The immune system is the collection of cells and cellular products that function to protect our body from foreign invaders such as bacteria and viruses. At its broadest level of organization, the immune system can be divided into two categories: the innate immune system, and the adaptive immune system.  Although the members of these two categories are interdependent and often interact within our bodies, they have been separated based upon an underlying difference in function—namely, how they recognize foreign cells that invade our bodies.  

The innate immune system

Physical Barriers

As the name implies, the components of innate immune system have a basal, or innate, ability to repel and destroy invading pathogens like bacteria and viruses in a nonspecific manner. There are three main components of the innate immune system.  The first comprises physical barriers formed by epithelial cells. These cells, which compose our skin and line our internal organs, provide the first line of defense against invaders, as they form tight junctions to prevent the entrance of microbes. They also secrete many anti-microbial substances like mucus, (prevents pathogens from colonizing epithelial surfaces), and antimicrobial peptides, (disrupt the bacterial cell wall to cause microbial death). Note that, while our epithelial cells are highly effective at preventing the entry of numerous pathogens, the mechanism of action is non-specific. Our body’s physical barriers do not exclude certain pathogens while purposefully permitting others – they provide global protection against pathogens, regardless of their identity. The global, non-specific nature of protection dictates the classification of physical barriers as being innate modes of immunity.

The Complement System

The second broad component of the innate immune system is the complement system, which consists of  approximately 30 proteins that circulate in the blood. When no infection is present, the complement system is inactive. However, upon pathogenic invasion, the proteins of the complement system employ multiple mechanisms to kill the invader. For instance, complement can bind to the surface of bacteria and create pores in the cell wall, causing bacterial lysis and death. They can also increase the phagocytosis, or ingestion, of pathogens by cells of the innate immune system (discussed below). Similar to the function of epithelial barriers, the complement system does not specifically target certain pathogens. Rather, it exists to provide another global line of defense against invaders.

Innate Immune Cells

The final components of the innate immune system are the innate immune cells themselves. These cells are classified as innate because they are able to recognize features common to many different pathogens, called PAMPs (Pathogen Associated Molecular Patterns). While shared among many pathogens, PAMPs are absent from our cells, meaning that they provide useful criteria by which innate immune cells can distinguish self from non-self and thus avoid autoimmunity.  A prototypical example of a PAMP is lipopolysaccharide (LPS), a component of many bacterial exterior membranes. When cells of the innate immune system recognize LPS or other PAMPs, they can initiate anti-microbial mechanisms, such as phagocytosis of the invader. Because these cells recognize features common to many pathogens, rather than specific types of pathogens, they are again classified as being part of the innate immune system.

 

The adaptive immune system

Overview

The adaptive immune system comprises many different types of cells that can recognize and kill foreign invaders in the body. These cells include B-cells, which produce antibodies, T-cells, and many more. Two key features separate adaptive cells from those of the innate immune system: the ability of adaptive immune cells to recognize very specific features of pathogens, and the ability of these cells to “remember” the pathogens that they’ve encountered in the past.

Specificity

The adaptive immune system consists of a vast repertoire of cells, each of which expresses a different protein (such as an antibody) that is capable of recognizing specific pathogen-associated molecules. In contrast to the widely-expressed danger signals recognized by the innate immune system, these pathogenic molecules are generally only expressed by certain pathogens, such as a particular type of bacteria or virus.

As an example, let’s consider the case of Streptococcus pneumoniae which causes pneumonia, ear infections, and a host of other ailments. S. pneumoniae expresses a protein on its surface called choline-binding protein A, or CbpA. Unlike LPS, which is expressed on many different types of bacteria, S. pneumoniae expresses a unique version of CbpA, making this protein a very specific marker of  S. pneumoniae infection. When this bacteria is present in our bodies, our antibody-producing B cells can generate antibodies that specifically recognize and bind to CbpA, effectively flagging the bacteria as foreign and dangerous. Once marked by antibodies, the bacteria can be more easily recognized by other immune cells, including innate immune cells, that can kill the bacteria. In this way, the adaptive immune system is able to protect our bodies against pathogen on a molecule-by molecule and pathogen-by-pathogen basis.

Memory

In addition to the ability of adaptive immune cells to recognize specific pathogenic molecules, they are also able to form immunological memory, a phenomenon whereby adaptive immune cells “remember” pathogen-associated molecules that they have encountered in the past. Because each adaptive immune cell is so specific for particular pathogenic molecules, a relatively small number of cells initially exists with the capacity to recognize any given pathogen. However, after an initial exposure, the few cells that are able to recognize a certain pathogen, like S. pneumoniae, divide and multiply in an effort to fight and kill the invader. After the infection in cleared, this population of pathogen-specific adaptive cells does not just disappear. Rather, a pool of adaptive memory cells form to maintain a higher number of cells that can recognize and eradicate S. pneumoniae. In this way, if you were to become infected by S. pneumoniae in the future, these adaptive memory cells would galvanize into action to quickly and efficiently eliminate the bacteria, ideally before you even experienced symptoms of an infection.

Innate and adaptive: the necessity of both

The innate and adaptive systems are interconnected and interdependent. Neither is sufficient to protect our bodies from the vast array of pathogenic insults that we must cope with on a daily basis. The innate system provides a first line of defence, as it is always present and can recognize the common features of many foreign invaders. However, pathogens can often overcome the innate system by multiplying too quickly, or mutating in such a way that the innate system can no longer recognize them (immune evasion). This is where the adaptive system comes into play. The initial adaptive response to a pathogen is not as immediate as the innate immune response, as it takes multiple days for the adaptive immune cells to recognize pathogens and produce very specific proteins and cells to combat them. However, the adaptive immune system offers the advantages of specificity and memory. With regards to specificity, even if a bacterial cell mutates to reduce PAMP expression (thereby avoiding the innate immune system), the adaptive system is there to specifically target other pathogenic molecules. Using its specificity, the adaptive immune system can also make the innate immune system more effective, as in the example of S. pneumoniae where antibodies against CbpA help flag the bacterial cells for destruction by innate cells. Finally, adaptive immunity offers the advantage of memory, meaning that once our bodies experience an adaptive immune response against a certain pathogen, those specific adaptive immune cells will always exist in our bodies to protect us more quickly and robustly against subsequent exposures to the same pathogen.

 

Featured Image: 2.0 Generic, Flickr CC BY 2.0