2.6 Pathology Lecture 6.pptx

Pathogens and Infectious Disease SCI1018-N PATHOLOGY Dr. Ahmad Khundakar Learning outcomes •You should now be able to: • Analyse the major causes of infectious diseases globally • Assess the stages of viral pathogenesis • Understand the structure, pathophysiology and detection of COVID-19 • Examin...

Pathogens and Infectious Disease SCI1018-N PATHOLOGY Dr. Ahmad Khundakar Learning outcomes •You should now be able to: • Analyse the major causes of infectious diseases globally • Assess the stages of viral pathogenesis • Understand the structure, pathophysiology and detection of COVID-19 • Examine the impact and diagnosis of common pathogenic bacteria Infectious Diseases • Disorders caused by organisms, usually microscopic in size • passed, directly or indirectly, from one person to another • Leading cause of death worldwide, particularly in low-income countries, especially in young children • In 2018, two infectious diseases - lower respiratory infections and diarrheal diseases - ranked in the top ten causes of death worldwide by the World Health Organization (WHO) • Both can be caused by a variety of infectious agents Infectious Diseases • Disorders caused by organisms, usually microscopic in size • passed, directly or indirectly, from one person to another • Leading cause of death worldwide, particularly in low-income countries, especially in young children • In 2018, two infectious diseases - lower respiratory infections and diarrheal diseases - ranked in the top ten causes of death worldwide by the World Health Organization (WHO) • Both can be caused by a variety of infectious agents • But, in 2020, things changed… Infection • Can affect any tissue in the body • Produces cell damage/inflammatory reactions • Five types of infectious agents (microbes) • Bacteria, protozoa, fungi, and helminth generally visible under light microscope • Specific staining techniques for different agents • Viruses only visible with electron microscope (presence inferred by tissue changes) Common Infectious Diseases • Majority of agents that cause disease in humans caused by viruses and bacteria • Common disease caused by viruses include COVID19, influenza, HIV/AIDS, ebola, diarrhoeal diseases, hepatitis, and West Nile • Common diseases caused by bacteria include anthrax, tuberculosis, salmonella, and respiratory and diarrhoeal diseases • Though the parasite that causes malaria is a notable example of a protozoan! Impact of Infectious Diseases Impact of Infectious Diseases Center for Systems Science and Engineering (CSSE) at Johns Hopkins University The twenty-first century has witnessed a wave of severe infectious disease outbreaks, not least the COVID-19 pandemic, which has had a devastating impact on lives and livelihoods around the globe: 2003 Severe acute respiratory syndrome coronavirus 2009 Swine flu 2012 Middle East respiratory syndrome coronavirus 2013–2016 Ebola virus disease epidemic in West Africa 2015 Zika virus disease epidemic 2020– COVID-19 What factors have led to this upsurge? Viruses • Small collection of genetic code, either DNA or RNA, surrounded by a protein coat (capsid) • Cannot replicate alone • Must infect cells and use components of the host cell to make copies of themselves • Often kill the host cell in the process • Cause damage to the host organism • An individual who has a viral infection but does not display disease symptoms is known as a carrier • Transmission from a host with an infection to a second host • • • Must be sufficient quantity of virus available to initiate infection. Cells at the site of infection must be accessible so virus can exploit for entry into the cell Host anti-viral defence systems must be ineffective or absent Viral Pathogenesis • Process by which viruses produce disease in the host • Involves five stages: 1. Entry of the virus into the body 2. Local replication in susceptible cells 3. Dissemination and spread to secondary tissues and target organs 4. Shedding of the virus into the environment 5. Onward transmission to third host Viral Pathogenesis • Process by which viruses produce disease in the host • Involves five stages: 1. Entry of the virus into the body Viral Pathogenesis • Process by which viruses produce disease in the host • Involves five stages: 2. Local replication in susceptible cells • Replicated virus from the initially infected cell then disperse to infect neighbouring susceptible cells • Results in a localised infection • E.g. common cold (rhinovirus), flu (parainfluenza), gastrointestinal infections (rotavirus) or skin infections (papillomavirus) Viral Pathogenesis • Process by which viruses produce disease in the host • Involves five stages: 3. Dissemination and spread to secondary tissues and target organs • However, in other cases, the virus can cause systemic disease through a disseminated infection spread throughout the body. • Predominant mode of viral dissemination occurs through the blood or lymphatic system • E.g. chickenpox (varicella zoster virus), smallpox (variola), HIV (human immunodeficiency virus) Viral Pathogenesis • Process by which viruses produce disease in the host • Involves five stages: 4. Shedding of the virus into the environment • Viruses spread to sites where shedding into the environment can occur • The respiratory, alimentary and urogenital tracts and the blood are the most frequent sites of shedding in the form of bodily fluids, aerosols, skin, excrement Viral Pathogenesis • Process by which viruses produce disease in the host • Involves five stages: 5. Onward transmission to third host • The virus goes on to be transmitted to another person and establish the infection cycle again! Viral pathogenesis – cellular effects • Once inside host cells, viruses can destroy cells through a variety of mechanisms • • • • Often induce direct cytopathic effects to disrupt cellular functions Through releasing enzymes to degrade host metabolic precursors Releasing proteins that inhibit the synthesis of important host factors, proteins, DNA and/or RNA Persistent viruses can sometimes transform host cells into cancer cells • • Can stimulate