Antigen-presenting cells

BACKGROUND

Antigen-presenting cells (APC) are specialized white blood cells that help fight off foreign substances that enter the body. These cells send out signals to T-cells (other immune system cells) when an antigen enters the body. Each type of T-cell is specially equipped to deal with different pathogens, which may be a bacteria, virus or toxin.

First, the APC engulfs the antigen. Enzymes inside the APC break down the antigen into smaller particles. The processed antigens are transported to the surface of the APC, bound with either an MHC (major histocompatibility complex) class I or class II molecule. This complex forms epitopes (part of a foreign substance that can be recognized by the immune system), which the T-cell receptor (TCR) recognizes and binds to.

The APCs are divided into two categories - professional and non-professional APCs. Professional APCs express MHC class II while non-professional APCs express MHC class I. Only professional APCs are able to activate a helper T-cell that has never encountered its antigen before. There are three main types of professional antigen-presenting cells - macrophages, dendritic cells and B-cells. These cells are able to engulf the antigen quickly during a process called phagocytosis. Once the T-cell recognizes and binds to the MHC molecule complex, the APC sends out an additional co-stimulatory signal to activate the T-cell.

Non-professional APCs include fibroblasts (skin cells), thymic epithelial cells, thyroid epithelial cells, glial cells (brain cells), pancreatic beta cells and vascular endothelial cells.

While almost every cell in the body is technically an APC because they can present antigens to T-cells, the term is usually used to describe professional APCs.

MACROPHAGES

Macrophages are white blood cells that are found inside the tissues of all vertebrates. These cells originate from monocytes in the bone marrow. Macrophages are phagocytes, which means they are able to engulf antigens that enter the body. The lifespan of macrophages ranges from months to years, and they can digest more than 100 bacteria before they die.

Macrophages are in a resting state until they are activated by an immune response. Upon activation, these cells travel toward the site of injury, and they engulf pathogens. Once a macrophage ingests a pathogen, the pathogen is trapped inside the cell's food vacuole, which then fuses with a lysosome. Enzymes and toxic peroxides inside the cell start to ingest the foreign substance. The cells then secrete interferons, lysozyme and other factors that stimulate lymphocytes and other immune cells to respond to the antigens.

During chronic inflammation, macrophages can form granulomas (inflammatory lesions). They are also the predominant cells that form the progressive plaque lesions associated with atherosclerosis (hardening of the arteries).

DENDRITIC CELLS

Dendritic cells are present in small amounts in the body tissues that frequently come into contact with the external environment. They are present in the skin (where they are often called langerhans cells) and the inner lining of the nose, stomach, lungs and intestines. These cells have branched projections, called dendrites.

Immature dendritic cells (also called veiled cells) are found in the bloodstream. Immature dendritic cells are characterized by high endocytic activity and low T-cell activation potential. Their pattern recognition receptors (PRRs) are constantly sampling their surroundings for pathogens, such as bacteria and viruses. Once the dendritic cell comes into contact with a pathogen, they are activated to engulf the invading substance. Once the antigen is engulfed, the dendritic cell matures and combines the broken down antigen with MHC. This complex is then presented to T-cells on its cell surface.

B-CELLS

Unlike the other two APCs, they produce antibodies (immunoglobulin) that are specific to certain antigens. B-cells are able to efficiently present the antigen to which their antibody is directed, but they are considered inefficient APCs for most other antigens.

B-cells are continually produced in the bone marrow. Immature B-cells only express IgM on their cell membrane. The immunoglobulin is on the cell surface. It is not secreted.

Once the B-cell reaches maturity, it can express both IgM and IgD on the cell surface. This mature cell is now able to respond to antigens. If the B-cell starts to mature abnormally, it will die in a process called apoptosis (programmed cell death).

Once the immunoglobulin molecule interacts with an antigen, the B-cell becomes activated and begins to divide and differentiate into many antibody-producing cells (plasma cells). Each plasma cell secretes millions of identical antibody molecules, which are released into the bloodstream.

Some of the plasma cells undergo isotype switching. During this process, the cell starts to express other isotypes of immunoglobulin, including IgA, IgE and IgG.

INTERACTION WITH T-CELLS

Once APCs engulf pathogens, they usually migrate toward the lymph nodes, where most T-cells are located. They migrate chemotactically, which means that chemokines (chemical mediators in the blood that are produced by cytokines) attract the APCs to move toward the lymph nodes.

During the migration, the APC cells mature. They lose most of their ability to engulf pathogens, and they develop an increased ability to communicate with T-cells.

Enzymes inside the APC cell digest the engulfed pathogen into smaller pieces, which contain epitopes (part of a foreign substance that can be recognized by the immune system). These epitopes are combined with MHC and presented to the T-cells on their cell surface.

The helper T-cell then activates the APC to produce more antibodies against the pathogen.

Recent research suggests that only certain epitopes of an antigen are presented by they APC because they are immunodominant. This may be the result of their binding affinity to the MHC molecule. The stronger binding affinity allows the complex to remain kinetically stable long enough for the T-cells to recognize it.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• Li J, Barreda DR, Zhang YA, et al. B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities. Nat Immunol. 2006 Oct;7(10):1116-24. View abstract
• Ludwig Institute for Cancer Research. Antigen Presenting Cell. www.ludwig.edu.au.
• McKenna, K, Beignon AS, Bhardwaj N. Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity. J Virol. 2005 Jan;79(1):17-27. View abstract
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2008.