The cells that serve specialized roles in innate and adaptive immune responses are phagocytes, dendritic cells, antigen-specific lymphocytes, and various other leukocytes that function to eliminate antigens. Although most of these cells are found in the blood, their responses to microbes usually occur in lymphoid and other tissues.
Phagocytes, including neutrophils and macrophages, are cells whose primary function is to ingest and destroy microbes and get rid of damaged tissues. The functional responses of phagocytes in host defense consist of sequential steps: recruitment of the cells to the sites of infection, recognition of and activation by microbes, ingestion of the microbes by the process of phagocytosis, and destruction of ingested microbes.
Neutrophils, also called polymorphonuclear leukocytes, are the most abundant population of circulating white blood cells and mediate the earliest phases of inflammatory reactions. Neutrophils circulate as spherical cells about 12 to 15 μm in diameter with numerous membranous projections. The cytoplasm contains granules of two types. Specific granules filled with enzymes such as lysozyme, collagenase, and elastase. These granules do not stain strongly with either basic or acidic dyes (hematoxylin and eosin, respectively), which distinguishes neutrophil granules from those of two other types of circulating granulocytes, called basophils and eosinophils. The remainder of the granules of neutrophils, called azurophilic granules, are lysosomes that contain enzymes and other microbicidal substances, including defensins and cathelicidins.
The mononuclear phagocyte system includes circulating cells called monocytes and tissue resident cells called macrophages. Monocytes are 10 to 15 μm in diameter, and they have bean-shaped nuclei and finely granular cytoplasm containing lysosomes, phagocytic vacuoles, and cytoskeletal filaments. Monocytes that migrate into tissues in response to infection can differentiate into specific tissue macrophages. Some macrophages are long-term residents in tissues and play an important role in regulating their repair and regeneration.
Other macrophages participate in the innate immune response and undergo a number of key changes when they are stimulated by encounters with pathogens or tissue damage. These are referred to as inflammatory macrophages and play a dual role in the immune system as effective phagocytes that can contribute to the clearance of pathogens from a tissue, as well as antigen-presenting cells that can activate T lymphocytes. Osteoclasts in the bone, microglial cells in the central nervous system, and alveolar macrophages in the lung are tissue-specific examples of macrophages with these properties.
Mast cells are bone marrow–derived cells present in the skin and mucosal epithelia, which contain abundant cytoplasmic granules filled with histamine and other mediators. Mast cells express high affinity plasma membrane receptors for a type of antibody called IgE and are usually coated with these antibodies. When the antibodies on the mast cell surface bind antigen, signaling events are induced that lead to release of the cytoplasmic granule contents into the extracellular space. The released granule contents, including histamine, promote changes in the blood vessels that cause inflammation. Mast cells function as sentinels in tissues, where they recognize microbial products and respond by producing cytokines and other mediators that induce inflammation.
Basophils are blood granulocytes with many structural and functional similarities to mast cells. Although they are normally not present in tissues, basophils may be recruited to some inflammatory sites. Like mast cells, basophils express IgE receptors, bind IgE, and can be triggered by antigen binding to the IgE. Because basophil numbers are low in tissues, their importance in host defense and allergic reactions is uncertain.
Eosinophils are blood granulocytes that express cytoplasmic granules containing enzymes that are harmful to the cell walls of parasites but can also damage host tissues. Some eosinophils are normally present in peripheral tissues, especially in mucosal linings of the respiratory, gastrointestinal, and genitourinary tracts, and their numbers can increase by recruitment from the blood in the setting of inflammation.
Antigen-presenting cells (APCs) are cells that capture microbial and other antigens, display them to lymphocytes, and provide signals that stimulate the proliferation and differentiation of the lymphocytes. The major type of APC that is involved in initiating T cell responses is the dendritic cell. Macrophages and B cells present antigens to T lymphocytes in cell mediated and humoral immune responses.
Dendritic cells are the most important APCs for activating naive T cells, and they play major roles in innate responses to infections and in linking innate and adaptive immune responses. They have long membranous projections and phagocytic capabilities and are widely distributed in lymphoid tissues, mucosal epithelium, and organ parenchyma. Most dendritic cells are part of the myeloid lineage of hematopoietic cells and arise from a precursor that can also differentiate into monocytes but not granulocytes.
Lymphocytes are the principal cell players in the adaptive immune response. They represent 20% to 40% of circulating white blood cells and 99% of cells in the lymph. Lymphocytes can be broadly subdivided into three major populations on the basis of functional and phenotypic differences:
- B lymphocytes (B cells)
- T lymphocytes (T cells)
- Natural killer (NK) cells.
Each B or T cell also expresses an antigen-specific receptor (the B cell receptor (BCR) or the T cell receptor (TCR), respectively) on its surface.
B lymphocyte (B cell) derived its letter designation from its site of maturation, in the bursa of Fabricius in birds; activated B cells differentiate into effector cells known as plasma cells. Plasma cells lose expression of surface immunoglobulin and become highly specialized for secretion of antibody.
T lymphocytes (T cells) derive their letter designation from their site of maturation in the thymus. T-cell receptors only recognize processed pieces of antigen (typically peptides) bound to cell membrane proteins called major histocompatibility complex (MHC) molecules. They become activated, proliferate, and differentiate into an effector cell called a cytotoxic T lymphocyte (CTL). The CTL has a vital function inmonitoring the cells of the body and eliminating any cells that display foreign antigen complexed with class I MHC,
Natural Killer Cells
Natural killer (NK) cells are lymphoid cells that are closely related to B and T cells. However, they do not express antigen specific receptors. NK cells constitute 5% to 10% of lymphocytes in human peripheral blood. They are efficient cell killers and attack a variety of abnormal cells, including some tumor cells and some cells infected with virus.