Itt írjon a(z) PlateletImmunity-ról/rő

= Platelets = Introduction

Platelets are a unique type of mammalian blood cell. They are anucleate molecules which play an integral role in host homeostasis, immune defence and repair. At sites of infection or injury in a host organism, platelets will be deployed rapidly where they will display their role in defence and signalling. Platelets are activated by agonists, of which there are several. Thrombin, collagen, ADP, platelet activating factor (PAF) and other factors all promote the activation of platelets. There are two types of platelet activation, primary and secondary, both of which lead to platelet aggregation. Primary platelet aggregation occurs when the specialised surface receptors of platelets bind to the negative charges of injured endothelial area (exposed collagen) whilst secondary platelet activation refers to activation of the platelets by their actin and microtubule system as well as by their secretion of coagulation factors. The potency of platelet agonist varies depending on the activation response

Hemostasis

Platelets' foremost role is hemostasis. It not only helps the animal from blood loss but it also prevents microorganisms from entering the animal which may cause disease. The role of Platelets in homeostasis would suggest evolution from more primitive multifunctional innate defensive cells as although highly differentiated they have inflammatory and antimicrobial systems and link clotting and immune cascades (A.S Weyrich et al). Hemostasis is crucial to animals, when a blood vessel of theirs becomes damaged or injured. It is the first stage of wound healing. Platelets are present in the blood circulation at a volume of 2-8 x 1011/l, depending on the species. They are unable to move themselves so they passively move with the blood circulation (page 131). After an injury to a blood vessel occurs, vascular constriction is the organisms initial reaction. Platelets are not usually attracted to endothelial surfaces. When an injury of a blood vessel happens, platelets combine with their specialized surface receptors to the negative charges of the endothelial regions. This is primary aggregation (page 200-201). Also, Von Willebrand factor, which is a multimeric glycoprotein released by the endothelial cells plays a key role in the adhesion of platelets to the subendothelium.(M. Hermmann et al). This allows platelet aggregation to increase. Secondary activation follows. The microtubule system which is located beneath the plasma membrane and the actin cytoskeleton system of the platelets activate the reaction (S. Severin et al). This causes white thrombosis to arise. This happens when by filopodia are produced which provides the framework for platelets to attach to each other and also collagen fibres. Endothelial production of prostacyclines and nitrogen monoxyde ceases. Their role is to prevent the production of factors responsible for aggregation. Accordingly, the thrombocytes can now produce their own stimulating factors. These include TXA2, serotonin, adenosine-diphosphates that will stimulate other thrombocytes increasing the aggregation as well as the secretion of coagulation factors (page 201 and 202). This shows how platelets are pivitol in hemostasis. Without them, a relatively innocuous injury to a blood vessel may be fatal. They help heal wounds and by doing this help to prevent harmful microorganisms which could be disease causing from entering the animal. If these disease causing microorganisms were to off got into the body the animal would have to endure processes such as the production of antibodies to fight the infection. These processes are energy consuming and put the animal under stress. Therefore platelet's role in hemostasis can be looked upon as a temporary mechanical barrier between the organism and the outer environment, reducing the threat of disease when an animal is wounded.

A.S Weyrich et al The evolving role of platelets in inflammation J.Thromb. Haemost., 1 (2003), pp. 1897-1905) http://www.jstor.org/discover/10.2307/30107584?searchUri=%2Faction%2FdoBasicSearch%3FQuery%3Dvon%2Bwillebrand%26Search%3DSearch%26gw%3Djtx%26prq%3Dplatelets%2Bvon%2Bwillebrand%26hp%3D25%26acc%3Doff%26aori%3Doff%26wc%3Don%26fc%3Doff&Search=yes&searchText=von&searchText=willebrand&uid=3738216&uid=2129&uid=2134&uid=2&uid=70&uid=4&sid=21102878826017 http://onlinelibrary.wiley.com/doi/10.1111/jth.12053/pdf

PLATELET MEDIATED MODULATION OF ADAPTIVE IMMUNITY Platelets play a major role in immunity through hemostasis and insuring structural composition of the vessel wall. Recently scientists have discovered platelets have a broader purpose than initially thought in the role of immunity. Platelets are also significantly important in the modulation of inflammation.

A molecule of great influence is CD154 which platelets express upon activation. Through CD154 expression, activated CD4+ T cells provide the signals required for the differentiation of T cell dependent B lymphocyte responses. A process that includes isotype switching. Yang and Wilson 1996, Renshaw et al. 1994, and Caux et al. 1994. CD154 expression on activated CD4+ T cells augment the DC maturation process. A requirement for cross priming and enhancing cytotoxic CD8+ T cells responses through the classical pathway. Ridge et al. 1998, Schoenberger et al. 1998and Bennett et al. 1998. The following experiments prove these theorys and therefore the importance of platelet derived CD154 in immunity. Adoptive transfer studies demonstrate that platelets activated physiologically with adenoviral infection (splenic and hepatic inflammation) are sufficient via CD154 for the induction of isotype switching by B cells and augmentation of the CD8+ T cell response during a viral infection Normal mice depleted of platelets prior to adenovirus infection exhibit decreased efficiency of production of adenovirus specific IgG underscoring the importance of platelets in the generation of an optimal adaptive immune response. Cd154 only present on activated platelets In previous experimental studies (Henn et al 1998, Henn et al. 2001, Ahmad et al. 2001, Diacovoet al 1994, Bombelo et al. 1998, Geba et al. 1996, Collins et al. 1994, Gawaz et al. 2000 and Barry et al. 1998) it was proven that platelet derived CD154 was only present in activated platelets. (platelet activation discussed previously) In the experiment, unactivated platelets and platelets activated with thrombin or collagen were tested for surface CD154. Results show that only activated platelets expressed surface CD 154. CD154 causes Dentritic cell maturation In later experiments, bone marrow derived dentritic cells were generated and incubated with activated platelets. The production of interleukins which are produced naturally by dendritic cells in response to antigenic stimulation was measured. The results show how activated platelets induced the interleukin production by the DC’s in a CD154 dependent mannor. CD154 induces B cell isotype switching The ability of B lymphocytes to switch from the production of IgM/IgD to IgG or other Ig isotypes requires CD40 activation (Renshaw et al. 1994). B cell activation in the absence of CD40 ligation results in hyper IgM syndrome with minimal switching to IgG secretion. As documented by Zhang et al. 2001 and Jaffee et al. 1992 mice injected with andenovirus result in splenic and hepatic inflammation. With this knowledge, experiments were carried out to assess the ability of platelet derived CD154 to induce B lymphocyte isotype switching in mice deficient in CD154 Adenovirus was injected intravenously into a CD154 deficient mouse. Activated platelets from normal mice were injected and then adenovirus specific Ig isotypes were measured. Therefore the transfer of normal activated platelets was sufficient to induce isotype switching Isotype switching was abrogated by anti- CD154. Although adenovirus specific IgM was produced IgG was not, therefore linking CD154 to the isotype switch to IgG. CD154 modulates CD 8+ T cell responses In the experiment, platelets derived from normal an CD154 derived mice were transferred in CD154 derived mice hosts. The mice were then challenged iv with Ad5-mOVA. Ten days later the spleens were isolated and ova-specific lytic activity was measured. Results show that there is adenovirus induced cytolytic T lymphocyte activity in CD154 derived mice , however it show lytic activity equivilant to mice receiving diluents without platelet transfer. Results in mice receiving normal platelets containing CD145 on the surface exhibit enhanced CTL activity. These findings indicate that platelet derived CD154 is sufficient to modulate CD8+ T cell responses.