Connection between Platelets and Immunity

Platelets play a central role in both innate and adaptive immunity.

Platelets are a unique type of mammalian blood cell. They are anucleate molecules which play an integral role in host hemostasis, innate and immune defence and repair. Platelets are present in blood circulation but they are unable to move themselves so they passively move with the blood circulation. At sites of infection or injury in a host organism, platelets will be deployed rapidly where they will display their role in defence and signaling.

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Innate Immunity

Innate immunity refers to non specific defence mechanisms that come into play immediately or within hours of antigens appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood and immune system cells that attack foreign cells in the body. The innate immune response is activated by chemical properties of the antigen (The Biology Project, University of Arizona, 2000).

Adaptive Immunity

Adaptive immunity refers to antigen specific immune response. The adaptive immune response is more complex than the innate. The antige first must be processed and recognised. Once an antigen has been recognised, the adaptive immune system creates an army of immune cells specifically designed to attack that antigen. Adaptive immunity also includes "memory" that makes future responses against a specific antigen more efficient (The Biology Project, University of Arizona, 2000).

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Hemostasis

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Hemostasis

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Hemostasis is a process which causes bleeding to stop and retention of blood within a damaged blood vessel. Hemostasis is crucial to animals in the case of a damaged blood vessel. It is the first stage of wound heeling.

Activation of Platelets

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There are two types of platelet activation, primary and secondary, both of which lead to platelet aggregation.

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There are two types of platelet activation, primary and secondary, both which lead to platelet aggregation.

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Primary platelet activation occurs when the specialised surface receptors of platelets bind to the negative charges of an injured endothelial area (expose collagen).

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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 activation response (S. Severin et al, 2013).

The Process of Activation

Platelets are not usually attracted to endothelial surfaces. As endothelial surfaces act to inhibit platelet activation by producing:

Primary Activation

Under physiological conditions, collagen is not exposed to the bloodstream. However, when an injury of a blood vessel occurs, collagen and Von Willebrand Factor (vWF), from the subendthelium is exposed to the bloodstream. vWF is a glycomeric protein produced by endothelial cells, which acts as a cell adhesion ligand enabling endthelial cells to adhere to collagen in the basement membrane. When the platelets come in contact with collagen or vWF they are activated (M. Hermann et al, 1997).

Examples of platelet activating factors:

Secondary Activation

Following primary activation, the microtubule system which is located below the plasma membrane and the actin cytoskeleton system of the platelets activate the reaction (S. Severin et al, 2013). This increases aggregation.

A thrombus or blood clot is the final product in the blood coagulation set of hemostasis. This happens when filopodia are produced which provide the framework for platelets to attach to each other and also collagen fibres. Endothelial production of prostacyclines and nitrogen monoxide ceases. Their role is to prevent the factors production of factors responsible for aggregation. Accordingly, the thrombocytes can now produce their own stimulating factors. TXA2, serotonin, adenosine Diphosphate that will stimulate other thrombocytes increasing the aggregation as well as the secretion of coagulation factors (Szent István Egyetem, 2011).

Aggregation at Sites of Bacterial Invasion

Previous studies (P. B. Maguire, D. J. Fitzgerald) would indicate that platelets also:

With these abilities the platelets should have the capability of performing rapid targeting mechanism thus localizing platelets to both intravascular compartments and the extravascular milieu in incidents of injury, microbial invasion and inflammation. (A. S. Wreyrich, G. A. Zimmerman)

====Cell-Cell Interactions Involving Platelets====

Once activated, platelets interact with and transfer information to other cells of immune defence, such as monocytes or neutrophils. Should platelets accumulate in the vessels or in the extracellular space, they also posess the ability to signal mast cell, macrophages and dendritic cells. Simultaneously these tissue surveillance cells or sentinel cells can also transfer signals to the platelets through the production of substances such as Platelet Activating Factor (PAF). PAF is an inflammatory mediator that is recognized by a receptor on the platelet plasma membrane. Therefore platelets can both supply and respond to signals at early points of control in inflammation and immune progression.

Activated platelets participate in crucial cell-cell interactions and provide signals in the immune continuum. (A. S. Wreyrich et al, 2003) The following are examples of cellular interactions with the potential to induce, amplify or modify multiple inflammatory or adaptive immune events.

  1. Activated human platelets adhere to and signal monocytes, forming mixed cellular aggregates which will induce expression of inflammatory gene products. B. Activated platelets synthesize and release interleukin-1beta, which can then signal endothelial cells and other target cells. A consequence of signalling by this mechanism is the expression of genes that code for adhesion molecules and chemokines that mediate targeting and local activation of neutrophils and monocytes.

    C.Platelets signal maturation and activation of dendritic cells in vitro. This may prove to be a key cellular interaction that enables platelets to modify T- and B- Lymphocyte functions in response to experimental viral challenge in vitro

====Platelet Expression of CD40L/CD154 in Adaptive Immunity====

CD40L is a trimeric, transmembrane protein of the tumour necrosis factor family that was origionally identified on cells of the immune system (activated CD4+ cells, mast cells, basophils, eosinophils and natural killer cells) subsequently on several cells of the vasculature such as endothelial cells, smooth muscal cells, macrophages and monocytes. The role of CD40L in the immune response involves binding to its receptor on B cells, CD40, to induce B- cell proliferation, generate memory B cells, block B- apoptosis, and mediate antibody class switching. Additionallz, the pioneering work of Henn and collaborators showed that CD40L and CD40 also exist in platelets. CD40L is cryptic in unactivated platelets but is rapidly presented on the platelet surface after platelet activation. ( Henn V. et al, 2001) Studies on the cellular distribution of CD40L indicate that >95% of the circulating CD40L exists in platelets. This suggests that platelet activation events must be considered in the biological and pathological context of CD40L function.

The following experiments prove the importance of platelet derived CD154 in immunity.

CD154 only present on activated platelets

In previous experimental studies (Henn et al, 1998, Henn et al, 2001, Diacovo et al, 1994, Bombelo et al, 1998, Geba et al, 1996, Collins et al, 1994, Gawaz et al, 2000, Barry et al, 1998) It was proven that platelet derived CD154 was only present in activated platelets. (Platelet activation discussed