growth of tumours in infected hosts E.g. Human papillomavirus (HPV) Viral pathogenesis – cellular effects • Lytic viruses capable of destroying host cells by incurring and/or interfering with the specialised functions of host cells • E.g. triggering of necrosis in host cells infected with virus • Can also trigger cell death via apoptosis through host signalling cascades by immune cells! • Induction of apoptosis in major immune cells or antigen-presenting cells may also act as a mechanism of immunosuppression in persistent infections (e.g. in HIV) Puronen et al, 2019 COronaVIrus-associated acute respiratory disease (COVID-19) • Coronaviruses - group of viruses affecting a variety of animal species • Most recent SARS-CoV-2 considered same virus species as SARS but different strain • Third major epidemic caused by coronavirus in last 20 years (after SARS and MERS) Why has COVID-19 been so deadly? SARS-CoV-2 Structure • Single-stranded RNA virus • Entire genome on one strand! • Like other coronaviruses ‘crown-like’, spherical particles, with ’spike-like’ proteins on surface • Viruses use spikes to attach to receptors on human cells • Allows virus membrane to fuse with human cell membrane • Viral genome can enter host cell and make copies of itself Mechanisms of SARS-CoV-2 Viral Entry BioRender (2021), from https://app.biorender.com/biorendertemplates/figures/5e99f5395fd61e0028682c01/t5f99eb1307ef9a009f1c61e0-mechanism-of-sars-cov-2-viral-entry Mechanisms of SARS-CoV-2 Viral Entry BioRender (2021), from https://app.biorender.com/biorendertemplates/figures/5e99f5395fd61e0028682c01/t5f99eb1307ef9a009f1c61e0-mechanism-of-sars-cov-2-viral-entry Thinking about the pathophysiogical processes, why does long COVID happen? BioRender (2021) https://app.biorender.com/biorender-templates/figure s/5e99f5395fd61e0028682c01/t5f29c81e5e120f00ad5f6858-covid-19-fact-sheet Polymerase Chain Reaction (PCR) • Amplifies a single copy or a few copies of a segment of DNA • several orders of magnitude, generates thousands to millions of copies of a particular DNA sequence • Mainstay for molecular laboratories • • • • • Gene cloning and manipulation Gene mutagenesis Functional analysis of genes Diagnosis and monitoring of hereditary diseases Detection of microorganisms Reverse Transcription PCR • Targets RNA, rather than DNA • Same as PCR but starts with reverse transcription step 1. RNA + primers + reverse transcriptase > DNA 2. Denaturation (melting two DNA strands) 3. Annealing (primers bind to single strand) 4. Elongation Reverse transcription ELISA • Enzyme-linked immunosorbent assay (ELISA) • Uses antibodies and colour change to identify an antigen (e.g. protein) Bacteria • Small, single-celled organisms • Usually few micrometres in length • Constitute a large domain of prokaryotic microorganisms • Found almost everywhere on Earth • among the first life forms to appear on Earth • vital to the planet's ecosystems • can live under extreme conditions of temperature and pressure • Most bacteria in the body are harmless, some helpful! • A relatively small number of species cause disease. Gut microbiome • Humans and most animals carry millions (perhaps billions) of bacteria • Most in gut, but also on skin • Microbiome contains microorganisms, including bacteria, archaea and microscopic eukaryotes, that live in the digestive tracts of humans • Thought to have a role in resistance to pathogens, maintaining the intestinal epithelium, metabolising dietary and pharmaceutical compounds, controlling immune function, and even behaviour through the gut-brain axis! Pathogenic Bacteria • Bacteria form interactions with cells resulting in: • Mutualistic interactions – bacteria classed as ‘good’ • Commensal interactions – bacteria classed as ‘neutral’ • Pathogenic interactions – bacteria classed as ‘bad’ Pathogenic Bacteria • Bacteria that can cause disease • Far fewer in number than bacteria initiating commensal or mutualistic interactions • Estimated to be fewer than a hundred in humans • Several thousand species are part of the gut flora present in the digestive tract • Specially adapted and endowed with mechanisms for overcoming normal body defences • Can invade parts of the body, such as the blood, where bacteria are not normally found • E.g. through surface epithelium, skin or mucous membrane, traveling more deeply, spreading through the tissues and disseminating via Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth https://www.youtube.com/watch?v=bY85ET2gXGQ Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Top 10 Most Dangerous Bacteria on Earth Bacteria in Disease • Pathogenic bacteria usually overcome by immune system response • However, infection usually occurs if the body's defence mechanisms damaged by local trauma or underlying debilitating disease • E.g. wounding intoxication, chilling, fatigue, and malnutrition Can cause damage by • Direct cell death – through entry in host cells or changes to cellular metabolism/proliferation • Release of toxins – kill cells at a distance through enzyme release or damage blood vessels (ischemic necrosis) • Induce immune responses – causes additional inflammation Diagnosing Bacterial Agents • Gold standard for diagnosis of infections: • Culture https://www.youtube.com/watch?v=afM7 DGjSVn4 • Biochemical identification • (e.g. gram stain for bacteria) https://www.youtube.com/watch?v=sxa46 xKfIOY • Serologic identification • Detects and measures levels of antibodies in blood samples Histochemical staining of Microorganisms • Histochemical staining not preferred method for identifying microbes • However, detection in stained tissue can aid diagnosis Protozoa in Lung Tissue (Martínez-Girón et al, 2008) Spirochites in horse foot (Kuwano et al, 2012) Fungal hyphae (Bristol University) Learning outcomes •You should now be able to: • Analyse the major causes of infectious diseases globally • Assess the stages of viral pathogenesis • Understand the structure, pathophysiology and detection of COVID-19 • Examine the impact and diagnosis of common pathogenic bacteria Quiz Time! 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