The following points highlight the seven important cells of immune system. The cells are: 1. Hematopoietic Stem Cell 2. Lymphocytes 3. Monocytes 4. Macrophages 5. Granulocytes 6. Dendritic Cells 7. Mast Cells.
Cell # 1. Hematopoietic Stem Cell:
All blood cells arise from a type of cell called hematopoietic stem cell (HSC) (or stem cell). The stem cells are self-renewing, maintain their population by cell division, and differentiate into other cell types. This process of formation and development of blood cells (red and white blood cells) is called hematopoiesis.
It is remarkable that every functionally specialised, mature blood cell is derived from the same type of hematopoietic stem cell. In contrast to a unipotent cell, which differentiates into a single cell type, a hematopoietic stem cell is multi-potent or pluripotent as it is able to differentiate in various ways and thereby gives rise to various type of blood cells.
In humans, the formation and development of blood cells begins in the embryonic yolk sac during the first weeks of development. The hematopoietic stem cells differentiate into primitive erythroid cells that contain embryonic haemoglobin. In the third month of gestation, hematopoietic stem cells migrate from the yolk sac to the foetal liver and then to the spleen.
Liver and spleen play major roles in hematopoiesis from the third to the seventh months of gestation. In later months, hematopoietic stem cells differentiate in the bone marrow and play major role in hematopoiesis, and by birth there is little or no hematopoiesis in the liver and spleen.
Multi-potent hematopoietic stem cell (or stem cell) in the bone marrow differentiates to form two lineages:
(1) Common-lymphoid progenitor cell and
(2) Common myeloid progenitor cell (Fig. 42.7).
The progenitor cells, unlike hematopoietic stem cell that is self-renewing, loss the capacity for self-renewal, and are committed to their specific cell linkage.
The common lymphoid progenitor cells give rise to B-lymphocytes (B-cells) that differentiate into antibody secreting plasma cells. T-lymphocytes (T-cells) that become activated T-cells. natural killer (NK) cells, and some dentritic cells.
The common myeloid progenitor cells give rise to erythroblasts that produce erythrocytes (red blood cells), megakaryoblasts that produce platelets (thrombocytes), myeloblasts that produce granulocytes (eosinophils, basophils, neutrophils), monoblasts that differentiate into monocytes which give rise to macrophages and dendritic cells, and an unknown precursor that produces mast cells.
However, B-lymphocytes (B-cells) T-lymphocytes (T-cells) and natural killer (NK) cells produced by lymphoid progenitor cell lineage and eosinophils, basophils, neutrophils, macrophages, and dendritic cells produced by myeloid progenitor cell lineage are collectively called white blood cells or leucocytes (Gk. leucos = white, kytos = cell). White blood cells or leucocytes are the cells that are responsible for nonspecific and specific immunity in the body.
Cell # 2. Lymphocytes:
Lymphocytes (L. lympha = water, cyte = cell) are the most important effector cells of many cells involved in specific immune response. These cells are small, round and 5-15 μm in diameter. They are found in peripheral blood, lymph, lymphoid organs, and in many other tissues. Lymphocytes constitute 20% – 40% of the white blood cell (leucocyte) population in the body and 99% of the cells in the lymph.
They may be small (5-8 μm), medium (8-12 μm). and large (12-15 μm). The small lymphocytes are more numerous and may be short-lived with a life-span about two weeks or long-lived with a life-span of three years or more or even for life.
Short-lived lymphocytes act as effector cells in immune response, while long-lived ones function as memory cells. Long-lived lymphocytes are mainly thymus derived. The formation and development of lymphocytes, i.e.. lymphopoiesis takes place in bone marrow, primary or central lymphoid organs, and secondary or peripheral lymphoid organs.
Lymphocytes are approximately 1011 in number in a human body; their number ranges from 1010 to 1012 depending on body size and age. Lymphocytes can be broadly subdivided into three populations: B-lymphocytes or B-cells, T-lymphocytes or T-cells, and null cells (natural killer cells or NK cells are included in this group).
1. B-Lymphocytes or B-Cells:
B-lymphocytes or B-cells derive their name from their site of maturation. They are so named since they were first detected in the bursa of Fabricius of birds and later from bone marrow of a number of mammalian species, including humans and mice. In birds, the multi-potent hematopoietic stem cells originating in the bone marrow migrate to the bursa of Fabricius and differentiate there into antibody synthesizing cells.
The bursa is a small pouch-like organ in the embryonic hind-gut of birds and is absent in mammals. In a number of mammalian species including humans and mice, the B-cells originate in the foetal lever and later migrate to the bone marrow which becomes the site for production of B-cells after embryonic life.
B-lymphocytes do not have the ability to synthesize antibody molecule during undifferentiated stage. During differentiation, each lymphocyte acquires the ability to synthesize antibody molecules when provoked by antigens.
