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Term Paper on the Immune System
Term Paper # 1.
Cells of the Immune System:
The immune system in our body is a defensive system in host which consists of widely distributed cells, tissues and organs which recognize foreign substances and many micro-organisms and then neutralizes or destroys them. The cell which is responsible for both non-specific and specific immunity mainly consists of the leukocytes or white blood cells. Leukocytes generally originate from pluripotent stem cell in the fetal liver and in the bone marrow of the animal.
Pluripotent stem cells which are present in the bone marrow get divided into two blood cell forms. First is the lymphoid stem cell which gives rise to B cells, T cells and natural killer cells (NK cells). The common myeloid progenitor cell gives rise to the granulocytes (neutrophils, eosinophils, basophils), and monocytes gives rise to macrophages and dendritic cells. There is unknown procedure that give rise to mast cells, megakaryocytes produces platelets, and the erythroblast produces RBCs.
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1. Lymphocytes:
Lymphocytes responsible for adaptive immune response are mononuclear leukocyte. They constitute 20 to 40% of WBC. They are generally present in blood, lymph and in lymphoid organs such as the thymus, lymph nodes, spleen and appendix. 99% of lymphocytic cells are found in lymph.
Lymphocytes are of three types:
i. B Lymphocytes or B-Cells:
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B lymphocyte mature in the bone marrow i.e., in birds is Bursa of Fabricius and expresses membrane-bound antibody. When it interacts with antigen, it gets differentiated into antibody-secreting plasma cells and memory cells. These are cell types which are capable of producing antibody molecules and therefore the central cellular component of humoral immune responses. B-cells also serve as antigen presenting cells (APC).
ii. T Lymphocytes or T-Cells:
T lymphocytes arise in the bone marrow. But unlike B cells, they mature in the thymus gland. During their maturation within the thymus, the T-cell comes to express a unique antigen-binding molecule, called the T-cell receptor, on the membrane. T-cells do not make any antibodies but perform various effector functions. When APC bring antigens into the secondary lymphoid organ, the T-cells help in eliminating APCs, cancer cells, virus-infected cells or grafts which have altered self-cells.
T-cells generally express distinct membrane molecules. On the basis of presence of one or the other of two membrane molecules, CD4+ and CD8+, there are two sub-population of T-cells – T helper (TH) cells which carries CD4+ membrane glycoprotein on their surfaces and T cytotoxic (Tc) cells which carries CD8+ membrane glycoprotein on their surfaces.
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In addition, all the T-cell subpopulations express the T-cell receptor which includes CD3. The ratio of CD4+ and CD8+ T cells is approximately 2:1 in normal human peripheral blood, but it may be significantly altered by immunodeficiency and autoimmune diseases. Secondly, cytotoxic T cells provide protection against intracellular pathogens mainly viruses, bacteria and parasites which multiply in the host-cell cytoplasm, where they get protection from the attack of antibodies.
They provide this protection by killing the infected cell before the microbes can proliferate and escape from the infected cell to infect neighboring cells. Helper cells help to stimulate B cells to make the antibodies which inactivate or eliminate extra-cellular pathogens and their toxic products. They also activate to destroy any intracellular pathogens multiplying within the macrophage’s phagosomes, and they help to activate cytotoxic T cells to kill infected target cells.
iii. Natural Killer (NK) Cells:
Natural killer cells (NK cells) are a class of lymphocytes that are different from cytotoxic T cells. NK cells play an important role in destroying cells which are infected by intracellular pathogens. NK cells are neither T cells nor B cells. They constitute 5-10% of lymphocyte population.
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Their numbers are not enhanced, nor do they exhibit memory after stimulation. NK cells mainly destroy the target cells which are not killed by phagocytosis but by releasing biologically potent molecules. They resemble Tc cells in their ability to destroy infected cells. For example, NK cells also use enzymes to kill their targets.
However, NK cells differ from Tc cells in the way that they kill targets in the absence of a specific antigen. NK cells are capable of destroying malignant and virus-infected cells without previous exposure or contact with the foreign antigen. For example, in Chediak-Higashi syndrome – an autosomal recessive disorder – associated with lack of NK cells.
