Adaptive immune defenses: Antibodies

With the looming prospect of mass immunization against influenza, it’s important to understand how vaccines work. To do this we must have a good understanding of adaptive immune defenses. Today we’ll begin a discussion of the humoral arm of the adaptive immune response – antibodies.

Antibodies are large proteins produced by vertebrates that play important roles in identifying and eliminating foreign objects. The basic structural unit is composed of two heavy chains and two light chains, as shown in this diagram.


Antibodies bind other molecules known as antigens. Binding occurs in a small region near the ends of the heavy and light chain called the hypervariable region (labeled only on one arm in the figure). As the name implies, this region is extremely variable, which is why vertebrates can produce millions of antibodies that can bind many different antigens. The part of the antigen that is recognized by the antibody is known as an epitope.

There are five classes of immunoglobulin—IgA, IgD, IgE, IgG, and IgM—defined by the amino acid sequence of the heavy chain. They have different roles in immune responses; IgG, IgA, and IgM are commonly produced after viral infection.

During the first encounter with a virus, a primary antibody response occurs. IgM antibody appears first, followed by IgA on mucosal surfaces or IgG in the serum. The IgG antibody is the major antibody of the response and is very stable, with a half-life of 7 to 21 days. When an infection occurs with the same or a similar virus, a rapid antibody response occurs that is called the secondary antibody response. The specificity and memory of the antibody response are illustrated in the following graph.


A typical adaptive antibody response is shown as the relative concentration of serum antibodies weeks after injection of an animal with antigen A or a mixture of antigens A and B. Maximal primary response to antigen A occurs in 3 to 4 weeks. When the animal is injected with a mixture of both antigens A and B at 7 weeks, the secondary response to antigen A is more rapid and stronger than the primary response, demonstrating immunological memory. As expected, the primary response to antigen B requires 3 – 4 weeks. Antibody levels (also called antibody titers) decline with time after each immunization, a property known as self-limitation or resolution.

Antibodies are critical for preventing many viral infections, and may also contribute to the resolution of infection. We’ll next explore how antibodies accomplish these diverse activities.

Adaptive immune defenses

adaptive-immune-systemThe immune response to viral infection comprises innate and adaptive defenses. The innate response, which we have discussed previously, functions continuously in a normal host without exposure to any virus. Most viral infections are controlled by the innate immune system. However, if viral replication outpaces innate defenses, the adaptive response must be mobilized.

The adaptive defense consists of antibodies and lymphocytes, often called the humoral response and the cell mediated response. The term ‘adaptive’ refers to the differentiation of self from non-self, and the tailoring of the response to the particular foreign invader. The ability to shape the response in a virus-specific manner depends upon communication between the innate and adaptive systems. This communication is carried out by cytokines that bind to cells, and by cell-cell interactions between dendritic cells and lymphocytes in lymph nodes. This interaction is so crucial that the adaptive response cannot occur without an innate immune system.

The cells of the adaptive immune system are lymphocytes – B cells and T cells. B cells, which are derived from the bone marrow, become the cells that produce antibodies. T cells, which mature in the thymus, differentiate into cells that either participate in lymphocyte maturation, or kill virus-infected cells.

Both humoral and cell mediated responses are essential for antiviral defense. The contribution of each varies, depending on the virus and the host. Antibodies generally bind to virus particles in the blood and at mucosal surfaces, thereby blocking the spread of infection. In contrast, T cells recognize and kill infected cells.

A key feature of the adaptive immune system is memory. Repeat infections by the same virus are met immediately with a strong and specific response that usually effectively stops the infection with less reliance on the innate system. When we say we are immune to infection with a virus, we are talking about immune memory. Vaccines protect us against infection because of immune memory. The first adaptive response against a virus – called the primary response – often takes days to mature. In contrast, a memory response develops within hours of infection. Memory is maintained by a subset of B and T lymphocytes called memory cells which survive for years in the body. Memory cells remain ready to respond rapidly and efficiently to a subsequent encounter with a pathogen. This so-called secondary response is often stronger than the primary response to infection. Consequently, childhood infections protect adults, and immunity conferred by vaccination can last for years.

The nature of the adaptive immune response can clearly determine whether a virus infection is cleared or causes damage to the host. However, an uncontrolled or inappropriate adaptive response can also be damaging. A complete understanding of how viruses cause cause disease requires an appreciation of the adaptive immune response, a subject we’ll take on over the coming weeks.