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Antibody

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Each antibody binds to a specific antigen; an interaction similar to a lock and key.

An antibody or immunoglobulin is a large Y-shaped glycoprotein belonging to the immunoglobulin superfamily; used by the immune system to identify and neutralize foreign objects like bacteria and viruses. An antibody contains two sites called paratopes that recognize a specific target, which is called an antigen.[1] Paratopes can be thought of as similar to locks and are specific for just one particular part of the antigen called an epitope, which can be considered similar to a key. This specific lock and key interaction allows an antibody to tag a microbe or an infected cell for attack by other parts of the immune system. The binding of an antibody can also neutralize its antigen target directly by, for example, blocking a part of a microbe that is essential for its survival and growth in the body.[2] The production of antibodies is the main function of the humoral immune system.[3]

Antibodies occur in two forms: a soluble form that is secreted from cells and released into the blood and tissue fluids, and a membrane-bound form that is attached to the surface of a B cell and is called the B cell receptor (BCR). The BCR on the surface of B cells allows the B cell to detect when a specific antigen is present in the body. Once the B cell binds to an antigen the B cell can be activated - interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell.[4] The activated B cell differentiates into either soluble antibody generating factories called plasma cells, or into memory cells that will survive in the body for years afterwards, allowing an organism to remember that antigen and respond faster upon future exposures.[5]

Immunoglobulin isotypes

In mammals there are five types of antibody, each named with an "Ig" prefix, where Ig stands for immunoglobulin and known as IgM, IgD, IgG, IgA and IgE. Each immunoglobulin class differs in its biological properties and locations, and has evolved to deal with different antigens.[6] Immature B cells express only cell surface bound IgM. Once the naive B cell reaches maturity, it can express both IgM and IgD - it is the co-expression of both these immunoglobulin isotypes that renders the B cell 'mature' and ready to respond to antigen.[7] Following engagement of the immunoglobulin molecule with an antigen, the B cell activates, and begins to divide and differentiate into an antibody producing cell called a plasma cell. In this activated form, the B cell produces immunoglobulin in a secreted form rather than a membrane-bound form. Some daughter cells of the activated B cells undergo isotype switching, a mechanism that induces production of other antibody isotypes such as IgE, IgA or, more commonly, IgG.[8] In birds, IgG in often called IgY, and is found in serum and yolk.[9]


Immunoglobulin isotypes of mammals
Name Types Description
IgM 1 IgM is expressed on the surface of B cells and also in a secreted form with very high affinity for eliminating pathogens in the early stages of B cell mediated immunity before there is sufficient IgG to do the job.[3][10]
IgD 1 IgD functions mainly as an antigen receptor on B cells.[10] Its function is less well known than that of the other types.
IgG 4 IgG, in its four forms, provides the majority of antibody-based immunity against invading pathogens.[3]
IgA 2 IgA can be found in areas containing mucus such as the gut, the respiratory tract or the urogenital tract, and prevents the colonization of mucosal areas by pathogens.[11]
IgE 1 IgE binds to allergens and triggers histamine release from mast cells, and is an important underlying mechanism of allergy. IgE also provides protection against parasitic worms.[3]

Structure

Some antibodies form complexes that bind to multiple antigen molecules.

Immunoglobulins are heavy plasma proteins, with sugar chains added to amino acid residues by N-linked glycosylation and occasionally (e.g. IgA1 and IgD) by O-linked glycosylation.[12] In other words, antibodies are glycoproteins. The basic unit of each antibody is a monomer with one Ig unit but secreted antibody can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units, (like teleost fish IgM), or pentameric with five Ig units, like mammalian IgM.[13]

Chains

The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds.[6]

1. Fab region
2. Fc region
3. heavy chain (consists of VH, CH1, hinge, CH2 and CH3 regions: from N-term)
4. light chain (consists of VL and VH regions: from N-term)
5. antigen binding site
6. hinge regions
File:Antibody IgG.png
An antibody molecule. The two heavy chains are colored red and blue and the two light chains green and yellow. See also:[1]

Heavy chain

There are five types of mammalian immunoglobulin heavy chain denoted by the Greek letters: γ, δ, α, μ and ε.[1] They define the classes of immunoglobulins and correspond to IgG, IgD, IgA, IgM and IgE antibodies, respectively.[2] Heavy chains α and γ have approximately 450 amino acids, while μ and ε have approximately 550 amino acids.[1]

Each heavy chain has two regions:

  • a constant region which is the same for all immunoglobulins of the same class but differs between each class of immunoglobulins.
    • Heavy chains γ , α and δ have a constant region composed of three tandem (in a line next to each other) immunoglobulin domains, and a hinge region for added flexibility.[6]
    • Heavy chains μ and ε have a constant region composed of four immunoglobulin domains.[1]
  • a variable region that is different among each B cell, but is the same for all immunoglobulins produced by the same B cell or B cell clone. The variable domain of any heavy chain is composed of a single immunoglobulin domain. These domains are about 110 amino acids long.

