An antigen is a substance capable of triggering an immune response within the body. The term exogenous specifies that these substances originate from outside the body’s own cells. They gain entry through pathways like inhalation, ingestion, or breaks in the skin. Common examples include bacteria, free viruses, pollen, fungi, and various parasites.
These foreign materials circulate in body fluids, such as blood and lymph, but do not initially enter the cells themselves. Their presence in these extracellular spaces sets in motion a targeted immune defense. The immune system recognizes these invaders as “non-self” and initiates a process to neutralize them before they can cause harm or illness.
Antigen Presentation by Immune Cells
The first step in mounting a defense against external threats involves a specialized group of immune cells known as Antigen-Presenting Cells (APCs). The primary APCs are dendritic cells, macrophages, and B cells. Dendritic cells are found in tissues like the skin and the linings of the nose, lungs, and intestines, acting as sentinels at common entry points for pathogens.
When an APC encounters an exogenous antigen, it initiates a process called phagocytosis. The APC’s cell membrane extends and wraps around the antigen, enclosing it within an intracellular vesicle. This newly formed membrane-bound sac is called a phagosome.
This act of internalization serves to contain the microorganism or foreign substance. By sequestering the antigen inside the phagosome, the APC can safely transport and process it without the invader causing immediate harm to the cell itself.
The MHC Class II Pathway
Once the antigen is secured within the phagosome, the vesicle fuses with another called a lysosome, which contains digestive enzymes. The resulting hybrid vesicle, now known as a phagolysosome, becomes an environment where the captured antigen is broken down. Within this compartment, enzymes cleave the antigen’s proteins into smaller fragments called peptides.
While the antigen is being processed, the APC simultaneously synthesizes Major Histocompatibility Complex (MHC) Class II molecules in its endoplasmic reticulum. These MHC II molecules are designed to bind with foreign peptides. To prevent them from binding to the cell’s own proteins, their binding site is initially blocked by a placeholder protein called the invariant chain.
The MHC II molecules are transported from the endoplasmic reticulum and merge with the phagolysosome containing the peptide fragments. Inside this compartment, the invariant chain is degraded, leaving only a small fragment called CLIP blocking the binding groove. A molecule, HLA-DM, then removes CLIP, allowing one of the newly generated antigen peptides to lock into the MHC II molecule’s groove. This stable peptide-MHC II complex is then transported to the surface of the APC.
T-Helper Cell Activation and Immune Cascade
The presentation of the antigen-MHC II complex on the APC’s surface serves as a signal to a T-helper cell (also known as a CD4+ T cell). These T-helper cells cannot recognize free-floating antigens; they must be shown the antigen by an APC. Each T-helper cell has a unique T-cell receptor (TCR) on its surface, capable of recognizing a specific peptide-MHC II complex.
When a T-helper cell with a matching receptor encounters the APC displaying its specific antigen, it binds to the complex. This binding, along with a co-stimulatory signal provided by the APC, activates the T-helper cell. Activation triggers the T-helper cell to rapidly divide, creating a large clone of identical cells all programmed to recognize the same antigen.
Once activated, these T-helper cells release chemical signaling molecules called cytokines. Cytokines like interleukin-2 act as messengers, coordinating a broader immune attack. These signals stimulate other immune cells, most notably B cells, which are responsible for producing antibodies. The activated B cells then generate large quantities of antibodies specifically designed to find and neutralize the same exogenous antigen throughout the body.
Distinguishing from Endogenous Antigens
The process for handling exogenous antigens is distinct from the system used for threats that arise from within the body’s own cells, known as endogenous antigens. These antigens include proteins produced by viruses that have successfully infected a host cell or abnormal proteins made by cancerous cells.
Instead of the MHC Class II pathway, endogenous antigens are processed via the MHC Class I pathway. In this system, fragments of the internal foreign proteins are loaded onto MHC Class I molecules, which are present on the surface of nearly all nucleated cells in the body. This pathway’s purpose is to signal that the cell itself has been compromised.
The MHC Class I-antigen complex is presented not to T-helper cells, but to a different T cell type called Cytotoxic T-lymphocytes (CD8+ cells). When a cytotoxic T cell recognizes an MHC Class I complex displaying a foreign or abnormal peptide, its function is to kill the infected or cancerous host cell directly, thereby eliminating the source of the endogenous antigens.