In the initial phase of an infection, the innate immune system generates a rapid inflammatory response that blocks the growth and dissemination of the infectious agent. This response is followed, in vertebrates, by the development of an acquired immune response in which highly specific B and T cell receptors recognize the pathogen and induce responses that lead to its elimination (Janeway, Jr. et al., 2002). The antigen receptors of the acquired immune system are well characterized. They consist of many structurally similar molecules with different binding specificities created by somatic rearrangements and mutations within the binding site regions of the B and T cell receptor variable domains (Jung et al., 2004;Schatz et al., 2005). By contrast, the receptors of the innate immune …show more content…
All ECDs assume the typical horseshoe-shape, but their structures cannot be superimposed because of variations in curvature. In the known structures, the glycans are
Botos et al. Page 3
Structure. Author manuscript; available in PMC 2012 April 13.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript distributed throughout the molecule, except for the lateral face formed by the ascending loops of the LRRs (Figure 2). This glycan-free face is involved in dimerization upon ligand binding in the known TLR/ligand structures (see below).
The TLR1/2/6/10 subfamily
TLR2 resides on the plasma membrane where it responds to lipid-containing PAMPs such as lipoteichoic acid and di- and tri-acylated cysteine-containing lipopeptides (Takeda et al.,
2003). It does this by forming dimeric complexes with either TLR1 or TLR6 on the plasma membrane. The structures of TLR2/TLR1 and TLR2/TLR6 with lipopeptide ligands have been determined (Jin et al., 2007;Kang et al., 2009). To facilitate crystallization and structure determination the LRR-CT and the last one or two LRRs of TLRs 1, 2, and 6
The innate and adaptive immune response start with exposure to an antigen in the epithelium of
DN2 is a vital phase, it occurs in the subcapsular cortex of the thymus. It is here that the “genes for the gamma, delta and beta T-cell receptor (TCR) chains” [3] start their rearrangement process. The alpha chain does not commence its rearrangement, as the recombinase machinery cannot reach its gene. In this phase, cells fully commit to the T-cell lineage and the expression of c-kit and CD25 on their membranes declines.
Explain the involvement of immune cells (B, C, T, antigen presenting cells and immune complex).
Overwhelming, deleterious host immune response to an infection due to release of chemicals to fight the infection 2• 1
Microorganisms that enter a living organism encounters the effective mechanisms of the innate immune system. The innate immune system is also known as a non-specific immune system. It is a significant aspect of the overall immune system. The cells in the innate immune system notice and respond to pathogens in a generalized
as the cytosine at position 34, cytosine at position 12, and tyrosine at position 29. In
The mechanisms whereby a lack of microbial stimuli results in dysregulation of the immune system are poorly defined but are often attributed to a dysregulation of Th1 and Th2 responses. Douwes et al. explains that microbes are often recognized by innate immune cells through the binding of pathogen recognition receptors (PRR). This recognition results in the induction of Th1 responses which in turn down regulate the Th2 responses that are commonly associated with chronic inflammatory disorders (Barnes). While this is a candidate mechanism it is vastly incomplete; downstream affects of PRR induction are highly dependent on the stimulus and may result in proinflammatory induction rather than an anti-inflammatory Th1 response (Kielian). While this lack of a defined mechanism has lead some to reject the hygiene hypothesis, others have looked to animal models can case studies to support
In the first process, NK cells recognize the target cell through its cell surface receptors. Here the infected cells coated with immunoglobulin G (IgG) antibodies bind to the IgG specific receptors (FcγR) expressed on the surface of NK cells. This receptor-ligand interaction activates the downstream signaling cascade of NK cells, which direct them to destroy the target cell by a process called antibody-dependent cellular cytotoxicity. The second mechanism of recognition relies on the expression of killer activating (KAR) and inhibiting receptors (KIR) expressed on its cell surface. These receptors recognize a range of different molecules present on the surface of nucleated cells and regulate the functional outcome of NK cells. Once the activating receptor is engaged, a “Kill” instruction is issued to NK cells, that in turn activates perforin and granzyme mediated cytolysis. The “kill” signal, conversely, can be overridden when the signal is sent from the inhibitory receptor, a mode typically exploited by viruses in the suppression of NK cell-mediated cytotoxicity (Delves and Roitt, 2000). Other immune cells such as eosinophils, basophils, and mast cells also make a major contribution to the first line of defense mechanism. Basophils and mast cells contain IgE specific cell surface receptors (FceR) and exhibit high affinity for pathogens coated with the IgE antibodies. These cells are particularly important in the case of atopic allergies such as asthma and hay fever, wherein the allergen binds to IgE cross-links FceR and triggers the secretion of inflammatory mediators such as histamines and prostaglandins. Eosinophils, on the other hand, act as weak phagocytic cells and function mainly through the release of cationic proteins and reactive oxygen species (ROS) into the extracellular fluid. Collectively, these immune cells stimulate a rapid and
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.