The heavy chain expression in fish differs significantly (see heavy chain for details).

Light chain

There are only two types of light chain in mammals, λ and κ .[1] Other types of light chains are found in lower vertebrates as the Ig-Light-Iota chain in Chondrichthyes and Teleostei. In each antibody, only one type of light chain is present and the two chains are identical. Each light chain has two successive domains: one constant and one variable domain. The approximate length of a light chain is 211 to 217 amino acids.[1]

Regions

The tip of the Y contains the paratope and is important for binding to antigen, while the base of the Y is important for binding to specific receptors, such as Fc receptors, and allows for modulation of immune responses so that the response is appropriate for a given antigen.[14]

In an experimental setting, enzymes can be used to cleave the antibody into Fc and Fab fragments, which have several uses:

Enzyme Location of cleavage First fragment Second fragment
papain at hinge region two Fab fragments Fc fragment
pepsin below hinge region one F(ab')2 fragment Fc fragment
  • Fab region: Each end of the forked portion of the "Y" on the antibody is called the Fab region (Fragment, antigen binding). It is composed of one constant and one variable domain of each of the heavy and the light chain.[16] These domains shape the paratope—the antigen binding site—at the amino terminal end of the monomer. The two variable domains bind the epitope on their specific antigens.

The variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv), which is only half the size of the Fab fragment yet retains the original specificity of the parent immunoglobulin.[17]

Immunoglobulin diversity

The success of antibodies to recognize and eradicate many different types of microbe requires their wide diversity; antibodies vary from one another in their amino acid composition allowing them to interact with different antigens.[18] An individual vertebrate possesses a large number of different antibodies, each capable of binding to a distinct antigen or epitope from a foreign object. However, although a huge number of different antibodies are generated, there is not an equally large array of genes available, in a single individual, to make such a huge repertoire of antibodies. Vertebrate B cells have several mechanisms that allow them to generate large antibody diversity from a relatively small number of immunoglobulin genes.[19]

V(D)J recombination

Somatic recombination, also known as V(D)J recombination, of immunoglobulins involves the random selection and combination of genes encoding each segment of the immunoglobulin variable region in a manner that generates a huge repertoire of antibodies with different paratopes. These segments are called variable (V), diversity (D) and joining (J) segments.[19] V, D and J segments are found in Ig heavy chains but only V and J segments are found in Ig light chains. Multiple copies of the V, D and J segments exist tandemly arranged in the genomes of mammals. Their selection for recombination within the individual B cell is also called gene rearrangement.[20] A B cell that successfully produces a functional immunoglobulin gene during its V(D)J recombination will suppress the expression of any other variable region gene by a process known as allelic exclusion.[21] Thus, the variable regions of all the immunoglobulin molecules within one given B cell will be the same, although the constant domains of the heavy chains can differ.[1] The diversity generated by this mechanism in the variable region of the heavy chain - to be specific, in the area that these V, D and J genes encode, otherwise known as the complementarity determining region 3 (CDR3) - provides the vertebrate immune system its ability to bind so many distinct antigens.

Somatic hypermutation

A further mechanism for generating antibody diversity exists for the mature B cell after antigen stimulation. Activated B cells are more prone to somatic hypermutation in their immunoglobulin variable chain genes.[22] This generates slight changes in the amino acid sequence of the variable domains of both the light and heavy chains between clones of the same activated B cell, and ultimately, differences in the affinity or strength of interaction that the B cell has with its specific antigen.[23] Thus, B cells expressing immunoglobulins with higher affinity for the antigen will outcompete those with weaker immunoglobulin for function and survival in a process known as affinity maturation.[24]

Class switching

Isotype switching (or class switching) occurs after the process of V(D)J recombination and following activation of the mature B cell (see above) to generate the different classes of antibody, all with the same variable domains as the original immunoglobulin generated in the immature B cell during recombination, but possessing distinct constant domains in their heavy chains.[20]

