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Mononuclear Cell Infiltration

Mononuclear cells are the fundamental backbone of the adaptive and innate immune system. These cells gather at the point of infection of inflammatory lesions and are responsible for clearing out any opportunistic pathogens and stimulating other parts of the immune response. Mononuclear cells also play an important role in creating a biological database for antigens that may enter the body to help mitigate damages that could be caused by potential future infections. There are a wide variety of mononuclear cells, most of which fall under the jurisdiction of the lymphoid system. There are also macrophages and dentritic cells which are derived from monocytes.

The Lymphoid System

Lymphocytes are cells commonly found as a part of the immune system such as T cells and B cells, and contain receptors which recognize foreign molecules. These cells are derived from lymphoid progenitor cells which develop and mature in the primary lymphoid tissues located in bone marrow as well as the thymus. These cells are then stimulated and expand in secondary lymphoid tissues which include the lymph nodes, spleen, and some sections of gut tissue known as Peyer's patches.

T cells:

Overview of T cell maturation

There are several kinds of T cells that can be found in the immune response. Among the most important are CD8+ cytotoxic T cells which kill off virus infected particles and other abnormal cell types. Cytotoxic T cells release an enzyme known as perforin which penetrates the target cell wall or membrane. This is followed by the secretion of granzymes which cause the target cell to undergo programmed cell death. This process is something very similar to what we see in NK cells. Another main type of T cells are CD4+ helper T cells which are used for multiple purposes. Helper T cells recruit macrophages to gather at the site of infection as well as stimulate B cells to create antibodies. Helper T cells can also induce the production of memory helper T cells and memory cytotoxic T cells which become very useful if the same infection is to reoccur in the host.

Maturation of Helper T cells:

Helper T cells are activated when an antigen-presenting cell presents a bound antigen using the major histocompatibility complex class II. The helper T cell binds itself to the complex by CD4+ and cytokines are released from both the APC and the helper T cell. This causes the T cell to develop into one of two helper T cells depending on the local cytokines released. Th-1 cells stimulate more T cells and macrophages while Th-2 cells stimulate a response from B cells.

Maturation of Cytotoxic T cells:

Cytotoxic T cells undergo a similar maturation process to helper T cells. An abnormal cell presents an antigen using the major histocompatibility complex class I. The cytotoxic T cell binds to the complex via CD8+ and awaits a cytokine release from a Th-1 cell. This promotes the maturation of an effector Tc cell which will go off and kill pathogenic microbes within the host.

B cells:

B cells are stimulated by extracellular antigens and helper T cells in order to mature into plasma cells. These plasma cells can produce antibodies or immunoglobulins which have receptors to recognize specific pathogen or some chemical components released by pathogens.

Maturation of B cells:

B cells also utilizes the major histocompatibility complex class II. When an antigen or pathogen is bound to a B cell it undergoes degradation and is absorbed into the B cell. The proteins of the pathogen are processed and presented to a Th-2 cell via MHC class II. The Th-2 cell then releases cytokines which when recognized by the B cell causes it to proliferate and become a plasma cell. Antibodies for the pathogen can then be produced by the plasma cell.

NK cells: (Natural Killer cells)

NK cells are slightly different from both T cells and B cells. These cells are large granular lymphocytes which contain toxic enzymes to induce programmed cell death, (apoptosis). NK cells contain perforin, an enzyme which forms a channel through the target cells membrane. It then releases what are known as 'granzymes' into the target cell to cause the cell to undergo apoptosis. NK cells target host cells lacking a vital receptor called the Major Histocompatibility complex or MHC. This helps protect the body from viruses and tumor cells.

Monocytes

Monocytes are the largest of the white blood cells and are used for a variety of functions in the immune system. They originate in the bone marrow, half are stored in the spleen to aid T cells in recognition of foreign invaders. The other half transition into the bloodstream where they are more readily available and mature into cells called macrophages. Monocytes can also derive themselves into dentritic cells although this is a rare occurrence and very few percentage of monocytes within the immune system undergo this process.

Macrophages:

Macrophages develop from monocytes which are present in the blood. The main function of macrophages is to search for pathogens and degrade them via phagocytosis. Macrophages are capable of phagocytosis due to the fact that they contain a specialized vesicle called a phagosome. As the cell matures the phagosome fuses with a lysozome creating a phagolysozome which is primarily responsible for killing pathogens. They reside in host cell tissue and engulf harmful microbes while simultaneously secreting inflammatory cytokines in order to attract neutrophiles to the site of infection. Inflammatory cytokines are secreted by various immune cells and are used primarily to stimulate the response of other immune cells in the adaptive immune response.

Dendritic cells:

Dendritic cells are another type of cell derived from monocytes. They have a star-shaped morphology and reside in host cell tissues. Dendritic cells interact with foreign antigens and activate T cells and B cells. These cells are then relocated to the lymph nodes where they help to shape the adaptive immune response alongside T cells and B cells.

Interactions of the Innate and Adaptive Immune Response

When a pathogen infects a host cell there is a cascade of responses from a variety of immune cells that help to target, kill, and clear the site of infection. Phagocytes and neutrophils among the first to respond to the site of infection. Phagocytes kill infectious microbes and release inflammatory cytokines. Phagocytes also act to present antigens to adaptive immune cells in order to activate T cells and B cells. The next layer of protection comes from macrophages. These cells engulf microbes as well as recruit more neutrophils to the site of infection. After the innate immune system has taken care of the primary infection it is time now for the adaptive immune response. This is initiated by antigen-presenting cells or APC's. APC's bind antigens and transport them to helper T cells or cytotoxic T cells depending on which major histocompatility complex is bound to the antigen. MHC class I is associated with CD8+ cytotoxic T cells and activate maturation of cytotoxic T cells. This results in T cells actively searching for and destroying the newly recognizable pathogen via forced apoptosis. MHC class II will stimulate the process of the maturation of helper T cells. This results in a split between two different T cells. The first being Th-1 cell which is a cellular immunity cell that stimulates more T cells and macrophages. The other is a Th2-cell which is responsible for the humoral immmunity by stimulation of B cells. MHC class II is also the complex require for binding and maturation of B cells into plasma cells. Plasma cells produce specific antibodies which can attach to pathogens and flag them for detruction by cytotoxic T cells.