Intravascular immunity

Intravascular immunity describes the immune response in the bloodstream, and its role is to fight and prevent the spread of pathogens.^[1][2] Components of intravascular immunity include the cellular immune response and the macromolecules secreted by these cells. It can result in responses such as inflammation and immunothrombosis.^[3][4] Dysregulated intravascular immune response or pathogen evasion can create conditions like thrombosis, sepsis, or disseminated intravascular coagulation.^{[1][5][4][6][3][2]}

Cellular Defenses

In a healthy individual, immune cells patrol blood vessels to detect and respond to danger through molecules frequently found on pathogens called PAMPs, and molecules that are released by damaged cells, DAMPs.^[1][2] Immune cells involved in intravascular surveillance are neutrophils, monocytes, invariant natural killer T cells, kupffer cells, platelets, and mast cells.^[1][2] These cells express particular receptors such as toll-like receptors and proteins like CD36 that allow them to recognize and respond to danger signals.^[2] Endothelial cells lining the vasculature are also a part of the intravasculature's cellular defense system. They express molecules such as, CD14, TLR2, TLR4, TLR9, MD2, and MyD88, to detect bacteria in the blood.^[2]

Leukocytes move through blood vessels using protein-protein interactions between cells and are also assisted by blood flow.^[2] Circulating immune cells behave differently in the presence and absence of an infection. For example, in the absence of an invader, monocytes migrate randomly throughout the microvasculature, cerebral vessels, and mesentery vessels. However, in the presence of an invader, monocytes emigrate to the infected area.^[2] Similarly, neutrophils use a rolling mechanism to counteract the blood flow and localize to the infected area.^[4][2] In a healthy state, neutrophils have been observed to exhibit a similar but brief crawling mechanism. The function and precise mechanism is not yet known.^[2]