The neutrophils, eosinophils, and basophils are all types of granulocytes. Each are designed to play different roles in the game of immunology. Neutrophils provide an effective defense against bacteria and fungal infections and are the main leukocytes that serve in phagocytosis and can produce a local inflammatory response. Eosinophils and basophils are players in allergic/hypersensitivity reactions. The granules of basophils contain histamine which is responsible for allergic responses. Eosinophils work to moderate or control the basophils.

Cells of the Innate Immune System

The phagocytes belong to two major types – mono/macrophages and polymorphonuclear granulocytes.

Granulocytes Granulocytes are divided into three groups: neutrophils, basophils, and eosinophils. Neutrophils are released from the bone marrow at a rate of approximately 7 million per minute. The formation of an inflammatory response is initiated mainly by neutrophils and monocytes. They live only 2-3 days and play an important role in inflammation against micoorganisms, espcially bacteria. They comprise over 95% of circulating granulocytes. Eosinophils have a bilobed nucleus and have many large cytoplasmic granules that stain bright red with acidic dyes such as eosin. They make up 2-5% blood leukocytes in the normal cell population. They are capable of phagocytosing and killing microorganisms. Eosinophils play a major role in immunity to parasitic worms and they release histaminase. The function of the eosinophil is to moderate by reducing the inflammatory process and reducing granulocyte migration into the site of invasion. Basophils are found in very small numbers in the normal individual. They have a high concentration of heparin and histamine in their granules, which play an important role in acute, systemic, and hypersensitivity reactions. Although basophils and eosinophils are capable of participating in phagocytosis, they possess less phagocytic activity than neutrophils. Granulocyte

Neutrophils Eosinophils Basophils Granulocyte

Monocytes/Macrophages
Monocytes/Macrophages are considered to constitute a physiologic system, which includes promonocytes and precursors in the bone marrow, monocytes in the circulating blood, and macrophages in the tissues. They may exist as fixed or wandering cells. Macrophages and monocytes may migrate freely into the tissue from blood to replenish and reinforce the macrophage population. Cells of the macrophage system originate in the bone marrow from the multipotential stem cell. This cell is a committed progenitor cell that can differentiate into either the granulocytes or monocyte-macrophage pathway, depending on the microenvironment and chemical regulators. The monocytes may continue to have a multipotential and give rise to different types of macrophages. Macrophages can be activated during infections by the release of macrophage-activating cytokine such as interferon gamma and granulocyte-colony stimulating factor, from T lymphocytes. This interaction constitutes the basis of cell mediated natural immunity. The host defense functions of monocytes-macrophages includes:

1. Phagocytosis
2. Antigen presentation to lymphocytes and induction of an immune response
3. Secretion of biologically active molescules known as monokines. One example of monkine is Interleukin-1 which can induce the fever and production of acute phase reactants which characterize inflammation.

Monocyte	Monocyte
Macrophage

Cells of the Adaptive Cells of the Immune System

Lymphocytes

Normal Lymphocyte

There are large numbers of lymphocytes produced daily in the primary lymphoid organs (thymus and bone marrow). Some of these cells migrate via the circulation into the secondary lymphoid tissues (spleen, lymph nodes and mucosa-associated lymphoid tissues). The average human adult has about 2 x 1012 lymphoid cells and the lymphoid tissue as a whole represents about 2% of total body weight. The lymphocyte is the “key player” in immune response. The majority of circulating lymphocytes in the peripheral blood (60 to 80%) are T cells and these become differentiated in the thymus. Lymphoid cells account for approximately 20%-40% of the leukocytes in the adult circulation. Many mature lymphoid cells are long-lived, and persist as memory cells for many years. Lymphocytes represent the only immunologically specific cellular components of the immune system. They recognize foreign antigens, destroy some cells, and produce antibodies as plasma cells.

Lymphocyte

The primary lymphoid organs are the thymus and the bone marrow. The thymus exercises control over the entire immune system. The development of diversity occurs mainly in these primary lymphoid organs. Progenitor cells that migrate to the thymus divide and differentiate under the influence of the humoral factor. The thymus also regulate immune function by secretion of multiple soluble hormones. The thymus gradually loses up to 95% of its mass during the first 50 years of life. This may account for the increased susceptibility of older adults to infections, autoimmune disease, and neoplasms. The bone marrow is the source of the progenitor cells. These cells can differentiate into lymphocytes and other hematopoietic cells (granulocytes, erythrocytes, and megakaryocyte populations).

