Humoral immunity 338526 216265379 2008-05-31T21:42:32Z Kipmaster 503211 interwiki The '''Humoral Immune Response''' (HIR) is the aspect of [[immunity (medical)|immunity]] that is mediated by secreted [[antibodies]] (as opposed to [[cell-mediated immunity]] which involves T lymphocytes) produced in the cells of the B [[lymphocyte]] lineage ([[B cell]]). Secreted antibodies bind to [[antigen]]s on the surfaces of invading microbes (such as viruses or bacteria), which flags them for destruction.<ref name=Pier>{{cite book | author = Pier GB, Lyczak JB, Wetzler LM | title = Immunology, Infection, and Immunity | edition = | publisher = ASM Press| year = 2004 | id = ISBN 1-55581-246-5}}</ref> Humoral immunity is called as such, because it involves substances found in the [[humours]], or body fluids. The study of the molecular and cellular components that comprise the [[immune system]], including their function and interaction, is the central science of [[immunology]]. The immune system is divided into a more primitive [[innate immune system]], and acquired or [[adaptive immune system]] of vertebrates, the latter of which is further divided into '''humoral''' and [[cellular immunity|cellular]] components. Humoral immunity refers to antibody production, and the accessory processes that accompany it, including: [[Th2]] activation and [[cytokine]] production, [[germinal center]] formation and [[isotype]] switching, [[affinity maturation]] and [[memory cell]] generation. It also refers to the [[effector (biology)|effector]] functions of antibody, which include pathogen and toxin neutralization, classical [[Complement system|complement]] activation, and [[opsonin]] promotion of [[phagocytosis]] and pathogen elimination.<ref name=Janeway5>{{cite book | author = [[Charles Janeway|Janeway CA, Jr.]] ''et al'' | title = Immunobiology. | edition = 5th ed. | publisher = Garland Publishing | year = 2001 | id = [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10 (electronic full text via NCBI Bookshelf)] ISBN 0-8153-3642-X }}</ref> ==History== The concept of humoral immunity developed based on analysis of [[antibacterial]] activity of the components of serum. [[Hans Buchner]] is credited with the development of the humoral theory.<ref name= Metch>[[Elie Metchnikoff|Metchnikoff, Elie]] (1905) [http://books.google.com/books?vid=OCLC03666307&id=ywKp9YhK5t0C&printsec=titlepage&vq=Ehrlich&dq=history+of+humoral+immunity Immunity in infectious disease] (Full Text Version) Cambridge University Press</ref> In 1890 he described alexins, or “protective substances”, which exist in the serum and other bodily fluids and are capable of killing microorganisms. Alexins, later redefined "complement" by [[Paul Ehrlich]], were shown to be the [[soluble]] components of the innate response that lead to a combination of cellular and humoral immunity, and bridged the features of innate and acquired immunity.<ref name= Metch/> Following the 1888 discovery of [[diphtheria]] and [[tetanus]], [[Emil von Behring]] and [[Shibasaburo Kitasato]] showed that disease need not be caused by microorganisms themselves. They discovered that cell-free filtrates were sufficient to cause disease. In 1890, filtrates of diphtheria (later named [[diphtheria toxin]]s) were used to [[vaccination|immunize]] animals in an attempt to demonstrate that immunized serum contained an [[antitoxin]] that could neutralize the activity of the toxin and could transfer immunity to non immune animals.<ref name= G.E>Gherardi E. [http://nfs.unipv.it/nfs/minf/dispense/immunology/expfound.html The experimental foundations of Immunology] Immunology Course Medical School, University of Pavia.</ref> In 1897, Paul Ehrlich showed that antibodies form against the plant toxins [[ricin]] and [[abrin]], and proposed that these antibodies are responsible for immunity.<ref name= Metch/> Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern [[immunotherapy]].