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[[Image:LH Antibody.png|thumb|200px|right|'''Immunoglobulin''' <br>  Je_at_uwo 2006, WikiMedia Commons]]

[[Image:LH Antibody.png|thumb|200px|right|'''Immunoglobulin''' <br>  Je_at_uwo 2006, WikiMedia Commons]]

Also known as '''''antibodies

Also known as '''''antibodies

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At the carboxyl terminus of B-cell expressed Ig is a region that holds the antibody molecule in the cell membrane. Secreted 'free' antibodies do not possess this region. The '''Fab''' fragments of the immunoglobulin is the '''antigen binding fragment''' generated from the light chains when digested by papain (proteolytic enzyme). The  '''Fc''' fragment is the fragment produced by '''papain from the heavy chains''' and this fragment '''mediates phagocytosis''', triggers '''inflammation''' and '''targets Ig''' to certain tissues.

At the carboxyl terminus of B-cell expressed Ig is a region that holds the antibody molecule in the cell membrane. Secreted 'free' antibodies do not possess this region. The '''Fab''' fragments of the immunoglobulin is the '''antigen binding fragment''' generated from the light chains when digested by papain (proteolytic enzyme). The  '''Fc''' fragment is the fragment produced by '''papain from the heavy chains''' and this fragment '''mediates [[Phagocytosis|phagocytosis]]''', triggers '''[[Inflammation|inflammation]]''', activates '''[[Complement|complement]]''' and '''targets Ig''' to certain tissues.

==Function==

==Function==

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==='''Promotion of phagocytosis'''===

==='''Promotion of phagocytosis'''===

Antibodies also have a function to facilitate [[Phagocytosis|phagocytosis]]. Phagocytes have receptors for the '''Fc''' portion of antibody, using '''Fc receptors (FcR)'''. FcR bind the Fc portion of antibody on antigen/antibody complexes, although the antibody alone does not interact with FcR. Interaction of FcR with Ab/Ag complexes stimulates '''cellular activation''' which greatly increases the efficiency of phagocytosis. This process is called '''opsonisation'''. Opsonisation promotes the '''production of intracellular enzymes''' and therefore promotes the killing and digestion of internalised micro-organisms. Systems used by phagocytes that are important in intracellular killing include free radicals such as oxygen and chlorine, hydrogen peroxidase and nitric oxide produced by nitric oxide synthase. Ultimately phagocytes undergo '''degranulation''' resulting in the '''secretion of certain enzymes and cytotoxic molecules'''. These systems are also activated by the interferons, especially the immune interferon – IFN & gamma. Antibody-mediated opsonisation of micro organisms is much more efficient that innate immune system receptors. Phagocytes also have receptors for iC3b, a [[Complement|complement]] component which is also a major initiator of opsonisation. Two particulary important phagocytic cells that have FcR are the [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]].

Antibodies also have a function to facilitate [[Phagocytosis|phagocytosis]]. Phagocytes have receptors for the '''Fc''' portion of antibody, using '''Fc receptors (FcR)'''. FcR bind the Fc portion of antibody on antigen/antibody (Ag/Ab) complexes, although the antibody alone does not interact with FcR. Interaction of FcR with Ag/Ab complexes stimulates '''cellular activation''' which greatly increases the efficiency of phagocytosis. This process is called '''opsonisation'''. Opsonisation promotes the '''production of intracellular enzymes''' and therefore promotes the killing and digestion of internalised micro-organisms. Systems used by phagocytes that are important in intracellular killing include free radicals such as oxygen and chlorine, hydrogen peroxidase and nitric oxide produced by nitric oxide synthase. Ultimately phagocytes undergo '''degranulation''' resulting in the '''secretion of certain enzymes and cytotoxic molecules'''. These systems are also activated by the interferons, especially the immune interferon, interferon gamma (IFNγ). Antibody-mediated opsonisation of micro organisms is much more efficient that innate immune system receptors. Phagocytes also have receptors for iC3b, a [[Complement|complement]] component which is also a major initiator of opsonisation. Two particulary important phagocytic cells that have FcR are the [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]].

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==='''Degranulation of [[Mast Cells|mast cells]]/ [[Eosinophils|eosinophils]]'''===

==='''Degranulation of [[Mast Cells|mast cells]]/[[Eosinophils|eosinophils]]'''===

Antibodies play an important role in the [[Innate Cellular Immune Response|innate immune response]] to parasites.

Antibodies play an important role in the [[Innate Immunity Cellular Responses|innate immune response]] to parasites. The Eosinophils and Mast Cells have FcR that are specific to IgE. When the IgE are cross-linked by antigen the eosinophils and Mast cells can interact with the IgE causing the release of their granules through the process known as exocytosis (granule fusion with the plasma membrane). This causes proteolytic enzyme release from eosinophils, and vasoactive peptide and cytokine release by Mast cells which then activates the innate immune response. Interestingly, this response is also responsible for the Type I hypersensitivity reaction.

==='''[[Complement|Complement fixation]]'''===

==='''[[Complement|Complement fixation]]'''===

==Classes==

==Classes==

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===Immunoglobulin Class Switching===

===Immunoglobulin Class Switching===

Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are four different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;

Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are five different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;

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* '''&mu; chain - [[IgM]] '''

* '''&mu; chain - [[IgM]] '''

* '''&gamma; chain -[ [IgG]]'''

* '''&gamma; chain -[[IgG]]'''

* '''&epsilon; chain - [[IgE]]'''

* '''&epsilon; chain - [[IgE]]'''

* '''&alpha; chain - [[IgA]]'''  

* '''&alpha; chain - [[IgA]]'''

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In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]]. The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers and IgE and IgA producers can also be generated. These immunoglobulins tend to be produced within lymphoid tissue associated with mucosal surfaces.

The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]⁺ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers, with [[IgE]] and [[IgA]] producers generated under certain immune responses. These immunoglobulins (IgA and IgE) tend to be produced within lymphoid tissue associated with mucosal surfaces.

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{{Jim Bee 2007}}

{{Jim Bee 2007}}

[[Category:Immunoglobulins|A]]

[[Category:Immunoglobulins|A]]

[[Category:A&P Done]]

[[Category:A&P Done]]