Activation of inflammasome Dissertation Example | Topics and Well Written Essays - 3500 words

Activation of inflammasome - Dissertation Example There is a connection between deficiencies in the molecular underpinnings of the adaptive immune system and vulnerability to infections that this report will explore. This study will investigate the most immediate pathogenic effects resulting from this disorder using cells infected with S.typhimurium and L.Monocytogenes to demonstrate vulnerability to infections. Homozygous mutants suffered the highest mortality rates. Assays were conducted to determine the molecular cofactors most involved during the acute disease state by examining the process of inflammasome formation. Mutations along several stages of the process elucidate the cofactors involved. Ataxia Telangiectasia alters the formation of the inflammasomes complex based on caspase recruitment, and is characterized by deficiencies in interleukins as opposed to tumor necrosis factors. The identification of cofactor levels corresponding with the autosomal recessive genotype could potentially support the development of enhanced sc reening or diagnostic techniques with an ultimate goal of corrective therapy. INTRODUCTION The Immune system offers protection to the body from internal and external threats. Mammalian Immune system is classified into innate and adaptive immunity. Adaptive immune system appeared later in the evolutionary time line and it is more specific than the innate immunity. Through feature called immunological memory, adaptive immune system evokes a quick immune response upon subsequent exposure to similar pathogenic stimuli. These responses are typically dependent on T-cells, which involve not only the removal of active pathogens; but also the elimination by cell-death (Apoptosis). Innate immune system has no immunological memory. This analysis depends upon the genetic basis underlying failure in the immune system due to molecular changes. Innate immunity is the body’s first line of defense. Innate immune recognition and responsiveness to biological danger is mediated by germ-line enco ded innate immune receptors called pattern recognition receptors (PRRs). PRRs recognize conserved motifs on pathogens called Pathogen associated molecular patterns (PAMPs) or endogenous molecules called Damage Associated Molecular Patterns (DAMPs) that are released by stressed of dead cells6. PRRs are classified into trans-membrane receptors: Toll like receptors (TLRs) and C-type lectin receptors (CLRs), the cytoplamic families of PRRs: Nucleotide-binding oligomerization (NOD)-like receptor (NLRs), RIG-I like receptors (RLRs) and cytoplasmic DNA receptors (CDRs)6. Cytoplasmic DNA Receptors (CDRs) consist a diverse and growing number of receptors that recognize DNA in the cytoplasm. Members of this family include DAI, IFI16, LRRFIP15. TLRs are type-I trans-membrane proteins composed of an ectodomain domain rich in leucine-rich repeats that play a role in the recognition of PAMPs, trans-membrane region and cytosolic Toll-IL-1 receptor (TIR) domain which are involved in the activation of downstream signaling pathways. 10 and 12 TLRs have been identified in human and mouse, respectively. TLRs are localized at the cell surface and endosomal compartments where they recognize a broad range of bacterial, viral, fungal, protozoan PAMPs such as lipoproteins (recognized by TLR1, TLR2, and TLR6), double-stranded (dsRNA) (by TLR3), lipopolysaccharide (LPS) (by TLR4), flagellin (by TLR5), single-stranded RNA (ssRNA) (by TLR7 and TLR8), and DNA (by TLR9)1. NLRs consists of a large family of receptors that recognize broad spectrum of PAMPs and DAMPs in the cytoplasm8. Till now 34 murine and 23 human NLR genes have been identified. Plants contain NLR orthologues as R genes. Plants lacking adaptive immune s