<ref name= G.E/> The presence and specificity of antibodies became the major tool for standardizing the state of [[immunity (medical)|immunity]] and identifying the presence of previous infections.<ref name= G.E/> {| class="wikitable" style="margin: 1em auto 1em auto" |+ '''Major discoveries in the study of humoral immunity'''<ref name= G.E/> ! Substance|| Activity || Discovery |- | Alexin(s) <br> [[Complement system|Complement]]||Soluble components in the serum<br> that are capable of killing microorganisms ||Buchner (1890),<br> Ehrlich (1892)<ref name= Metch/> |- | [[Antitoxins]]||Substances in the serum that can neutralize<br> the activity of toxins, enabling [[passive immunization]] ||von Bhering and Kitasato (1890)<ref>von Behring E, Kitasato S. (1890) On the acquisition of immunity against diptheria and tetanus in animals (German). Dtsch. Med. Wochenschr. 16: 1145-1148</ref> |- | [[Bacteriolysin]]s ||Serum substances that work with the<br> complement proteins to induce bacterial lysis || [[Richard Friedrich Johannes Pfeiffer|Richard Pfeiffer]] (1895)<ref>[http://links.jstor.org/sici?sici=0080-4606(195611)2%3C237%3ARFJP1%3E2.0.CO%3B2-E Peer biography by Paul Fildes] Biographical Memoirs of Fellows of the Royal Society, Vol. 2, Nov., 1956 (Nov., 1956), pp. 237-247</ref> |- | Bacterial [[agglutinin]]s <br>& [[precipitin]]s|| Serum substances that agglutinate bacteria<br> and precipitate bacterial toxins ||[[Max von Gruber|von Gruber]] and Durham (1896),<ref>[http://www.med-serv.de/medizin-buch-hygiene_geschlechtsleben-0-1-2.html hygiene of the sexual life] (German, fulltext)</ref><br> Kraus (1897)<ref>Mentioned in [http://links.jstor.org/sici?sici=0003-0147%28190111%2935%3A419%3C927%3AOTFOSA%3E2.0.CO%3B2-R&size=LARGE On the Formation of Specific Anti-Bodies in the Blood, Following Upon Treatment with the Sera of Different Animals], George H. F. Nuttall American Naturalist, Vol. 35, No. 419 (Nov., 1901), pp. 927-932</ref> |- | [[Hemolysis (microbiology)|Hemolysins]] || Serum substances that work with complement<br> to lyse red blood cells || Belfanti and Carbone (1898)<ref>BELFANTI, S. AND CARBONE, T.: ''Produzione di sostanze tossiche mmcl siero di animale inoculati con sangue eterogeneo.'' Gior. d.r. Accad. di. med. di Torino, Series 4, 46: 321, 1898.</ref> <br>[[Jules Bordet]] (1899)<ref>Bordet, J. 1898. Sur l'agglutination et la dissolution des globules rouges par le serum d'animaux injectes de sang defibrine. Ann. De l'Inst. Pasteur. xii: 688-695.</ref> |- | [[Opsonin]]s|| serum substances that coat the outer membrane<br>of foreign substances and enhance the rate of<br> phagocytosis by macrophages ||Wright and Douglas (1903)<ref>Wright, A. E., and S. R. Douglas. 1904. An experimental investigation of the role of the body fluids in connection with phagocytosis. Proc. R. Soc. London 72:357-370.</ref> |- | [[Antibody]] || formation (1900), antigen-antibody binding<br> hypothesis (1938), produced by B cells (1948),<br> structure (1972), immunoglobulin genes (1976)|| Founder: P Ehrlich<ref name= Metch/> |} ==Complement system== {{main|Complement system}} The complement system is a biochemical cascade of the immune system that helps clear pathogens from an organism. It is derived from many small plasma [[proteins]] that work together to disrupt the target cell's [[plasma membrane]] leading to cytolysis of the cell. The complement system consists of more than 35 soluble and cell-bound proteins, 12 of which are directly involved in the complement pathways.