Nkt Organs And The Role Of Type II NKT Cells

The DN4 phase is the last stage of early T-cell development. Here, the alpha gene of

These cells are recombinant receptors that have been developed specifically for this purpose. These CARs are usually composed of an extracellular antigen recognition receptor that is attached by a spacer to a transmembrane domain. Around these transmembrane domains could be additional domains that function as co-stimulator to produce a further immune response. In a normal t-cell, there is a requirement of an MHC molecule to bind and recognize the antigen, however, the CAR T-cells are capable of overcoming the limitation. So CAR T-cells are able to bind directly and independent of this system allowing the cell to read a much diverse pool.

Molecular Cell Biology, 7th Edition, 2013, Lodish, Berk, Kaiser, Krieger, Bretscher. Ploegh, Amon, and Scott. W.H. Freeman and Company (ISBN-13: 978-1-4292-3413-9)

Despite the wide-range of microbes affected by the innate immune system, the activity of peptides associated with the immune response seem to be highly sequence specific. The peptides specifically target areas of the membrane with high curvature. (Mark, 601)

CD117 is a membrane tyrosine kinase receptor (Type III receptor tyrosine kinase family), encoded by the c-kit proto-oncogene. The Type I transmembrane glycoprotein locates on chromosome 4q11 and 4q12 and has a total length of 90 kb. It has a molecular mass of 145 kDa. The extra-cellular domain consists of 519 amino acids. It contains 5 Ig-like domains. D1-D3 are responsible for c-kit binding to stem cell factor, and D4 and D5 are the dimerization domains. The transmembrane region consists of 23 amino acids and the juxta-membrane domain is made up of 433 amino acids. The tyrosine kinase domain is inserted by approximately 80 amino acid residues.

Central region-C possess DNA-binding domain (DBD) which is said to be the most conserved region and possess similarity in their structure. DBD contains an important short motif known as P-box which is responsible for direct DNA interaction and detection of specificity for DNA-binding. DBD also possess additional sequences that are required for the homo or heterodimerization of nuclear receptors. A pair of zinc fingers present in domain C is critically responsible for DNA specific contacts and interaction. Domain D is the less conserved domain among nuclear receptors which acts as a flexible hinge in between two domains such as C (DBD) and E (LBD) domains. In addition, domain D possesses the nuclear localization signal (NLS) that regulates the sub cellular distribution of nuclear receptors. The E region contains ligand-binding domain (LBD) is

The central α-helix is located at the base of two grooves i.e., front- and back-side groove. Additionally, back-side groove is larger and more exposed than the front-side groove. The TSST-1 mutants revealed that residues on the back side of the central α-helix were required for the superantigenic activity of TSST-1. A model of the TSST-1 interaction with MHC class II via TCR complex is based on mutation analysis of TSST-1 and on the published crystal structure of TSST-1 in complex with HLA-DR1 (Figure 3.). Residues Y115, E132, H135, I140, H141 and Y144 were found to be involved in TCR binding, which is important for mitogenic activity of TSST-1. Moreover, residues H135 and other residues situated on the same α-2 helix can cause affect to TCR-Vβ2

The innate immune system contains a range of effector cells that are evolutionarily primitive and plays a key role

TLRs are primary transmembrane proteins of immune cells, that contain leucine repeats in their extracellular domains and a cytoplasmic tail that contains a conserved region called the Toll / IL1 receptor (TIR) domain.

NK cells are one of the most sophisticated weapons in the innate immune systems arsenal however, they a short lived. Cytotoxic effector cell which resemble NK cells have been a part of the innate immune system for approximately 500 million years, long before the arrival of T and B cells of the adaptive immune system (Caligiuri, 2008). NK cells are best known for their role in the innate defense against viral infection and potential tumour cells. However, more recently they are being recognized with roles in the coordination of immunity, immunoregulation and the modulation of autoreactivity. NK cells got their name ‘natural killer’ due to the nature of being able to cause cell death instantly without priming, effector

These experiments tell us that the CD40L on the surface of activated T cells must bind to the CD40 on the macrophage surface to activate the macrophages against Pneumocystis jirovecii organisms.

The κ loci is located on human chromosome 2, the cluster of V gene segments is followed by a cluster of J gene segments and then a single C gene. The light chain VJ segment cannot be a product of κ or λ hybridization because in order for that to occur, they would have to be located on the same chromosome (Murphy 2012). Production of a complete antigen receptor includes two series of gene segment rearrangements, one for each receptor chain locus. Each of these rearrangements continues until a complete protein is made and the cell moves on to the next stage in development. The most important factor is the V regions that are encoded by separate gene segments (V, D and J segments), which are brought together by somatic recombination to create a complete V region exon. The V region of an immunoglobulin heavy or light chain is encoded by multiple gene segments. For the light chain, the V domain is made up of 2 gene segments, the V gene segment and the J gene segment. The joining of the V and J segments creates an exon that encodes the entire light chain V

Advancements in passive immunotherapy are also underway, for instance in the formulation of antibodies specific for TcdA and TcdB. (Abougergi and Kwon

A cascade of intracellular signalling events are stimulated via TCR expression, leading to naïve T cell activation. The following sequences of this activation include: proliferation (clonal expansion), migration into the site of invasion and induction of T effector such as cell-mediated cytotoxicity and cytokines upregulation. Cytotoxic CD8+ T cells which are induced the apoptosis pathway through expression of tumour necrosis factor (TNF) which binds to its receptor(TNFR) on the target cell. Then the Fac ligand of the Tc binds to

Hook proteins have been suggested to mediate the tethering of different vesicles to the microtubule network (Walenta et al., 2001, Maldonado-Baez et al., 2013). Recently, it has been shown that the microtubule-binding protein, HkRP3 which also interacts with the dynein complex, appears as puncta coating the microtubule network and accumulates at the MTOC (Ham et al., 2015). Thus, it is possible that lytic granules at the NK cell synapse follow the microtubule movements by virtue of being directly attached to the microtubules via HkRP3 or other hook proteins.