Choose a type of pathogen (e.g., a virus or bacterium) and take your pathogen on

Question

Choose a type of pathogen (e.g., a virus or bacterium) and take your pathogen on a tour of the human body. Your goal is to provide the pathogen with as much information as possible so that it can effectively navigate the human immune system and establish an infection. Write a 1,050- to 1,400-word report that answers the following questions: 1.Choose a point of entry into the human body, and outline potential barriers the pathogen might encounter. 2.Provide an overview of the normal flora in the human body that your pathogen may interact with, and include some challenges that the flora might present. 3.Provide an overview of the workings of the innate immune system, including the major components. Are there ways in which your pathogen might slow down or avoid the innate immune system? 4.Provide an overview of the workings of the adaptive immune system, including the major components. Are there ways in which your pathogen might slow down or avoid the adaptive immune system?

Explanation / Answer

Answer:

1. Point of entry: Respiratory tract
The most common route of Influenza viral entry is through the respiratory tract. The combined absorptive
area of the human lung is almost 140 m2 . Humans have a resting ventilation rate of 6 liters of air per minute, which introduces large numbers of foreign particles and aerosolized droplets into the lungs with every breath. Many of these particles and droplets contain viruses. Fortunately, there are numerous host defense mechanisms to block respiratory tract infection. Mechanical barriers play a significant role in anti-viral defense. For example, the tract is lined with a mucociliary blanket consisting of ciliated cells, mucous-secreting goblet cells, and sub-epithelial mucous-secreting glands.Foreign particles deposited in the nasal cavity or upper respiratory tract are trapped in mucus, carried to the back of the throat, and swallowed. In the lower respiratory tract, particles trapped in mucus are brought up from the lungs to the throat by ciliary action. The lowest portions of the tract, the alveoli, lack cilia or mucus, but macrophages lining the alveoli ingest and destroy particles.

Viruses may enter the respiratory tract in the form of aerosolized droplets expelled by an infected individual by coughing or sneezing, or through contact with saliva from an infected individual.Larger virus-containing droplets are deposited in the nose, while smaller droplets find their way into the airways or the alveoli.

2. Interaction with normal flora:
Respiratory infectious diseases are mainly caused by viruses or bacteria that often interact with one another. Although their presence is a prerequisite for subsequent infections, viruses and bacteria may be present in the nasopharynx without causing any respiratory symptoms. The upper respiratory tract hosts a vast range of commensals and potential pathogenic bacteria, which form a complex microbial community. This community is assumed to be constantly subject to synergistic and competitive interspecies interactions. Disturbances in the equilibrium, for instance due to the acquisition of new bacteria or viruses, may lead to overgrowth and invasion.

In a balanced state, this ecosystem as a part of the complete human microbiome is assumed to play a major beneficial role for the human host. However, imbalances in this respiratory microbial community can contribute to acquisition of a new bacterial or viral pathogen, carriage of multiple potential pathogenic bacteria, or a viral co-infection. Subsequently, imbalances in the ecosystem may result in overgrowth and invasion by bacterial pathogens, causing respiratory or invasive diseases, especially in children with an immature immune system.

The authors reported an increase in H. influenzae density when S. pneumoniae was present, suggesting synergism between these bacterial species.

3.Influenza virus is a member of the family Orthomyxo-viridae, and is an enveloped virus that contains a genome composed of eight segments of negative-sense single-stranded RNA (ssRNA) tightly surrounded by nucleoprotein (NP). Haemagglutinin (HA) and neuraminidase (NA) are the major viral glycoproteins that are detected by antibodies, and that define the subtype of the virus. Influenza viruses are classified as seasonal or pandemic depending on the genetic changes that are incorporated from year to year that dictate the severity of disease outcome.
A specialized immune system exists at distinct mucosal surfaces to combat invasion by pathogens. The viral RNA that is present within infected cells is recognized as foreign by various pattern recognition receptors (PRRs), which leads to the secretion of type I interferons (IFNs), pro-inflammatory cytokines, eicosanoids and chemokines. Type I IFNs — produced by macrophages, pneumocytes, DCs and plasmacytoid DCs (pDCs) — stimulate the expression of hundreds of genes that are collectively known as IFN-stimulated genes (ISGs) in neighbouring cells, which induce an antiviral state. Pro-inflammatory cytokines and eicosanoids cause local and systemic inflammation, induce fever and anorexia, and instruct the adaptive immune response to influenza virus. Chemokines that are produced at the site of infection recruit additional immune cells, including neutrophils, monocytes and natural killer (NK) cells, to the airways.

Escape from Innate Immunity:
Influenza A viruses have adopted various strategies to evade the antiviral nature of the innate immune system.

In particular, the NS1 protein contributes to antagonizing the antiviral innate immune response. Cells infected with genetically modified influenza viruses with a non-functional NS1 gene displayed stronger IFN responses than cells infected with wild type virus. Viruses with a NS1 defect also display reduced virulence after infection of mice and pigs.NS1 inhibits RIG-I receptor signaling by various means.

NS1 is not the only viral protein that restrains the innate immune system. Both influenza PB2 (especially variants containing an aspartic acid at position 9) and PB1-F2 (only variants containing a serine at position 66) limit the production of IFN- through association with MAVS.

4. The adaptive immune response consists of humoral (virusspecific antibodies) and cellular (virus-specific CD4+ and CD8+ T cells) immunity. Other way of defense against influenza virus infection is the adaptive immune response(highly specific).

Influenza virus infection induces the production of influenza virus-specific antibodies by B cells.

Antibodies directed to the trimeric globular head of hemaglutinin (HA) can afford sterilizing immunity to influenza virus infection. By binding to the HA receptor binding site located in this region they can block virus attachment to host cells and/or block receptor-mediated endocytosis. However, most antibodies directed against HA are influenza virus strain-specific and fail to neutralize intrasubtypic drift variants and viruses of other subtypes.This is mainly due to the high variability in the HA globular head.
Antibodies to the other major glycoprotein, the viral neuraminidase (NA), interfere with the last phase of the viral replication cycle and also exert protective immunity. NA is a sialydase and removes sialic acids from infected cells and budded virions, thereby facilitating efficient release and spread of newly formed viral particles.

In addition to HA and NA, influenza virus particles contain the minor glycoprotein M2. This tetrameric transmembrane protein has ion channel activity and plays an important role in unpacking the virus in the endosome.

Influenza A virus infection induces a cellular immune response, including virus-specific CD4+ T cells and CD8+ T cells. These cells play an important role in regulation of the immune response and viral clearance respectively.

Escape from adaptive immunity:
Various mechanisms contribute to immune evasion of influenza A viruses from the humoral immune response. Due to the lack of proofreading activity, the transcription of viral RNA by the viral RNA polymerase is error prone and results in mis-incorporation of nucleotides. As a result, quasi species of viruses are formed with random mutations in the genome. Under the selective pressure of antibodies that are present in the human population, induced after influenza virus infections and/or vaccination, variants are positively selected from the quasi species that have accumulated amino acid substitutions in the antigenic sites of HA that are recognized by virus-neutralizing antibodies. This phenomenon is known as antigenic drift and allows the virus to evade recognition by antibodies and to cause recurrent influenza epidemics yearly.

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