_ACQUIRED IMMUNITY
_Acquired
or adaptive immunity develops following exposure to an antigen,
and is mediated by B lymphocytes (B cells), or T
lymphocytes (T cells), or both, having specific surface
receptor
for
the same antigen.
T cells are two types: (1) CD4 T cells or helper T (Th) cells and (2) CD8 T cells or cytotoxic T (Tc) cells.
Characteristics of acquired immunity. B and T cells are specific immune cells responsible for these characteristics. (1) Antigenic specificity (Permits to distinguish among antigens, and their actions are specifically directed against the antigen that initiated the response), (2) Diversity (Antigens are recognized by different lymphocytes), (3) Immunologic memory (Re-exposure to the same antigen induces more rapid and effective response), and (4) Self / nonself discrimination.
Recognition of antigen : B and T cells recognize and bind antigens or epitopes which are specific sites on antigen by their specific antigen-binding surface receptors. Antigen specific receptor on B cells is IgM monomer. B cells recognize and bind the antigen directly with its specific receptor IgM. Antigen specific receptor on T cells is TCR (T cell receptor). TCR of T cells recognize and bind the antigen only in association with MHC (major histocompatibility complex). TCR of CD4 helper T cell (Th cell) binds peptide antigen in association with class II MHC protein which appear on the surface of antigen presenting cell (APC), e.g. macrophage. This is the essential first step in activation of most immune responses (Fig. 63.1(1)). TCR of CD8 cytotoxic T cell (Tc cell) binds peptide antigen in association with class I MHC molecule that appears on the surface of a cell like virus infected cell (altered self-cell).
Antigen recognition molecules are : (1) Antibodies and B cell surface receptor for antigen, (2) Antigen specific T cell surface receptor, and (3) Major histocompatibility complex to present peptide antigens to T cells.
Immune response: Immune response is the development of acquired immunity against an antigen (Fig. 63.1). The two arms of the immune response: antibody-mediated (humoral) and cell-mediated develop concurrently. Immune response occurs due to activation of B and/or T cells on recognition of specific antigen. Activation of lymphocytes leads to their proliferation (divides repeatedly), and differentiation into effector cells and memory cells. Activation of B cells develops humoral (antibody-mediated) immune response, and activation of T cells develops cell-mediated immune response. Exposure to an antigen by an individual for the first time is called primary immune response and re-exposure to the same antigen is called secondary immune response which develops due to immunologic memory. After the first exposure, antigen-specific "memory cells" are formed which are responsible for immunologic memory. On subsequent exposure even months or years after, there is rapid response by the memory cells.
T cells are two types: (1) CD4 T cells or helper T (Th) cells and (2) CD8 T cells or cytotoxic T (Tc) cells.
Characteristics of acquired immunity. B and T cells are specific immune cells responsible for these characteristics. (1) Antigenic specificity (Permits to distinguish among antigens, and their actions are specifically directed against the antigen that initiated the response), (2) Diversity (Antigens are recognized by different lymphocytes), (3) Immunologic memory (Re-exposure to the same antigen induces more rapid and effective response), and (4) Self / nonself discrimination.
Recognition of antigen : B and T cells recognize and bind antigens or epitopes which are specific sites on antigen by their specific antigen-binding surface receptors. Antigen specific receptor on B cells is IgM monomer. B cells recognize and bind the antigen directly with its specific receptor IgM. Antigen specific receptor on T cells is TCR (T cell receptor). TCR of T cells recognize and bind the antigen only in association with MHC (major histocompatibility complex). TCR of CD4 helper T cell (Th cell) binds peptide antigen in association with class II MHC protein which appear on the surface of antigen presenting cell (APC), e.g. macrophage. This is the essential first step in activation of most immune responses (Fig. 63.1(1)). TCR of CD8 cytotoxic T cell (Tc cell) binds peptide antigen in association with class I MHC molecule that appears on the surface of a cell like virus infected cell (altered self-cell).
Antigen recognition molecules are : (1) Antibodies and B cell surface receptor for antigen, (2) Antigen specific T cell surface receptor, and (3) Major histocompatibility complex to present peptide antigens to T cells.
Immune response: Immune response is the development of acquired immunity against an antigen (Fig. 63.1). The two arms of the immune response: antibody-mediated (humoral) and cell-mediated develop concurrently. Immune response occurs due to activation of B and/or T cells on recognition of specific antigen. Activation of lymphocytes leads to their proliferation (divides repeatedly), and differentiation into effector cells and memory cells. Activation of B cells develops humoral (antibody-mediated) immune response, and activation of T cells develops cell-mediated immune response. Exposure to an antigen by an individual for the first time is called primary immune response and re-exposure to the same antigen is called secondary immune response which develops due to immunologic memory. After the first exposure, antigen-specific "memory cells" are formed which are responsible for immunologic memory. On subsequent exposure even months or years after, there is rapid response by the memory cells.
