An Introduction to the Immune System and Vaccines
Patricia G. Melloy in Viruses and Society, 2023
Many immunologists have spent their careers trying to figure out the critical question in immunology: how the body recognizes “self” versus “nonself” (Nicholson 2016). More specifically, scientists wonder what the body is recognizing when the immune cells identify something as nonself. How does the body know a foreign invader is present? It turns out that immune cells can recognize viral proteins, like proteins that coat the outside of the virus, as well as viral DNA or RNA. These molecules, when identified in a virus, are called pathogen associated molecular patterns (PAMPs). Certain immune cells can display pattern recognition receptors (PRRs) on their cell membranes or internal endosomal membranes that can detect PAMPs and stimulate the release of cytokines. In addition, other immune cells can actually recognize if damage has occurred from a viral infection. This is a way that the body can detect the virus in a secondary manner through signs of a viral presence, not the virus itself (Mueller and Rouse 2008; Amarante-Mendes et al. 2018). Interestingly, the cells of the immune system are said to be surveying the environment and putting proteins that they find in the body in particular categories. They are “continuously sampling these proteins” in the form of short peptides (protein fragments) to ensure the security of the body (Nicholson 2016). Scientists note that about 70% of lymphocytes in the body are circulating, checking for signs of foreign invaders (Ross and Pawlina 2011).
Tumor Suppression
John Melford in Pocket Guide to Cancer, 2017
Killer cells of the innate immune system routinely distinguish between cells that are self, and should be left alone, and cells that are foreign, which should be eliminated. To discriminate between friend and foe, the innate immune system has evolved the capability to recognize conserved molecular targets present in commonly encountered pathogens, but are not present in native cells. These targets, referred to as pathogen-associated molecular patterns (PAMPs), are widespread in microorganisms. Innate killer cells have evolved receptors that recognize PAMPs to which they bind. Examples of PAMPs include DNA found in viruses, molecules found in the cell walls of bacteria, and flagellin found in the flagella of bacteria. Killer cells of our innate immune system are armed with receptors on their outer cell membrane that recognize PAMPs. It has been estimated that several hundred exist in vertebrates and are so vital to life that they are encoded in our genes.
Infection-driven periodontal disease
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
To combat the onslaught of microorganisms at mucosal surfaces and to maintain homeostasis in contaminated environments such as the oral cavity, the host has evolved mechanisms to detect bacteria: the recognition of structural components of the bacterial surface. Lipopolysaccharides (LPSs), peptidoglycan (PGN), and other cell-surface components such as fimbriae are essential structural components of bacteria. Structural variation of these bacterial components between various species, or even between different strains of the same species, creates incredible structural diversity in prokaryotes. Despite structural heterogeneity, there are conserved motifs known as pathogen-associated molecular patterns (PAMPs). PAMPs and their receptors are considered in more detail in Chapter 16. Host cells have PAMP receptors termed pattern-recognition receptors (PRRs). These innate immune receptors are highly conserved and presumably evolved to detect invading bacteria. Binding of PAMPs by PRRs initiates an inflammatory response. On mucosal surfaces colonized by commensal organisms, the balance between constant inflammatory stimulus and maintenance of homeostasis is often lost, resulting in local inflammation of colonized tissues, as in gingivitis.
Promising vaccines for treating glioblastoma
Published in Expert Opinion on Biological Therapy, 2018
Adam M. Swartz, Steven H. Shen, Miguel A. Salgado, Kendra L. Congdon, Luis Sanchez-Perez
Peptide vaccines contain peptides of about 8–30 amino acids in length and are, therefore, among the simplest forms of cancer vaccines. They are designed to encompass tumor-associated or tumor-specific epitopes that can be recognized by immunoglobulins or, when bound to MHC molecules, by TCRs. The identification of MHC-restricted tumor epitopes has been greatly facilitated by the use of in silico MHC binding algorithms which predict peptide binding to class I or class II molecules [20]. Peptide vaccines are typically administered with an immunostimulatory adjuvant capable of eliciting local inflammation. These include inflammatory cytokines and pathogen-derived molecules called pathogen-associated molecular patterns (PAMPs). While cytokines can mediate inflammation directly, PAMPs have to be recognized by pattern recognition receptors (PRRs), which in turn lead to the induction of inflammatory cytokines. One of the most studied and promising PRR family is the Toll-like receptors (TLRs) [21]. The ease by which GMP-grade peptides and TLRs ligands can be synthesized, their relative stability and low cost makes adjuvant peptide vaccines very amenable to the clinical setting.
Microneedle arrays for vaccine delivery: the possibilities, challenges and use of nanoparticles as a combinatorial approach for enhanced vaccine immunogenicity
Published in Expert Opinion on Drug Delivery, 2018
Aoife Maria Rodgers, Ana Sara Cordeiro, Adrien Kissenpfennig, Ryan F Donnelly
In addition to the logistical and safety concerns, there is also a requirement for increased vaccine effectiveness from an immunological perspective. Most effective traditional vaccines are based on live-attenuated variants of the targeted pathogen. Such vaccines do not require adjuvants because they comprise bacterial or viral compounds that activate the innate immune system to enhance immunity [8]. Administration of these vaccines induces asymptomatic infections and generates long-lived memory, similar to what would be achieved in an individual following natural infection. Despite the impressive success of these vaccines, their potential toxicity and reactogenicity have led to the search for optimized antigens [18]. While the use of inactivated pathogens, synthetic peptides and recombinant protein subunits is advantageous in terms of safety and cost-effectiveness, these often exhibit poorer immunogenicity [19]. Thus, the co-delivery of adjuvants is pivotal to facilitate the induction of robust protective immunity [20]. Adjuvants can function like a pathogen-associated molecular pattern (PAMP), triggering innate immune responses through different mechanisms. This in turn, results in the activation and maturation of APCs and initiation of adaptive immune response [21].
Glycyrrhizin and Omega-3 fatty acids have hepatoprotective roles through toll-like receptor-4
Published in Egyptian Journal of Basic and Applied Sciences, 2019
Nada F. Abo El-Magd, Amro El-Karef, Mamdouh M. El-Shishtawy, Laila A. Eissa
Toll-like receptor-4 (TLR-4) has a critical role in innate immunity as the first line of host defense. Dimerization of two receptor molecules precedes TLR-4 activation [4]. The TLR-4 pathway consists of two different signaling pathways, the myeloid differentiating primary response gene 88 (MyD88)-dependent and the MyD88-independent pathway. (MyD88)-dependent pathway results in the production of pro-inflammatory cytokines through activation of nuclear factor-κB (NF-κB), while the MyD88-independent pathway results in the production of type 1 interferons [5]. Innate immune responses are initiated when danger associated molecule patterns and pathogen-associated molecular patterns (PAMP) are recognized by pattern recognition receptors including TLR-4 [6]. A classical PAMP is a lipopolysaccharide (LPS) from gram-negative bacteria which activates high mobility group box1 (HMGB1). HMGB1 is a highly conserved protein released by injured or dying cells as a result of pathogenic products [7]. HMGB1 may trigger an inflammatory response via activation of TLR-4 pathway which activates NF-κB. This consequently causes an enhancement in the production of tumor necrosis factor α (TNF-α), interleukin-1b (IL-1b) and nitric oxide [8].
Related Knowledge Centers
- Glycan
- Interferon
- Nucleic Acid
- Pattern Recognition Receptor
- Rna
- Virus
- Toll-Like Receptor
- Glycoconjugate
- Toll-Like Receptor 5
- Toll-Like Receptor 3