SCI4011 Pathobiology of Infectious Diseases

Q1

1. a) Ans-

The Process is usually initiated by the mechanism called Endocytosis where a larger vesicle (phagocytosis) take in the extracellular materials. In addition, for any degrading molecule which is usually taken up by the endocytosis, the lysosomes digest the material which is derived from the two other routes known as “phagocytosis” and “autophagy”. Thus, in the process of phagocytosis, a specialized cell such as the macrophages, generally take up and degrades the large particle, which includes the bacteria, debris of cell and aged cells, which are needed to eliminate from the body, such larger particle is taken by the phagocytic vacuoles is named as phagosomes which then fuses with lysosomes to form phagolysosomes (Levin, Grinstein and Canton 2016).

1. b) Ans-

A phagosome is an in-hospital niche because they typically reside in the host cell, the cell-autonomous defence typically includes the proteases, the nucleases and the lysozyme which digest the microorganism the mature acidic phagosomes. The phagosome as well the bacteria that usually escapes the phagolysosomes which can be also targeted for elimination concerning selective autophagy (Archer et al. 2020). Thus, to emphasize for it autonomous strategy that is developed for the antimicrobial with the macrophage and are very much distinctive to macrophages. Thus, the inhospitality of macrophages which are compared with the other known cell types is not absolute it is only a matter of degree. Following toxin, the endocytosis the activation in the cytosol and the epithelial cell usually undergo necrosis which then typically leads to the loss of integrity of the intestinal membrane the host usually expose to the intestinal microorganism and activation for the host inflammatory response (Chelakkot, Ghim and Ryu 2018).

1. c)  

The bacteria usually reside in the phagosomes because they prevent the discharge of the lysosomal contents present into the phagosome environment. Particularly the “ phagolysosome” formation is typically inhibited into the phagocyte. And this the strategy that is usually employed by Salmonella tuberculosis the species of legionella the  “chlamydia”.

• For tuberculosis, bacteria cell wall component are typically thought to be released from the phagosomes and modifies the lysosomal membrane. To inhibit fusion
• In Chlamydiasome elements of the bacteria wall appear and modified the membrane of phagosomes.
• Salmonella typhimurium- the pH develops, and also phagosome engulfment induces the bacterial gene products which are essential for surviving in the macrophage (Pauwels et al. 2017).

Q5 Ans

1. a)  Clostridium difficileinfection has a significant clinical impact particularly on the elderly and or the immunocompromised patients the role of pathogenicity for the Clostridium difficile is mainly functioned or mediated by the two exotoxins namely exotoxin A also known as “Tcd A and toxin B Tcd B”. these are the toxins that primarily disrupts the cytoskeletal; structure and in the extracellular matrix especially in the tight junction of the target, cells causing the cell to round and which ultimately leads to cell death (Czepiel et al. 2019). Clostridium difficiletoxaemia is strongly associated with the fulminant disease;  It is well known in the intestinal damage (Lessa et al. 2015). Clostridium difficile typically produce a toxin that specially targets the intestinal epithelial cell.
2. b)  

Clostridium difficile is considered to be an opportunistic pathogen because they are normally associated with the various parts of the human body.  They usually do not cause any disease in a healthy individual, but they usually can cause disease under a certain condition for those who have and weaken the immune system (Ahn and Simonne 2018). And when our immune system becomes compromised the normal microflora usually overpopulated or typically moves to the area of the body where they do not normally occur which can cause int opportunistic infection for Clostridium difficile. Thus, the opportunistic pathogen Clostridium difficile is usually different from the other pathogen that is commonly causing disease. Clostridium difficile cause a spectrum of disease which is ranging from antibiotic-associated diarrhoea to the pseudomembranous colitis. When opportunistic pathogens cause infection, they are known to be called opportunistic infections (Gao, Howden and Stinear 2018). It has been seen that since the clinical and pathological a characteristic of C. difficile is usually associated diseases and are not distinguished from those of other gastrointestinal diseases. Which include ulcerative colitis,  and chronic inflammatory bowel diseases.

