AssessmentsInnate immune system
Content Reviewers:Rishi Desai, MD, MPH
Key features of the innate immune response are that the cells are non-specific, meaning that they don’t distinguish one invader from another invader, the response is really fast - occurring within minutes to hours, and that there’s no memory associated with innate responses.
In other words, the innate response will respond to the same pathogen in the exact same way no matter how many times it sees the pathogen.
The innate immune response includes things that you may not even think of as being part of the immune system.
Things like chemical barriers, like lysozymes in the tears and a low pH in the stomach, as well as physical barriers like the epithelium in the skin and gut, and the cilia which line the airways to keep invaders out.
Now if a pathogen happens to get in, then the immune system kicks in and it usually begins with the macrophage - which is the garbage truck of the body.
Macrophages eat up dead and dying cells, so that the tissue doesn’t become cluttered with them, and that makes room for new cells. They also eat invading pathogens.
Since macrophages live in the tissue they begin recognizing pathogens within minutes of an infection.
And the way that a macrophage figures out if something is a healthy host cell or a pathogen is by the molecules that a cell or pathogen has on it’s surface.
This is because cells of the innate immune response don’t distinguish one invader from another invader.
You see - pathogens have molecules that humans don’t have and they’re called pathogen associated molecular patterns or PAMPs.
PAMPs include bacterial wall components like peptidoglycan, lipopolysaccharide or LPS, and lipoteichoic acid, fungal wall components like mannan, and flagella proteins which can be found on some parasites and bacteria.
For intracellular pathogens, like viruses, PAMPs might include the viral RNA or DNA.
Now, PAMPs are recognized by Pattern Recognition Receptors or PRRs which are receptors on various immune cells including macrophages, neutrophils, eosinophils, basophils, and mast cells.
There are two main groups of PRRs - phagocytic PRRs and signaling PRRs.
Phagocytic PRRs bind to PAMPs so that a phagocyte can gobble it up, but they don’t allow for cytokines to be released to other cells.
This is important! - because it allows the macrophage to investigate and eliminate the threat before signaling that there’s an invader.
A little like investigating a noise before calling the cops - after all, it might just be a chicken wandering around on the roof.
So if there are just a few pathogens around, then the phagocytic PRRs will get activated, and phagocytes will eliminate the pathogens.
Going back to our garbage-truck macrophage let’s say that it’s PRR recognizes a PAMP on a bacterial cell.
It will then swallow up the bacteria, and then trap it in a vesicle called a phagosome.
The phagosome then fuses with another vesicle called the lysosome and forms the phagolysosome.
At this point the phagocyte will undergo a variety of chemical reactions to kill the pathogen.
First off, the phagolysosome contains two types of granules, specific granules and azurophilic granules, which help destroy the bacteria.
The specific granules go to work first - they contain proteases and hydrolases which are active at a neutral pH.
As the organisms die, potassium and hydrogen ions are drawn into the phagolysosome decreasing the pH, this allows the enzymes in the azurophilic granules to go to work.
The azurophilic granules contain hydrolases like Cathepsin G and oxidative enzymes like myeloperoxidase, which work best in an acidic pH.