Innate Immunity : An Early Phase Of Defence Mechanism Against Intruding Microorganisms

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)

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

By cloning the LPS locus, he was able to identify a ‘toll-like receptor’ (TLR4) which acted sense the presence of invading microbes bearing LPS. Receptors of the same family, ten of which are now known to exist in humans, each ‘tuned’ to detect different kinds of microbes, also initiate inflammation to combat infection, but sometimes shock as well. It was for this work that Beutler won the Nobel Prize, and his team at the University of Texas Southwestern Medical Center continues to search for proteins that protect mammals against defined infections. In the process, they have identified genes required for other functions, including the regulation of iron absorption, hearing and the development of embryos

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.

Once a pathogen is inside its host, it must evade recognition and killing by the host’s immune system. As the pathogen

The immune system is a crucial and essential defense mechanism in the human body as it allows the differentiation of cells that are self from cells that are non-self (reviewed by Spiering, 2015). The immune system is subdivided into two major categories: the innate immune system and the adaptive immune system (reviewed by Spiering, 2015). The innate immune system, also known as the non-specific immune system, is composed of cells and structures that are acquired from birth and defend and protect the host against invaders and harmful agents(reviewed by Hendry et al., 2013). The Innate immune system is activates by proteins that recognize familiar features present in pathogens known as pattern recognition receptors (PRRs) which recognize specific evolutionarily conserved molecules on pathogens through what is known as pathogen-associated molecular patterns (PAMPs) (Mogensen). Among the many PRRs, is the Toll-like receptors which are known to me studied extensively (Mogensen).

The immune system is a network of tissues, cells, and organs which cooperate with each other to shield the body from infectious diseases. When the body is invaded with foreign microbes, the immune system attempts to identify the microbes by triggering responses. When an individual is exposed to the Measles disease, the immune system response results to the patient having a high fever, coughing and having a runny nose. This is an innate response of the body to eliminate fatal infections and diseases. However, this innate response is controlled by the receptors which are embedded in the genes of the individual. Therefore, it is only able to control certain patterns of pathogens and is unable to record new pathogens that enter the body. This is where the adaptive immunity response comes to record all new findings of the invading pathogen and bacteria and the best defence to fight off the infection. The adaptive immunity consists of two different types of cells that defend the body. The T-cell and B-cell receptors have specific roles to help the immune system to defend from infections. The B-cell receptors contain molecules that recognises numerous types of viruses and bacteria. The T-cell receptor has similar molecule structure of relating to immunoglobulins. The difference between the T-cell receptors to the B-cell receptors is the ability to recognise short peptide

The mutated protein is seen to possess a leucine rich region (LRR) and a family of receptors known as Toll/interleukin-1 receptor (TIR). We see from Kobe and Kajava (2001), that repeated amino acids seem to be structurally and functionally important. Leucine rich regions are usually involved in interactions with other proteins. LRRs are involved in several biological activities including development in early mammals, interactions involving receptors and hormones, cell adhesion and polarization, resistance to plant diseases and many others. Meyers et al. (2002), says that the TIR domain possess three conserved regions and a stretch of 200 amino acids that may link TLR receptors with signalling pathways. Plant resistant disease proteins (R-proteins) in Arabidopsis have two large families and TIR domain belongs to one of them. LRR repeats located at the c-terminal and a nucleotide binding site(NBS) are contained in many disease resistant genes (R-genes). Additionally, some of these NBS-LRR resistance proteins contain TIR domains at their N-terminus. These NLR proteins are immune receptors involved in intracellular downstream signalling which plays a huge role in how pathogens are recognized and how quick the innate immune system would respond to an infection (Narusaka et al., 2016). Therefore, when comparing the

— Interleukin-2- These are part of the body’s natural response to microbial infection by discriminating between foreign non-self-cells and self-cells. This protein regulates the body’s wbc, leukocytes and lymphocytes that are responsible

Pattern-recognition receptors (PRRs) are representative receptors in innate immune system function as eliminating the invading pathogens. Compared with adaptive immune receptors, PRRs present three characters, including universally expressed, fast response and recognize kinds of pathogens. Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs) belongs to PRRs that sense to nucleic acids/bacterial fragments derived from viruses and trigger antiviral innate immune responses. Upon recognition of these ligand species, TLRs, RLRs, and NLRs recruit specific intracellular adaptor proteins to initiate signaling pathways culminating in activation of nuclear factor κB (NF-κB), mitogen-activated protein (MAP) kinases, and

The best characterised signalling PRRs are the Toll-like receptors (TLRs). They are present in plants, invertebrates and vertebrates, and represent a primitive host defence mechanism against bacteria, fungi and viruses.

The body’s ability to contain, neutralize and kill foreign pathogens is a key attribute of the human immune system .Naturally, the immune system made up of organs such the bone marrow, Spleen, thymus, tonsils and lymph nodes in addition to cells like T cells cells, Natural killer cells, Macrophages, Polymorph nuclear (PMN) Leukocytes and dendritic cells should automatically coordinated and clear off pathogens from the body.

If a pathogen breaches barriers: innate immune response result into an immediate effect of non- specific response. All Innate immune systems derived from plants and animals, when a pathogen evades the innate response, a third layer of protection is possessed by vertebrates in which activation of adaptive immune system takes place. The immune system response adopts itself within an infection and pathogen recognition is improved. As a result of the improved response, its then retains itself when the pathogen is eliminated in form of an immunological memory and allows the adaptive immune system to mount faster and stronger when pathogen is encountered each time.

Microbial organisms are also responsible for activating the macrophages and leads to the development of the inflammatory mediators. However, inflammation caused by the microbial infections include Shigella, Clostridium difficile, Salmonella typhimurium, etc., called as Infectious Arthritis (Li et al., 2013).

The purpose of the immune system is to prevent and minimize infections; this is how the body protects us from microbes that would otherwise make us ill or kill us (Dugdale, 2013). The immune system works by differentiating between our own cells (self-antigens), foreign cells (antigens), and pathogenic microbes (Dugdale, 2013). When our cells discover anything unfamiliar, our immune system works to destroy it(Dug dale, 2013). If the immune system cannot activate to kill foreign cells, we can get infections (Dugdale, 2013). Conversely, if it is activated without any foreign cells present it can cause pathopysiological problems (Dugdale,2013). This paper will focus on the