<ref name=Janeway5/> The complement system is involved in the activities of both innate immunity and acquired immunity. Activation of this system leads to [[cytolysis]], [[chemotaxis]], [[opsonization]], immune clearance, and [[inflammation]], as well as the marking of pathogens for [[phagocytosis]]. The proteins account for 5% of the [[serum]] [[globulin]] fraction. Most of these proteins circulate as [[zymogen]]s, which are inactive until [[proteolytic cleavage]]. Three biochemical pathways activate the complement system: the [[classical complement pathway]], the [[alternate complement pathway]], and the [[mannose-binding lectin pathway]]. The classical complement pathway typically requires antibodies for activation and is a specific immune response, while the alternate pathway can be activated without the presence of antibodies and is considered a non-specific immune response.<ref name=Janeway5/> Antibodies, in particular the IgG1 class, can also "fix" complement. ==Antibodies== {{main|Antibody}} Immunoglobulins are glycoproteins in the immunoglobulin superfamily that function as antibodies. The terms ''antibody'' and ''immunoglobulin'' are often used interchangeably. They are found in the blood and tissue fluids, as well as many secretions. In structure, they are large Y-shaped globular proteins. In mammals there are five types of antibody: IgA, IgD, IgE, IgG, and IgM. Each immunoglobulin class differs in its biological properties and has evolved to deal with different antigens.<ref name=Pier/> Antibodies are synthesized and secreted by plasma cells that are derived from the B cells of the immune system. An antibody is used by the immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. By binding their specific antigens, antibodies can cause [[Agglutination_(biology)|agglutination]] and precipitation of antibody-antigen products, prime for phagocytosis by macrophages and other cells, block [[viral]] receptors, and stimulate other immune responses, such as the complement pathway. An incompatible [[blood transfusion]], causes a [[transfusion reaction]], which is mediated by the humoral immune response. This type of reaction, called an acute hemolytic reaction, results in the rapid destruction ([[hemolysis]]) of the donor [[red blood cell]]s by host antibodies. The cause is usually a clerical error (i.e. the wrong unit of blood being given to the wrong patient). The symptoms are fever and chills, sometimes with back pain and pink or red [[urine]] ([[hemoglobinuria]]). The major complication is that [[hemoglobin]] released by the destruction of red blood cells can cause [[acute renal failure]]. ==B cells== {{main|B cell}} The principal function of B cells is to make antibodies against soluble antigens. B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal [[proliferation]] and terminal [[differentiation]] into [[plasma cell]]s). Naive B cells can be activated in a T-cell dependent or independent manner, but two signals are always required to initiate activation. B-cell activation depends on one of three mechanisms: ''Type 1 T cell-independent'' ([[polyclonal response|polyclonal]]) activation, ''Type 2 T cell-independent'' activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells), and, T cell-dependent activation. During [[T cell]]-dependent activation, an [[antigen presenting cell]] (APC) presents a processed antigen to a helper T (T<sub>h</sub>) cell, priming it. When a B cell processes and presents the ''same'' antigen to the ''primed T<sub>h</sub> cell'', the T cell releases [[cytokine]]s that activate the B cell.<ref name=Janeway5/> ==See also== * [[Immune system]] * [[Immunity (medical)|Immunity]] * [[Polyclonal response]] ==References== {{Reflist}} ==Further reading== *The following article reviews some of the early experiments that laid the foundations of the humoral theory: Meltzer, S. J. and Charles Norris (1897) [http://www.jem.org/cgi/reprintframed/2/6/701 The Bactericidal Action of Lymph Taken From the Thoracic Duct of the Dog. (Full Text-pdf)] Journal of Experimental Medicine Vol. 2, Issue 6, 701-709. {{immune_system}} [[Category:Immune system]] [[es:Inmunidad humoral]] [[fr:Immunité humorale]] [[ko:체액 면역]] [[it:immunità umorale]] [[he:מערכת הומוראלית]] [[pl:Odpowiedź odpornościowa humoralna]] [[pt:Imunidade humoral]] [[zh:体液免疫]] [[ja:液性免疫]]