Week 2 Lec 1 8.31.46 pm.pdf

integers deaths 251 ally pre job BIOL341/981: Infection & Immunity Microbial Diseases and Preventio...

integers deaths 251 ally pre job BIOL341/981: Infection & Immunity Microbial Diseases and Prevention Martina Sanderson-Smith Lecture 3, Week 2 [email protected] 31st July 2024 1 Page 1  Lecture 3 Outline 1. Development and progression of disease 2. Viral infection: SARS as an example 3. Bacterial infection: H. pylori 4. Host susceptibility and resistance 2 Page 2  Lecture 3 Outline 1. Development and progression of disease 2. Viral infection: SARS as an example 3. Bacterial infection: H. pylori 4. Host susceptibility and resistance 3 Page 3  Agents of Infectious Disease Viruses Bacteria Protozoa (protists) Fungi Helminths (worms) 4 Page 4  b if The Progression and Outcome of Infection and Disease i S Eration my station relo ifeng.dtens fm.ir 5 inflationcontinually Youldreopers Page 5  Stages of Disease Progression met Incubation period: time between entryexposure v8path 1. of the microbe and onset of symptoms. 2. Prodromal: mild signs or symptoms. i think I'm getting sick 3. Acute: symptoms are most intense and disease-specific. Also called 4. the climax. most disease specificsymptoms Decline: A period of decline occurs as signs and symptoms subside. Might 5. Convalescence: Return to normal health Figure 20.10: The course of an infectious disease. JE 6 rigging ayy.my yggggyyy stops proliferating does Imagine system has restructured body a lot medication tissue cells used of energy to allow this phase endary infection occur fail to do so Page 6  guitarists Sequence of events leading to an infectious disease Eisai_want Invasiveness: Portal of entry: Linked to virulence determinants midriff The route by which an exogenous pathogen enters the host Figure 20.5 Infectious Dose: The number of microorganisms or viral particles needed to initiate infection 7 eg typhoid 100 cells few million cells cholera dose infectious according to risk variys Page 7 gffidsPortals of exit from the body Portal of Exit: Many portal of exit are the same sites as portal of entry. Pathogens often leave the body via bodily secretions and excretions produced at those sites. Figure 20.9 Figure 20.13 8 Page 8  Modes of Infectious Disease e 9 Transmission S Direct: Indirect Idiots EE o Person-person contact o Inanimate objects o Exchange of bodily fluids o Vector transmission (arthropods) o Droplet/aerosols Biological Vector o o Animal contact During labour or delivery www.Ii.int Mechanical Vector o Vehicle Transmission Water Food See Figure 20.12 in Pommerville Page 9  Examples & Comparison wifsiftin Mode of transmission Bacteria away Virus Parasite Person to person contact Eg. Neisseria gonorrhoeae - Eg. HIV - acquired immune Eg. scabies mites, hair gonorrhoea in mucus deficiency syndrome from lice secretions semen/vaginal fluid; Ebola virus in blood Aerosols Eg. Bordetella pertussis - Eg. Influenza virus Rarely... whooping cough Food or water contamination Eg. Samonella typhi - Eg. Rota virus - diarrhoea Eg. Giardia lamblia – Salmonellosis (diarrhoea, Giardiasis fever) (gastroenteritis) Insect bite Eg. Yersinia pestis – Bubonic Eg. Ross River virus - Ross Eg. Plasmodium spp. - plague (via flea) River fever (via mosquito) malaria (via mosquito); Trypanosoma - African sleeping sickness (via Tsetse fly) Animal carrier Eg. Bacillus anthracis – Eg. Lyssavirus – includes Eg. Echinococcus Anthrax (via domesticated or rabies and other diseases granulosus - hydatid wild animals) (via bats) disease (via dogs) 10 Page 10  Lecture 3 Outline 1. Development and progression of disease 2. Viral infection: SARS as an example 3. Bacterial infection: H. pylori 4. Host susceptibility and resistance 11 Page 11  Viral Infectious Disease Viruses cause many different types of disease: o Colds (Rhinovirus, Coronavirus, Coxsackie virus and Echovirus) o Flu (Influenza virus type A, B and C) o Diarrhoea (Rotavirus) o Polio o Hepatitis (Hepatitis virus type A, B and C) o Smallpox o SARS - severe acute respiratory syndrome (Coronavirus) 12 Page 12  Viral Infectious Disease © Gary Gaugler/Medical Images RM. SARS is an emerging infectious disease caused by the coronavirus SARS CoV. 2000s early o SARS spreads through close person- to-person contact. Figure 16.7: Coronaviruses. o Many patients are asymptomatic. o May result in only dry cough and labored breathing, but severe infections cause pneumonia and may require mechanical ventilation due to lack of oxygen reaching the blood. Middle East respiratory syndrome (MERS) is similar to but more dangerous than SARS. to not who announced Spread of SARS. named based on region Just L Emine 13 elitetenographic Page 13  Viral Infectious Disease SARS - severe acute respiratory syndrome (Coronavirus) SARS emerged in China in November 2002. The outbreak became a global epidemic after a doctor from Guangdon infected several people at a Hong Kong hotel. From Hong Kong, the disease spread rapidly to more than 24 countries in North and South America, Europe and Asia. SARS spread so rapidly because symptoms were delayed 2-7 days, via air travel. WHO reports that 8,000 people were infected, with a death rate of 10%. 