of the phagocyte contains enzyme oxidase that converts oxygen to a superoxide anionÂÂ (O2-), this anion combines with water to form hydrogen peroxide and hydroxide radicals which are reactive oxygen species (ROS) which destroy microbes. In macrophages Nitric Oxide (NO) can combine with Hydrogen Peroxide to form peroxynitrite radicals. Macrophages also secrete out inflammatory cytokines such as Interleukin 1 (IL-1) which promote inflammatory response (Roitt & Delves, 2001).
Oxidase also acts as an electron pump that pumps in protons (H+) inside the phagosome, this in turn reduces the pH within the phagosome and so when the phagolysosome forms the pH is correct for acid hydrolases to break down cellular protein.
Oxygen Independent system:
The granules of the lysosome contain several constituents that allow them to kill infectious pathogens, for example, lysozyme an enzyme that breaks down the bacterial coat of oligosaccharides, defensins which are peptides that alter the cytoplasmic membrane by producing holes hence killing microbes and other any digestive enzymes that break down proteins, RNA, phosphate compounds, lipids, and carbohydrates. These all selectively exposes the ingested microbe and causes it to degrade and destruct (Kumar, Abbas, Fausto, & Mitchell, 2007). The digestive contents of the phagolysosome are then eliminated from the phagocyte by a process of exocytosis.
In conclusion, phagocytosis is a critical process in the immune system that require phagocytes such as macrophages which are long lived cells whose main role is to filter off pathogens such as bacteria. There are three main steps to for this to occur. Firstly the pathogen has to undergo opsonisation in order to be recognised and attach to the specific receptor on the macrophage. Secondly the phagocyte is engulfed by the macrophage forming a phagosome. Then it fuses with cytoplasmic lysosome forming a phagolysosome, where killing and degradation of the ingested material occurs as a result of the lysosome granules.