The secondary lymphoid tissues include lymph nodes, spleen and blood. Mature lymphocytes and accessory cells (antigen-presenting cells, APC’s) are found throughout the body, although the relative percentages of T and B cells are different in different locations. Proliferation of the T and B lymphocytes in the secondary and peripheral lymphoid tissues is dependent on antigenic stimulation.
Blood is the most frequently tested lymphoid organ.

Proteins that appear on cell surfaces can be used as markers to differentiate T cells and B cells. Proteins can also be used to distinguish the developmental stages of the two types of cells according to when these proteins appear. A number of laboratories have developed monoclonal antibodies, and each used its own nomenclature for the sets of antigens found. In an attempt to relate research findings and standardize the nomenclature scientist came up with the “clusters of differentiation” (CD) term. As each antigen, or CD, was found it was assigned a number. The name cluster of differentiation came about because the exact nature of the proteins identified by the various antibodies was not known. These antigens are most important in characterizing T and B lymphocytes.

The lymphocytes are classified as the following:

• T Cell Lymphocytes
  Most lymphocytes are T cells derived from progenitor cells from the bone marrow that mature in the thymus. These cells are responsible for the cellular or cell-mediated immune response and help the B lymphocytes.
  • T Helper Cells – These cells have CD4 cell receptors.
    
    Helper T lymphocytes can be assigned to one of several subsets:
    • T_H1 – are responsible for cell-mediated effector mechanism.
    • T_H2 – play a greater role in the regulation of antibody production
    • T_H0 – are an intermediate category

    T_H1 and T_H2 cells can promote development of cytotoxic cells and are believed to develop from T_H0 cells. T_H1 cells interact most effectively with mononuclear phagocytes. T_H2 release cytokines that are required for B cell differentiation.

  • T Cytotoxic
    T_C are effector cells found in the peripheral blood that are capable of directly destroying virally infected target cells or tumor cells. Most T_C are CD8 +. T_C are the major effectors in allograft organ rejection.
  • T Suppressor
    T_S cells are functionally defined T cells that downregulate the action of other T and B cells. These cells have no unique markers. Many scientists believe the T suppressor cells are critical in various phases of immunoregulation, peripheral tolerance, and autoimmunity. Their mode of action is unclear. Many are CD8+.
    
    
    
• B Cell Lymphocytes
  These cells are responsible for the humoral immune response by reacting to antigenic stimuli and dividing and differentiating into plasma cells which secrete antibodies. These cells are the primary defense against microorganisms especially bacteria.
  
  B cells represent a small percent of the circulating peripheral blood lymphocytes. They are derived from progenitor cells in the bone marrow. The plasma cells are the antibody forming cells and are differentiated B cells. The antibody is the primary host defense against microorganisms. Patients with defects in B cell function have recurrent bacterial infections such as ear infections, pneumonia, and sinusitis.
  
  
• Natural Killer Cells and K Cells
  Natural Killer cells and K cells are a subpopulation of circulating lymphocytes that lack the conventional antigen receptors of T or B cells. These lymphocytes produce cytokines such as interferon and IL-2.
  
  
  • Natural Killer Cells
    70% to 80% of NK cells have the appearances of large granular lymphocytes (LGL). These cells destroy target cells through an extracellular nonphagocytic process called cytotoxic reaction. The target cells include tumor cells, some cells of the embryo, cells of normal bone marrow, and microbial agents. NK cells will actively kill virally infected target cells and certain tumor cells.
  • K Cells
    These mononuclear lymphocytes are also cytotoxic but can only kill target cells sensitized with antibody. Most K cells are non T, non B lymphocytes.  K cells are also capable of lyzing tumor cells.
    
    

Plasma Cells
Plasma cells are large, spherical or ellipsoidal cells between 1—20 um in size and are characterized by the presence of abundant cytoplasmic immunoglobulins and little or no surface immunoglobulin. This represents the most fully differentiated lymphocyte, and its main function is antibody production. Plasma cells are not normally found in the blood, but are located in the germinal centers in the peripheral lymphoid organs. After several days of antibody production, they die without further proliferation. Memory cells are found in germinal centers and have a much longer life span than resting B cells. Memory B cells are capable of responding to antigens with increased speed and intensity. They are similar in appearance to unstimulated B cells, but they remain in an activated state for months or years, ready to respond to the initial antigen.

Plasma Cells	Plasma Cells
Plasma Cells	Plasma Cells

Characteristic of Humoral-and Cell-Mediated Immunity

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