Pathogen Recognition and Phagocytosis

harmful to the human host. This is what can happen in superantigen infections like toxic shock syndrome. In such cases, the fever can be life-threatening.

PATHOGEN RECOGNITION AND PHAGOCYTOSIS

Phagocytosis happens in phagocytes. It is the process of engulfing and killing pathogens as a way of nonspecifically killing off the infection. It starts with the extravasation or diapedesis of white blood cells, which involves the cells leaving the blood vessels through gaps in the endothelial lining because of complement factor C5a and the release of cytokines. This process is also called transendothelial migration. Extravasation only happens in the capillaries because they have very thin walls and low levels of turbulence. The white blood cells need to adhere to the endothelium before they can get through the capillary walls.

Remember that opsonization occurs because of complement factors, lectins, and antibodies that bind to the pathogen. This leads to pathogen recognition, necessary for the phagocytic process. Not all organisms need to be opsonized before they are recognized as pathogens. There are some parts of pathogens that are inherently seen as pathogenic. These are called pathogen-associated molecular patterns or PAMPs.

Some PAMPs, which are automatically recognized as pathogenic, include peptidoglycan cell wall material, lipopolysaccharide from gram-negative bacteria, bacterial lipopeptides, flagellin seen in bacterial flagella, and bacterial or viral nucleic acid fragments.

There are specialized structures on phagocytic cells that specifically recognize PAMPs. These are called pattern recognition receptors. One type of these is called a toll-like receptor, which binds to certain PAMPs to cause phagocytosis. Some are on the cell membrane, while others are on internal organelle membrane.

The binding of a pattern recognition receptor and a PAMP will activate the phagocyte so that it becomes ready to engulf the pathogen. More cytokines are released to enhance the inflammatory response and bring in more phagocytes. This leads to a larger response than could happen with just one or a few phagocytes. In addition, proliferation of the phagocyte occurs as part of the process.

After attachment and activation, the phagocyte engulfs the pathogen, bringing it inside the cell into a vesicle. This vesicle is called a phagosome. It later becomes fused with lysosomes, causing the formation of a phagolysosome. This acidifies the vesicle and activates lysosomal enzymes, hydrogen peroxide, and reactive oxygen species. The lysosomal enzymes include phospholipase, lysozyme, and proteases. Each of these participates in digesting the pathogen. There is an increased oxygen need, which is necessary to make the reactive oxygen species that help to destroy the pathogen. There are also reactive nitrogen compounds that kill the cell similar to reactive oxygen species.

After digestion and degradation, there will be leftover waste from the pathogen. These are mostly excreted by the cell as part of exocytosis. Not all of the pathogen does this, however. Both macrophages and dendritic cells are called antigen-presenting cells. They take up antigenic proteins from the pathogen and present them on their cell surface in order to activate the adaptive immune response, which will be discussed next.