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Humoral vs Cell-Mediated Immunity

A B cell, antibodies and a T cell, with CD8 and CD4 T cells illustrated.
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Humoral immunity and cell-mediated immunity are two types of an adaptive immune response that enable the human body to defend itself in a targeted way against harmful agents such as bacteria, viruses and toxins. Whilst there is some overlap between these arms of the immune response - both rely on the functions of lymphoid cells - there are also some important differences.

One can acquire humoral immunity to a specific infection or disease if administered with antibodies from someone who was previously been exposed to the same infection, circumventing the humoral response. However, antibody-mediated immunity involves a set of molecular components and processes that differ from cell-mediated immunity. In this article, we define humoral immunity and cell-mediated immunity, discussing the different immune processes, purposes and important cell types.

Humoral vs cell-mediated immunity

Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells. Cell-mediated immunity on the other hand does not depend on antibodies for its adaptive immune functions and is primarily driven by mature T cells, macrophages and the release of cytokines in response to an antigen.

What is humoral immunity?

Humoral immunity is an antibody-mediated response that occurs when foreign material - antigens - are detected in the body. This foreign material typically includes extracellular invaders such as bacteria. This mechanism is primarily driven by B cell lymphocytes, a type of immune cell that produces antibodies after the detection of a specific antigen.

Naïve B cells are lymphocytes that circulate throughout the body in the lymphatic system. These lymphocytes express a variety of antigen-specific molecules that are essential for the detection of infectious agents in the human body. Whenever naïve B cells encounter an antigen in the lymphatic system, they undergo a differentiation process that leads to the creation of memory B cells and effector B cells.

A diagram showing humoral and cellular immunity.

A diagram showing humoral and cellular immunity. 

During this differentiation, memory B cells and effector B cells produce the same antigen-specific molecules as their parent naïve B cell. With the help of T cell lymphocytes, in turn activated by MHC class II receptors that recognize microbial-associated antigens, the activated memory B cells express these antigen-specific molecules on their surface while the effector B cells secrete these molecules in the blood to bind the antigen of interest.

What is an antibody?
Antibodies are heavy proteins that are approximately 10 nanometers in size. These molecules are produced by B cells in order to identify and neutralize harmful agents such as infectious bacteria, fungi, and viruses. These Y-shaped proteins contain antigen-binding sites that specifically bind to their target antigens.
Once antibodies effectively bind to their target antigen, they can either neutralize their target antigen directly by blocking normal antigen binding or they can induce the recruitment of other immune cells or molecules that promote the antigens removal or destruction. In mammals, such antibodies come in a variety of forms commonly known as isotypes.

How are antibodies produced?

Each B cell produces its own set of antibodies with unique antigen-specific binding sites. Initially, naïve B cells produce antibodies that remain bound to the cellular surface so that their exposed antigen-binding sites can detect potential pathogens, toxins and foreign material. This surface-bound form of an antibody is known as an immunoglobulin.

When an antigen matching the antigen-binding site binds to a naïve or memory B cell, it activates the B cell to produce and secrete more antigen-specific antibodies. Once a B cell fully matures, it is known as a plasma cell and will continue to produce and secrete antigen-specific antibodies for the remainder of its life cycle.

What do antibodies do to fight pathogens?

Once antibodies are in the blood stream, these free-floating proteins are ready to function as defensive molecules with direct and indirect immune functions. These functions include:

  • neutralization of infectious agents – via blocking or antibody-dependent cellular cytotoxicity
  • activation of the complement system – compliment dependent cytotoxicity
  • binding of foreign substances to be destroyed - opsonization and phagocytosis

Antibodies neutralize antigens primarily through mechanisms of attachment and accumulation. For example, the aggregation of neutralizing antibodies upon antigen-matching viral particles would block this virus’s ability to infect other cells.

Antibodies can also participate in processes that lead to the lysis or killing of infected or antigen-presenting cells through the activation of the complement cascade or interaction with effector cells and release of cytokines. The complement system is a part of innate immunity that enhances the ability of antibodies and lymphocytes to clear the body of pathogens and infected cells. Lastly, antibodies that coat pathogens or infected cells can attract (opsonize) and become internalized by macrophages during phagocytosis.

Humoral immunity depends on lymphocytes to confer protection against infection through antibody-mediated functions, but it is not the only form of adaptive immunity that involves bone marrow lymphocytes.

What is cell-mediated immunity?

Unlike humoral immunity, cell-mediated immunity does not depend on antibodies for its adaptive immune functions. Cell-mediated immunity is primarily driven by mature T cells, macrophages, and the release of cytokines in response to an antigen.

T cells involved in cell-mediated immunity rely on antigen-presenting cells that contain membrane-bound MHC class I proteins in order to recognize intracellular target antigens. The binding specificity between MHC proteins and foreign antigens is essential for the maturation and differentiation of naïve T cells into helper or killer T cells.

Cell-mediated immunity typically comes into play at body sites where cells are infected by a virus, bacteria, or fungi (intracellular invaders). With the assistance of MHC class I proteins, T cells can also recognize cancerous cells.

What lymphocytes are involved in cell-mediated immunity?

The main types of lymphocytes involved in cell-mediated immunity include naïve T cells, helper T cells, killer T cells, and macrophages. Naïve T cells, which have not yet become activated, circulate in the bloodstream and the lymphatic system. When they encounter an antigen-presenting cell, these naïve cells become activated, rapidly proliferating into different T-cell subsets. These subsets perform different functions  CD4+ helper T cells, for example, release a set of signaling proteins called cytokines. These cytokines can damage the target cell directly or help activate “killer” T cells and macrophages. CD8+ killer T cells, also called cytotoxic T cells, perform direct lysis of target cells, while macrophages, which are a type of antigen-presenting cell, also play an important role in T-cell activation. 

Humoral vs cell-mediated immunity: table

HumoralCell Mediated
TypeAntibody-mediated responseT cell-mediated response
Site of Activity
Extracellular fluids
Location of antigen-presenting tissue
Main Cell Types Involved
B cellsT cells
Speed of Onset
Fast response upon detectionSlow response
Antigen Type
Extracellular pathogensIntracellular pathogens, cancer cells
Method of Removal
Antibody-mediated destruction or neutralization
Cell lysis and programed death
MHC Proteins Involved
MHC class II proteinsMHC class I proteins