Naïve B cells produce both IgM and IgD that have identical antigen binding regions. After activation by antigen, some B cells undergo a biological process known as class switching, which allows them to produce antibodies of the IgG, IgA or IgE classes. During class switching, the constant region of the immunoglobulin heavy chain changes but the variable regions, and therefore antigen specificity, stay the same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes.[25]

Class switching occurs by a mechanism called class switch recombination (CSR). This process uses conserved nucleotide motifs, called switch (S) regions, found in DNA upstream from each of the antibody heavy chain constant region genes, except the δ-chain. DNA is nicked and broken at two selected S-regions by the activity of a series of enzymes, including Activation-Induced (Cytidine) Deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases.[26][27] The intervening DNA between the S-regions is subsequently deleted from the chromosome, removing unwanted μ or δ heavy chain constant region genes and allowing substitution of the γ, α or ε constant region genes. The free ends of the DNA are rejoined by a process called non-homologous end joining (NHEJ) to link the variable domain exon to the desired downstream constant domain exon of the immunoglobulin heavy chain.[28]

The secreted mammalian IgM molecule, with its five Ig units.

Affinity versus avidity

Depending on the structure of the antibody, which varies with the isotype, and the structure of the antigen, an antibody may have only one monovalent binding interaction with the antigen, or the interaction may be multivalent—have multiple simultaneous interactions .[1]

  • Affinity is the binding strength of a single antibody–antigen interaction.
  • Avidity is the compound affinity of multiple antibody–antigen interactions when more than one takes place between the two molecules.

Avidity can be orders of magnitude greater than affinity, helping for instance poorly affinity-matured but highly multivalent IgM still bind antigen efficiently.[29]

Function

Further information: [[:Immune system]]

Since antibodies exist freely in the bloodstream or bound to cell membranes, they are said to be part of the humoral immune system. The circulating antibodies are produced by clonal B cells that are specific to only one antigen, a virus hull protein fragment, for example. In binding their specific antigens, the antibodies can cause agglutination and precipitation of antibody-antigen products primed for phagocytosis by macrophages and other cells, block viral receptors, and stimulate other immune responses, such as the complement pathway.[30]

Neutralization

Antibodies that recognize viruses can block these by binding them directly.[3] In doing so, the virus will be unable to dock to its preferred receptor on a host cell in order to infect it. Some antibodies, like IgA, also directly bind to microbes in mucus to prevent the colonization of mucosal tissues. Antibodies, like those in antivenoms, neutralize toxins by binding to them.[31] Certain viruses may be able to evade the immune system if antibody neutralization is inadequate. For example, when certain viruses such as HIV, are not completely covered by neutralizing antibody, the presence of the antibodies can actually enhance viral infectivity instead of inhibiting it; HIV prefers to infect the cells that bind to antibodies.[32] Antibodies cannot attack pathogens within cells, and certain viruses (such as HIV, HSV and HBV) "hide" inside cells for long periods of time to avoid them.[3] This is the reason for the chronic nature of many minor skin diseases (such as cold sores); any given outbreak is quickly suppressed by the immune system, but the infection is never truly eradicated because some cells retain viruses that will reactivate later, causing a resurgence of symptoms.[3]

Agglutination

Antibodies are clonally generated for binding single specific antigens. Antibodies can link these viruses or cells together, causing them to agglutinate, or coagulate, so that phagocytes can capture them more effectively.[3]

Schematic diagram showing Fc receptor interaction with an antibody-coated microbial pathogen.

Activation of complement

Antibodies that bind to surface antigens on, for example a bacterium, will attract the first component of the complement cascade with their Fc region and initiate activation of the "classical" complement system.[30] This results in the killing of bacteria in two ways.[3] First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization. These phagocytes are attracted by some of the complement molecules that are generated in the complement cascade. Secondly, some complement system components form a membrane attack complex to assist the antibodies killing the bacteria directly.[33]

Activation of effector cells

Mast cells and phagocytes have specific receptors on their cell surface that bind antibodies. These are called Fc receptors, and, as the name suggests, these receptors interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers the effector function of that cell (e.g. phagocytes will phagocytose, mast cells will degranulate) that will ultimately result in destruction of the invading microbe. The Fc receptors are isotype-specific, which gives a great flexibility to the immune system, because different situations require only certain immune mechanisms to respond to antigens.[1]

Medical applications

Detection of particular antibodies is a very common form of medical diagnostics, and applications such as serology depend on these methods.[34] In biochemical assays for disease diagnosis,[35] a titer of Epstein-Barr virus or Lyme disease will look for antibodies produced by the body that are specific to those antigens in the blood. If those antibodies are not present, either the person has not been infected, or the infection occurred a very long time ago, and the antibodies have naturally decayed.

Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia can be detected with the Coombs test.[36] The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women.[36]

"Targeted" monoclonal antibody therapy has been employed to treat diseases such as rheumatoid arthritis,[37] multiple sclerosis,[38] psoriasis,[39] and in many forms of cancer including non-Hodgkin's lymphoma,[40] colorectal cancer, head and neck cancer and breast cancer.[41]

Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia result in partial or complete lack of antibodies.[42] These diseases are often treated by inducing a short term form of immunity called passive immunity. Passive immunity is achieved through the transfer of ready made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected individual.[43]

Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients whom the diagnosis is unclear.[2] For example, elevated IgA indicates alcoholic cirrhosis, elevated IgM indicates viral hepatitis and primary biliary cirrhosis, while IgG is elevated in viral hepatitis, autoimmune hepatitis and cirrhosis.

RHOGAM antibodies

RHOGAM antibodies are a trade name for Rho(D) Immune Globulin antibodies specific to the human Rh D antigen.[44] The Rhesus factor (also known as the D antigen) is an antigen found on red blood cells in the blood. People that are Rh+ have this antigen on their red blood cells. People that are Rh- don't have this antigen on their red blood cells.

In the course of regular childbirth, delivery trauma or other prenatal complications can cause blood from the fetus to occasionally enter the mother's system. In the case of an Rh-incompatible mother and child, blood mixing from this trauma may 'sensitize' the Rh-negative mother to the Rh antigen, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn.[45] RhoGAM is administered as part of a pre-natal treatment regimen to prevent any sensitization that may occur when a Rhesus-negative mother has a fetus that is Rhesus-positive.

Treatment of an mother with RhoGAM antibodies prior to and immediately after trauma and delivery destroys any Rh antigen incidentally in the mother's system from the fetus. Importantly, this will happen before the antigen can stimulate the mother's memory-mediated immune response B cells to "remember" Rh antigen. Therefore, her humoral immune system will never be stimulated to make anti-Rh antibodies, and will not attack the current, or any potential subsequent, baby's Rhesus antigens. RhoGAM prevents 'sensitization' that can lead to Rh disease, but does not prevent or treat the underlying disease itself.[44]

Research applications

Immunofluorescence image of the eukaryotic cytoskeleton. Actin filaments are shown in red, microtubules in green, and the nuclei in blue.

Purified antibodies are often produced by injecting the antigen into a small mammal, such as a mouse or rabbit. Sometimes, in order to obtain large quantity of antibodies, goats, sheep, or horses are used. Blood isolated from these animals contains polyclonal antibodies -- multiple antibodies that bind to the same antigen. The serum, also known as the antiserum, now contains the desired antibodies, and is commonly purified with Protein A/G purification or antigen affinity chromatography.[46] If the lymphocytes that produce the antibodies can be isolated and immortalized, then a monoclonal antibody can be obtained.

In research, purified antibodies are used in many applications. The most common is the identification and localization of intracellular and extracellular proteins. Antibodies are used in flow cytometry to differentiate cell types,[47] in immunoprecipitation to separate proteins (and anything bound to them) from the other molecules in a cell lysate,[48] in a Western blot to identify proteins after electrophoresis,[49] or in immunohistochemistry to examine protein expression in tissues,[50] and to examine the localization of proteins within cells by immunofluorescence.[47]

