Pathogen Recognition and Immune Activation

SCENARIO 1 The body's defense when initially exposed to an antigen The body has a defense system that can recognize antigens or pathogens. The body's initial defense system is always ready and has a non-specific response that can destroy pathogens. These immune components can be in the form of skin, mucosal epithelium, mucous membranes, respiratory tract cilia movement, IgA Explain the mechanism by which pathogens are presented to the non-specific immune system Guidance Questions for LO 3: a. How can antigens be recognized by the non-specific immune system? Microbial protein antigens entering the body are captured mainly by dendritic cells and concentrated in peripheral lymphoid organs, where the immune response is initiated.Antigens/microbes usually enter the body through the skin (through contact), the digestive tract (through eating), and the respiratory tract (through inhalation). Some insect-borne microbes can enter the bloodstream as a result of insect bites, and some infections can pass through the genitourinary tract. Antigens/microbes can also be present in infected tissue. Because of the large surface area of epithelium and the large volume of blood, connective tissue, and internal organs, it is impossible for lymphocytes or immune cells to efficiently patrol all these locations in search of infecting foreign antigens; instead, antigens are carried to lymphoid organs via circulating lymphocytes. This process involves a series of events after the dendritic cells recognize the microbe—antigen capture, activation of the dendritic cells, migration of antigen-bearing cells to the lymph node, and presentation of the antigen to T cells. All interactions between the body and the external environment are covered by the epithelium, whose main function is as a barrier against infection. Epithelial and subepithelial tissues contain dendritic cells; Dendritic cells are similarly present in T cell-rich areas of peripheral lymphoid organs and in most other organs in smaller numbers. There are two main populations of dendritic cells, called classical and plasmacytoid, which are differentiated based on their location and response. The majority of dendritic cells in lymphoid tissues and organs belong to the classical type of dendritic cells. In the skin, epidermal dendritic cells are called Langerhans cells. Plasmacytoid dendritic cells are named because of their morphological similarity to plasma cells; they are present in the blood and tissues. Plasmacytoid dendritic cells are also the main source of type I interferon in the innate immune response to viral infections. Dendritic cells use a variety of membrane receptors to bind microbes, for example lectin receptors that recognize carbohydrate structures typical of microbes and not mammalian glycoproteins. Microbes or their antigens enter dendritic cells via receptormediated phagocytosis or endocytosis. At the same time that the dendritic cells capture the antigen, the microbial products stimulate a natural immune reaction by bindingToll Like Receptor (TLR) andpattern recognition receptors(other innate PRR) in dendritic cells, tissue epithelial cells, and resident macrophages. After the microbe binds to the receptor, the production of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) will occur. Combination of TLR signals andCytokines activate dendritic cells, resulting in several changes in phenotype, migration, and function. Upon activation by these signals, classical dendritic cells lose their adhesion to the epithelium and begin to express the chemokine receptor CCR7, which is specific for cytokines.chemoattracting(chemokines) produced by the lymphatic endothelium and by stromal cells in the T cell zone of the lymph node. These chemokines direct dendritic cells to exit the epithelium and migrate through the lymphatic vessels to the lymph nodes. During the migration process, dendritic cells mature from cells designed to capture antigens into APCs capable of stimulating T lymphocytes. This maturation is reflected by increased synthesis and stable expression of MHC molecules, which present antigens to T cells, necessary for the activation of the T cell response. Antigens dissolved in the lymph are captured by dendritic cells in the lymph nodes, and antigens in the blood circulation are captured in the same way by dendritic cells in the spleen.The result of this series of events is that microbial antigen proteins that enter the body are transported and concentrated to the lymph node area where the antigen is most likely to encounter T lymphocytes.