For the second part of the experiment, one had to use the knowledge learn from viewing protein molecules in FirstGlance in Jmol to analyze the protein PDB ID: 4EEY. The analysis of this protein was done using the RSCB protein data bank (PDB) at (http://www.rcsb.org/pdb/home/home.do).2
Immunity depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells against microbial pathogens. Innate receptors are conserved germ-line-encoded proteins and include TLRs (toll-like receptors), RLRs [RIG-1 like receptors (retinoic acid-inducible gene-1)] and NLRs (nod-like receptors). Receptors recognize pathogens or pathogen-derived products in different cellular compartments, for instance plasma membrane, endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate molecules to eliminate pathogens and instruct pathogen specific adaptive immune response.
It is present in oligomer as nonself-recognizing lectin from the hemolymph plasma and it has propeller-like arrangement. This structure gives the protein flexibility which is very important for the specific interactions tachylectin-5A makes with the pathogen associated
Natural killer T cells (NKT), not to be confused with Natural Killer cells or killer T cells (CTL), are a heterogeneous subset of T cells recognized by their unique innate and adaptive molecular characteristics and markers. Perhaps the most defining characteristic of natural killer T cell is the ability to recognize lipid antigens in the context of CD1d molecules, associated to β2-microglobulin (Laurent, Renault, Farce, Chavatte, & Hénon, 2014). CD1d molecules are predominantly expressed by Antigen Presenting cells, particularly Marginal Zone B cells (MZB). NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR α-chain and recognize α-galactosylceramide (α-GalCer), a powerful antitumor stimulant, and type II NKT cells that use a more diverse αβ TCR repertoire and do not recognize α-GalCer (Macho-Fernandez & Brigl, 2015. Notably, α-GalCer-activated Type I NKT cells are capable of substantial crosstalk with other cell types of the innate and adaptive immune systems (Matsuda et al. 2008; Parekh et al. 2007). However, Type II NKT cells display more of a heterogeneous TCR and lack Vα14-Jα18 rearrangement, thus the reason for their inability to recognize α-GalCer. Conversely, type II NKT cells recognize a naturally occurring self-glycolipid and sulfatide, which is enriched in several membranes, including myelin in the central nervous system (CNS), β-cells in the pancreas, kidney, and liver (Marrero, Ware, & Kumar,
Previous studies have shown that killer T cells that protects us from bacterial damage plays a major role in the
Introduction : B lymphocytes are the effectors of humoral immunity and provides defense against pathogens by producing antibody. B cells constitute approximately 15% of peripheral blood leukocytes and arise from progenitors and precursors in the bone marrow. B lymphocytes undergo random immunoglobulin variable gene rearrangements at the heavy and light chain loci. These chains pair with the Igα and Igβ polypeptides to form the mature B-cell receptor which is then transported onto the cell surface where it can bind antigen and signal inside the cell. Different populations of B cells result in pre immune pools where each cell in these quiescent populations expresses a B cell antigen receptor with a unique specificity. The BCRs come in contact with their specific antigen and generate several intracellular signals are which leads activation, differentiation, and formation of plasma cells and memory B cells. This process mediates the response to subsequent antigen challenges. B lymphocytes play an essential role by not only producing antibodies but also functioning as antigen-presenting cells and certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell to cell contact. Newly generated immature B cells are selected to enter the peripheral mature B-cell pool only if they do not