Humoral
immune response due to activation of B cells leads
to production of humoral or antibody-mediated immunity,
and cell-mediated immune response due to activation
of T cells leads to production of cell-mediated immunity.
On immune response the two arms of acquired immunity are :
1. Humoral (Antibody-mediated) Immunity
Humoral immune response: Activation of B cell needs binding of the antigen to specific surface receptor IgM on B cell. Activation of B cells by most antigens requires the participation of helper T cells (T-cell dependent antigens). APC, e.g. macrophage ingest foreign substance, e.g. microorganism and process into antigen or epitope which in association with class II MHC appear on the surface of the macrophage and interact with specific TCR of helper T cell. Activated helper T cell produces IL-2 (T cell growth factor), IL-4 (B cell growth factor) and IL-5 (B cell differentiation factor). IL-4 and IL-5 are required to activate B cell. Activation of B cells leads to their proliferation and differentiation into effector plasma cells and memory cells. Plasma cells produce and secrete antibody (immunoglobulin) specific for the antigen.
Functions. Humoral or antibody-mediated immunity develops mainly against extracellular pathogens such as staphylococci, streptococci; encapsulated pathogens (e.g. pneurnococcus, neisseria, haemophilus); and against pathogens that produce exotoxin (e.g. Corynebacterium diphtheriae). Antibodies neutralize exotoxins and some viruses (e.g. hepatitis A virus, hepatitis B virus, rabies virus). IgM and IgG can activate the complement system which can opsonize pathogens leading to ingestion by phagocytic cells, or can cause lysis of the organism.
_
1. Humoral (Antibody-mediated) Immunity
Humoral immune response: Activation of B cell needs binding of the antigen to specific surface receptor IgM on B cell. Activation of B cells by most antigens requires the participation of helper T cells (T-cell dependent antigens). APC, e.g. macrophage ingest foreign substance, e.g. microorganism and process into antigen or epitope which in association with class II MHC appear on the surface of the macrophage and interact with specific TCR of helper T cell. Activated helper T cell produces IL-2 (T cell growth factor), IL-4 (B cell growth factor) and IL-5 (B cell differentiation factor). IL-4 and IL-5 are required to activate B cell. Activation of B cells leads to their proliferation and differentiation into effector plasma cells and memory cells. Plasma cells produce and secrete antibody (immunoglobulin) specific for the antigen.
Functions. Humoral or antibody-mediated immunity develops mainly against extracellular pathogens such as staphylococci, streptococci; encapsulated pathogens (e.g. pneurnococcus, neisseria, haemophilus); and against pathogens that produce exotoxin (e.g. Corynebacterium diphtheriae). Antibodies neutralize exotoxins and some viruses (e.g. hepatitis A virus, hepatitis B virus, rabies virus). IgM and IgG can activate the complement system which can opsonize pathogens leading to ingestion by phagocytic cells, or can cause lysis of the organism.
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_ 2. Cell-mediated Immunity (CMI)
T cell-mediated immunity has two components depending on cell type involved: CD4 T cell and CD8 T cell-mediated immunity.
(a) CD4 T cell (Th cell)- mediated immunity: Delayed hypersensitivity also develops.
An example : Macrophage (APC) ingest microorganism, e.g. Mycobacterium tuberculosis which has entered the body. The bacterium is broken down into peptide antigens or epitopes which in association with class II MHC protein appear on the surface of macrophage and interact with TCR of specific CD4 helper T cell. Th cell is activated and serves as an effector cell. Cytokines particularly IL-2, TNF and IFN-y are produced. Memory Th cells are also produced. Macrophages are activated by IFN-y. Activated Th cells and activated macrophages mediate effector functions. Delayed hypersensitivity reaction is an important component of cellular immunity.
Functions: The main defence is against intracellular pathogens like mycobacteria, viruses, fungi and protozoa. It may be involved in tumour immunity.
(b) CD8 T cell (Tc cell)- mediated immunity : T cell cytotoxicity
An example : A cell is infected with virus. A viral antigen combined with class I MHC molecule express on the surface of infected cell, and binds to specific TCR of CD8 cytotoxic T cell. Helper T cell is activated by recognizing viral antigen combined with class II MHC molecule on macrophage. IL-2 produced by activated Th cell stimulates proliferation and differentiation into effector and memory Tc cells. Activated Tc cell exhibits cytotoxic activity. Such effector cells are also called cytotoxic T lymphocytes (CTL).