NK cells recognize targets through two ways – In some, they employ NK cells receptors which can detect abnormalities such as low MHC I display and unusual markers on cancer cells and cells infected by some viruses. Another way in which NK cells recognize potential target cells based upon the fact that some tumor cells and cells infected by certain viruses display antigens against which the immune system has made an antibody response, so that anti-tumor or antiviral antibodies are bound to their surfaces. NK cells expresses membrane receptor CD16 for the IgG, they can bind to these antibodies, and subsequently destroy the targeted cells. This whole process is known as antibody-dependent cell-mediated cytotoxicity (ADCC).
2. Granulocytes:
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Granulocytes are irregular-shaped nuclei with 2-5 lobes and are also known as poly-morphonuclear leukocytes. Their cytoplasmic matrix consists of granules which contain reactive substances that kill micro-organisms and enhance inflammation.
There are four types of granulocytes:
i. Neutrophils
ii. Eosinophils,
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iii. Basophils, and
iv. Mast cells.
i. Neutrophils:
The neutrophils have a multi-lobed nucleus and a granulated cytoplasm. Neutrophils get stained with both acidic and basic dyes. Due to their irregular-shaped nuclei, they are also called as poly-morphonuclear neutrophils or PMNs. Neutrophils are produced by hematopoiesis in the bone marrow. They are released into the peripheral blood and circulate for 7-10 hour before migrating into the tissues, where they have a life span of only a few days. Like macrophages, neutrophils are active phagocytic cells.
ii. Eosinophils:
Eosinophils have bilobed nucleus and stain with acidic dye eosin. It comprises of 2-5% of WBCs. Eosinophils are motile phagocytic cells that can migrate from the blood into the tissue space. They play an important role in the defense against protozoan and helminth parasites, mainly by releasing cationic peptides and reactive oxygen intermediates into the extra-cellular fluid.
iii. Basophils:
Basophils have lobed nucleus and stains with basic dye methylene blue. It comprises less than 1% of total WBCs. They are non-phagocytic, and they release substances that cause an allergic response. These molecules include histamine, prostaglandins, serotonin, and leukotrienes. Basophils and mast cells possess high affinity receptors for one type of antibody, known as IgE.
iv. Mast Cells:
Mast-cell precursors are formed in bone-marrow and released into blood in an undifferentiated state, unless and until they reach tissues. They have large number of cytoplasmic granules containing histamine. Mast cells and basophils play role in allergic responses.
3. Mononuclear Phagocytes:
The mononuclear phagocytes include monocytes circulating in the blood and macrophages in the tissues.
i. Monocytes:
Monocytes are mononuclear phagocytic leukocytes that circulate briefly in the blood stream before migrating into the tissues where it becomes macrophages or dendritic cells.
ii. Macrophages:
Macrophages are phagocytes which are derived from blood monocytes. Monocyte is a small, spherical cell with few projections, abundant cytoplasm, and many granules.
Macrophages play a role in phagocytosis, which includes the following:
a. Alveolar macrophages, in the lung.
b. Peritoneal macrophages, free-floating in peritoneal fluid.
c. Mesangial cells, in the kidney.
d. Splenic macrophages, in the white pulp.
e. Kupffer cells, in the liver; large cells with many cytoplasmic projections.
f. Osteoclasts, in bone.
g. Microglial cells, in the central nervous tissue.
iii. Dendritic Cells:
Dendritic cells are derived from bone marrow cells that descend through the myeloid and lymphoid lineages and are specialized for antigen presentation to helper T-cells.
Dendritic cells are classified into four types:
a. Langerhans cells.
b. Interstitial dendritic cells.
c. Myeloid dendritic cells.
d. Lymphoid dendritic cells.
Despite their differences they all consist of high levels of class II MHC molecules. Dendritic cells acquire antigen by phagocytosis; the antigen is processed, and mature dendritic cells present it to TH cells.
Term Paper # 2.
Organs of the Immune System:
The lymphatic organs are those organs in which B and T-lymphocytes are maturated, differentiated, and proliferated.
They are generally divided into two categories:
A. Primary Lymphoid Organs:
The primary (central) lymphoid organs are those in which the maturation of T and B lymphocytes occurs. Bone marrow and thymus are examples of primary (central) lymphoid organs.
