Four mechanistic models explaining how immunothrombosis provides protection against invading pathogens. (1) Immunothrombosis limits microbial dissemination by containing microbes within thrombi. (2) Thrombi form protective barricades inside and/or around blood vessels that limit microbial movement in and out of the vessels. (3) Fibrin, fibrinogen, and fibrin/fibrinogen degradation products promote recruitment and activation of leukocytes, such as neutrophils and macrophages, coordinating cellular immune responses to pathogens at sites of infection. (4) Intravascular thrombi yield a distinct compartment where antimicrobial peptides are concentrated and have increased opportunities to come into contact with pathogens.