What is humoral immunity?

Humoral immunity is a specific response of the immune system involving the recognition of antigens and the production of antibodies. Unlike cellular immunity, in which microorganisms and their toxins are attacked directly by cells, humoral immunity is attacked by antibodies that inactivate and/or mark potentially dangerous agents for destruction.

Humoral immunity is part of acquired immunity, also called adaptive, and is activated in response to a specific attack. Unlike innate immunity, which is non-specific and, although continuously active, is less effective. The other part of acquired immunity is cellular, or cell-mediated, immunity, in which certain cells of the immune system release toxins to kill invaders without the intervention of antibodies.

The term “humoral” is due to the fact that this type of immunity involves cells found in the blood and lymph, two of the four humors of the humoral theory adopted by philosophers and physicians of ancient Greek and Roman civilizations. When research on immune responses began in the 19th century, there was still some influence from these ancient theories on the conception of disease and health.

How it works?

Humoral immunity begins with the recognition of foreign antigens by B lymphocytes (cells that are part of white blood cells and are produced in the bone marrow). Antigens are molecules, mainly of a protein nature, that are usually located on the surface of microorganisms, such as viruses and bacteria. There are different strains of B lymphocytes, each designed to recognize specific antigens.

When the presence of a foreign antigen, which does not belong to the organism itself, is recognized, B cells specific to that antigen are activated and multiply (clonal expansion), generating a multitude of B cells that secrete antibodies specifically designed to react with the detected antigen. It can be said that B lymphocytes become antibody factories in the blood. These antibodies bind to the antigens for which they were designed and in this way the invading organism is tagged and can be identified to be destroyed by phagocytes (macrophages, neutrophils, monocytes, etc.).

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When the invader is eliminated, many of the B lymphocytes produced in response to the attack will simply die, but others will remain in the body stored in the bone marrow, called lymphocytes or memory B cells. Memory lymphocytes enable faster action in future attacks by the same invading agent. At birth there is a set of B cells capable of recognizing large groups of antigens common in certain organisms that can be a threat. But humoral immunity is acquired as the immune system is exposed to viruses, bacteria, and other harmful substances. Through these contacts with infectious agents, the body creates an arsenal of memory B cells and specific immunity is thus acquired against the diseases they cause.

Primary and secondary humoral response

The first exposure of B cells to a particular antigen is called the primary humoral response. In antigens of a protein nature (the majority), the collaboration of B cells with T helper lymphocytes (T-helpers), especially those CD4 T Lymphocytes. In non-protein antigens (lipids, polysaccharides) the humoral response does not require the participation of T lymphocytes, which is why we speak of T-dependent and T-independent antigens.

The primary humoral response is the one that occurs the first time a B lymphocyte encounters a particular antigen and recognizes it as potentially dangerous. B lymphocytes then initiate clonal expansion and differentiation into a cell lineage that:

They first secrete IgM (immunoglobulin M)-type antibodies. Depending on the stimuli present, they switch to another immunoglobulin isotype, such as IgG, IgA, or IgE. Maturation towards more specific antibodies with high affinity against the antigen Finally, there is a remnant of the B cell lineage produced that will act as memory lymphocytes.

In this primary humoral response, the maximum antibody peak is usually reached between 5 and 10 days after contact with the foreign agent, there is usually a greater production of IgM relative to other antibody isotypes, and high doses of infection are usually required to trigger the answer.

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The second and subsequent times the organism faces the same offending agent, it will be recognized and an attack will occur. secondary humoral response characterized by activation of memory B lymphocytes. This response is faster and the maximum concentration of antibodies is reached in approximately 3 days with higher production of IgG (in some cases IgA or IgE) and lower production of IgM, that is, antibodies have greater affinity for the antigen. The dose of the infectious agent needed to trigger the secondary humoral response is usually lower and, in addition, lasts longer, as the fall of antibodies in the blood is slower.


Memory B cells are the foundation of how vaccines work. With vaccination, disease-causing viruses and bacteria are inoculated but are inoculated dead or in inactivated forms that do not represent an actual attack but still have the ability to stimulate the humoral response. In this way, if in the future the vaccinated person is exposed to the actual virulent agent, there will be a quick and effective secondary humoral response that will eliminate the pathogen before it can cause any serious harm.

However, vaccination is not equally effective for all types of infections, either because the vaccine was not optimally manufactured or due to the very nature of the pathogen and the immune response it triggers. For example, smallpox vaccination around the world has managed to eliminate this disease and it is currently considered an eradicated disease. For some viruses and bacteria that mutate frequently, on the other hand, it is very difficult to find a really effective vaccine. People vaccinated against these viruses may not be immunized against new strains that mutate to have different antigens that are no longer recognized by memory B cells; this is what happens, for example, with flu vaccines.

Immune system related problems and illnesses

When there are humoral immunity problems, the person is more susceptible to contracting and developing certain diseases, such as infections, allergies or autoimmune diseases. For example, the HIV virus (Human Immunodeficiency Virus, AIDS virus) directly attacks immune system cells (CD4 T lymphocytes), making the humoral response less functional. Humoral immunity can also be compromised by the use of some drugs, such as chemotherapy for cancer treatment or immunosuppressive drugs used in organ transplants to decrease the chances of rejection. In patients with a depressed immune system, any type of infection must be treated as soon as possible because the body cannot fight the infection on its own.

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Autoimmune diseases are those in which the immune system recognizes certain self cells as foreign bodies. For example, 90% of cases of pernicious anemia are due to an autoimmune reaction against intrinsic factor or against the parietal cells of the gastric mucosa that produce it; intrinsic factor is essential for the absorption of vitamin B12, a vitamin whose deficiency produces anemia (see Pernicious Anemia on MedLine).

Allergies are also a form of alteration of the immune system, as they result from a reaction against substances that do not represent a real threat and against which most people, under normal conditions, do not develop any type of immune response.

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