The Process Of Hematopoiesis And How Its Controlled Biology Essay

The Process Of haemopoiesis And How Its Controlled Biology EssayIn humoral mediated result of the insubordinate system, the clonal proliferation results into antibody secreting plasma electric cellular telephones and memory B-cells. The first response has a staff of about 5-7 mean solar days during which the B-cells becomes trigger off by the antigen and T-helper cells. During the lag period, differentiation and proliferation of B-cells egresss arse into plasma cells. Antibody level begins to increase and reaches its peak at about day 14 and the drop begins once the plasma cells die. In the secondary response, clonal expansion of memory B-cells takes place and the antibody levels atomic number 18 much higher. These memory cells serve more(prenominal) rapidly to the antigen. Moreover, since many memory cells argon pitch for the first response, the number of plasma cells generated argon more in the secondary response and the antibody levels argon higher 2.3.Briefly desc ribe the functions of the following cells of the immune system dendritic cells macrophages neutrophils T helper cells.Ans) Dendritic Cell These cells resemble the dendrites of the nerve cells and deal a long membrane extensions. They give the axe be either hold on the epidermis (skin) and mucous membranes (langehans cell) heart , lungs, kidney, GI tract (interstital dendritic cell) T-cell are of secondary lymphoid and thymic medulla ( Interdigitating dendritic cell) and in line of business and lymph (circulating dendritic cell). They set high levels of class II MHC molecules. Dendritic cells are APCs. They engulf the antigen by phagocytosis/endocytosis and carry it to the various lymphoid organs where they represent the antigen to T lymphocytes 2. Macrophages They arise from monocytes. It functions as a scavenger that ingest debris, disgraced and dying cells as well as foreign beingness. They either revert class II MHC molecules or the co-stimulatory B7 membrane molecul es. Once the foreign organism is inside the macrophage, they are either killed by lysosomal enzymes or by O2 bare(a) radicals which is released by phagosomes1.Neutrophils They are active phagocytic cells and always reach the berth of inflammation. The foreign body is killed by the various lytic and bactericidal substances which are present within the primary and secondary granules. They employ both O2 dependent and O2 sovereign pathway to generate antimicrobial substances. It is better than macrophage since they exhibit larger respiratory burst and express higher level of defensins 2.T-helper cells- T-cells are formed in the bone marrow but mature in the thymus. There are two compositors cases of T-cells- TH and TC .TH cells have CD4 whereas TC has CD8. The TH cells gets jauntd when the cell recognizes and interacts with an antigen. After it is activated, it forms into an effector cell and secretes growth factors known as cytokines. These cytokines play an important role in act ivating B cells, Tc cells, macrophages and elicits an immune response. Different types of immune response occurs collectible to different types of cytokines2.4) What are the two fundamental approaches to medicate find?Ans) The two approaches to medicate baring are rational drug design and molecular diversity.Rational drug design The drugs work in the body by interacting with the receptor and they garble the activities in such a way that it brings about a advance of the body. This method aims the information about structure of the drug receptor or create a candidate drug. The 3-D structure of the protein can be determined using methods such as roentgenogram crystallography or nuclear magnetic resonance spectroscopy. The researchers in the pharmaceutical industry can use whatever information is available on the databases and find a chemic compound which can react with the receptor and can be time-tested in the labs. If the interacting compound cannot be found then former(a) programmes can be used to find the compounds with similar properties to known ligands. This method is through with(p) to avoid the expenses. The first drug produced by this method is Relenza which is used to report influenza. The other drugs developed to treat HIV transmissions are Ritonivir and Indinavir 3.molecular(a) diversity The strategy applied in molecular diversity is the closing off of bioactive molecules molecular libraries such as nucleic bitings, amino acids and niggling organic molecules. The main goal is to isolate molecules from libraries of chemical compounds or proteins and study the structure or shape of their target with the vertebral column with affinity and specificity. The anti-inflammatory mAb Humira is a biolgic degage from molecular diversity.5. How does the flu computer computer virus infect cells? Give a truncated overview of how the flu drug relenza was discovered. (Note Relenza is not as biologic but a small molecule drug).Ans) Influenza vira l particles are surrounded by an outer windbag a lipid bilayer which they acquire from the plasma membrane of the infected host cell during the process by budding. In the envelope the two glycoproteins which are present are Hemagglutinin (HA) and neuraminidase (NA). HA is responsible for attaching the virus to the host cell. HA is a trimer and it binds to the sialic acid groups on host cell glycoproteins and glycolipids by conserving the amino acid sequence to form a small groove in the HA molecule. Neuraminidase cleaves N-acetylneuraminic (sialic) acid from the viral glycoproteins and the host cell membrane glycoproteins. This facilitates viral budding from the infected host cell. Once the virus is inside the host cell, the HA binds to the walls of the endosome (acidic nature) because of which the viral coating collapses. Within the envelope, matrix protein surrounds the nucleocapsid which consist of 8 different strands of single stranded (ssribonucleic acid) and are associated with protein and RNA polymerase. Once inside the cell, the RNA strand encodes one or more different influenza proteins. Many copies of the virus are made in the nucleus and then it moves to the cytoplasm to form viral proteins including HA and NA. The rising viruses which are formed move out of the cell by forming buds and pitiable out against the plasma membrane2.RelenzaThis drug is created by using rational design. The discovery was funded by the Australian biotech company Biota. The structure of neuraminidase was known by X-ray crystallography. A competitive inhibitor which is a sialic acid analogue, is an inhibitor of neuraminidase. The general function of neuraminidase is that it cleaves sialic acid from the virus and the cell surface and prevent clumping and allows the virus to spread to other cells. Relenza induces clumping and reduces viral spreading.6.What is meant by pharmacogenomics and how might pharmacogenomics be applied to drug festering in the future? What is an e xample of a biologic where longanimous ancestral profiling is used to evaluate the suitability of the patient for therapy?Ans) Pharmacogenomic is the study of the roles of transmitted variation in the response to drugs. It includes information from genomics, proteomics, bioinformatics and other disciplines such as biochemistry and toxicology in order to synthesize newer and safer drugs. As the sequences of all our genes and the protein they encode for are determined, this will reveal many new targets for drug actions. It also reveals pleomorphism of enzymes and proteins related to drug metabolism, action and toxicity DNA probes which are confident of detecting them will be synthesized, permitting screening of individuals for potentially harmful pleomorphism prior to the start of the therapy. As the structures of relevant proteins and their polymorphism are revealed, beat building and other technique will permit the design of drugs that take into account both the normal protein targets and their polymorphism. In simple words, the drugs will be tailor-made for individuals based on their genetic profiles4. This is the application of pharmacogenomics in drug development. The example where genetic profiling is used to evaluate the suitability of the patient is ERBB2 is a 185 kDa tyrosine kinase receptor over expressed in approximately 25-30% of humane breast cancer .7. Give an example where over expression of a cytokine results in a disease kingdom. What biologics, if any, have been developed to treat this disease state?Ans) Rheumatoid arthritis is a an inflammatory disease. The major symptom is inveterate inflammation of the voices including shoulders, ankles, elbows and knees. It is characterized by the inflammation of the synovium along with the the destruction of the joint cartilage and bone. The over expression of cytokines such as TNF, IL-1, IL-8, IFN have been notice in the synovial fluid. Cytokines such as TNF activate the synovial cells which pro duce proteolytic enzyme such as collagenase which leads to the destruction of tendons, ligaments and cartilage. The cytokines are produced due to the bodily function of T cell and macrophage activation. A number of biologics have been canonic for treating rheumatoid arthritis5. They are cimzia, enbrel, humira, kineret, orencia, remicade, rituxan and simponi6. Rituxan Rituximab is sold under the trade name Rituxan. Rituxan is a chimeric monoclonal antibody against the protein CD20 which is found on the surface of B cells. Rituxan when habituated in combination with methotrexate is given to adult patients with minor to crisp conditions who had an inadequate response to one or more TNF opposer therapies. The side effect of rituxan is that patients show hypertension, nausea, upper respiratory tract infection, febrility etc.7 .8. Interferons are used as biologics to treat viral infections. How does interferon induce the anti-viral state in cells?Ans) Interferons are antiviral and show their effect in a signaling pathway. There are two types of interferons, type I and type II. IFN-I is produced by cells under appropriate conditions including IFN-/. IFN-II are produced by a hardly a(prenominal) number of cells such as NK cells, T-helper cells and dendritic cells. IFN-II includes IFN-. IFN-I plays an important role in the innate antiviral response. IFN-/is responsible for inducing the anti-viral activity by binding to IFN receptor on the cell surface, which leads to activation of receptor-associated JAKs (Janus Kinase) such as JAK-1 and TYK-2. This activates the STATs (signal transducer and activator of transcription) due to phosphorylation which leads to the formation of ISG factor (ISGF)-3 complex which consists of STAT-1 and -2 and p48. After phosphorylation at Tyr701 and 692 of IFN receptors by IFN-1, STAT-1, and -2, in that location is formation of a heterodimer which translocates to the nucleus and forms an association with p48(IRF-9). The complex (STA T-1 and -2 and IRF-9) is called as ISGF-3 and it associates with ISREs to activate ISGs. The 3 antiviral proteins involved in IFN-mediated inhibition of virus infection are 1) The Rnase L pathway which degrades viral RNAs and then activates dsRNA.2) PKR inhibits informational RNA translation by phosphorylating translation initiation factor3) Mx proteins possessing GTPase activity which restricts virus infection at many stages such as primary transcription, transcription and intracellular trafficking of viral proteins or genomes. Thus, interferons induce the anti-viral state in cells8.