_IMMUNE SYSTEM AND IMMUNE RESPONSE
_ Organs of the Immune
System
1.Primary (central) lymphoid organs. In human these are bone marrow and thymus where lymphocytes mature and become antigenically committed in postnatal life.
2.Secondary (Peripheral) lymphoid organs. These are lymph nodes, spleen, and MALT (mucosal-associated lymphoid tissues- like tonsils, Peyer's patches, appendix). In secondary lymphoid organs, mature B and T lymphocytes interact with the antigen, become activated and undergo clonal proliferation and differentiation into effector and memory cells.
3.Tertiary lymphoid tissue, e.g. cutaneous-associated lymphoid tissue.
Cells of Immune System
1. B and T lymphocytes are the cells of the immune system responsible for specific acquired immunity.
2.Antigen presenting cells (APC). These are macrophages, dendritic cells, Langerhans' cells and B cells. APC ingests the foreign material which is degraded, and fragments of antigen in conjunction with class II MHC proteins are presented on the cell surface for interaction with TCR of CD4 helper T cells.
3.Phagocytes. Neutrophils, macrophages and other cells of the mononuclear phagocyte system.
Macrophages have three main functions which are greatly enhanced when activation of macrophage occurs : (a) Phagocytosis, (b) Antigen presentation, and (c) Cytokine production: IL-1, IL-8 and TNF are important ones.
4.NK cells (Natural Killer cells). Nk cells can kill virus-infected cells and cancer cells. Killing is nonspecific, i.e. not specific for viral or cancer antigens. They kill by producing perforins and granzymes, which cause apoptosis of target cells.
5.Eosinophils, basophils and mast cells play nonspecific roles.
1.Primary (central) lymphoid organs. In human these are bone marrow and thymus where lymphocytes mature and become antigenically committed in postnatal life.
2.Secondary (Peripheral) lymphoid organs. These are lymph nodes, spleen, and MALT (mucosal-associated lymphoid tissues- like tonsils, Peyer's patches, appendix). In secondary lymphoid organs, mature B and T lymphocytes interact with the antigen, become activated and undergo clonal proliferation and differentiation into effector and memory cells.
3.Tertiary lymphoid tissue, e.g. cutaneous-associated lymphoid tissue.
Cells of Immune System
1. B and T lymphocytes are the cells of the immune system responsible for specific acquired immunity.
2.Antigen presenting cells (APC). These are macrophages, dendritic cells, Langerhans' cells and B cells. APC ingests the foreign material which is degraded, and fragments of antigen in conjunction with class II MHC proteins are presented on the cell surface for interaction with TCR of CD4 helper T cells.
3.Phagocytes. Neutrophils, macrophages and other cells of the mononuclear phagocyte system.
Macrophages have three main functions which are greatly enhanced when activation of macrophage occurs : (a) Phagocytosis, (b) Antigen presentation, and (c) Cytokine production: IL-1, IL-8 and TNF are important ones.
4.NK cells (Natural Killer cells). Nk cells can kill virus-infected cells and cancer cells. Killing is nonspecific, i.e. not specific for viral or cancer antigens. They kill by producing perforins and granzymes, which cause apoptosis of target cells.
5.Eosinophils, basophils and mast cells play nonspecific roles.
_B AND T LYMPHOCYTES (B cells and T cells)
The
letter "B" was derived from the first letter of "Bursa of Fabricius"
where B cells mature in birds. In human B cells mature in bone
marrow. T cells derive their names from first letter of thymus where they mature.
B cells and T cells are the specific immune cells for acquired immunity, i.e. they are capable of mounting immune response. B cells can function as antigen-presenting cell for helper T cells.
Origin and Differentiation: Development and differentiation of B and T cells occur in two stages :
1. Antigen-independent stage occurs within primary lymphoid organs. In the bone marrow lymphoid stem cells originate from haematopoietic stem cells. The lymphoid stem cells differentiate into pre-B and pre-T cells. Further development of pre-B cells occurs within bone marrow in mammals. Pre-T cells migrate within thymus where further development and differentiation occurs. B and T cells mature and each of these cells becomes committed to an epitope (particular antigenic specificity) within the primary lymphoid organs. The specificity of these cells depends on their "antigen specific receptors" on the surface. These are mature or immunocompetent B and T cells capable of mounting an immune response. The mature B and T cells migrate into blood and secondary lymphoid tissues. All the progeny cells derived from a single mature lymphocyte constitute a lymphocyte clone.
2.Antigen-dependent activation of B and T cells by antigens occurs within secondary lymphoid organs. Interactions between cells occur either directly or via interleukins. Exposure to an antigen selectively binds to the cells having its specific receptor without affecting other cells in the population- a phenomenon known as clonal selection. On antigenic activation the cells undergo clonal proliferation and differentiation into effector cells and memory cells.
In lymph nodes, the follicles contain B lymphocytes and are the sites of antibody production. Following antigenic stimulation, secondary follicles develop. Juxtamedullary area contains T lymphocytes. In the spleen, B cells are located in white pulp and T cells ensheath the arteries. There is recirculation of lymphocytes between the blood and lymphoid tissues.
In peripheral blood, T cells are 70-80%, B cells 10-15% and NK cells 5-10 %. B cells have a shorter life span of 5 to 7 days, and T cells have a long life span of months to years.