14 Page 14 regiviredpeknetsenogntae oa.it Epidemiology of SARS Outbreak Primary Index Case Individual persons infected by primary Secondary cases and index case in Honk contacts who spread Kong Hotel the infection 15 Page 15  Viral Infectious Disease of SARS - symptoms and spread: system portal entry SARS symptoms include resp o high fever o diarrhoea o headache and body ache o dry cough after 2-7 days o atypical pneumonia SARS is spread via air droplets and www.cdc.gov close contact and can survive for 6+ hours on tissue or as an aerosol 16 Page 16  Viral Infectious Disease SARS – pathogenesis: o Enters the body through the respiratory tract o Infects the epithelial cells of the respiratory tract then infects infiltrating and circulating immune cells. o Circulating immune cells carry the virus to other organs (spleen, lymphoid tissue etc) o Weakened immune system leads to rapid deterioration and pneumonia the vulnerable elderly ghildren immunocompromised Gu et al. 2005 202 (3) p415–424 17 Page 17  Viral Infectious Disease SARS - genome sequence: The genome sequence of the SARS coronavirus was published in May 2003. Coronavirus belong to Group IV single-stranded (+) sense RNA. 5 Kb 10 Kb 15 Kb 20 Kb 25 Kb 30 Kb i.info is Replicase 1A Replicase 1B Structural proteins Replicase is a polymerase enzyme that catalyses self replication of single stranded RNA and made up a significant portion of its 30Kb genome. 18 Science 300: 1399‐1404 Tiny genome, relative to bacterial (~ 5 million bp) or human (3 billion). SARS-COV-2 similar size. Page 18  Viral Infectious Disease greastfated IBV BCoV SARS - phylogeny:  Molecular phylogeny based on the MHV TGEV gene sequence of the Replicase 1A gene suggests SARS virus is not HCoV-229E SARS closely related to other coronaviruses. SARS - origin:  Epidemiological (PCR and sequence analysis) studies have shown that bats are the natural reservoir of SARS virus. 19 against wave wous Etf circuit see.is atem Page 19  Lecture 3 Outline 1. Development and progression of disease 2. Viral infection: SARS as an example 3. Bacterial infection: H. pylori 4. Host susceptibility and resistance 20 Page 20  Bacterial Infectious Disease Bacteria cause many different types of disease: o Sore throat and flesh eating disease (Streptococcus pyogenes) o Anthrax (Bacillus anthracis) o Tetanus (Clostridium tetani) o Tuberculosis (Mycobacterium tuberculosis) o Gonorrhoea (Neisseria gonorrhoeae) o Plague (Yersinia pestis) o Stomach ulcers (Helicobacter pylori) 21 Page 21  Bacterial Infectious Disease Helicobacter pylori - the causative agent of gastritis and EGstomach ulcers o Helicobacter pylori first described by Barry Marshall and Robin Warren in 1983 in Perth - awarded the 2005 Nobel prize o Stomach and duodenal ulcers originally thought to be caused by stress and diet not elective by postulates o Treatment by antacids originally but now antibiotics o Approximately 2/3 of the human population is infected with H. pylori, yet the majority do not develop disease whitemicrobiome weather.fmtffgfatsa https://www.mja.com.au/journal/2005/183/11/2005-nobel-prize-physiology-or-medicine#0_i1091639 22 Page 22  Bacterial Infectious Disease Helicobacter pylori - symptoms and spread: H. pylori symptoms include: o burning stomach pain o nausea o vomiting o inflammation and bleeding www.gicare.com The transmission method of H. pylori is not completely understood, but it is more common with increased age and in less developed countries. Faecal-oral, oral-oral transmission? Contaminated food or water sources? 23 Page 23  Bacterial infectious disease Helicobacter pylori – infection: H. pylori resides in the mucosal layers of the stomach. The helical jÉÉ shape is thought to facilitate movement through the mucosal layer. to H. pylori urease breaks down urea in the stomach into ammonia. The production of an "ammonia cloud" around the bacterium mine protects it from the low pH of the stomach, where few other organisms are able to survive. urease C=O(NH2)2 + 2H2O CO2 + 2NH3 urea 24 Page 24  is.ms iii Bacterial Infectious Disease Helicobacter pylori - infection: I expose Tsified 25 Page 25  Genomic 1 may changesthe way 26 host cells behave Page 26  Bacterial Infectious Disease Helicobacter pylori - gastric cancer: prisoner  Epidemiological studies have shown an association between H. pylori and the development of stomach cancer. H. pylori infection is considered a major risk factor, though not necessarily a