Review of bacteria, viruses, and prions and Immune responses to infectious disease

1. Review of bacteria, viruses, and prions and Immune responses to infectious disease Lecture 47 Tuesday, April 24, 2007 Required reading: Basic Pathology Chapter 9 ( p. 307-322) and p. 830-2 and Kuby Immunology Chapter 18 Refs: Brock Biology of Microorganisms, and

2. Gram-negative and gram-positive bacteria. Both can have capsule. Both can secrete exotoxins. BP 9-9

3. Flagellar arrangements: (a) peritrichous(b) polar, (c) lophotrichous Brock 4.38

4. Bacterial flagellum Brock 4.41

5. Assembly of bacterial flagellum Brock 4.42

6. Chlamydia, rickettsia, and mycoplasmas • Are considered lineages within the domain Bacteria • Similar to other bacteria they divide by binary fission and are susceptible to antibiotics. • Differences from other bacteria: • Chlamydia lack ATP synthesis. • Mycoplasmas lack a cell wall • Rickettsia are usually transmitted by insect vectors • Typhus by lice • Rocky Mountain Spotted Fever by ticks • Many are unable to oxidize glucose and organic acids

7. Viruses • Cause a major share of human infections • Do not have genus and species names • Latin family names • 7 classes based on type of genetic material and transcription/translation mechanisms • Main groups • DNA or RNA • Within each may be single or double stranded • Enveloped or nonenveloped

8. Basic viral structures Brock 9.3

9. Baltimore classification • Class I ds DNA herpesvirus, pox • Class II ss DNA parvovirus • Class III ds RNA reoviruses • Class IV ss RNA + poliovirus • Class V ss RNA - influenza, rabies • Class VI ss RNA + DNA intermediate • Class VII ds DNA RNA intermediate

10. Methods of forming mRNA after viral infection Brock 9.11

11. Variations in size and structure • Nucleocapsid shapes • Icosahedral = 20 facets • helical • Envelope proteins • Segmented vs nonsegmented genome • Segmented rearrangement of segments between strains • Influenza • Rotavirus • Bunyaviridae and arenaviridae

12. DNA viral structures Brock 9.22a

13. RNA viral structures Brock 9.22b

14. Misnomers and confusing terms • “-Pox” diseases not always caused by poxviruses • Chickenpox is caused by varicella-zoster a herpesvirus. • Smallpox is caused by a poxvirus, variola major virus. • Vaccinia is a poxvirus and was used as a vaccine for smallpox. • Historically vaccinia was called cowpox but is distinct from it. • The 5 hepatitis viruses are each from a different family. • A Picornaviridae SS RNA • B Hepadnaviridae DS DNA; D viroid-like SS RNA • C Flaviviridae SS RNA • E Norwalk-like SS RNA • Herpesviruses include: • Varicella-zoster, herpes simplex 1, herpes simplex 2, cytomegalovirus, Epstein-Barr virus

15. Spongiform encephalopathies • Creutzfeldt-Jakob disease (CJD) • New-variant Creutzfeldt-Jakob • Kuru • Gerstmann-Sträussler (GSS) • Fatal familial insomnia • Scrapie • Transmissible mink encephalopathy • Chronic wasting disease of elk and deer • Bovine spongiform encephalopathy (BSE)

16. Prions • Infectious agents without nucleic acids. • Accumulation of abnormally folded protein causes disease. • Protein is a GPI-linked 30-kD surface protein found on normal cells. • Highly conserved • Normal conformation is rich in a helices • Expressed at high levels in neurons • Pathogenesis of disease can be: • infectious (oral transmission naturally) • sporadic ( majority of cases) • genetic (more than 20 mutations in aa sequence)

17. Pathogenesis of prion disease BP 23-21

18. Spongiform encephalopathy BP 23-22Creutzfeldt-Jakob Disease

19. Pathogens face innate and adaptive immunity • Innate • Epithelial barrier (physical and chemical) • Normal flora • commensals • Macrophages, neutrophils, and NK cells • Complement- activation of alternative pathway • Interferons a and b • Adaptive • Humoral • Cell-mediated

20. Methods used by microbes to evade host immunity • Intracellular survival • Antibodies are ineffective while it is intracellular. • Shed surface antigens. • Variation in surface antigens • Camouflage: • Express host-like proteins. • Envelop in host cell-membrane molecules. • Suppress host immunity • Decrease antigen processing and presentation. • Shift host response to an ineffective form.

21. Infectious diseases Infectious diseases remain a problem despite antimicrobial drugs. Health care delivery Increasing antimicrobial resistance Nosocomial infections are often resistant. Diseases for which no vaccine has been developed e.g. malaria, respiratory syncytial virus, HIV Antigenic variation Trypanosomiasis, influenza, etc. New pathogens

22. Data from 1998WHO Goldsby 17-1

23. Possible effects of viruses on the cells they infect Brock 9.23

24. Examples of different outcomes of viral infection • Transformation of infected cells • Human papilloma virus, HHV-8 (Kaposi sarcoma), Human T-cell leukemia virus, Epstein-Barr virus • Lysis of infected cell • Budding of virus from infected cell • Persistent infection • Latent infection (in animal cells usually the viral DNA is not integrated into host DNA) • Varicella-zoster, herpes simplex virus • Retroviruses do integrate into host DNA e.g. HIV

25. Interferons a and b can inhibit viral protein synthesis and block viral replication Imm 18-2

26. Immune responses to viruses • Innate responses are important in containing viral infection until adaptive immunity develops • Interferons alpha and beta • Induce synthesis of 2’-5’ oligo-adenylate synthetase and protein kinase R • NK cells (review Chapter 14 p. 328-334) • IFNa and b increase the killing activity of NK cells • Adaptive responses are important in containing the spread to other cells and preventing reinfection • Antibody • Cell-mediated

27. Goldsby table 17-1

28. Direct antiviral effect of IFN-g? • Although this chapter claims that IFN-g acts directly by inducing an antiviral state in cells, other texts do not confirm that. • Type 1 interferons do induce and an antiviral state. • IFN-g activates macrophages, induces growth and differentiation of Th1 cells, B cells, and NK cells. It increases expression of MHC class I and class II and antigen presentation.