The humoral immune response
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
INTRODUCTION AND DEFINITIONS
The term "humoral" refers to the liquid, noncellular components of the blood and other tissues, such as plasma and lymphatic fluid. The humoral immune response denotes immunologic responses that are mediated by antibodies. However, both B and T lymphocytes as well as dendritic cells and other antigen-presenting cells are necessary for the formation of antigen-specific antibody.
Natural antibodies — "Natural antibodies" are so-called because they are produced naturally, without any antigen exposure. Vertebrate animals, even in germ-free environments, produce natural antibodies. For human infants, these antibodies, along with maternal immunoglobulin G (IgG) that is transported across the placenta into the fetus in the third trimester of gestation, are important for protection of the newborn. Immediately after birth, neonates leave a sterile environment and are bombarded by microbes and other antigens. Therefore, antigen-stimulated antibody production is rapidly superimposed on natural antibodies. However, that process takes time (months) and in the interim, natural antibody and maternal antibody are important.
Natural antibodies are often polyspecific, meaning that they react with multiple endogenous and/or exogenous antigens bearing no readily identifiable structural similarity (eg, histones, polynucleotides, other immunoglobulins). Some recognize "oxidation-specific" epitopes, which are epitopes generated during the oxidative processes involved in metabolism, aging, and inflammation. These epitopes are ubiquitous on both microbes and aging and apoptotic host cells and represent a class of pathogen- or damage-associated molecular pattern (PAMP or DAMP) recognized by receptors of the innate immune system. Thus, natural antibodies appear to function as a type of pattern recognition receptor (PRR) for these molecular structures. Natural antibodies are primarily of the immunoglobulin M (IgM) isotype. They are produced by a distinct subset of B cells known as B-1 cells, which produce antibody without any requirement of prior antigenic stimulation .
Natural antibodies appear to have at least two important functions. The first is to provide early protection against infections with a rapid immune response against pathogens, before more specific antibodies can be produced. The second role is assisting in homeostasis by binding to aging and apoptotic cells and cellular debris, which if not cleared, could create a proinflammatory and immunogenic environment. Natural antibodies are discussed further elsewhere. (See "Function and clinical applications of immunoglobulins", section on 'Natural antibodies'.)
Humoral immunity includes the primary and secondary immune responses to antigen. During the primary immune response, an antigen is encountered by the host for the first time. Virgin B cells need to be activated and proliferate before an effective antibody response can be generated. This primary antibody response may be too slow to protect against many pathogens, therefore polyspecific natural antibodies with low affinity and the innate immune system may be utilized to limit microbial replication at the onset of infection. By comparison, the secondary antibody response, which results from the activation of a memory B cell, is faster and more effective in halting the progress of infection due to increased antibody-binding affinities.
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- INTRODUCTION AND DEFINITIONS
- Natural antibodies
- PASSIVE AND ACTIVE HUMORAL IMMUNITY
- Antibody levels in infancy and childhood
- ANTIGEN-DEPENDENT B CELL DEVELOPMENT
- ACTIVATION SIGNALS
- Cross-linking of immunoglobulin receptor
- TYPES OF ANTIGENS
- Type 1 antigens
- Type 2 antigens
- - TACI, BAFF, and APRIL
- Additional activating signals
- Thymus-dependent antigens
- - Cognate T cell help
- - CD40 and CD40 ligand
- Immune complexes and Fc regions
- CELLULAR EVENTS IN B CELL ACTIVATION
- Activating events
- Intracellular signaling
- GERMINAL CENTERS
- IMMUNOLOGIC MEMORY
- Primary immune response
- - Affinity maturation
- Secondary immune response