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B cells and T cells are the specific immune cells for acquired immunity, i.e. they are capable of mounting immune response. B cells can function as antigen-presenting cell for helper T cells.
Origin and Differentiation: Development and differentiation of B and T cells occur in two stages :
1. Antigen-independent stage occurs within primary lymphoid organs. In the bone marrow lymphoid stem cells originate from haematopoietic stem cells. The lymphoid stem cells differentiate into pre-B and pre-T cells. Further development of pre-B cells occurs within bone marrow in mammals. Pre-T cells migrate within thymus where further development and differentiation occurs. B and T cells mature and each of these cells becomes committed to an epitope (particular antigenic specificity) within the primary lymphoid organs. The specificity of these cells depends on their "antigen specific receptors" on the surface. These are mature or immunocompetent B and T cells capable of mounting an immune response. The mature B and T cells migrate into blood and secondary lymphoid tissues. All the progeny cells derived from a single mature lymphocyte constitute a lymphocyte clone.
2.Antigen-dependent activation of B and T cells by antigens occurs within secondary lymphoid organs. Interactions between cells occur either directly or via interleukins. Exposure to an antigen selectively binds to the cells having its specific receptor without affecting other cells in the population- a phenomenon known as clonal selection. On antigenic activation the cells undergo clonal proliferation and differentiation into effector cells and memory cells.
In lymph nodes, the follicles contain B lymphocytes and are the sites of antibody production. Following antigenic stimulation, secondary follicles develop. Juxtamedullary area contains T lymphocytes. In the spleen, B cells are located in white pulp and T cells ensheath the arteries. There is recirculation of lymphocytes between the blood and lymphoid tissues.
In peripheral blood, T cells are 70-80%, B cells 10-15% and NK cells 5-10 %. B cells have a shorter life span of 5 to 7 days, and T cells have a long life span of months to years.
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_B lymphocytes (B cells)
_ B cells are responsible
for humoral immune response due to synthesis and secretion of antibody by
plasma cells.
Antigen-independent development: Lymphoid stem cells derived from haematopoietic stem cell differentiate into pre-B cells to mature B cells in bone marrow. During maturation B cells develop antigenic specificity by gene rearrangement. Pre-B cells express cytoplasmic µ chains but no light chains or surface immunoglobulin. B cells display immunoglobulin molecules (105/cell). Mature B cells express monomer IgM on the surface. Surface IgM binds the antigen itself. Surface receptor IgM has the same antigen binding specificity as the secreted IgM antibody. IgD is also a surface receptor for antigen on B cells. Each B cell is programmed to make only one antibody (immunoglobulin) which is placed on the cell surface as receptor (one cell one antibody). Each individual has about 1011 immunologically responsive B cells, i.e. there are about 10" different specificities. These immunocompetent or mature B cells move to the blood and peripheral lymphoid tissue.
B cells bearing antigen receptors for self antigens undergo deletion, a process that induces self-tolerance and prevents autoimmune disease.
Antigen-dependent activation. B cells can recognize foreign proteins, carbohydrates, lipids and other types of molecules as antigen. An antigen selects B cell by clonal selection, i.e. it selects B cells programmed to make its own antibody. Activation of B cells (clone) by specific antigen leads to proliferation (clonal expansion), and differentiation of the B cells of the clone into plasma cells and memory cells. Plasma cells synthesize and secrete antibody. Secreted free antibody IgM is a pentamer.
Activation of B cells
Virtually all antigens require help by helper T cells to generate an humoral or antibody response and thus these are thymus or T cell-dependent antigens. Some antigens are T cell-independent.
I. Humoral immune response by T cell-dependent antigen requires the participation of CD4 helper T cells. Two signals are needed for B cell activation.
Antigen-independent development: Lymphoid stem cells derived from haematopoietic stem cell differentiate into pre-B cells to mature B cells in bone marrow. During maturation B cells develop antigenic specificity by gene rearrangement. Pre-B cells express cytoplasmic µ chains but no light chains or surface immunoglobulin. B cells display immunoglobulin molecules (105/cell). Mature B cells express monomer IgM on the surface. Surface IgM binds the antigen itself. Surface receptor IgM has the same antigen binding specificity as the secreted IgM antibody. IgD is also a surface receptor for antigen on B cells. Each B cell is programmed to make only one antibody (immunoglobulin) which is placed on the cell surface as receptor (one cell one antibody). Each individual has about 1011 immunologically responsive B cells, i.e. there are about 10" different specificities. These immunocompetent or mature B cells move to the blood and peripheral lymphoid tissue.
B cells bearing antigen receptors for self antigens undergo deletion, a process that induces self-tolerance and prevents autoimmune disease.
Antigen-dependent activation. B cells can recognize foreign proteins, carbohydrates, lipids and other types of molecules as antigen. An antigen selects B cell by clonal selection, i.e. it selects B cells programmed to make its own antibody. Activation of B cells (clone) by specific antigen leads to proliferation (clonal expansion), and differentiation of the B cells of the clone into plasma cells and memory cells. Plasma cells synthesize and secrete antibody. Secreted free antibody IgM is a pentamer.
Activation of B cells
Virtually all antigens require help by helper T cells to generate an humoral or antibody response and thus these are thymus or T cell-dependent antigens. Some antigens are T cell-independent.
I. Humoral immune response by T cell-dependent antigen requires the participation of CD4 helper T cells. Two signals are needed for B cell activation.