Cell-mediated Immunity Vs. Humoral Immunity

Major Histocompatibility Complex (MHC) is a specific marker that sticks out on the membrane of every cell in the human body; this marker indicates that the cell belongs to the body. This helps the immune system identify the pathogen or foreign invader.

A healthy immune system is essential for our survival, as we are constantly exposed to pathogens or disease-causing agents.

The skin and the mucous membranes serve as the first line of defense, whereas phagocytes, macrophages, non-phagocytic leukocytes, complementary proteins, chemokines, etc., come to the rescue when the pathogens make it past the physical barriers such as the skin or the mucous membranes. 

However, these are responsible for generalized response to infections, and are a part of the non-specific or innate immune system. The specific/adaptive immune system is the third line of defense, which caters to the infections or threats that cannot be handled by the innate immune system. 

Only vertebrates have specific immune responses, which are characterized by a targeted response against a specific pathogen.

The specific immunity facilitates a targeted response against a specific pathogen. Together, innate immunity and adaptive immunity are responsible for immune responses that protect the body from dangerous cells (cancerous cells), allergens, foreign bodies, pathogens (bacteria, viruses, fungi, parasites), etc. The 

The adaptive immune system includes immune responses called 'cell-mediated immunity' and 'humoral immunity', which recognize specific antigens. The term 'antigens' is derived from the term 'antibody generator', and refers to substances which trigger an immune response or the production of antibodies by the immune system. 

An interesting feature of the adaptive immunity is that after neutralizing the foreign invader or pathogen, a few B cells or T cells stay in the body as memory cells. If the same pathogen attacks in the future, these recognize the pathogen, and mount an attack.

In order to understand the difference between cell-mediated and humoral immunity, we need to understand the function and nature of B cells and T cells, which are an integral part of the adaptive immune system.

T cells, as well as the B cells are lymphocytes, which in turn, are a type of leukocyte (white blood cell). These are dedicated cells that are triggered in the presence of an antigen. 

These are essential for the targeted response against a specific disease-causing agent. Humoral immunity refers to the immune response that involves the use of antibodies produced by B cells for attacking a foreign invader. Therefore, this type of immune response is also referred to as antibody-mediated immunity.

The use of the term 'humoral' is also due to the fact that the antibodies which bind to the antigen and trigger a response are dissolved in the humor (bodily fluids such as blood, lymph). 

On the other hand, the cell-mediated immunity involves the destruction of cells that are damaged by mutations or infected by viruses with the help of Helper T cells (CD4+) and cytotoxic T cells (CD8+). 

The T cells bind to the surface of other antigen presenting cells (cells that display the antigen), thereby triggering a response. Other types of T cells that are present include NK (Natural Killer) cells, regulatory T cells, etc.

The T cells, which are produced in the bone marrow and mature in the thymus, play a vital role in the immune response, as these attack the cells that have been infected by pathogens, or the cells that have become cancerous due to the abnormal and uncontrolled cell division.

When the immune system identifies a threat, specialized immune cells called macrophages, granulocytes, and dendritic cells, respond to the threat by engulfing and digesting pathogens. Macrophages keep parts of the cell markers of the pathogen or invader and display them on the surface of their own membrane.

This process is called antigen presentation. The macrophages also help activate the rest of the immune system by traveling to the nearest lymph node, where they present an antigen fragment from the pathogen.

T cells get activated when the receptor of a Helper T cell identifies the antigen and binds to it. Once activated, Helper T cells divide and produce cytokines (cell-signaling protein molecule). The cytokines help activate both B cells and T cells. 

They increase phagocytotic activity (digestion of pathogens by the phagocytes), and give rise to T cell proliferation, T cell differentiation, and increased cytokine secretion. They can also direct the infected body cells to self-destruct, so as to destroy the pathogen.

T cells can also secrete a substance called perforin, which penetrates through membranes and destroys those cells.

