Preface

The environment comprises a variety of infectious microbial agents. Many of them can cause pathological disorders and even death in organisms exposed to them if they multiply uncontrollably. However, organisms can control infections caused by pathogens thanks to the existence of the immune system. The immune system is a set of biological processes that prevents an organism from infectious diseases [1]. In vertebrates, the immune system is divided into the innate and the adaptive immune systems. The innate immune system is the most ancient form of defense. It is the first mechanism to respond to infections and the main defense mechanism in invertebrates [2]. It is characterized as non-pathogen-specific and does not provide specific long-lasting immunity to the host [3]. The components of the innate system comprise the physical barrier (the skin), molecular effectors (complement system, antimicrobial peptides, and cytokines), and immune cells (granulocytes, monocytes, macrophages, and natural killer cells) [3].

The innate immune system has certain specificity in the recognition of pathogens through pattern recognition receptors (PRRs). These receptors are expressed in many cell types, and they are strategically located throughout cells. PRRs are in cell membranes where they mediate recognition of extracellular pathogens, and in endosomes and cytoplasm where they detect intracellular pathogens. PRRs recognize small molecular motifs characteristic of pathogens called pathogen-associated molecular patterns (PAMPs) [4], which are conserved through evolution. There is a variety of PAMPs, for example, bacterial flagellin, bacterial lipopolysaccharides (LPS), peptidoglycans, or nucleic acid variants from viruses [double-stranded RNA (dsRNA) or nonmethylated viral 5'-C-phosphate-G-3′ (CpG)-containing DNA] [4]. The activation of PRRs with their PAMPs activates the signaling networks that modulate the expression of cytokines such as type I interferon and antiviral proteins to protect the organism against infections [5].

In addition, vertebrates possess the adaptive immune system, which consists of a specific immune response based on immune memory against recurrent pathogens [6]. B and T lymphocytes are principally responsible for the specificity of the adaptive immune responses [7]. This system is highly specific and can discriminate between self- and non-self-cells. Both the innate and adaptive immune systems do not act separately; they are completely integrated to protect the organism against the attack of pathogens [1].

Nowadays, the immune system of higher vertebrates like mammals is being more studied in depth in comparison with the immune system of lower vertebrates such as teleosts. The immune system of teleosts is physiologically comparable to that of higher vertebrates, despite certain differences such as the fact that the main haematopoietic organ of teleosts is the head kidney, as they do not have bone marrow (the main haematopoietic organ in mammals) [8]. Apart from that, teleosts possess a less complex adaptive immune system compared to higher vertebrates and therefore rely heavily on innate immune responses to face continuous pathogen attacks. Teleosts reside in extremely distinct environments from those in which mammalians have evolved, so it is not misbegotten that aquatic vertebrates have


**Table 1.**

*Comparison of key immune response elements between teleosts and mammals, modified from [8].*

many immunological differences from terrestrial vertebrates [9]. As to the innate immune response, in lower vertebrates it is similar to that of higher vertebrates, and the main cell types involved in this response are macrophages, monocytes, NK-like cells, and granulocytes [10]. A difference between the immune system of teleosts and mammals is the red blood cells (RBCs), since in contrast to mammalian RBCs, the RBCs of fish are nucleated. Nucleated RBCs, characteristic of fish, amphibians, reptiles, and birds, have been recently stated as multifunctional cells because in addition to being involved in gas exchange and transport, they also can actively participate in the immune response to several pathogens [11]. Regarding the adaptive immune response, it is known that teleost B lymphocytes do not possess the same repertoire of immunoglobulins as humans [12], and they also have different antibody affinity maturation and lymphocyte proliferation processes [13]. **Table 1** compiles some of these and other differences.

This book presents current investigations regarding the humoral and/or cellular mechanisms responsible for the induction of antiviral and antibacterial immune responses in different immune-reactive organs, for example, skin, lungs, gut, bone marrow, kidney, spleen, blood, liver, and reproductive organs.

Additionally, this book provides the reader with an overview of the mechanisms that have been the target of interest in terms of therapeutics or prophylactics against viral or bacterial infections. The purpose of this book is to show an up-to-date revision of the antimicrobial mechanisms triggered across different animal species, from lower to higher vertebrates.

> **Veronica Chico and Maria del Mar Ortega-Villaizan** Instituto de Investigación, Desarrollo e innovación en Biotecnología Sanitaria de Elche (IDIBE) Universidad Miguel Hernández (IDIBE-UMH), Elche, Spain

> > **V**

[1] Roitt, I.; Brostoff, J.; Male, D.K. *Immunology*. Gower Medical Publishing Immune cell mediators of the antiviral response. *PLoS Pathog* **2018**, *14*,

[12] Bengten, E.; Clem, L.W.; Miller, N.W.; Warr, G.W.; Wilson, M. Channel catfish immunoglobulins: Repertoire and expression. *Dev Comp Immunol* 

[13] Du Pasquier, L. Antibody diversity in lower vertebrates--why is it so restricted? *Nature* **1982**, *296*, 311-313.

e1006910.

