Friday, December 25, 2009

The cells of the Immune System

The basic functional units of the immune system are diverse cells belonging to the lymphoid and reticuloendothelial system. The immunoreactive cells are lymphocytes, monocytes, macrophages, mast cells and a few granulocytes. Lymphocytes are mainly responsible for specific immune responses. Immune cells move through the body in blood and lymph. Immune cells have the capacity to react when appropriately stimulated by antigens.
The lymphocytes are classified into T and B lymphocytes. T lymphocytes are responsible for cell mediated immunity. B lymphocytes are responsible for the expression of humoral mediated immunity (antibody production).


Origin of  Immune reactive cells

1. The lymphoid lineage gives rise to T lymphocytes (T cells), B lymphocytes (B cells) and natural killer cells (NK cells)
2. The myeloid lineage gives rise to monocytes, macrophages, Langerhans cells, dendritic cells, megakaryocytes and granulocytes (eosinophils, neutrophils, basophils)

Types of leucocytes

Agranulocytes: They have a clear cytoplasm and also known as mononuclear leukocytes. They include monocytes (4%) and lymphocytes (24%). The monocytes transform into the tissue macrophages, which are active phagocytes, and have become resident in connective tissue
Granulocytes: They contain abundant granules in their cytoplasm. They are also known as polymorphonuclear leukocytes. (PMNs), because of their lobed nuclei. The granulocytes are identified as different types, based on their staining characteristics with certain dyes as neutrophils (72% of white cells), eosinophils (1.5%), and basophils (0.5%). The granulocytes are predominantly important in the removal of bacteria and parasites from the body. They engulf these foreign bodies and degrade them using their powerful enzymes.

Kinds of Granulocytes 

Neutrophils are phagocytic as well as granulocytic. Neutrophils use granulocytic chemicals to destroy microorganisms which they ingest. They have a multi-lobed nucleus. They are about 50-70% of circulating leucocytes (WBC )(higher numbers suggestive of bacterial infection). The fine granules stain poorly with acidic and basic dyes neutrophil. The primary granules are electron dense which contain bactericidal enzymes like Lysozyme, myeloperoxidase; neutral proteases (i.e. elastase); and acid hydrolases (B-glucoronidase). The secondary granules are smaller, not electron dense. They contain lysozyme, collagenase and lactoferrin and cathepsin B. Neutrophils are the 1st cells to arrive at the inflammatory site. They phagocytose and kill the ingested microorganisms in the phagosome.
Eosinophils release granulocytic chemicals into surrounding tissues, to destroy nearby infectious agents. They represent 1-3% of circulating WBCs. They possess a bi-lobed nucleus and a heavily granulated cytoplasm. Granules stain orange/red with the acidic dye Eosin Y. They are somewhat phagocytic but DO NOT act as APCs. The major role of the eosinophil is believed to be against parasites, particularly parasitic worms
.Basophils -  They have Lobed nucleus with large coarse granules stain blue with basic dye methylene blue. Like eosinophils, basophils release granulocytic chemicals, to destroy nearby microorganisms and stimulate the inflammatory response. They play a major role in the allergic response when they release their granules (containing histamine, serotonin, heparin, prostaglandin, etc into the bloodstream following exposure to specific allergens). Basophils bear Fc receptors for IgE . When an individual is exposed to an allergen, allergen specific IgE is produced. This IgE binds to the surface of basophils.

Lymphocytes

Lymphocytes are the main actors of the immune system and responsible for the specific immune responses. They represent 20-40% of circulating WBC in blood extravasate and enter the tissues – return 99% of cells in lymph. They are small 6µm, contain a single nucleus, little visible cytoplasm around their nucleus. Lymphocytes include T lymphocytes and B lymphocytes and natural killer cells.
T and B lymphocytes are small, motile, non-phagocytic cells which cannot be distinguished from each other morphologically. Once stimulated with antigen enlarges 15µm into a blast cell. Lymphoblasts further differentiate into effector cells or memory cells(Plasma cells, T-helper cells, T-cytotoxic cells). The memory cells are long-lived cells that reside in the Go phase of the cell cycle until activated by a secondary encounter with antigen. Different maturational stages of lymphocytes can be distinguished by their expression of membrane CD molecules (Cluster of Differentiation (CD).
T cells are chiefly responsible for cell mediated immunity. B cells are primarily responsible for humoral mediated immunity (relating to antibodies). T cells are named such because these lymphocytes mature in the thymus; B cells, named for the Bursa of fabricius in which they mature in bird species, are thought to mature in the bone marrow in humans. In the presence of an antigen, B cells can become much more metabolically active and differentiate into plasma cells, which secrete large quantities of antibodies.