See also

References

  1. ^ a b c d e f g h i j Janeway CA, Jr.; et al. (2001). Immunobiology (5th ed. ed.). Garland Publishing. (electronic full text via NCBI Bookshelf) ISBN 0-8153-3642-X. {{cite book}}: |edition= has extra text (help); Explicit use of et al. in: |author= (help)
  2. ^ a b c Rhoades RA, Pflanzer RG (2002). Human Physiology (4th ed. ed.). Thomson Learning. ISBN 0-534-42174-1. {{cite book}}: |edition= has extra text (help)
  3. ^ a b c d e f g h i Pier GB, Lyczak JB, Wetzler LM (2004). Immunology, Infection, and Immunity. ASM Press. ISBN 1-55581-246-5.{{cite book}}: CS1 maint: multiple names: authors list (link)
  4. ^ Parker D (1993). "T cell-dependent B cell activation". Annu Rev Immunol. 11: 331–60. PMID 8476565.
  5. ^ Borghesi L, Milcarek C (2006). "From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion". Immunol Res. 36 (1–3): 27–32. PMID 17337763.
  6. ^ a b c d Woof J, Burton D (2004). "Human antibody-Fc receptor interactions illuminated by crystal structures". Nat Rev Immunol. 4 (2): 89–99. PMID 15040582.
  7. ^ Goding J. "Allotypes of IgM and IgD receptors in the mouse: a probe for lymphocyte differentiation". Contemp Top Immunobiol. 8: 203–43. PMID 357078.
  8. ^ Neuberger M, Ehrenstein M, Rada C, Sale J, Batista F, Williams G, Milstein C (2000). "Memory in the B-cell compartment: antibody affinity maturation". Philos Trans R Soc Lond B Biol Sci. 355 (1395): 357–60. PMID 10794054.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ http://www.sigmaaldrich.com/Brands/Sigma_Genosys/Custom_Antisera/Key_Resources/Antisera_FAQ/Chicken_Antibody.html
  10. ^ a b Geisberger R, Lamers M, Achatz G (2006). "The riddle of the dual expression of IgM and IgD". Immunology. 118 (4): 429–37. PMID 16895553.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Underdown B, Schiff J (1986). "Immunoglobulin A: strategic defense initiative at the mucosal surface". Annu Rev Immunol. 4: 389–417. PMID 3518747.
  12. ^ Mattu T, Pleass R, Willis A, Kilian M, Wormald M, Lellouch A, Rudd P, Woof J, Dwek R (1998). "The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fc alpha receptor interactions". J Biol Chem. 273 (4): 2260–72. PMID 9442070.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Roux K (1999). "Immunoglobulin structure and function as revealed by electron microscopy". Int Arch Allergy Immunol. 120 (2): 85–99. PMID 10545762.
  14. ^ Huber R (1980). "Spatial structure of immunoglobulin molecules". Klin Wochenschr. 58 (22): 1217–31. PMID 6780722.
  15. ^ Heyman B (1996). "Complement and Fc-receptors in regulation of the antibody response". Immunol Lett. 54 (2–3): 195–9. PMID 9052877.
  16. ^ Putnam FW, Liu YS, Low TL (1979). "Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain". J Biol Chem. 254 (8): 2865–74. PMID 107164.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Wu A, Yazaki P (2000). "Designer genes: recombinant antibody fragments for biological imaging". Q J Nucl Med. 44 (3): 268–83. PMID 11105590.
  18. ^ Mian I, Bradwell A, Olson A (1991). "Structure, function and properties of antibody binding sites". J Mol Biol. 217 (1): 133–51. PMID 1988675.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b Nemazee D (2006). "Receptor editing in lymphocyte development and central tolerance". Nat Rev Immunol. 6 (10): 728–40. PMID 16998507.
  20. ^ a b Eleonora Market, F. Nina Papavasiliou (2003) V(D)J Recombination and the Evolution of the Adaptive Immune System PLoS Biology1(1): e16.
  21. ^ Bergman Y, Cedar H (2004). "A stepwise epigenetic process controls immunoglobulin allelic exclusion". Nat Rev Immunol. 4 (10): 753–61. PMID 15459667.
  22. ^ Diaz M, Casali P (2002). "Somatic immunoglobulin hypermutation". Curr Opin Immunol. 14 (2): 235–40. PMID 11869898.
  23. ^ Honjo T, Habu S (1985). "Origin of immune diversity: genetic variation and selection". Annu Rev Biochem. 54: 803–30. PMID 3927822.
  24. ^ Neuberger M, Ehrenstein M, Rada C, Sale J, Batista F, Williams G, Milstein C (2000). "Memory in the B-cell compartment: antibody affinity maturation". Philos Trans R Soc Lond B Biol Sci. 355 (1395): 357–60. PMID 10794054.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Stavnezer J, Amemiya CT (2004). "Evolution of isotype switching". Semin. Immunol. 16 (4): 257–75. PMID 15522624.
  26. ^ Durandy A (2003). "Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation". Eur. J. Immunol. 33 (8): 2069–73. PMID 12884279.
