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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'''===

* Phagocytes hace receptors for the Fc portion of antibody

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]].

** Fc receptors - FcR

* FcR bind the Fc portion of antibody on antigen/antibody complexes

** Antibody alone does not interact with FcR

 

* Interaction of FcR with Ab/Ag complexes stimulates:

** '''Cellular activation'''

*** Causes greatly increased efficiency of phagocytosis - '''opsonisation'''

** '''Production of intracellular enzymes'''

*** Promotes the killing and digestion of internalised micro organisms

*** Systems important in intracellular killing include:

**** Free radicals

***** Oxygen and chlorine free radicals

**** Hydrogen peroxidase

**** Nitric oxide

***** Produced by nitric oxide synthase

** '''Secretion of certain enzymes and cytotoxic molecules'''

** '''The degranulation of phagocytes'''

* 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 receptors

* Phagocytes also have receptors for iC3b, a [[Complement|complement]] component

** A major initiator of opsonisation

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

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

==Classes==

==Classes==

==Variation==

==Variation==

===Subclasses===

===Subclasses===

Subclasses of the five major classes also exist. These occur in the '''heavy chains''' and are coded for by the IGH gene. For examples horses have six subclasses of the [[IgG]] immunoglobulin coded for by the genes IGHG1→ IGHG6 while cattle and sheep only have three subclasses (IGHG1→ IGHG3).

Subclasses of the five major classes also exist. These occur in the '''heavy chains''' and are coded for by the IGH gene. For examples horses have six subclasses of the [[IgG]] immunoglobulin coded for by the genes IGHG1→ IGHG6 while cattle and sheep only have three subclasses (IGHG1→ IGHG3). Therefore within the [[IgG]] class there are '''several subclasses depending on the species'''. Humans and rodents have four [[IgG]] subclasses, dogs have three subclasses, ruminants have two or three subclasses and in some species there are also two IgA subclasses. Antibody specificity is unrelated to class. Different classes of antibody can be associated with the same V domains and have the same specificity. It is possible for a single B-cell to produce antibody of one specificity but two or more classes. A mature B-cell has the genetic capacity to produce antibody of all classes and subclasses but of one specificity only.

* Within the [[IgG]] class there are several subclasses depending on the species

** Humans and rodents have four [[IgG]] subclasses

** Dogs have three subclasses

** Ruminants have two or three subclasses

* In some species there are also two IgA subclasses

* Specificity is unrelated to class

** Different classes of antibody can be associated with the same V domains and have the same specificity

** It is possible for a single B-cell to produce antibody of one specificity but two or more classes

*** A mature B-cell has the genetic capacity to produce antibody of all classes and subclasses but of one specificity only

 

===Allo & Idiotypes===

===Allo & Idiotypes===

<p>Allotypes are differences in immunoglobulins between individuals of a particular species. They are inheritable. Idiotypes are variations in the sequences of amino acids in the variable regions of the light and heavy chains.</p>

Allotypes are differences in immunoglobulins between individuals of a particular species. They are inheritable. Idiotypes are variations in the sequences of amino acids in the variable regions of the light and heavy chains.

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===Immunoglobulin Class Switching===

===Immunoglobulin Class Switching===

* Different classes of antibody differ from each other in:

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;

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

** Amino acid composition

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

** Associated carbohydrate

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

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

* Immunoglobulin heavy and light chains are encoded by separate genes

** The first 300 bases of each gene encodes the variable part of each protein chain

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 combination of the VH and VL contribute to the antigenic specificity

**** Any individual has the capability of producing over 100 million different antibody specificities

** The rest of the antibody gene encodes all the constant domains.

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.

*** There are four different types of heavy chain constant domains - μ, γ, ε, α

**** Different heavy chains are associated with different classes of antibody

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

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

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

***** '''&alpha; chain - [[IgA]]'''  

*** 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

* 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 the variable domain

* After antigenic exposure the [[IgM]]+ B-cells differentiate

** Begin to synthesise other classes of immunoglobulin

*** Only under the '''direct influence of a T-cell'''

*** Known as '''immunoglobulin heavy chain switch'''

* 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 switch

*** The B-cells mature from [[IgM]] to [[IgG]] producers

* IgE and IgA producers can be generated

** These immunoglobulins tend to be produced within lymphoid tissue associated with mucosal surfaces

==Clinical Uses==

==Clinical Uses==

[[Immunological Testing]]

[[Immunological Testing]]

==[[Immunoglobulins Flashcards]]==

|flashcards = [[Immunoglobulins Flashcards]]

==Links==

==Links==

'''Websites'''

'''Websites'''

*http://www.cellsalive.com

*http://www.cellsalive.com

[[Category:Immunoglobulins|A]]

[[Category:Immunoglobulins|A]]

[[Category:To Do - A&P]]

[[Category:A&P Done]]