Q6 Ans  

A

Coronaviruses are typically an exceptionally large family virus, which causes an illness in people,  and other species also. Rarely the animal form of coronavirus can spread to human and then they are spread between the peoples. The zoonotic coronavirus has emerged in recent years that cause a human outbreak which is now been to be “Covid-19” or the “SARS Cov-2”. The illness for the human is usually manifested as a respiratory infection or sometimes a gastrointestinal but in severe cases, it can lead to multiorgan failure. Usually, the clinical symptom of the disease varies from no symptoms to mild and severe symptoms seen in human. It impacted human health with both physical and mental difficulty, As a public health emergency impacted human health because of isolation, containment and keeping us locked in the room has created our social life imbalance but it is for the betterment of saving human lives from the government. This infection has also dominated peoples mental well-being.  

B  Ans

It has been seen that all the structural features of the novel SAR-CoV 2 virus particles usually occurs in a related coronavirus in nature. It is usually enveloped and non-segmented positive-sense ssRNA virus that includes the sarbecovirus and “ortho corona” and is of the virinae subfamily. Its diameter is about 65 to 125nm which has crown likes spikes on the outer surface It is a Beta coronavirus form.  

The attachment occurs in the binding domain for S protein of “these virus receptors which are usually presented in three hundred thirty-one to five hundred twenty-four resides and can bind to human ACE 2. The viral entry mechanism is done by fusion which occurs in type II transmembrane serine protease is usually present in the host cell that will clear the ACE 2 and activate the receptor that is attached to the spike-like S proteins (Ibrahim et al. 2020).

The usual size of the genome ranges from 26 to 32 Kb and is comprised of 6-11 open reading frame ORFs that is encoding the 9680 amino acid polyproteins.  this the nsps, four major structural proteins are “spike surface glycoproteins” (S), “membrane nucleocapsid proteins” (N)  envelop an accessory protein is usually encoded by the open reading frames.  Also, an N-terminal glycosylated ectodomain which is present at the N-terminal and end of M protein that has three transmembrane domains. The M and E proteins are needed for the virus morphology, assembly and budding causing virion to releases (Romano et al. 2020).

Reference

Ahn, S. and Simonne, A., 2018. Clostridium difficile: An Important Opportunistic Pathogen in Healthcare Settings. EDIS, 2018(1). \

Archer, N., Egan, S.A., Coffey, T.J., Emes, R.D., Addis, M.F., Ward, P.N., Blanchard, A.M. and Leigh, J.A., 2020. A Paradox in Bacterial Pathogenesis: Activation of the Local Macrophage Inflammasome Is Required for Virulence of Streptococcus uberis. Pathogens, 9(12), p.997.

Chelakkot, C., Ghim, J. and Ryu, S.H., 2018. Mechanisms regulating intestinal barrier integrity and its pathological implications. Experimental & molecular medicine, 50(8), pp.1-9.

Czepiel, J., Dróżdż, M., Pituch, H., Kuijper, E.J., Perucki, W., Mielimonka, A., Goldman, S., WultaÅ„ska, D., Garlicki, A. and Biesiada, G., 2019. Clostridium difficile infection. European Journal of Clinical Microbiology & Infectious Diseases, 38(7), pp.1211-1221.

Gao, W., Howden, B.P. and Stinear, T.P., 2018. Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen. Current opinion in microbiology, 41, pp.76-82.

Ibrahim, I.M., Abdelmalek, D.H., Elshahat, M.E. and Elfiky, A.A., 2020. COVID-19 spike-host cell receptor GRP78 binding site prediction. Journal of Infection, 80(5), pp.554-562.

Lessa, F.C., Mu, Y., Bamberg, W.M., Beldavs, Z.G., Dumyati, G.K., Dunn, J.R., Farley, M.M., Holzbauer, S.M., Meek, J.I., Phipps, E.C. and Wilson, L.E., 2015. Burden of Clostridium difficile infection in the United States. New England Journal of Medicine, 372(9), pp.825-834.

Levin, R., Grinstein, S. and Canton, J., 2016. The life cycle of phagosomes: formation, maturation, and resolution. Immunological reviews, 273(1), pp.156-179.

Pauwels, A.M., Trost, M., Beyaert, R. and Hoffmann, E., 2017. Patterns, receptors, and signals: regulation of phagosome maturation. Trends in immunology, 38(6), pp.407-422.

Romano, M., Ruggiero, A., Squeglia, F., Maga, G. and Berisio, R., 2020. A structural view of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping. Cells, 9(5), p.1267.

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