Functions: Activated cytotoxic T cells eliminate virus-infected cells, tumour cell and cells of foreign tissue graft. cytotoxic T cells specifically kill virus-infected cells by releasing perforins that destroy the membrane of the infected cell.
Active immunity and Passive immunity
On mode of acquirement adaptive immunity is classified into active immunity and passive immunity (Table 63.2). Differences between active and passive immunity are given in table 63.3.
Active immunity is induced actively after contact with foreign antigens, e.g. microorganisms. This contact may consist of (1) clinical or subclinical infection, e.g. typhoid fever, measles, chickenpox, diphtheria, and (2) Immunization with an antigen which may be killed or live attenuated vaccine, or toxoid. An individual himself actively produces the antibody and/or effector T cells after contact with foreign antigen. Active immunity develops usually in 7 to 10 days but can be longer depending on nature and dose of antigen and route of administration. Main advantage of active immunity is that the resistance is long-term. A life long immunity may develop, e.g. in diphtheria and measles. Major disadvantage is its slow onset, especially in primary response. Primary and secondary immune responses are evident.
T cell-mediated immunity has two components depending on cell type involved: CD4 T cell and CD8 T cell-mediated immunity.
(a) CD4 T cell (Th cell)- mediated immunity: Delayed hypersensitivity also develops.
An example : Macrophage (APC) ingest microorganism, e.g. Mycobacterium tuberculosis which has entered the body. The bacterium is broken down into peptide antigens or epitopes which in association with class II MHC protein appear on the surface of macrophage and interact with TCR of specific CD4 helper T cell. Th cell is activated and serves as an effector cell. Cytokines particularly IL-2, TNF and IFN-y are produced. Memory Th cells are also produced. Macrophages are activated by IFN-y. Activated Th cells and activated macrophages mediate effector functions. Delayed hypersensitivity reaction is an important component of cellular immunity.
Functions: The main defence is against intracellular pathogens like mycobacteria, viruses, fungi and protozoa. It may be involved in tumour immunity.
(b) CD8 T cell (Tc cell)- mediated immunity : T cell cytotoxicity
An example : A cell is infected with virus. A viral antigen combined with class I MHC molecule express on the surface of infected cell, and binds to specific TCR of CD8 cytotoxic T cell. Helper T cell is activated by recognizing viral antigen combined with class II MHC molecule on macrophage. IL-2 produced by activated Th cell stimulates proliferation and differentiation into effector and memory Tc cells. Activated Tc cell exhibits cytotoxic activity. Such effector cells are also called cytotoxic T lymphocytes (CTL).
Functions: Activated cytotoxic T cells eliminate virus-infected cells, tumour cell and cells of foreign tissue graft. cytotoxic T cells specifically kill virus-infected cells by releasing perforins that destroy the membrane of the infected cell.
Active immunity and Passive immunity
On mode of acquirement adaptive immunity is classified into active immunity and passive immunity (Table 63.2). Differences between active and passive immunity are given in table 63.3.
Active immunity is induced actively after contact with foreign antigens, e.g. microorganisms. This contact may consist of (1) clinical or subclinical infection, e.g. typhoid fever, measles, chickenpox, diphtheria, and (2) Immunization with an antigen which may be killed or live attenuated vaccine, or toxoid. An individual himself actively produces the antibody and/or effector T cells after contact with foreign antigen. Active immunity develops usually in 7 to 10 days but can be longer depending on nature and dose of antigen and route of administration. Main advantage of active immunity is that the resistance is long-term. A life long immunity may develop, e.g. in diphtheria and measles. Major disadvantage is its slow onset, especially in primary response. Primary and secondary immune responses are evident.
Passive
immunity develops when a preformed antibody from
another host is administered. Passive immunity may be induced
by : (1) transfer of IgG antibodies across the placenta from mother to fetus,
(2) transfer of IgA antibodies in mother's milk, and (3) administration of
antibody-containing preparation antisera or immune globulin, e.g.
against diphtheria, tetanus, botulism, hepatitis A, hepatitis
B, rabies. Main advantage of passive immunization is the prompt
availability of large amounts of antibody. Disadvantages are
the short life-span of these antibodies and possible
hypersensitivity reactions which may occur if
antibodies from another species (e.g. horse) is administered.
Passive-active immunity involves giving both preformed antibodies in preparations called immune globulins to provide immediate protection and a vaccine to provide long-term protection. This is used in the prevention of hepatitis B, tetanus and rabies._
Passive-active immunity involves giving both preformed antibodies in preparations called immune globulins to provide immediate protection and a vaccine to provide long-term protection. This is used in the prevention of hepatitis B, tetanus and rabies._