Kinds of T lymphocytes


Helper T cells are responsible for activating and orchestrating the response against an invading organism. Cytotoxic (or Killer) T Cells are responsible for destruction of virus-infected or malignant (cancerous) body cells. Suppressor T cells are responsible for turning off the immune response after an infection has been cleared. T- helper cells interact with B- lymphocytes and help them to divide, differentiate and antibodies. T- helper cells interact with mononuclear phagocytes and help them destroy pathogens.
T- cytotoxic cells are responsible for the destruction of host cells infected with viruses or other intracellular pathogens.

B lymphocytes

B cells perform antibody mediated immunity. B lymphocytes have receptors on its surface to recognize one unique antigen. Antigens stimulate B cells to convert into plasma cells that produce antibodies (specific to that antigen). A plasma cell produces antibody molecules that can combine with a specific kind of antigen (like a lock & key). All antibodies eventually enter the blood or lymph. B-cells specialize in fighting bacterial invaders.
Plasma cells - B-cells on stimulation, grow, proliferate and differentiate into plasma cells. Plasma cells have a nucleus with chromatin arranged in a wheel-spoke pattern and an abundant, basophilic cytoplasm. Their extensive granular endoplasmic reticulum produces immunoglobulins. After completing secretion, most plasma cells die; however, some may survive for months or even years and serve as memory cells.
Natural killer cells (lymphocyte-like cells) attack & destroy virus-infected cells and cancer cells on first exposure to them. They lyse (rupture) cell membranes upon first exposure to these cells. NK cells provide an immediate, nonspecific defense. They act to slow the spread of viruses & cancer cells until the more specific adaptive immune cells can be mobilized.

Macrophages

These cells are derived from the bone marrow and have a variety of functions in the immune response. Macrophages are phagocytic cells responsible for engulfing and digesting foreign invaders. Examples of tissue-specific macrophages include: alveolar macrophages (in the lungs), mesangial Macrophages (in the kidneys), microglial cells (in the brain) and Kupffer cells (in the liver). In the tissues monocytes mature into different types of macrophages at different anatomical locations. Macrophages are activated by a variety of stimuli in the course of an immune response. One of the earliest activating signals comes from chemokines. Phagocyotosis itself is an important activating stimulus. Macrophages are further activated by cytokines secreted by T helper cells [IFN-gamma], by mediators of the inflammatory response and by various microbial products (such as LPS).
Macrophages play the following important roles: As scavengers, they rid the body of worn-out cells and other debris. They display bits of foreign antigen in a way that draws the attention of matching lymphocytes. They churn out an amazing variety of powerful chemical signals, known as monokines, which are vital to the immune responses.
1) phagocytosis
2) antimicrobial activity
3) secretion of soluble factors

Dendritic Cells

They originate in the bone marrow and function as antigen presenting cells (APC). They are found in the structural compartment of the lymphoid organs, in the bloodstream and other tissues of the body. They capture antigen or bring it to the lymphoid organs where an immune response is initiated. They stationed in skin and particularly susceptible to infection by viruses.

Mast cells (or mastocyte)

It is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens. It is found in the lungs, skin, tongue, and linings of the nose and intestinal tract, where it is responsible for the symptoms of allergy. Mast cells are released from the bone marrow as undifferentiated precursor cells and do not differentiate until they enter the tissues (skin, connective tissue, mucosal epithelium, etc.). Mast cells bear Fc receptors for IgE (FcRs) and contain large numbers of cytoplasmic granules which also play a very important role in the allergic response. They produce a variety of cytokines. TNF is produced and stored within the cytoplasm of the mast cell, and it can be released quickly following mast cell activation.

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