24.2:
Cell-mediated Immune Responses
Cell-mediated immunity is an adaptive cellular response to prevent the spread of infection.
When a foreign pathogen, an infectious particle like a bacterium is detected in the body, specific white blood cells called macrophages are called in as the first line of defense. Via phagocytosis they engulf and digest the harmful pathogens that contain unique proteins, known as antigens, on their surface.
The antigens are then fragmented within the phagolysosome and transported to the macrophage's surface, which is why they are referred to as antigen-presenting cells or APCs. Other proteins, major histocompatibility class or MHC molecules embed the antigen fragments for presentation on the surface of the APC.
The complex can now be detected by T lymphocytes or T cells, another type of white blood cell, that rapidly multiplies by mitosis to generate specialized T cells to combat the infection.
The main ones, helper T cells, secrete chemicals to stimulate the growth and differentiation of cytotoxic T cells which kill damaged cells. They can also remain in the host, memory T cells, after the infection has been cleared, just in case the same pathogen is re-encountered at a later time. Once the infection is under control, suppressor T cells inhibit the immune system to prevent further distraction to the host tissue.
24.2:
Cell-mediated Immune Responses
Overview
The cell-mediated immune system is the host’s primary response against invasive bacteria and viruses that cause intracellular infections. It is also essential for fighting against and destroying cancer cells. Furthermore, the cell-mediated immune system plays a role in the rejection of organ transplants or graft tissue.
The Innate Immune System Activates the Adaptive Immune System
Phagocytic cells of the innate immune system, such as macrophages or dendritic cells, are the first to recognize a foreign particle. These cells engulf the foreign particle and digest it. Small molecules of the foreign particle, called antigens, remain intact and are presented at the surface of the phagocytic cell. The presentation is facilitated by proteins of the major histocompatibility complex (MHC), which binds the antigen and protrude from the cell. The phagocytic cell is therefore also called an antigen presenting cell (APC). The MHC-antigen complex activates cells of the adaptive immune system, which eventually fight the source of the foreign particle.
T Cells Carry Out Many Functions in the Adaptive Immune System
T cells are a type of lymphocyte that are named after their location of maturation—the thymus. In the thymus, precursor T cells differentiate into two main types, CD4+ and CD8+ T cells. These cell types are named after the surface receptor that determines the cell’s function. All T cells carry T-cell receptors, but the coreceptor CD4+ or CD8+ confers specificity. A T cell expressing the CD4+ coreceptor can interact with the MHC class II complex on an APC. In contrast, a T cell carrying CD8+ recognizes the antigen-MHC class I complex on an infected or cancer cell. After it identifies such a cell, the CD8+ cell differentiates into a cytotoxic T lymphocyte (CTL) which ultimately destroys the infected or cancer cell.
Let’s turn our attention back to the CD4+ cells. Before a CD4+ cell meets a matching antigen presented by an APC, it is referred to as naive. Once a naive CD4+ T cell becomes activated, it can differentiate into a memory T cell or several variants of helper T cells. Helper T cell type 1 (Th1) produce the cytokinin interferon that triggers pathogen digestion in APCs and stimulates CTL and B cell activity. Th2 cells produce interleukins that primarily promote B cell activity.
The Adaptive Immune System Remembers Pathogen Encounters
Memory T cells are a variant of T cells that remain in the body long after the first attack triggered by a specific antigen. Some human memory T cells primarily rest in the bone marrow and provide long-lasting immunity against systemic pathogens. Others strategically locate to mucous membranes and the lymphatic fluid or bloodstream. Once a memory T cell encounters its antigen, it mounts a faster and stronger immune response compared to the first encounter. Each T cell is only set into action by a single, specific antigen. Likewise, memory T cells will only activate when this particular antigen is reencountered. The more antigens an organism encounters during its lifetime, the larger becomes its arsenal of different T cells that fight successive infections. This effect is also used in vaccinations, that means the controlled introduction of an antigen that triggers the production of B and T cells. If the real pathogen with the same antigen enters the body, the adaptive immune system is already primed by vaccination to fight this infection.
The Adaptive Immune System Can Hinder the Successful Transplantation of Graft Tissue
Skin, liver, and bone tissues, among others, can be transplanted from a healthy donor to a recipient in which the respective tissue is diseased or destroyed. Such tissues are known as graft tissues. The success of such a medical procedure is often dependent on compatibility between the graft tissue and the recipient's immune system. If the host and the graft are incompatible, damage of the graft tissue can be initiated by two pathways. The direct pathway of graft rejection involves APCs in the graft that present antigens to the host’s helper and CTL cells. In the indirect pathway, the host’s APCs recognize the graft as non-self and present graft-derived antigens to helper T cells. In both scenarios, the host’s adaptive immune cells are directed against the graft tissue and contribute to its damage. To improve the success rate of tissue or organ transplantation, parts of the recipient’s immune system are suppressed by medication.
Suggested Reading
Chaplin, David D. “Overview of the Immune Response.” The Journal of Allergy and Clinical Immunology 125, no. 2 Suppl 2 (February 2010): S3-23. [Source]