direct cause. www.gastrolab.net 27 Page 27  Fungal, protozoan, and parasitic infectious disease Eukaryote micro-organisms also cause many different types of disease: o Thrush (Candida albicans) o AIDS-related infections (Pneumocystis carinii) o Malaria (Plasmodium spp.) o African sleeping sickness (Trypanosoma brucei) o Intestinal worm infections (Ascaris spp.) o Hydatid disease (Echinococcus granulosus) my deportation POEX factors host 28 AND Page 28  Lecture 3 Outline 1. Development and progression of disease 2. Viral infection: SARS as an example 3. Bacterial infection: H. pylori 4. Host susceptibility and resistance 29 Page 29  Severity of Infectious Disease pod said Infectious disease severity is governed by; Virulence determinants of pathogens o Attachment systems o Toxins/enzymes o Self-destruction o Changing antigens o Camouflage Host factors o Human susceptibility o Resistance genes 30 Page 30  Severity of Infectious Disease Virulence determinants include: Virulence determinant Role during infectious disease ECM adhesins Colonisation Fimbriae/Flagella Colonisation Siderophores Iron acquisition Lactoferrin binding proteins Iron acquisition Proteases/Enzymes Disruption of immune system, nutrient acquisition, cell lysis, ECM/tissue damage Capsule Camouflage - anti-phagocytosis Toxins Disrupt host cells, host function, immunity Urease Protects against acid 31 Page 31  Severity of Infectious Disease Human susceptibility and resistance genes include: we Gene Resistance/ susceptibility Infectious agent malaria if Hbs (sickle cell gene) R Plasmodium falciparum Duffy blood group glycoprotein S Plasmodium vivax CCR5 receptor polymorphisms R HIV Vitamin D receptor polymorphisms R/S Mycobacterium tuberculosis Human leukocyte antigen (HLA) R/S Streptococcus pyogenes 32 Page 32  Host Resistance Genes 33 mid feed Progressing CCR5 polymorphism and HIV CD4+ T cells (Th cells) are the primary target of HIV infection forget CCR5 and CXCR4 are chemokine receptors present on immune cells HIV uses CCR5 as a secondary receptor to gain entry into macrophages phagocytes cell Mutations in CCR5 (e.g. CCR5-wt/Δ32) have been associated with a slower progression towards AIDS delayprogrammised CD4+ T cells = T-helper cells. They are the primary target of HIV infection. Their destruction leads to weakening immune system (basis for AIDS). Binding of gp120 to CD4 receptor causes conformational change and then binding to CCR5, and/or CXCR4. Page 33  Host Resistance Genes whataddthis.int dictates HIV tropism HIV strains display tropism for the different chemokine cCR5 receptors Some strains, known as X4- tropic or dual-tropic strains, can engage CXCR4 This strain can emerge as a result of mutation within the individual Kerina Duri (2012). Coreceptor Usage in HIV Infection, Can overcome host resistance Immunodeficiency, Prof. Krassimir Metodiev (Ed.), ISBN: 978-953-51-0791-0, InTech, DOI: 10.5772/52060 conferred by CCR5 mutation low 34 would evolve to CCRs infected it eg target CXCR4 rapid mechanisms wave negate come over Page 34  Host Susceptibility and Resistance Genes flesh eaffase Group A streptococcal invasive diseases include necrotising fasciitis I and toxic shock syndrome Severity is associated with human leukocyte antigen (HLA) class II polymorphism Patients with necrotising fasciitis, caused by S. pyogenes. Limb may require amputation for the survival of the patient. www.nnff.org www.nnff.org 35 Page 35  Host Susceptibility and Resistance Genes cells Human leukocyte antigen (HLA) site on surfimture HLA is the name given to the human form of the expressed Major Histocompatibility Complex (MHC) MHC is a large locus in all vertebrates that encodes for surface proteins essential in immune function. There are two classes of MHC HLA class II (also called MHC class II) are expressed primarily on antigen-presenting cells of the immune system, such as macrophages Importantly, HLA class II is highly polymorphic (variable) 36 Page 36  Host Susceptibility and Resistance Genes Usually, class II HLA binds to T cell N receptor specifically and reversibly This is a crucial process of the adaptive immune response APC Group A streptococci produce super- antigens that non-specifically cross- link HLA class II proteins and TCR This causes massive T cell over- f proliferation and inflammatory TCR cytokine production Excessive, systemic inflammatory response can lead to organ damage superantigen N and death TH cell Some HLA haplotypes are less vulnerable (more resistant) to superantigen-mediated cross-linking Nature Medicine 8: 1398-1404 37 Page 37  Lecture 3 Outline 1. Development and progression of disease 2. Viral infection: SARS as an example 3. Bacterial infection: H. pylori 4. Host susceptibility and resistance 38 severity reliant SARS Dyson PG affecting te piscate VIRAL Bacterial Page 38