Molecular receptors on the surface of T cells (T cell receptors) can recognize protein antigens and bind to their cognate antigens. The main difference between the T cells and B cells is that T cell receptors remain on the surface of the cell, whereas B cells can release the receptors as antibodies.

Moreover, B cell antibodies can recognize any organic molecule. Once the receptors of T cells are activated by a specific antigen, they replicate to create clones of T cells that are specifically programmed to counter that particular antigen.

As mentioned earlier, Major Histocompatibility Complex is the specific marker that helps the immune system differentiate between the invader and body's cells. While MHC-I markers are on every cell, MHC-II are present only on the antigen-presenting cells (APCs) and lymphocytes. In short, the steps of cell-mediated response include:

➠ Self-cells or APCs that present antigens bind to T cells.

➠ Cytokines or interleukins (secreted by APCs or helper T cells) trigger the activation of T cells.

➠ If MHC‐I and endogenous antigens are displayed on the plasma membrane, T cells proliferate, producing cytotoxic T cells. Cytotoxic T cells destroy cells that display the antigens.

➠ If MHC‐II and exogenous antigens are displayed on the plasma membrane, T cells proliferate, thereby stimulating the production of Helper T cells. Helper T cells release interleukins (and other cytokines), which in turn stimulate B cells to produce antibodies that bind to the antigens. These also induce NK cells and macrophages to destroy the antigens.

If the virus or pathogen enters the cell, it can replicate at a rapid rate and emerge through the cell walls, thereby infecting the surrounding cells. Under such circumstances, the T cells come to the rescue. The cell-mediated immunity involves the activation of NK cells, T lymphocytes, macrophages, and cytokines in response to an antigen.

The T cells are also instrumental in activating B cells to divide into plasma cells. They also activate phagocytes to destroy microbes, and activate killer T cells that identify and destroy the infected body cells. 

On the other hand, regulatory T cells (suppressor T cells) signal to put an end to the immune response or attack, once the situation in under control. Moreover, lymphocytes called the memory T cells can identify the antigen, previous vaccination, or a cancer cell, if there's another attack in the future.

B cells are produced from the stem cells in the bone marrow. They perform the vital task of the synthesis of antibodies (Y-shaped protein molecules that are produced in response to an antigen) that launch an attack on the disease-causing agents. Numerous receptors lie on the surface of a B cell. 

The B cells get activated after receiving an interleukin signal from a helper T cell, which in turn has been activated by a macrophage with a MHC-antigen complex. Once the B cell receptors (BCRs) identify a matching (or cognate) antigen, they bind to the antigen.

Thereafter, the B cells divide or proliferate rapidly into plasma cells (effector cells) and memory cells. They double every six hours for a period of 7 days. Once they reach a count of around 20,000, about 2,000 antibodies are released every second.

While the effector cells produce a large number of antibodies, the memory cells are responsible for the immune system's ability to remember an antigen and properly respond to it. So, the next time that pathogen attacks the body, the immune system gets activated immediately and destroys the pathogen before it is able to cause an infection.

In short, the steps of antibody-mediated immune response include:

➠ Antigens bind to B cells.

➠ Helper T cells or interleukins activate B cells. In most cases, both an antigen and a co-stimulator are required to activate a B cell and induce B cell proliferation.

➠ B cells replicate, thereby producing effector cells. The plasma cells bear antibodies that are specific to that antigen on the activated B cells. This is followed by the release of antibodies, which then bind to the antigens.

➠ B cells produce memory cells, which help activate the immune system if the same pathogen attacks in the future.

Thus, the immune response includes antigen presentation, antigen binding, co-stimulation, and destruction of the disease-causing agent. In case of humoral immunity, antibodies induce immediate responses to antigens, which in turn causes immediate hypersensitivity reactions.

The cell-mediated response is slower, but is quite potent. Moreover, the cell-mediated response becomes essential if the pathogen is able to enter the cell.