AssessmentsIntroduction to the immune system
Introduction to the immune system
Content Reviewers:Rishi Desai, MD, MPH
Despite being surrounded by harmful microorganisms, toxins, and the threat of our own cells turning into tumor cells, humans manage to survive; largely thanks to our immune system.
The immune system is made up of organs, tissues, cells, and molecules that all work together to generate an immune response that protects us from microorganisms, removes toxins, and destroys tumor cells - hopefully not all at once!
The immune response can identify a threat, mount an attack, eliminate a pathogen, and develop mechanisms to remember the offender in case you encounter it again - all within 10 days.
In some cases, like if the pathogen is particularly stubborn or if the immune system starts attacking something it shouldn’t like your own tissue, it can last much longer, for months to years, and that leads to chronic inflammation.
Your immune system is like the military - with two main branches, the first is the innate immune response.
The innate immune response includes cells that are non-specific, meaning that although they distinguish an invader from a human cell, they don’t distinguish one invader from another invader.
The innate response is also feverishly fast - working within minutes to hours. Get it? “Feverishly” - that’s cause it’s responsible for causing fevers.
The trade off for that speed is 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 line the airways to keep invaders out.
In contrast, the adaptive immune response is highly specific for each invader. The cells of the adaptive immune response have receptors that differentiate one pathogen from another by their unique parts - called antigens.
These receptors can distinguish between friendly bacteria and potentially deadly ones. The trade off is that the adaptive response relies on cells being primed or activated, so they can fully differentiate into the right kind of fighter to kill that pathogen, and that can take a few weeks.
But the great advantage of the adaptive immune response is immunologic memory. The cells that are activated in the adaptive immune response undergo clonal expansion which means that they massively proliferate.
And each time the adaptive cells see that same pathogen, they massively proliferate again, resulting in a stronger and faster response each time that pathogen comes around.
Once the pathogen is destroyed, most of the clonally expanded cells die off, that’s called clonal deletion.
But some of the clonally expanded cells live on as memory cells and they’re ready to expand once more if that pathogen ever resurfaces. Now, it’s time to meet the soldiers - which are the white blood cells or leukocytes.
Hematopoiesis is the process of forming white blood cells, as well as red blood cells, and platelets and it takes place in the bone marrow.
Hematopoiesis starts with a multipotent hematopoietic stem cell which can develop into various cell types - it’s future is undecided. Some become myeloid progenitor cells whereas others become lymphoid progenitor cells.
The myeloid progenitor cells develop into myeloid cells which include neutrophils, eosinophils, basophils, mast cells, dendritic cells, macrophages, and monocytes, all of which are part of the innate immune response and can be found in the blood as well as in the tissues.
The neutrophils, eosinophils, basophils, and mast cells are considered granulocytes, because they contain granules in their cytoplasm, and the trio of neutrophils, eosinophils, and basophils are also referred to as polymorphonuclear cells, or PMNs, because they’re nuclei contain multiple lobes instead of being round. The mast cells aren’t considered PMNs because their nucleus is round.
During an immune response, the bone marrow produces lots of PMNs, most of which are neutrophils.
Neutrophils use a process called phagocytosis - that’s where they get near a pathogen and reach around it with their cytoplasm to “swallow” it whole, so that it ends up in a phagosome.
From there, the neutrophils can destroy the pathogen using two methods - they can use their cytoplasmic granules or oxidative burst.
First, the cytoplasmic granules fuse with the phagosome to form the phagolysosome. The granules contain molecules that lower the pH of the phagolysosome, making it very acidic, and that kills about 2% of the pathogens.
Now, the neutrophil doesn’t stop there. It keeps swallowing up more and more pathogens until it’s full of pathogens, and at that point, it unleashes the oxidative burst.
During an oxidative burst, the neutrophil produces lots of highly reactive oxygen molecules like hydrogen peroxide.
These molecules start to destroy nearby proteins and nucleic acids. This process kills the neutrophil but each neutrophil takes out a lot of pathogens with it.
Now, in comparison to neutrophils, eosinophils and basophils are far less common. They both contain granules that contain histamine and other proinflammatory molecules.
Eosinophils stain pink with the dye eosin - which is where they get their name. Eosinophils are also phagocytic, and they’re best known for fighting large and unwieldy parasites because eosinophils are much larger than neutrophils and have receptors that are specific for parasites.
These cells are also involved in the pathogenesis of asthma where they can be found in the space just below the epithelial cell lining of bronchioles.
So, when an environmental trigger is breathed in, for example, cigarette smoke, the eosinophils degranulate and release histamine and other proinflammatory mediators.
This creates a strong inflammatory reaction in the bronchiolar walls and causes the contraction of smooth muscles around the bronchioles, eventually causing the constriction of bronchioles.
Next you have basophils, and they stain blue with the dye hematoxylin, and unlike neutrophils and eosinophils, basophils are non-phagocytic.
On the flip side, just like eosinophils, they have granules that contain histamine and other proinflammatory molecules; therefore, they are important in initiating allergic responses.
Finally, there are the mast cells which are also non-phagocytic and they’re involved in asthma and allergic responses.
Next up are the monocytes, macrophages, and dendritic cells which are also phagocytic cells - they gobble up pathogens, present antigens, and release cytokines - tiny molecules that help attract other immune cells to the area.
Monocytes only circulate in the blood. Some monocytes migrate into tissues and differentiate into macrophages, which remain in tissues and aren’t found in the blood.
Other monocytes differentiate into dendritic cells, the prototypical antigen presenting cell, which roam around in the lymph, blood, and tissue.
When dendritic cells are young and immature they’re excellent at phagocytosis, constantly eating large amounts of protein found in the interstitial fluid.
But when a dendritic cell phagocytoses a pathogen for the first time - it’s a life-changing, coming of age moment.