  27. ^ Casali P, Zan H (2004). "Class switching and Myc translocation: how does DNA break?". Nat. Immunol. 5 (11): 1101–3. PMID 15496946.
  28. ^ Lieber MR, Yu K, Raghavan SC (2006). "Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations". DNA Repair (Amst.). 5 (9–10): 1234–45. PMID 16793349.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Pancook J, Beuerlein G, Pecht G, Tang Y, Nie Y, Wu H, Huse W, Watkins J (2001). "In vitro affinity maturation of human IgM antibodies reactive with tumor-associated antigens". Hybrid Hybridomics. 20 (5–6): 383–96. PMID 11839257.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  30. ^ a b Ravetch J, Bolland S (2001). "IgG Fc receptors". Annu Rev Immunol. 19: 275–90. PMID 11244038.
  31. ^ Chippaux J, Goyffon M (1998). "Venoms, antivenoms and immunotherapy". Toxicon. 36 (6): 823–46. PMID 9663690.
  32. ^ Weiss R (2001). "Gulliver's travels in HIVland". Nature. 410 (6831): 963–7. PMID 11309625.
  33. ^ Rus H, Cudrici C, Niculescu F (2005). "The role of the complement system in innate immunity". Immunol Res. 33 (2): 103–12. PMID 16234578.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ "Animated depictions of how antibodies are used in [[ELISA]] assays". Cellular Technology Ltd.—Europe. Retrieved 2007-05-08. {{cite web}}: URL–wikilink conflict (help)
  35. ^ "Animated depictions of how antibodies are used in [[ELISPOT]] assays". Cellular Technology Ltd.—Europe. Retrieved 2007-05-08. {{cite web}}: URL–wikilink conflict (help)
  36. ^ a b Dean, Laura (2005). "Chapter 4: Hemolytic disease of the newborn". Blood Groups and Red Cell Antigens. NCBI Bethesda (MD): National Library of Medicine (US),. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help); External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)CS1 maint: extra punctuation (link)
  37. ^ Feldmann M, Maini R (2001). "Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?". Annu Rev Immunol. 19: 163–96. PMID 11244034.
  38. ^ Doggrell S (2003). "Is natalizumab a breakthrough in the treatment of multiple sclerosis?". Expert Opin Pharmacother. 4 (6): 999–1001. PMID 12783595.
  39. ^ Krueger G, Langley R, Leonardi C, Yeilding N, Guzzo C, Wang Y, Dooley L, Lebwohl M (2007). "A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis". N Engl J Med. 356 (6): 580–92. PMID 17287478.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  40. ^ Plosker G, Figgitt D (2003). "Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia". Drugs. 63 (8): 803–43. PMID 12662126.
  41. ^ Vogel C, Cobleigh M, Tripathy D, Gutheil J, Harris L, Fehrenbacher L, Slamon D, Murphy M, Novotny W, Burchmore M, Shak S, Stewart S (2001). "First-line Herceptin monotherapy in metastatic breast cancer". Oncology. 61 Suppl 2: 37–42. PMID 11694786.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ LeBien T (2000). "Fates of human B-cell precursors". Blood. 96 (1): 9–23. PMID 10891425.
  43. ^ Abdul Ghaffar (2006). "Immunization". Microbiology and Immunology On-Line Textbook. USC School of Medicine. Retrieved 2007-05-08. {{cite web}}: Cite has empty unknown parameters: |month= and |coauthors= (help)
  44. ^ a b Fung Kee Fung K, Eason E, Crane J, Armson A, De La Ronde S, Farine D, Keenan-Lindsay L, Leduc L, Reid G, Aerde J, Wilson R, Davies G, Désilets V, Summers A, Wyatt P, Young D (2003). "Prevention of Rh alloimmunization". J Obstet Gynaecol Can. 25 (9): 765–73. PMID 12970812.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. ^ Urbaniak S, Greiss M (2000). "RhD haemolytic disease of the fetus and the newborn". Blood Rev. 14 (1): 44–61. PMID 10805260.
  46. ^ Kabir S. "Immunoglobulin purification by affinity chromatography using protein A mimetic ligands prepared by combinatorial chemical synthesis". Immunol Invest. 31 (3–4): 263–78. PMID 12472184.
  47. ^ a b Brehm-Stecher B, Johnson E (2004). "Single-cell microbiology: tools, technologies, and applications". Microbiol Mol Biol Rev. 68 (3): 538–59. PMID 15353569.
  48. ^ Williams N (2000). "Immunoprecipitation procedures". Methods Cell Biol. 62: 449–53. PMID 10503210.
  49. ^ Kurien B, Scofield R (2006). "Western blotting". Methods. 38 (4): 283–93. PMID 16483794.
  50. ^ Scanziani E. "Immunohistochemical staining of fixed tissues". Methods Mol Biol. 104: 133–40. PMID 9711649.

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