**2006**, *30*, 77-92.

[2] Smith, N.C.; Rise, M.L.; Christian, S.L. A comparison of the innate and adaptive immune systems in cartilaginous fish, ray-finned fish, and lobe-finned fish. *Frontiers in immunology* 

[3] Uzman, A. Molecular biology of the cell (4th ed.): Alberts, b., johnson, a., lewis, j., raff, m., roberts, k., and walter, p. *Biochemistry and Molecular Biology* 

*Education* **2003**, *31*, 212-214.

[4] CA, J.; R, M. Innate immune recognition. . *Annual Review of Immunology.* **2002**, *20(1)*.

[5] Robertsen, B. The interferon system of teleost fish. *Fish & Shellfish Immunology* **2006**, *20*, 172-191.

[6] Gładysz, D.; Krzywdzińska, A.; Hozyasz, K.K. Immune abnormalities in autism spectrum disorder—could they hold promise for causative treatment? *Molecular Neurobiology* **2018**, *55*,

[7] Janeway, C., Travers, Paul, Walport, Mark, Shlomchik, M. *Immunobiology.6th.* . 2004.

[8] Sunyer, J.O. Fishing for mammalian paradigms in the teleost immune system. *Nat Immunol* **2013**, *14*, 320-326.

[9] DeWitte-Orr, S.; Edholm, E.-S.; Grayfer, L. Editorial: Innate immunity in aquatic vertebrates. *Frontiers in* 

[10] Secombes, C.J.; Wang, T. The innate and adaptive immune system of fish.

[11] Nombela, I.; Ortega-Villaizan, M.D.M. Nucleated red blood cells:

*immunology* **2019**, *10*.

**2012**, 3-68.

(Medsi), Londres: 1986.

**2019**, *10*, 2292.

**References**

6387-6435.

## **References**

[1] Roitt, I.; Brostoff, J.; Male, D.K. *Immunology*. Gower Medical Publishing (Medsi), Londres: 1986.

[2] Smith, N.C.; Rise, M.L.; Christian, S.L. A comparison of the innate and adaptive immune systems in cartilaginous fish, ray-finned fish, and lobe-finned fish. *Frontiers in immunology*  **2019**, *10*, 2292.

[3] Uzman, A. Molecular biology of the cell (4th ed.): Alberts, b., johnson, a., lewis, j., raff, m., roberts, k., and walter, p. *Biochemistry and Molecular Biology Education* **2003**, *31*, 212-214.

[4] CA, J.; R, M. Innate immune recognition. . *Annual Review of Immunology.* **2002**, *20(1)*.

[5] Robertsen, B. The interferon system of teleost fish. *Fish & Shellfish Immunology* **2006**, *20*, 172-191.

[6] Gładysz, D.; Krzywdzińska, A.; Hozyasz, K.K. Immune abnormalities in autism spectrum disorder—could they hold promise for causative treatment? *Molecular Neurobiology* **2018**, *55*, 6387-6435.

[7] Janeway, C., Travers, Paul, Walport, Mark, Shlomchik, M. *Immunobiology.6th.* . 2004.

[8] Sunyer, J.O. Fishing for mammalian paradigms in the teleost immune system. *Nat Immunol* **2013**, *14*, 320-326.

[9] DeWitte-Orr, S.; Edholm, E.-S.; Grayfer, L. Editorial: Innate immunity in aquatic vertebrates. *Frontiers in immunology* **2019**, *10*.

[10] Secombes, C.J.; Wang, T. The innate and adaptive immune system of fish. **2012**, 3-68.

[11] Nombela, I.; Ortega-Villaizan, M.D.M. Nucleated red blood cells: Immune cell mediators of the antiviral response. *PLoS Pathog* **2018**, *14*, e1006910.

[12] Bengten, E.; Clem, L.W.; Miller, N.W.; Warr, G.W.; Wilson, M. Channel catfish immunoglobulins: Repertoire and expression. *Dev Comp Immunol*  **2006**, *30*, 77-92.

[13] Du Pasquier, L. Antibody diversity in lower vertebrates--why is it so restricted? *Nature* **1982**, *296*, 311-313.

Acknowledgments

The editors would like to thank the staff at IntechOpen, particularly Commissioning Editor Jelena Germuth and Author Service Manager Maja Bozicevic, for their contri-

butions to the editorial process.
