Pathogen Recognition Receptors in Immune Signaling

The immune system has two main branches: innate and adaptive immunity. Innate immunity provides immediate defense against pathogens, while adaptive immunity remembers specific pathogens to mount a targeted response. Dendritic cells play a crucial role in connecting the two by recognizing pathogens through pattern recognition receptors (PRRs) and presenting antigens to T-cells. The essay highlights the importance of both immune systems working together to recognize and respond to different types of pathogens.

Immunity and Infection
Introduction
The primary role of immune system of the human body is to protect it against diseases or any
other harmful foreign bodies. That fact that our bodies are in constant exposure to the infectious
agents and yet we are able to thwart the infections. It is our immune system that comes into play
that resists these infections. It is one of the most complex systems of the human body that takes
care of all other systems such as respiratory system, nervous system etc. So, it is well equipped
to neutralize foreign bacteria, parasites, fungi and viruses as these pathogens have the propensity
to grow and multiply inside our bodies with destructive consequences (Qiao, 2006). In the
following essay, we will try to understand different aspects of immune system, particularly,
innate and adaptive immunities. What is their significance and how they work in tandem to fight
against foreign pathogens.
Failing to protect may Spell Trouble
Even though its greatly evolved mechanism of identifying and fighting the germs, the immune
system sometimes seems to be unable to give the protection that is paramount for us. This
complex system in turn relies on specialized elements such as T cells, B cells, macrophages
along with antibodies and biochemical. All of these units perform their specific tasks, while
coordinating with each other at the same time. So, if any of these units becomes dysfunctional,
there is a possibility that entire immune system can collapse (Lee & Mazmanian, 2010).
The Innate Immune System
The innate immune system is also known as the first line of defense against the pathogens that
invades the human body. Most of the encounters that our bodies have with the microorganisms
are detected and destroyed and within minutes or hours because innate immunity is at work all
the time. The cells that are involved in innate immune system are neutrophils, monocytes,
macrophages and dendritic cells. These important elements start developing during the fetal life
and mature at different stages of the human life.
The neutrophils are stimulated by granulocyte-colony just before birth. They get sharply
increased in number, however, show weak responses towards bacterial functions and
inflammatory stimuli. These deficits are more conspicuous in preborn infants. The monocytes
and macrophages are also immature in premature children (Ozinsky et al., 2000). In other words,
the innate immune system is relatively dormant at birth due to the fact that a fetus not only had to
go through non-shared maternal antigens but also tolerate the significant amount of stress and
remodeling taking place during its development. Which is why, the newborn is relatively
susceptible to viral and bacterial infections.

The Adaptive Immune System
The adaptive immune system primarily consists of antibodies and lymphocytes. This immune
system is often known as humoral response and cell mediated response. As the name suggests,
adaptive immunity is about tailoring its response to a particular foreign invader. The cells that
get involved in adaptive immune system are lymphocytes – B cells and T cells.
The B cells are produced by the bone marrow, which in turn produce antibodies. The B cells
after being produced in the bone marrow, move into lymphatic system in order to circulate and
present throughout the body. Inside this system, the B cells encounter antigens and get matured.
The B cells have distinctive antigen-specific receptors according to one’s DNA. So, when a
naïve B cell encounters membrane bound anti-body, it divides and forms either a memory B cell
or effector B cell. The T cells, on the other hand, differentiate into cells that either participate in
lymphocyte maturation or help in killing virus-infected cells (Randolph, 2005).
One of the key attributes of the adaptive immunity is its memory. Sometimes a repeat infection
occurs due to the same virus, then in such a situation it meets with a strong and specific response
because of the immune memory. A primary adaptive response may take days to mature, while
memory response shows its effects in hours after infection. The subsets of B and T lymphocytes
are responsible for immune memory. The fact that secondary responses are stronger than the
primary ones, the childhood infections, therefore, protect adults and immunity endowed by
vaccination could last for years.
Coordination of innate and adaptive immune systems
In general, the ability to produce response in a manner that is virus-specific is a lot dependent
communication between innate and adaptive immune systems. This particular communication
established between the two systems is established by cytokines that help in making cell-to-cell
interactions between dendritic cells and lymphocytes in lymph nodes. This interaction is so
important that it is impossible for adaptive response to occur without any help of innate
immunity.
The discovery of pathogen recognition receptors (PRRs) and dendritic cells allowed us to delve
deeper to expand our knowledge base regarding immune system by connecting innate immune
signaling and adaptive immunity. It provides a fair idea as to how the innate immunity regulates
and shapes our adaptive immune responses. In this the dendritic cells play a crucial role for the
immune signaling network because they are important phagocytic antigen-presenting cells that
know the onslaught of pathogens via PRRs. This response mechanism is characterized by Toll-
like receptors (TLRs) or Nod-like Receptors (NLRs), which is also responsible for activating
naïve T cell response (Watford, Moriguchi, Morinobu, & O’Shea, 2003).
In simple terms, the innate immune system lets the adaptive immune system know when will be
the right time for mounting a defense. It’s being done by making two types of changes on the
phagocyte surface that activate adaptive immunity. These changes are also important for the
activation of whole immune system. The phagocytes are also referred to as antigen-producing
cells because when it engulfs the invading pathogen, they produce the strands of protein derived