2. T-Lymphocytes or T-Cells:
T-Lymphocytes or T-cells derive their name from their site of maturation in the thymus. They are major players in the cell-mediated immune response and also have an important role in B-cell activation. T-cells themselves do not secrete antibodies (immunoglobulin) like B-cells.
They are immunologically specific and are directly involved in cell-mediated immune responses, can carry a vast repertoire of immunologic memory, and can function in a variety of effector and regulatory way.
The main effector functions include tuberculin reaction (delay-ed hypersensitivity response), destruction of tissue grafts, secretion of soluble chemical mediators called lymphokines and their ability to perform killer functions of other cells.
The regulatory functions involve their cooperation with B-lymphocytes to produce antibodies. In additions to these functions, some subpopulations of T-cells contribute immune responses such as cytotoxicity, suppression, and killer properties.
Like B-lymphocytes, T-lymphocytes have specific receptors on the plasma membrane surface for antigen. The receptors on T-cell membrane are called T-cell receptors (TCRs).
Although T-cell receptor (TCR) is structurally distinct from immuno-globulin (the membrane receptor of B-lymphocyte), it does share some common structural features with the immunoglobulin molecule, most notably in the structure of its antigen- binding site.
Unlike the membrane-bound antibody on B-cells that recognise free antigen, the T-cell receptor (TCR) does not recognize free antigen instead it recognizes the hound one to particular class of a self-molecule (e.g., major histocompatibility complex molecule or MHC molecule) displayed on self-cells (e.g., antigen presenting cells or APCs, virus-infected cells, cancer cells, and grafts). It is the T-cell system that helps eliminating these altered self-cells that threaten the normal functioning of the body.
Cell # 3. Monocytes:
Monocytes (G. monos = single; cyte = cell) are mononuclear phagocytic leucocytes possessing an oval or kidney-shaped nucleus and granules in the cytoplasm that stain grey-blue (Fig. 42.8).
Monocytes are produced in bone marrow. During hematopoiesis in bone marrow, granulocyte-monocyte progenitor cells differentiate into pro-monocytes, which-leave the bone marrow and enter the blood where they further differentiate into mature monocytes.
Mature monocytes circulate in the blood stream for about eight hours, enlarge in size, migrate into the tissues, and differentiate into specific tissue macrophages or into myeloid dendritic cells.
Cell # 4. Macrophages:
Macrophages (G. macros = large; phagein = to eat), as noted above, are differentiated from monocytes into the tissues of the body.
Differentiation of a monocyte into a tissue macrophage (Fig. 42.9) involves a number of changes:
(i) The monocyte enlarges five- to ten-fold,
(ii) Its intracellular organelles increase in both number (especially lysosomes and phagolysosomes) and complexity,
(iii) The cell acquires increased phagocytic ability,
(iv) Produces higher levels of hydrolytic enzymes,
(v) Begins to secrete a variety of soluble factors, and
(vi) Develops ruffles or microvilli on the surface of its plasma membrane.
Macrophages are transported throughout the body. Some macrophages reside in particular tissues and become fix macrophages. Others remain motile by amoeboid movement throughout the body and are called free or wondering macrophages.
Macrophages serve different functions i different tissues and are named according to their tissue location, e.g., histiocytes in connective tissues, osteoclasts in bone, microglial cells in the brain, alveolar macrophages in the lung, kupffer cells in the liver, and mesangial cells in the kidney.
Macrophages normally remain in a resting state and are activated for effective functioning. They are activated by a variety of stimuli such as interferon gamma (IFN-γ) secreted by activated T helper (TH) cells, mediators of inflammatory response, components of bacterial cell walls, etc.
Activated macrophages secrete different types of cytotoxic proteins that help them eliminate large number of pathogens including vims-infected cells, malignant cells, and intracellular bacteria.
Activated macrophages also display class II MHC molecules that allow them to act more effectively as antigen-presenting cells (APCs). Thus, macrophages and T helper (TH) cells facilitate each other’s activation during the immune response.
Macrophages are highly phagocytic and they are capable of ingesting and digesting exogenous antigens (e.g., whole microorganisms and insoluble particles) and exogenous matter (e.g., injured or dead host cells, cellular debris, activated clotting factors).
Cell # 5. Granulocytes:
Granulocytes (Fig. 42.10) are those white blood cells (leucocytes) which have irregular-shaped nuclei with two to five lobes and granulated cytoplasmic matrix.
Granules of cytoplasmic matrix contain reactive substances that kill microorganisms and enhance inflammation. Granulocytes are also called polymorphonuclear leucocytes (PMNs). Three types of granulocytes are recognised in the body and they are: basophils, eosinophils, and neutrophils.
1. Basophils:
Basophils (G. basis = base; philein = to love) possess bi-lobed irregular-shaped nucleus and cytoplasmic matrix granules that stain bluish-black with basic dyes (e.g., methylene blue). These granulocytes are non-phagocytic cell that function by releasing pharmacologically active substances (e.g., histamine, prostaglandins, serotonin, and leucotrienes) from their cytoplasmic granules upon appropriate stimulation.
