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Innate Immune Response

  • The Innate Immune Response refers to the aspects of the host immune response which are activated by general molecular patterns present on microbes or in damaged tissue and thus do not rely on the action of the antigen-specific Adaptive Immune Response. Because Innate Immunity does not rely on the development of antigen-specific cells, it is temporally the first aspect of the immune response to engage a pathogen. Evolutionarily, Innate Immunity developed earlier in phylogeny with many simple organisms possessing aspects of innate immunity while lacking adaptive immune mechanisms. In addition to its role in destroying pathogens, it is now becoming clear that innate immunity is critical for initiating and coordinating the subsequent adaptive immune response to microbes.
Innate Pathogen Recognition
  • Microbial Patterns
    • One of the fundamental aspects of innate immunity is the capacity to identify the presence of microbes through the recognition of general molecular patterns. This stands in contrast to cells of the adaptive immune system which recognize highly specific antigenic moieties that are present only on a single microbial species or even sub-species. Innate immune cells accomplish this general pattern recognition by identifying certain molecules which are synthesized by all types of microbes within a certain microbial class. For example, innate immune cells can recognize the presence of Gram Negative Bacteria by identifying Lipopolysaccharide (LPS), a critical component of the gram negative Bacterial Cell Wall. Alternatively, certain viral infections can be identified by recognition of the viral dsRNA genome.
  • Pattern Recognition Receptors
    • The molecular basis for the capacity of innate immune cells to recognize general molecular patterns has only recently become clear. Innate immune cells possess various classes of membrane receptors, termed "Pattern Recognition Receptors", which bind to molecules such as LPS, dsRNA, or other generic molecules which are produced only by microbes. Several families of Pattern Recognition Receptors proteins exist but the prototypical family is known as the "Toll-like Receptor" family. Pattern Recognition Receptors not only allow innate immune cells to recognize that a microbial infection is present, but depending on which receptors are activated allow innate immune cells to roughly determine what type of infection is occurring (i.e. bacterial, viral, fungal, etc.). Recognizing the basic category of infection assists the innate immune response in shpaing the later adaptive immune response in the most effective way.
Basic Sequence of Innate Immunity
  • Overview
    • Here we outline the steps of a prototypical innate immune response to the entry of a pathogen. As an example we will consider the introduction of a bacteria into the skin, possibly by an abrasion.
  • Tissue Recognition
    • Importantly, Pattern Recognition Receptors are present on nearly all cells and are not exclusively expressed on immune cells. Therefore, basic microbial patterns of the introduced bacteria will activate Pattern Recognition Receptors on a wide variety of local cells such as keratinocytes, dermal fibroblasts, or tissue macrophages. All of these cells will respond to engagement of their Pattern Recognition Receptors by secreting Cytokines which coordinate the recruitment of further immune cells as part of a general immunological sequence discussed in Acute Inflammation.
  • Effector Mechanisms
    • As a result of acute inflammation, innate immune effector cells such as neutrophils and macrophages are recruited to the site of infection in the skin. These cells rapidly phagocytose damaged cellular material along with any bacteria present which they then destroy. This rapid ingestion and digestion of bacteria allows the immune system to maintain fairly strong control over the infection prior to the initiation of the much more powerful Adaptive Immune Response. Once again, these cells roughly identify that the organism they have phagocytosed is a bacteria, rather than say a virus, based on which Pattern Recognition Receptors are activated.
  • Coordination of Adaptive Immunity
    • Innate immunity is not only important for rapid control of invading pathogens but also initiates and coordinates the adaptive immune response. The cells which connect innate immunity with adaptive immunity are functionally defined as Antigen Presenting Cells (APCs). A variety of cells have been shown to possess APC functionality but it appears that the most important class are Dendritic Cells. These cells are normally present throughout body's tissues and can also be recruited to sites of inflammation. They phagocytose pathogens and cellular debris and possess Pattern Recognition Receptors which can help identify the basic class of microbe internalized.
    • As in our example, local epidermal Dendritic Cells take up any bacteria present and degrade the microbes while migrating to local lymph nodes where they can come into contact with T-cells of the Adaptive Immune Response. Instead of merely recycling the bacterial macromolecules, Dendritic Cells "present" small pieces of the microbe on their surface using MHC proteins. While in the lymph node, antigen-specific T-cell]s sample the antigens present on any particular Dendritic Cell. If the antigen-specific T-cell recognizes the bacterial antigen it is then activated to proliferate and differentiate into an effector cell (This is discussed later in the Adaptive Immune Response).