2. Defense Cells in the Tissue: Dendritic Cells, Macrophages, and Mast Cells
a. Dendritic Cells (def)
Most dendritic cells are derived from monocytes and are referred to as myeloid dendritic cells. They are located throughout the epithelium of the skin, the respiratory tract, and the gastrointestinal tract, as well as lymphoid tissues and organ parenchyma (def). In these locations, in their immature form, they are attached by long cytoplasmic processes. Upon capturing antigens through pinocytosis and phagocytosis and becoming activated by inflammatory cytokines, the dendritic cells detach from their initial site, enter lymph vessels, and are carried to regional lymph nodes. By the time they enter the lymph nodes, they have matured and are now able to present antigen to the ever changing populations of naive T-lymphocytes (def) located in the cortex of the lymph nodes.
The primary function of dendritic cells is to capture and present protein antigens to naive T-lymphocytes . (Naive lymphocytes are those that have not yet encountered an antigen.) Dendritic cells engulf microorganisms and other materials and degrade them with their lysosomes. Peptides from microbial proteins are then bound to a groove of unique molecules called MHC-II molecules (def) produced by macrophages, dendritic cells, and B-lymphocytes. The peptide epitopes bound to the MHC-II molecules are then put on the surface of the dendritic cell (see Fig. 1) where they can be recognized by complementary shaped T-cell receptors (TCR) and CD4 molecules (def) on naive T4-lymphocyte (def) (see Fig. 2).
by Gary E. Kaiser, Ph.D.
Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work atBased on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.Last updated: August, 2019
Please send comments and inquiries to Dr. Gary Kaiser
In addition, dendritic cells can bind peptide epitopes to MHC-I molecules (def) and present them to naiveT8-lymphocytes. The MHC-I molecules with bound peptide on the dendritic cell are recognized by complementary shaped T-cell receptors (TCR) and CD8 molecules on naive T8-lymphocyte (def) (see Fig. 3).
by Gary E. Kaiser, Ph.D.
Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work atBased on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.Last updated: August, 2019
Please send comments and inquiries to Dr. Gary KaiserThese interactions enable the T4-lymphocytes or T8-lymphocytes to become activated, proliferate, and differentiate into effector cells (def). This will be discussed in detail in Unit 6.
Myeloid dendritic cells also use pattern-recognition receptors called toll-like receptors (TLRs) to recognize pathogen-associated molecular patterns or PAMPs (see Fig. 4). The interaction of the PAMP with its TLR stimulates the production of co-stimulatory molecules that are also required for T-lymphocyte activation. Dendritic cells produce many of the same inflammatory cytokines as macrophages, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8). They also can produce interleukin-12 (IL-12), a cytokine that can activate natural killer T-lymphocytes (NKT cells).
Another type of dendritic cell, the plasmacytoid dendritic cell, uses its TLRs to recognize viral PAMPs. This interaction results in the production and secretion of type I interferons (def).
Antigen-presenting cells (def) or APCs will be discussed in greater detail in Unit 6.
b. Macrophages (def)
When monocytes (def) leave the blood and enter the tissue, they become activated and differentiate into macrophages. Those that have recently left the blood during inflammation and move to the site of infection through positive chemotaxis (def) are sometimes referred to as wandering macrophages.
In addition, the body has macrophages already stationed throughout all tissues and organs of the body. These are sometimes referred to as fixed macrophages..
Many fixed macrophages are part of the mononuclear phagocytic (reticuloendothelial) system. They, along with B-lymphocytes (def) and T-lymphocytes (def), are found supported by reticular fibers in lymph nodules, lymph nodes (see Fig. 5), and the spleen where they filter out and phagocytose foreign matter such as microbes. Similar cells are also found in the liver (Kupffer cells), the kidneys (mesangial cells), the brain (microglia), the bones (osteoclasts), the lungs (alveolar macrophages), and the gastrointestinal tract (peritoneal macrophages).
Macrophages actually have a number of very important functions in body defense including:
1. Killing of microbes, infected cells, and tumor cells by phagocytosis.
Macrophages that have engulfed microorganisms become activated by a subset of T-helper lymphocytes called Th1 cells (see Fig. 6). Activated macrophages develop a ruffled cytoplasmic membrane and produce increased numbers of lysosomes.
by Gary E. Kaiser, Ph.D.
Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work atBased on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.Last updated: August, 2019
Please send comments and inquiries to Dr. Gary Kaiser2. Processing antigens so they can be recognized by effector T-lymphocytes (def) during the adaptive immune responses (def).
Macrophages, as well as the dendritic cells mentioned below, process antigens through phagocytosis and present them to T-lymphocytes. Because of this function, they are often referred to as antigen-presenting cells or APCs (def) .
Macrophages primarily capture and present protein antigens to effector T-lymphocytes. (Effector lymphocytes are lymphocytes that have encountered an antigen, proliferated, and matured into a form capable of actively carrying out immune defenses.) Macrophages engulf the microorganism and degrade it with their lysosomes. Peptides from microbial proteins are then bound to a groove of unique molecules called MHC-II molecules (def) produced by macrophages, dendritic cells (def), and B-lymphocytes (def). The peptide epitopes bound to the MHC-II molecules are then put on the surface of the macrophage (see Fig. 1) where they can be recognized by complementary shaped T-cell receptors (TCR) and CD4 molecules on an effector T4-lymphocyte (def) (see Fig. 2). This interaction leads to the activation of that macrophage. This will be discussed in detail in Unit 6.
Like dendritic cells discussed above, macrophages are also capable of capturing and presenting protein antigens to naive T-lymphocytes although they are not as important in this function.
- Scanning electron micrographs of a macrophage with pseudopods and a macrophage phagocytozing E. coli on a blood vessel; courtesy of Dennis Kunkel's Microscopy.
- To view a scanning electron micrograph of a macrophage presenting antigen to a T-lymphocyte, see the Cells Alive Web Page.
3. Secreting lipid mediators of inflammation such as leukotrienes, prostaglandins, and platelet-activating factor (PAF).
4. Secreting proteins called cytokines (def) that play a variety of roles in non-specific body defense.
Macrophage-produced cytokines promote inflammation and induce fever, increase phagocytosis and energy output, promote sleep, activate resting T-lymphocytes (def), attract and activate neutrophils (def), and stimulate the replication of endothelial cells (def) to form capillaries and fibroblasts (def) to form connective scar tissue. Four important cytokines that macrophages produce (as mentioned in Unit 1 under endotoxin) are tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8). Cytokines will be discussed in more detail in Unit 5 and Unit 6.
There is growing evidence that monocytes and macrophages can be “trained” by an earlier infection to do better in future infections, that is, develop memory. It is thought that microbial pathogen-associated molecular patterns (PAMPs) binding to pattern-recognition (PRRs) on monocytes and macrophages triggers the cell’s epigenome (def) to reprogram or train that cell to react better against new infections.
Macrophages show great functional diversity. In addition to the populations of macrophages involved in body defense and immunity, there are populations of macrophages that play important roles in:
1. The development of a variety of tissues and organs within the body, including the brain, blood cells, mammary gland, pancreas, and kidneys.
2. Modulating normal physiology and maintaining homeostasis in the body, including insulin resistance and sensitivity, long term nutrient storage, thermogenesis, and liver and pancreas function in response to caloric intake.
3. Tissue repair, including the formation of scar tissue and the growth of new capillaries into injured tissues.
c. Mast Cells (def)
Mast cells are typically the immunological first responders to infection and carry out many of the same inflammatory-mediating functions as basophils. There are two types of mast cells in the body: mast cells found in the connective tissue (def) and mast cells found throughout the mucous membranes.
The granules of mast cells contain such mediators as histamine (def), eosinophil chemotactic factor, neutrophil chemotactic factor, platelet activating factor (def), and cytokines (def) such as IL-3, IL-4, IL-5, IL-6, and TNF-alpha. They also possess pathways for synthesizing leukotrienes (def) and prostaglandins (def), chemicals that promote inflammation (def) by causing vasodilation (def), increasing capillary permeability, and increasing mucous production.
Mast cells have pattern-recognition receptors or PRRs (def) on their surface that interact with pathogen-associated molecular patterns or PAMPs (def) of microbes. After the PAMPs bind to their respective PRRs, they release the contents of their granules. These chemical mediators promote inflammation and attract neutrophils to the infected site.
- A photomicrograph of a mast cell can be found at Wikipedia .