Components and functions of the complement system

Components and functions of the complement system The complement system found in the blood of mammals is composed of heat labile substances (proteins) that combine with antibodies or cell surfaces. This complex, multicomponent system is composed of about 26 proteins. The complement cascade is constitutive and non-specific but it must be activated in order to function. The functions of complement include: making bacteria more susceptible to phagocytosis directly lysing some bacteria and foreign cells producing chemotactic substances increasing vascular permeability causing smooth muscle contraction promoting mast cell degranulation The complement system can be activated via two distinct pathways; the classical pathway and the alternate pathway. Once initiated, a cascade of events (the complement cascade) ensues, providing the functions listed above. Most of the complement components are numbered (e.g. C1, C2, C3, etc.) but some are simply referred to as Factors. Some of the components must be enzymatically cleaved to activate their function; others simply combine to form complexes that are active. The following table lists these components and their functions. Components of the Classical Pathway Native component Active component(s) Function(s) C1(q,r,s) C1q Binds to antibody that has bound antigen, activates C1r. C1r Cleaves C1s to activate protease function. C1s Cleaves C2 and C4. C2 C2a Unknown. C2b Active enzyme of classical pathway; cleaves C3 and C5. C3 C3a Mediates inflammation; anaphylatoxin. C3b Binds C5 for cleavage by C2b. Binds cell surfaces for opsonization and activation of alternate pathway. C4 C4a Mediates inflammation. C4b Binds C2 for cleavage by C1s. Binds cell surfaces for opsonization. Components of the Alternate Pathway Native component Active component(s) Function(s) C3 C3a Mediates inflammation; anaphylatoxin. C3b Binds cell surfaces for opsonization and activation of alternate pathway. Factor B B Binds membrane bound C3b. Cleaved by Factor D. Ba Unknown. Bb Cleaved form stabilized by P produces C3 convertase. Factor D D Cleaves Factor B when bound to C3b. Properdin P Binds and stabilizes membrane bound C3bBb. Components of the Membrane-Attack Complex Native component Active component(s) Function(s) C5 C5a Mediates inflammation; anaphylatoxin, chemotaxin. C5b Initiates assembly of the membrane-attack complex (MAC). C6 C6 Binds C5b, forms acceptor for C7. C7 C7 Binds C5b6, inserts into membrane, forms acceptor for C8. C8 C8 Binds C5b67, initiates C9 polymerization. C9 C9n Polymerizes around C5b678 to form channel that causes cell lysis. ACTIVATION OF THE COMPLEMENT CASCADE Classical Pathway The classical pathway starts with C1; C1 binds to immunoglobulin Fc (primarily IgM and IgG); C1 is recognition complex composed of 22 polypeptide chains in 3 subunits; C1q, C1r, C1s. C1q is the actual recognition portion, a glycoprotein containing hydroxyproline and hydroxylysine that looks like a tulip flower. Upon binding via C1q, C1r is activated to become a protease that cleaves C1s to a form that activates (cleaves) both C2 and C4 to C2a/b and C4a/b. C2b and C4b combine to produce C3 convertase (C3 activating enzyme). C4a has anaphylactic activity (inflammatory response). C3 is central to both the classical and alternative pathways. In classical, C4b2b convertase cleaves C3 into C3a/b. C3a is a potent anaphylatoxin. C3b combines with C4b2b to form C4b2b3b complex that is a C5 convertase. C3b can also bind directly to cells making them susceptible to phagocytosis. C5 is converted by C5 convertase (i.e. C4b2b3b) to C5a/b. C5a has potent anaphylatoxic and chemotaxic activities. C5b functions as an anchor on the target cell surface to which the lytic membrane-attack complex (MAC) forms. MAC includes C5b, C6, C7, C8 and C9. Once C9 polymerizes to form a hole in the cell wall, lysis ensues. Classical Pathway Component cleavage Enzymatic activity Component assembly Alternate Pathway The alternate pathway may be initiated by immunologic (e.g. IgA or IgE) or non-immunologic (e.g. LPS) means. The cascade begins with C3. A small amount of C3b is always found in circulation as a result of spontaneous cleavage of C3 but the concentrations are generally kept very low (see below). However, when C3b binds covalently to sugars on a cell surface, it can become protected. Then Factor B binds to C3b. In the presence of Factor D, bound Factor B is cleaved to Ba and Bb; Bb contains the active site for a C3 convertase. Next. properdin binds to C3bBb to stabilize the C3bBb convertase on cell surface leading to cleavage of C3. Finally, a C3bBb3b complex forms and this is a C5 convertase, cleaving C5 to C5a/b. Once formed, C5b initiates formation of the membrane attack complex as described above. Generally, only Gram-negative cells can be directly lysed by antibody plus complement; Gram-positive cells are mostly resistant. However, phagocytosis is greatly enhanced by C3b binding (phagocytes have C3b receptors on their surface) and antibody is not always required. In addition, complement can neutralize virus particles either by direct lysis or by preventing viral penetration of host cells. Alternate Pathway Component cleavage Enzymatic activity Component assembly REGULATION OF THE COMPLEMENT CASCADE Because both the classical and alternate pathways depend upon C3b, regulation of the complement cascade is mediated via 3 proteins that affect the levels and activities of this component. C1 Inhibitor inhibits the production of C3b by combining with and inactivating C1r and C1s. This prevents formation of the C3 convertase, C4b2b. Protein H inhibits the production of C3b by inhibiting the binding of Factor B to membrane-bound C3b, thereby preventing cleavage of B to Bb and production of the C3 convertase, C3bBb. Factor I inhibits the production of C3b by cleaving C3b into C3c and C3d, which are inactive. Factor I only works on cell membrane bound C3b, mostly on red blood cells (i.e. non-activator surfaces).

