Lymphatic system primer
The adaptive immune system is part of the human immune system and is made up of B lymphocytes and T lymphocytes. B lymphocytes, also known as B cells, are involved in the humoral immune response, differentiating into antibody-secreting plasma cells on activation and recognition of a disease-specific molecular structure known as an antigen. T lymphocytes, or T cells, participate primarily in the cell-mediated immune response and are capable of more specific antigen-directed recognition and elimination of pathogenic threats. T cells can be further segregated into distinct cell types, with the primary types being CD8+ T cells, which are also referred to as cytotoxic lymphocytes, or CTLs, and CD4+ “helper” T cells. CD8+ T cells specifically recognize and eliminate cells that are infected with viruses, other pathogens or cancer-associated mutations. In contrast, CD4+ T cells, which have limited cytotoxic activity, participate in the immune response by directing the activity of other cells, in particular B cells and CD8+ T cells. Antigen presenting cells, or APCs, are a functional class of immune cells capable of taking up antigens by a variety of mechanisms and then processing and presenting them to lymphocytes for recognition by the adaptive immune system. Dendritic cells, or DCs, are APCs that are particularly well suited to driving the adaptive immune response through direct interaction with adaptive immune cells to modulate and support their function.
The lymphatic system and its key role in effective immune response.
Lymph, a clear extracellular fluid, contains waste products and cellular debris derived from peripheral tissues. The lymphatic system is a complex network of interconnected vessels, nodes, and organs through which lymph flows. One of its primary functions involves collecting and concentrating molecular cues of health and disease that are monitored by the immune system.
The lymphatic system plays a major role in the production, differentiation and proliferation of both B cells and T cells, and the lymph nodes serve a critical role in lymphocyte activation and acquisition of essential functionality. Lymph nodes are found throughout the body and are located on the lymphatic vessels at various intervals along the lymphatic routes, where both T cells and B cells congregate together with APCs. Lymph fluid, containing antigens and other biomolecules derived from the tissues, drains into the lymph nodes, where it comes into contact with immune cells. Immune cells, such as APCs, in the lymph nodes function to constantly sample the lymph fluid searching for signs of potential threats within the tissues. APCs present these cues to lymphocytes within the lymph nodes, serving as sentinels to orient the cells of the adaptive immune response to develop a properly targeted and functional protective response. The activation of lymphocytes with proper specificity and functionality marks the genesis of the adaptive immune response whereby numerous disease-specific and functionally matured lymphocytes are expanded and deployed. After sufficient interaction with APCs within the lymph nodes, these activated lymphocytes exit the lymph nodes and eventually enter the bloodstream, which distributes them throughout the body, where they accumulate at disease sites. Critically, signaling delivered between immune cells that reside in the lymph nodes orchestrates the immune response to determine the magnitude, potency, persistence, functionality, specificity, and memory capacity of the developing response.
Many vaccine components and other small molecules commonly used as immunomodulators that help enhance the immune response easily pass through the blood vessel walls at the site of injection in the tissues and are quickly flushed away into the systemic circulation without entering into or engaging within lymph nodes. In consequence, these conventional antigens and immunomodulators are not readily detected by APCs ,B cells or T cells resident in the lymph nodes and fail to optimally stimulate immune responses, which in turn reduces their efficacy in eliminating disease. Larger molecules, such as proteins, on the other hand, are unable to fit through the pores lining small blood vessels in the tissues and are instead carried away from the tissues by the lymph flow into the lymph nodes. The improved delivery to the lymph nodes inherent with larger molecules holds great promise for enhanced immunological responses and therapeutic efficacy, and our AMP platform is designed to use this ability of larger molecules to deliver therapeutic payloads of interest to the lymphatic system.