**3. Fcγ receptors**

*Neutrophils*

**Figure 2.**

*2.2.2 Degranulation*

molecules are delivered into the phagosomal lumen, and the vesicle is transformed into a phagolysosome [19]. In the phagolysosome, reactive oxygen species (ROS) are produced by the NADPH oxidase on the phagosomal membrane, and the pH inside drops to 4.5–5. Also, hydrogen peroxide (H2O2) is converted to hypochlorous acid (HOCl) in a reaction catalyzed by myeloperoxidase (MPO) [20]. Together, these

*Antimicrobial mechanisms of neutrophils. Neutrophils can destroy microbial pathogens, such as bacteria by (a) degranulation, (b) phagocytosis, and (c) NETosis. During degranulation, antimicrobial proteins are released outside the neutrophil. In phagocytosis, the pathogen is ingested in a vacuole named phagosome, which then fuses to lysosomes and becomes a phagolysosome, where the pathogen is destroyed. During NETosis, DNA fibers decorated with histones and granular proteins, such as elastase and myeloperoxidase are released in* 

During neutrophil formation in the bone marrow, immature neutrophils synthesize proteins that are sorted into different granules [10]. Granules are classified into three different types based on their content. Azurophilic granules contain mainly myeloperoxidase, elastase, and cathepsin G. Specific granules contain mainly collagenase, lactoferrin, and lysozyme. Gelatinase granules contain mainly gelatinase, lysozyme, and cytochrome b558 [21]. Neutrophils also form secretory vesicles at the last step of their differentiation. These secretory vesicles contain several important receptors on their membrane, including complement receptors (CR1), Fc receptors (CD16), lipopolysaccharide (LPS) receptors (CD-14), and fMLF receptors. Granule heterogeneity is due to the controlled expression of the granule protein genes [22]. Mature neutrophils are released into the circulation and when they reach sites of infection, neutrophils can degranulate in order to deliver their antimicrobial proteins. Secretory vesicles present the greatest predisposition for extracellular release, followed by gelatinase granules, specific granules, and azurophil granules [23]. The hierarchical mobilization of neutrophil granules and secretory vesicles depend on intracellular Ca2+-level [24].

When neutrophils cannot ingest large microorganisms, they can display another antimicrobial strategy [25]. Neutrophils can release long chromatin fibers that are decorated with proteins from their granules. These fibers can trap microorganisms, and therefore, they have been called neutrophil extracellular traps (NETs) [26]. The process of NETs formation is called NETosis [27]. NETosis has been described as a special form of programmed cell death. The complete mechanisms of NETs formation are still unknown; it seems that NETosis requires NADPH oxidase activation, reactive oxygen species (ROS) production, myeloperoxidase (MPO), and neutro-

actions form a toxic environment for the microorganism.

*structures known as neutrophil extracellular traps (NETs).*

*2.2.3 Neutrophil extracellular traps (NETs)*

phil elastase (NE) release [28, 29] (**Figure 2**).

**26**

Antibodies produced by the adaptive immune response are mainly of the IgG class. These antibodies present higher affinity and greater specificity for their particular antigen. Thus, IgG antibodies are key for controlling infections from all types of pathogens, including viruses, bacteria, fungi, and protozoa [30]. However, IgG molecules do not directly damage the microorganisms they recognize. It is in fact, the cells of the innate immune system, which are responsible for the antimicrobial functions of these antibodies. Although, some antibodies can activate complement, which is then deposited on microorganisms to promote phagocytosis via complement receptors [17, 31], or to induce bacterial lysis via the formation of the membrane attack complex [32], most IgG antibodies bind to specific receptors on the membrane of leukocytes [7, 8]. These receptors recognize the fragment crystallizable (Fc) portion of IgG molecules and are therefore known as Fcγ receptors (FcγR). Cross-linking of FcγR on the surface of cells activates several antimicrobial functions [6].