Since these pharmacologically active substances influence the tone and diameter of blood vessels, they are collectively termed vasoactive mediators. Basophils possess high-affinity receptors for immunoglobulin-E (IgE) antibody and thereby become coated with these antibodies.
Once coated, antigens trigger the basophil cells to secrete vasoactive mediators which are inflammatory and play a major role in certain allergic responses (e.g., eczema, hay fever, and asthma). Basophils, however, comprise less than 1 % of white blood cells, are non-motile, and remain confined to the blood stream.
2. Eosinophils:
Eosinophils (G. eos = dawn; philein = to love) have a bi-lobed nucleus connected by a slender thread of chromatin and prominent acidophilic granules in cytoplasmic matrix. Eosinophils, like neutrophils, are motile cells that migrate from bloodstream into tissue spaces.
These granulocytes are considered to play a role in the defence against parasitic organisms (protozoans and helminth parasites) by phagocytosis.
They release mainly cationic proteins and reactive oxygen metabolites into the extracellular fluid. These substances damage the plasma membrane of the parasite. Eosinophils constitute only 3-5% of the white blood cells and their acidophilic granules stain red with acidic dyes.
3. Neutrophils:
Neutrophils (L. neuter – neither; philein = to love) possess a three- to five-lobed nucleus connected by slender threads of chromatin, and contain fine primary and secondary granules in cytoplasmic matrix. Neutrophils, like eosinophils, are motile cells that migrate from bloodstream into the tissue.
These granulocytes circulate in the bloodstream for 7 to 10 hours before their migration into the tissues where they enjoy a life span of only a few days. Approximately 60% of the circulating white blood cells (leucocytes) in human are the neutrophils. Like macrophages, the’ primary function of neutrophils is phagocytosis of foreign or dead cells and pinnocytosis of pathological immune complexes.
Phagocytosis by neutrophils is similar to that operated by macrophages except that the lytic enzymes and bactericidal substances in neutrophils are contained within primary and secondary granules instead of lysosomes in macrophages. The primary granules are larger and denser and contain peroxidase, lysozyme, and various hydrolytic enzymes.
The secondary granules are smaller and contain collagenase, lactoferrin, and lysozyme. Both primary and secondary granules fuse with phagosome, whose contents are then digested and the remains excreted much as they are in macrophages.
Neutrophils, like macrophages, also use oxygen-dependent and oxygen-independent pathways to generate antimicrobial substances and defensins to kill ingested microorganisms. Neutrophils generate more reactive oxygen intermediates and reactive nitrogen intermediates and express higher levels of defensins than macrophages do.
Cell # 6. Dendritic Cells:
Dendritic cells constitute only 0.2% of WBCs (leucocytes) in the blood and are present in even smaller numbers in skin and mucous membranes of the nose, lungs, and intestines. They derive their name due to long membrane extensions resembling the dendrites of nerve cells.
Dendritic cells arise from hematopoietic stem cells in the bone marrow via different pathways and in different locations (Fig. 42.11); they descend through both the myeloid and lymphoid lineages. Stem cell-originated dendritic cells are of four types: Langerhans cells, interstitial dendritic cells, myeloid dendritic cells, and lymphoid dendritic cells.
Despite differences, all the stem cell-originated mature dendritic cells perform the same major function of presenting antigen to T helper (TH) cells by expressing high levels of both class II MHC molecules and members of the co-stimulatory B-7 family, and thereby play an important accessory role in the specific immune response.
This pattern of functioning makes dendritic cells more potent antigen-presenting cells (APCs) than macrophages and B-lymphocytes, both of which need to be activated before they can function as antigen-presenting cells (APCs).
In addition to dendritic cells originated in bone marrow, there are another type of dendritic cells, the follicular dendritic cells, that do not arise in bone marrow and perform their function in a different ways as they do not express class II MHC molecules and do not act as antigen-presenting cells (APCs).
Follicular dendritic cells express high levels of membrane receptors for antibody; which allows the binding of antibody complexes. The interaction of B-lymphocytes with this bound antigen can have important effects on B-lymphocyte responses.
Cell # 7. Mast Cells:
Mast cell precursors originate in the bone marrow and are released into the blood as undifferentiated cells. Mast cells are not differentiated from their precursors until the latter leave the blood and enter the tissues. Mast cells are found in a variety of tissues including the skin, connective tissues of various organs, and mucosal epithelial tissue of the respiratory, genitourinary, and digestive tracts.
These cells, like basophils, possess large numbers of granules in cytoplasmic matrix. The granules in cytoplasm contain histamine and other pharmacologically active substances that contribute to the inflammatory response. Mast cells, together with basophils, play an important role in the development of allergies and hypersensitivities.