Marketing Communications Memo Essay

This year this organization has elected to erect a monument to honor the fallen military heroes of Jacksonville, Florida. Some demographics of this large city are its’ multigenerational and diverse ethnic population, varied socioeconomic span, and of course, the large military representation, both active duty, retired, veterans, and their families. The location of Jacksonville in northeast Florida is a great stopover spot for tourists making their way to Orlando or Tampa and the snowbirds on their journey to southern Florida for the winter. The location of the monument should be centralized and near a major highway, possibly Interstate 95 between Interstate 10 and Interstate 295 South. Jacksonville, Florida is a military town and rich in its military history. According to United States Census Bureau QuickFacts (Jacksonville, 2008-2012) approximately 81,000 veterans live here. This number represents 10.5% of the total Jacksonville population. When including Orange Park and Jacksonville Beach to these numbers the veterans’ total number increases to nearly 85,000. This number is not reflective of the family members surrounding the veterans. The QuickFacts sheet goes on to state that the average household in Jacksonville, Jacksonville Beach, and Orange Park, is approximately 2.50 persons. The number of individuals living in the greater Jacksonville, Florida area directly related to the military member adds another 127,500 people for a total of 170,000 (QuickFacts Orange Park, QuickFacts Jacksonville Beach & QuickFacts Jacksonville, 2008-2012). We will want to choose a central location for the monument as Jacksonville, Florida has the greatest land mass in the continental United States with 885 square miles (Insider’s Guide to Jacksonville, Florida, 2014). By centralizing the location we can attract as many of Jacksonville’s residents to visit the monument. We must also take into consideration the ease of access to the monument for out of state visitors. If the location is too complicated to get to many people will not visit the site. The monument site will also have a visitor/gift shop with smaller images of the Fallen Heroes Monument for sale, along with military memorabilia of the two naval military installations, Naval Air Station Jacksonville and Naval Station Mayport, and Marine Corps Support Facility Blount Island Command along with military collectables. The various National Guards outfits along with the Coast Guard will be represented as well. The gift store will be maintain and staffed by Naval Air Station Jacksonville and proceeds will help with the upkeep of the monument. We will build the store as part of the monument site. The City of Jacksonville has donated the land in the name of the local fallen heroes. The project hopes to capture national attention with its innovative design and availability of military collectables. We want not just the Jacksonville, Florida residents to take pride in this monument but the State of Florida and our nation. Fundraising will be accomplished by reaching out to local military and veteran organizations. The Veterans of Foreign War, American Legion, Student Veterans of America, and American Veterans are all onboard to help with fundraising events like car washes, cook-outs, and large yard sales. We have also partnered with the local motorcycle clubs in Jacksonville, Florida who have scheduled several Saturday rides throughout the state. Historically the bikers clubs have donated large sums of money to events such as ours. The Jacksonville Sheriff’s Office and Jacksonville Fire Department are also collecting donations to help defray the total cost of the monument. Naval Station Mayport and Naval Air Station Jacksonville will have golf tournaments to support the building of the monument. Grants from the City of Jacksonville and from the State of Florida have been pledged.  There will be a website featuring the future monument and donations can be accepted there as well. Military personnel come from all ages, racial ethnicities, socioeconomic levels, and religious backgrounds; it is a fair assessment to predict that the visitors to the monument will be of the same diversity. The marketing direction will be of one from pride in our nations’ military men and women, the good work they do the world over, and the sacrifices they have given. The local community is fully committed to the project and is evident by the large number of private contributors. References: Insider’s Guide to Jacksonville, Florida. (2014). Retrieved from http://www.insideflorida.com/city/info/Jacksonville QuickFacts from the US Census Bureau. (2008-2012). Florida. Retrieved from http://quickfacts.census.gov/qfd/states/12000.html QuickFacts from the US Census Bureau. (2008-2012). Jacksonville, Florida. Retrieved from http://quickfacts.census.gov/qfd/states/12/1235000.html QuickFacts from the US Census Bureau. (2008-2012). Jacksonville Beach, Florida. Retrieved from http://quickfacts.census.gov/qfd/states/12/1235050.html QuickFacts from the US Census Bureau. (2008-2012). Orange Park, Florida. Retrieved from http://quickfacts.census.gov/qfd/states/12/1252125.html