from the pathogen – called antigens. These antigens being produced on the surface of phagocytes
are also known as Major Histocompatibility Complex molecules (MHC). These molecules alert
the adaptive immunity and allow T cells to recognize an infected cell.
The mechanism so far is not enough to trigger the whole adaptive immune response. So, at this
instant there is a need for a danger signal or a flag signal to be emerged on the surface of the
phagocyte cells to allow adaptive immune system fling into action. Now, this is the time for
PRRs to play their role. The PRRs that are found inside phagocytes, help in recognizing the
pathogens that have common traits. With that a sequence of cellular events is being set resulting
in the display of flags that are required to trigger an adaptive immune response (Hoebe, Janssen,
& Beutler, 2004). They also trigger the release of certain chemical messengers that are known as
cytokines for calling adaptive immune system into action.
Fig. Dendritic cells initiate adaptive immune responses
Lymphocytic Activity
As the germ-line encoded receptors only recognize microorganisms bearing surface molecules
common to many pathogens. So, these microbes evolve more rapidly than the hosts. Moreover,
many bacteria form a protective capsule enabling them to conceal these molecules, thereby
preventing them from being recognized. Viruses, on the other hand, consists of no invariant
molecule that are similar to bacteria and therefore seldom recognized directly by macrophages.
Therefore, the recognition mechanism being used by lymphocytes of adaptive immunity, has
evolved in such a way that overcome the constraints posed to the innate immune system. This
recognition includes almost infinite diversity of antigens so that each and every pathogen could
be targeted specifically.
It should also be noted that although an independent lymphocyte contains receptors of only
single specificity, but the specificity of individual lymphocyte is unique. Because of that millions

of lymphocytes carry millions of unique antigen receptor specificities. During the lifetime of an
individual, undergo a process similar to natural selection. The lymphocytes that are encountered
with an antigen to which their receptors bind, are the only ones that are activated to proliferate
and differentiate into effector cells.
In 1960s, during an experimental phase, when very little was known about antigen receptors of
lymphocytes, James Gowans discovered that lymphocytes must be the units of clonal selection.
The question that emerged at this point was how do the lymphocytes prevented from recognizing
the antigens and attacking them? In response to that the biologist Burnet espoused that the
lymphocytes that are potentially self-reactive are removed well before they could mature
(Charles A Janeway, Travers, Walport, & Shlomchik, 2001).
Finally, an antibody is the central puzzle of adaptive immunity. It was found that an antibody
molecule consists of two distinct regions – constant region and variable region. The constant
phase can take only few distinguishable forms, while variable region can take countless variety
of subtly different forms.
Conclusion
The above essay highlights the importance of both innate and adaptive immune system. The
innate systems of defense are quite dependent on invariant receptors that recognize the common
features of pathogen. But sometimes they are evaded overcome by many pathogens, so, to
recognize all the pathogens is the unique feature of adaptive immunity. It shows that both the
immune systems are intertwined and collaboratively work together.

References
Charles A Janeway, J., Travers, P., Walport, M., & Shlomchik, M. (2001). Principles of innate
and adaptive immunity. Garland Science. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK27090/
Hoebe, K., Janssen, E., & Beutler, B. (2004). The interface between innate and adaptive
immunity.Nature Immunology, 5(10), 971-974. http://dx.doi.org/10.1038/ni1004-971
Lee, Y. & Mazmanian, S. (2010). Has the Microbiota Played a Critical Role in the Evolution of
the Adaptive Immune System?. Science, 330(6012), 1768-1773.
http://dx.doi.org/10.1126/science.1195568
Ozinsky, A., Underhill, D., Fontenot, J., Hajjar, A., Smith, K., & Wilson, C. et al. (2000). The
repertoire for pattern recognition of pathogens by the innate immune system is defined by
cooperation between Toll-like receptors. Proceedings Of The National Academy Of
Sciences, 97(25), 13766-13771. http://dx.doi.org/10.1073/pnas.250476497
Qiao, Y. (2006). An intrusion detection system based on immune mechanisms. SPIE Newsroom.
http://dx.doi.org/10.1117/2.1200609.0282
Randolph, D. (2005). The Neonatal Adaptive Immune System. Neoreviews, 6(10), e454-e462.
http://dx.doi.org/10.1542/neo.6-10-e454
Watford, W., Moriguchi, M., Morinobu, A., & O’Shea, J. (2003). The biology of IL-12:
coordinating innate and adaptive immune responses. Cytokine & Growth Factor
Reviews, 14(5), 361-368. http://dx.doi.org/10.1016/s1359-6101(03)00043-1