1. Thymus Gland:
Thymus is the site where T lymphocytes mature. Progenitor cells from the bone marrow migrate into the thymus gland, where they differentiate into T-lymphocytes. It is a flat, bilobed organ situated above the heart. Each lobe is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of connective tissue called trabeculae.
Each lobule is organized into two compartments – the outer compartment known as cortex and the inner compartment known as medulla. T lymphocytes mature in the cortex and migrate to the medulla, where they encounter macrophages and dendritic cells.
And undergo thymic selection, which results in the formation of mature, functional T cells which then leave to enter the peripheral blood circulation; from there they are transported to the secondary lymphoid organs. It is in secondary lymphoid organs where the T cells encounter and respond to foreign antigens.
2. Bursa of Fabricius and Bone Marrow:
A primary lymphoid organ was first discovered in birds. In birds, B cells undergo maturation in the bursa of fabricius. This organ, situated near the cloaca, consists of lymphoid centers that contain epithelial cells and lymphocytes. These lymphocytes consist solely of antibody-producing B cells.
Mammals do not have a bursa of fabricius. B cells differentiate from hematopoietic stem cells in the fetal liver. Each mature B lymphocyte bears antigen-specific receptors that have a structure and specificity identical to the antibody later synthesized by the B cell. The mature B cells are transported by the circulating blood to the secondary lymphoid organs, where they encounter and respond to foreign antigens.
B. Secondary Lymphoid Organs/Tissues:
Mature B and T lymphocytes migrate from bone marrow and thymus, respectively, through the bloodstream to the secondary (peripheral) lymphoid organs. These secondary (peripheral) lymphoid organs are those organs in which antigen-driven proliferation and differentiation take place.
The major secondary lymphoid organs are the spleen, the lymph nodes and mucosa associated lymphoid tissue (MALT). Spleen and lymph nodes are the highly organized secondary lymphoid organs.
The secondary lymphoid organs have two major functions:
i. They are highly efficient in trapping and concentrating foreign substances.
ii. They are the main sites of production of antibodies and the induction of antigen-specific T lymphocytes.
1. Spleen:
The spleen is the largest of the secondary lymphoid organs. It is highly efficient in trapping and concentrating foreign substances which are present in the blood. It is the major organ in the body in which antibodies are synthesized and from which they are released into the blood for circulation.
The interior of spleen is a compartmentalized structure. The compartments are of two types—Red pulp and White pulp. Red pulp is the site where old and defective RBCs are destroyed and removed, whereas white pulp forms PALS (Peri-Arteriolar Lymphoid Sheath) which are rich in T-cells. Approximately 50% of spleen cells are B lymphocytes; 30-40% is T lymphocytes.
2. Mucosa Associated Lymphoid Tissue:
The majority of secondary lymphoid tissue in the human body is located within the lining of respiratory, digestive and genitourinary tracts. These are collectively called as mucosa associated lymphoid tissue (MALT). There are several types of MALT. Two major MALT includes bronchial associated lymphoid tissue (BALT) and gut-associated/lymphoid tissue (GALT). GALT includes the tonsils, adenoids, and specialized regions in the small intestine called Peyer’s patches.
3. Lymph Nodes:
Lymph nodes are small encapsulated bean shaped structures which are normally < 1 cm in diameter and are found in various regions throughout the body. The lymph nodes are composed of a medulla and a cortex, which is surrounded by a capsule of connective tissue.
They are packed with lymphocytes, macrophages, and dendritic cells. The cortical region contains primary lymphoid follicles. After antigenic stimulation, these structures enlarge to form secondary lymphoid follicles with germinal centers containing dense populations of lymphocytes (mostly B cells).
The deep cortical area or para-cortical region contains T cells and dendritic cells. Antigens are brought into these areas by dendritic cells, which present antigen fragments to T cells. The medullary area of the lymph node contains antibody-secreting plasma cells that have traveled from the cortex to the medulla via lymphatic vessels.
Lymph nodes are highly efficient in trapping antigen that enters through the afferent lymphatic vessels. In the node, the antigen interacts with macrophages, T cells, and B cells, and that interaction, brings about in immune response, manifested by the generation of antibodies and antigen-specific T cells.