The Author Of Her Book Essay - 659 Words

In â€Å"The Author to Her Book,† Bradstreet is awash in indecision and internal conflicts over the merits and shortfalls of her creative abilities and the book that she produced. This elaborate internal struggle between pride and shame is manifested through a painstaking conceit in which she likens her book to her own child. An essential step in analyzing a poem is to provide a structural outline of the poem. Anne Bradstreet’s poem, â€Å"The Author to Her Book,† can be divided into seven sections. First, line one provides the general description of how she views her creation. She repeatedly speaks directly to her work in apostrophe, as if it were her own child. Second, lines two through five depict how she feels embarrassed that her private†¦show more content†¦Thus, Bradstreet conveys the embarrassment she feels due to her imperfect work. The main idea shows throughout the poem as Bradstreet struggles with the idea of her work being published when not fully perfected. Another useful tool in analyzing a poem is to identify poetic devices, meter, and a rhyme scheme. Through her deft use of extended metaphor, Bradstreet weaves an intricate web of parallels between parent and author and between child and book--both relationships of creator to creation. This use of metaphor allows the reader to relate emotionally to Bradstreet’s situation. In line seven, we see the uses of litotes, â€Å"At thy return my blushing was not small,† to express the depth of her embarrassment. She also uses metonymy in line eight to express her pain more clearly, â€Å"My rambling brat (in print) should mother call.† The simile used in line nine stresses her objection to the published work, â€Å"I cast thee by as one unfit for light.† Then in line 19, the poetic device of consonance is used which provides emphasis on her warning, â€Å"In this array ‘mongst vulgars may’st thou roam.† In this poem, through the use of personific ation and apostrophe Bradstreet conveys her feelings and emotions. Anne Bradstreet ensures her poem’s success by linking the triumph and tragedy of authorship with the pain and pleasure of creating and nurturing human life. The meter used isShow MoreRelatedThe Author To Her Book Anne Bradstreet1323 Words   |  6 PagesAnne Bradstreet in her poem, â€Å"The Author to Her Book†, elaborates on the true struggles of the publishing process that writers may experience in their writing careers. 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Advertising Has Targeted Women for Decades - 1888 Words

1 Research Proposal From television commercials to radio to print ads, advertising has defined the meaning of perfection. Most notably, advertising dictates what to eat, what to wear, where to go and who to be seen with. At the same time that childhood obesity is at an all time high, women in our society are facing advertising s idealized portrayal of unrealistic bodies. Anorexia nervosa, bulimia and a multitude of other self inflicted diseases are running rampant in societies nationwide. Our group was intrigued by the relationship between women and advertising. College aged women often find themselves as the target of many advertisements. At a time when women are told to define themselves and mature, advertisers recognize their†¦show more content†¦But exactly how much do advertisements affect the way women feel about themselves and the way they live their lives through dieting, clothing choices, exercise, etc? Previous studies show that viewing thin models increases weight-r elated anxiety to an extent that women internalize the thin ideal, and that this anxiety is heightened with the duration of the viewing time (Brown/Dittmar, 2005). In an experiment done by Brown and Dittmar, 75 women were exposed to either neutral advertisements (no models) or to thin models, at either low or high attention, manipulated by the exposure time and focus instructions. This article aimed to extend the understanding of why women come to feel bad about their own bodies after exposure to thin models. Since we are studying how advertisements affect women’s body image and perception of themselves, this article will be a great reference since it shows the correlation between media exposure that contain ultra-thin ideals to increased bodydissatisfaction and eating disorders. 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