The innate immune response is tasked with responding immediately to an invading pathogen and getting rid of it before disease develops.
You may wonder – how does the innate response recognize something as being an invading pathogen? How does it see the danger? How does it know something is foreign?
The cells of our innate immune response have receptors (termed pattern recognition receptors) that are able to recognize patterns and components of the microbes we are commonly exposed to.
Depending on function, these pathogen recognition receptors can be further described as being phagocytic receptors (which function to bring a particle into a cell) or toll-like receptors (which tell the innate immune cell that the given particle is in fact dangerous or foreign).
These receptors recognize pathogen-associated molecular patterns – parts of pathogens that are not found in the host, are widely-conserved across many pathogens, rarely undergo mutation, and are crucial to the pathogen’s lifestyle.
When a pathogen invades, it is immediately seen by macrophages that inhabit our tissues.
Pathogen recognition receptors that are expressed at the surface of the macrophage would recognize this pathogen.
The macrophage’s phagocytic receptors would attach to the components of the pathogen and initiate phagocytosis. The microbe is brought into the immune cell in a membrane-bound compartment, which becomes increasingly aciding. This compartment fuses with another compartment, forming a phagolysosome, which produces numerous enzymes and toxic substances that work to kill the microbe.
The macrophage’s toll-like receptors would attach to components of the pathogen and would activate signaling pathways within the macrophage. A transcription factor called NF-kB is activated, and the transcription of particular genes becomes increased. This increased transcription leads to the increased production of proteins called pro-inflammatory cytokines (which are central to the inflammatory element of the innate immune response) and chemokines (which create a gradient that functions to guide other immune cells from far-away locations).
Simultaneously, mast cells in the tissues can recognize the microbes and release a molecule called histamine alongside inflammatory cytokines.
Each of these products (histamine, inflammatory cytokines, etc) act as inflammatory mediators, acting upon our blood vessels to create a large innate immune response.
Histamine promotes the dilation of blood vessels, increasing blood flow to the site of infection.
Cytokines act upon the blood vessel walls directly, increasing the permeability and increasing the expression of adhesion molecules along the blood vessel surface.
With increased permeability, blood components may pass into the tissues with greater ease. Fluid, proteins, and immune cells (like neutrophils and immature macrophages) all are able to accumulate in the tissues. The increased adhesion molecules along the blood vessel surface brings even more of these players – slowing down the immune cells passing through the blood and helping them to pass into the tissues.
Now in the tissues, these immune cells migrate to the site of infection where the microbes have invaded, guided by the gradient of the aforementioned macrophage-produced chemokines.
Neutrophils and immature macrophages (which have now matured) seek out the pathogens and destroy them via phagocytosis.
This article’s content was created based upon the background accrued over the course of the author’s Honours BSc Degree in Microbiology & Immunology, which included Immunology, Virology, and Bacterial Pathogenesis course-work and exposure to topics from Janeway’s Immunobiology.
