10.2 Antigens, Antibodies and Adaptive Immunity

An antigen is a molecule or molecular region recognized by the adaptive immune system and capable of stimulating a response. Antigens often occur as proteins or glycoproteins on a pathogen surface, in a viral coat or within a toxin. One pathogen can carry many antigenic determinants, so several lymphocyte clones may respond. Antigen does not mean pathogen: an antigen is a molecular feature, while a pathogen is the infectious agent carrying or producing it.

Each naïve B lymphocyte carries membrane-bound receptors of one specificity. Before infection, only a small number of B cells happen to carry receptors complementary to any one unfamiliar antigen. Binding selects those cells from a much larger repertoire. Selection is followed by repeated mitosis, so specificity is converted into abundance. The antigen does not instruct a cell to invent a new receptor; it selects a pre-existing clone whose receptor already fits.

An antibody is a Y-shaped protein with two equivalent antigen-binding sites at the ends of its arms. The variable regions differ among antibody clones and form binding sites complementary in shape and chemical properties to an antigenic determinant. The constant region interacts with other immune components. Specificity depends on non-covalent interactions over a matching surface, not on the antibody destroying the antigen directly through its own digestive activity.

Antibody binding changes what happens to a target. It can neutralize a toxin or block a virus from attaching to a host receptor. Because one antibody can bind two targets and each target carries repeated antigens, antibodies can agglutinate cells or particles. Bound antibodies can mark targets for phagocytosis, and some antibody–antigen complexes activate proteins that damage membranes. Antibodies therefore combine molecular recognition with several routes to clearance.

Plasma cells are differentiated B cells specialized for intense antibody secretion. Their abundant rough endoplasmic reticulum and Golgi apparatus match this function because antibodies are exported proteins. A plasma cell releases antibody matching the receptor specificity of the selected parent B cell. Some daughter cells instead become long-lived memory B cells, retaining specificity without continuously secreting the same high antibody concentration.

Adaptive defence includes humoral and cell-mediated responses. Humoral immunity acts through antibodies in blood, lymph and tissue fluid and is especially important against extracellular pathogens and toxins. Cell-mediated immunity depends on T lymphocytes recognizing antigen presented on cell surfaces. The two branches cooperate: helper T cells activate other lymphocytes, while antibody-coated targets are more readily removed by innate phagocytes.

A macrophage digests a pathogen and presents a peptide fragment at its surface. A helper T cell with a complementary receptor binds the antigen-presenting complex and receives activating signals. That selected helper T cell proliferates. Effector helper T cells release signalling molecules that promote activation of a B cell which has bound and presented the same antigen. This double recognition reduces the chance of launching a powerful antibody response from one accidental interaction.

The activated B cell divides into plasma cells and memory B cells. Plasma cells secrete large quantities of antibody; memory cells persist. Helper T clones likewise include effector and memory cells. Cytotoxic T lymphocytes follow a different route: they recognize antigen presented by infected or mutated body cells and induce those cells to die, limiting viral replication or removal of some cancer cells. Cytotoxic T cells do not secrete antibodies, and antibodies cannot remove a virus genome already hidden inside every infected cell.

Because a pathogen usually displays several antigens, more than one compatible B-cell clone can be selected. This polyclonal response produces a mixture of antibodies binding different determinants, making it harder for one molecular change to eliminate all recognition and providing several ways to neutralize or mark the target. Clonal selection describes what happens to each matching lineage; polyclonal describes the combined response of multiple selected lineages.

During a first exposure, rare matching lymphocytes must be activated and expanded before antibody concentration becomes high. Symptoms can develop during this delay. After the pathogen is controlled, most effector cells die, but memory cells remain. On a second exposure to the same antigen, a larger starting population of responsive cells proliferates quickly, producing a faster and usually greater response. Immunity means resistance to disease, not an impenetrable barrier preventing every pathogen particle from entering.

Memory is specific. A memory population generated against one antigen may not recognize a pathogen whose relevant antigen has changed substantially. This explains why antigenic variation can permit reinfection and why some vaccines need updating. Cross-reactivity can occur when antigens share molecular features, but it cannot be assumed merely because two pathogens cause similar symptoms.

ABO blood groups are defined by antigens on erythrocytes and antibodies in plasma. Group A cells carry A antigen and group A plasma contains anti-B antibody. Group B reverses that pattern. Group AB cells carry both antigens and the plasma normally contains neither antibody; group O cells carry neither A nor B antigen and the plasma contains both antibodies. A recipient must not receive red cells carrying an antigen targeted by the recipient's plasma antibodies.

If incompatible red cells are transfused, antibodies cross-link them, causing agglutination and potentially haemolysis. Packed group O red cells lack A and B antigens and are often described as universal donor cells for the ABO system, but real transfusion practice also considers the Rhesus system, other antigens and whether plasma or whole blood is being transferred. The simplified rule is valid only when its assumptions are stated.

The same recognition principle explains why transplanted tissue can be rejected. Donor cells carry surface antigens that differ from those of the recipient, so cell-mediated and humoral responses may damage the graft. Matching donors and recipients reduces antigen differences, while immunosuppressive treatment reduces rejection at the cost of weaker defence against infection. Self recognition is therefore clinically important far beyond ABO transfusion.