Innate Immunity Archives • Microbe Online

The immune system consists of many different organs, tissues, and cells scattered throughout the body but connected via blood vessels or lymphatic channels. These cells communicate with each other using protein signals (cytokines, complement, and immunoglobulins) and provide defense against foreign invaders (pathogenic microorganisms). Some of these cells, such as B-cells and T-cells, require "training" or education before carrying out their effector functions. These cells are chief mediators of adaptive or acquired immunity. While other cells can carry out their functions without the need for training such immune cells are neutrophils, macrophages, natural killer (NK) cells. These cells are part of the innate immune system. All these specialized cells of the immune system arise from bone marrow's hematopoietic stem cells. Hematopoietic stem cells Hematopoietic (blood-forming) stem cells are self-renewing pluripotent cells, have the potential to differentiate and mature into the different cells of the immune system. They are responsible for the constant renewal of blood—the production of billions of new blood cells each day. Hematopoietic stem cells are the most important cell in bone marrow transplants as they can generate the entire immune system. Hematopoietic stem cell transplants are used to treat patients with cancers and other disorders of the blood and immune systems. About 1 in every 100,000 cells in the marrow is a stem cell; other cells present include stromal cells, stromal stem cells, blood progenitor cells, and mature and maturing WBCs and RBCs. Hematopoietic stem cell differentiate along one of two pathways, giving rise to either a common lymphoid progenitor cell or a common myeloid progenitor cell. Each of them differentiates further into various cell types. The presence of types and amounts of growth factors in the microenvironment of a particular stem cell or progenitor cell control its differentiation. Myeloid progenitor cells Progenitor cells have lost the capacity for self-renewal and are committed to a particular cell lineage. Myeloid stem cells generate progenitors of red blood cells, white blood cells (neutrophils, eosinophils, basophils, monocytes, mast cells, dendritic cells), and platelets. When appropriate factors and cytokines are present, progenitor cells proliferate and differentiate into corresponding cell types. Neutrophils Neutrophils or polymorphonuclear leukocytes (polys or PMN’s) are the most abundant population of circulating WBCs, making up about half or more of the total. They are found in the bloodstream and can migrate into sites of infection within a matter of minutes. These cells, like the other cells in the immune system, develop from hematopoietic stem cells in the bone marrow. Neutrophils appear on lab reports as part of a complete blood count (CBC with differential). Neutrophils increase in number in the bloodstream during infection and are in large part responsible for the elevated white blood cell count seen with some infections. Neutrophils may migrate to sites of infection within a few hours after the entry of microbes and are responsible for the formation of “pus.” Neutrophils mediate the earliest phase of inflammatory reactions, ingest bacteria or fungi, and kill them. They have little role in the defense against viruses. Monocytes Monocytes are closely related to neutrophils and are found circulating in the bloodstream. They make up 5-10 percent of the white blood cells. They also line the walls of blood vessels in organs like the liver and spleen. Here they capture microorganisms in the blood as the microorganisms pass by. When monocytes leave the bloodstream and enter the tissues, they change shape and size and become macrophages. Macrophages Macrophages are mononuclear, immune cells that arise from the myeloid progenitors of the hematopoietic system. They are involved in the detection, phagocytosis, and destruction of pathogens. Macrophages in different tissues have given special names, for example, microglial cells, kupffer cells, alveolar macrophages, and osteoclasts. Dendritic cells Dendritic cells are the most important antigen-presenting cells (APCs) for activating naïve T cells. They have long membranous projections and phagocytic capabilities. They display microbial antigens to T lymphocytes. Dendritic cells play major roles in innate responses to infections and in linking innate and adaptive immune responses. Basophils Basophils are blood granulocytes (these granules bind with basic dyes) with many structural and functional similarities to mast cells. They are derived from bone marrow progenitors and constitute less than 1% of blood leukocytes. Basophils are not present in tissues (normally) but may be recruited in some inflammatory reactions. Basophils express IgG and IgE receptors, bind IgE, and can be triggered by antigen binding to the IgE. Eosinophils Eosinophils are blood granulocytes that express cytoplasmic granules containing enzymes that are harmful to the cell walls of parasites. Eosinophils are responsible for participating in immediate allergic reactions, modulating inflammatory responses. The granules of Eosinophils contain basic proteins that bind acidic dyes such as eosin. Eosinophils are normally present in peripheral tissues, especially in mucosal linings of the respiratory, gastrointestinal, and genitourinary tracts. Lymphoid Progenitor Cell Common lymphoid progenitor cells give rise to B, T, and NK (natural killer) cells and some dendritic cells. Lymphocytes are the central cells of the immune system, responsible for adaptive immunity and immunologic memory. Other important attributes of lymphocytes are diversity, self/non-self recognition, and specificity. Lymphocytes constitute 20-40% of the body's white blood cells and 99% of the cells in the lymph. There are approximately 10^11 lymphocytes in our body. These lymphocytes continually circulate in our blood and lymph and migrate to infection sites whenever they get signals. B-Cells B-cells, also known as B-lymphocytes, are specialized cells of the immune system whose major function is to produce antibodies (also called immunoglobulins). B lymphocyte-derived its letter designation from its site of maturation, in the bursa of Fabricius in birds. B-cells develop from hematopoietic stem cells in the bone marrow where they also get immunological training and maturation. When B-cells encounter foreign antigens, they respond by transforming into antibodies secreting cells, called plasma cells. B-cells can also mature into memory cells, which are responsible for rapid and heightened secondary immune response. T-Cells T-cells, also known as T-lymphocytes, develop from hematopoietic stem cells in the bone marrow but complete their development in the thymus (the “T” stands for the thymus). Like B lymphocytes, these cells have membrane receptors for antigens called T-cell receptors (TCR). T-cells attack cells infected with viruses, and they also act as regulators of the immune system. T cells can be broadly categorized into three sub-types based on their functions. Cytotoxic or “killer” T-cells (CD8 T-cells): Kills virally infected cells or altered self cells. Helper T-cells (CD4 T-cells): activate B cells.Regulatory T-cells: helps to dampen the immune response. Natural Killer (NK) Cells Natural killer (NK) cells are so named because they easily kill cells infected with viruses without the requirement of thymic education (that T-cells require). NK cells kill virally infected cells and altered self cells (cancer cells). NK cells are present in relatively low numbers in the bloodstream and in tissues. They are large, granular lymphocytes that do not express the set of surface markers typical of B or T cells. References and further readings Hematopoietic Stem Cells, National Institute of Health. US Department of Health & Immune Services Kuby Immunology, 8th EditionCellular and Molecular Immunology, 9th EditionRoitt’s Essential Immunology, 13th Edition