Antimicrobial peptides and the innate immune system
Anyone who has taken a collegiate level introductory course in microbiology, medicine, or immunology is aware of the fact that modern multicellular organisms are constantly under assault by a barrage of pathogenic infectious microorganisms.
Thankfully, more than 1 billion years of evolution have equipped most multicellular life with a host of methods to intercept and destroy invading pathogens. Immunologists, who study in detail the biological response to infection, generally classify the defensive strategy adopted by an organism into two distinct but cooperative protective schemes: innate and adaptive immunity.
Adaptive immunity: a finely tuned, specific response to infection
Of the two methods, the adaptive immunological response is the most well-known and extensively studied. Adaptive or acquired immunity, present in most vertebrate animals, involves:
- Host screening to recognize and differentiate specific “non-self” targets from those native to the host.
- Host development of a finely tuned immunological response (e.g. antibodies) to identify, target, destroy, or neutralize specific targets perceived as non-self.
- Host retention of immunological memory to allow for rapid identification of and response to the same specific antigenic target in the event of future incursions.
The adaptive immune response is powerful because it allows the host to unleash potent defenses that identify, attack, and destroy invading pathogens without causing undue harm to surrounding tissue. However, it takes time for components of the adaptive immune system to clearly recognize a specific pathogen and mount a systematic, specific response to it. The innate immune system fills this gap by combating infection in localized, less specific manner.
Innate immunity: the first line of defense against infection
In contrast to the adaptive immune response, innate immunity encompasses a broad range of protective methods found in every form of life. Innate immunology does not cover a specific response scheme to a specific threat, but rather is a catch-all field representing many different groups of hard-coded immunological responses that attempt to disrupt, destroy, or block the activity of broad classes of pathogenic microorganisms.
A number of different cell types, readily recognizable to the avid student of immunology, play an important role in innate immunity. For example, Neutrophils are constituent components of blood that arrive at the site of infection, attracted by chemokines, and attack pathogenic microrganisms by phagocytosing them, releasing antimicrobial compounds into their environment, or by releasing cytokines which enhance and accelerate the adaptive immune response.
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Historically, innate immunity has not enjoyed the same deep level of interest and study as the adaptive immunological response. However, investigation of innate immunological response to infection has enjoyed a resurgence in recent years, due in part to interest in coopting elements of innate immunity for advanced therapeutic applications.
Antimicrobial peptides are one example of a research field that has recently gathered extensive interest. Antimicrobial peptides (or AMPs) are a diverse class highly of conserved of small peptide molecules that attack, destroy, and deactivate invading bacterial, viral, or fungal pathogens in a variety of different ways. Some classes of antimicrobial peptides function as potent, endogenously-produced, broad base antibiotics. This makes them particularly interesting and relevant targets in a rapidly approaching post-antibiotic era.
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In addition to their traditional antibiotic roles (e.g. disrupting bacterial membranes, inhibiting DNA replication/transcription) several papers also provide strong evidence suggesting that many antimicrobial peptides act as immunomodulators, rapidly stimulating a “ramped-up” adaptive immunological response. The recently identified role of antimicrobial peptides as regulators of adaptive immunity implicates them in a diverse set of roles, from aggravators of well-known autoimmune disease to internally produced anticancer agents.
In 2014, more than 100 new antimicrobial peptides were identified and registered in the AMP database. The rapid growth in identification of new antimicrobial peptides, coupled with an ever-increasing awareness of their versatility and the imperative drive to find new more powerful tools to combat infection, will ensure that the study of innate immunity no-longer takes a back-seat in biomedical research.