MedMicroTest1ppt1

Understanding why it is that most host-microbe contacts DO NOT result in disease, and what changes to make disease arise.

• More than 20%
• Infectious diseases are a major problem in the resource-poor world
• Economic costs are enormous

• 1. Acute respiratory infections ~6.8 million
• 2. HIV/AIDS (1 agent) ~3.2 million
• 3. Diarrheal diseases ~3.1 million
• 4. TB (1 agent) ~1.8 million
• 5. Malaria ~1.2 million
• 6. Measles ~1.2 million

• Re-emerging: TB, malaria, hepatits, cholera, dengue fever
• Emerging: 25+ since 1980
• HIV is most important

• Non-cellular microbes
• viruses and viroids: have genetic material but lack cell membranes, cytoplasm, and the machinery for synthesizing macrmolecules
• Prions: proteinaceous infectious particles that cause diseass such as Creutzfeldt-Jakob disease, and kuru
• Cellular microbes
• prokaryotes: Bacteria and Archaea
• eukaryotes: Eukarya

• Viruses have a capsid surrounding them
• Viroids are "naked" RNA that is only found to infect plants

• Microparasites: viruses, bacteria, protozoa and fungi
• Often complete a full life cycle within one host
• Can multiply to produce a very large number of progeny (overwhelming infection)
• Macroparasites: worms, arthropods
• Often grow in one host and reproduce outside that host

• Exploitation by the pathogen of the host to obtain metabolic materials
• Nutrients (cellular pathogens)
• Synthetic machinery (viral pathogens)

• Extracellular pathogens: live either within tissues or on the surface of the body cavities (between cells).
• Macroparasites are almost always extracellular
• Obligate intracellular pathogens: must invade host cells to replicate.
• Viruses, Chlamydia, Rickettsia
• Facultative intracellular pathogens: can replicate either in or out of cell
• Mycobacteria

• Access to host's nutrient supply
• Access to host's genetic machinery
• Escape from host's defense mechanisms and antimicrobial defenses

• Intracellular killing mechanisms may destroy the host cell (tissue damage)
• It is difficult for drugs or antibiotics to achieve selective action against the pathogen while leaving the host cell intact (mitochondria may be targeted)
• Many intracellular pathogens live inside cells responsible for immune response, depressing their defensive capabilities

Can grow, reproduce freely, and move extensively within the tissues of the body

• Spread rapidly through extracellular fluids or move rapidly over surface resulting in a widespread infection quickly
• Require different defense mechanisms than intracellular parasites

• Antibodies are primary defense, and they function in 3 major ways
• 1. neutralization: binding can block the association of the pathogen with its target
• 2. opsonization: binding can facilitate its uptake/destruction by phagocytes
• 3. complement activation: binding can activate a complement cascade resulting in lysis of bacterial cells

• Cell-mediated responses are the primary defense, which vary based on location of pathogen
• Viruses and bacteria in the cytoplasm: T_cyto recognizes and induces apoptosis in infected cells
• Bacteria and parasites within endosomes: T_H1 recognizes and activates infected cells to destroy the pathogen inside

• Shape: cocci, spiral, bacilli
• Gram reaction: +/-
• Gram+ has thick peptidoglycan layer
• Gram- has thin peptidoglycan layer with outer membrane
• Atmosphere: obligate anaerobe, microaerophile, obligate anaerobe, facultative anaerobe, capnophile (increased CO2 levels)
• Spores: presence, shape, and position within bacterial cell
• Biochemistry: oxidase, catalase, lactase, etc
• Serolgy: interaction with antibodies
• Genetics: DNA sequences of key genes

• GRAM-POSITIVE COCCI
• Staphylococci (catalase+):
• S. aureus (yellow colonies)
• Steptococci (catalase-):
• S. pyogenese (sore throat/rheumatic fever)
• S. agalactiae (neonatal meningitis and pneumonia)
• GRAM-NEGATIVE COCCI
• N. meningitides (meningitis)
• N. gonorrhoeae (urethritis, gonorrhea)
• GRAM-NEGATIVE COCOBACILLI
• Haemophilus and Bordetella (respiratory pathogens)
• Brucella and Pasteurella (zoonotic agents)
• GRAM-POSITIVE BACILLI
• Sporing aerobic:
• Bacillus
• Sporing anaerobic:
• Clostridium
• Non-sporing:
• Listeria monocytogens andCorynebacterium
• GRAM-NEGATIVE BACILLI
• Salmonella (diarrhea)
• Shigella (bloody diarrhea)
• Yersinia (deadly)
• Escherichia, Proteus, Pseudomonas, Burkholderia, and Legionella
• SPIRAL BACTERIA
• Helicobacter (stomach cancer)
• Campylobacter (food born acute diarrhea)
• Treponema (syphyllus)
• Borrelia and Leptospira
• MYCOPLASMA AND CHLAMYDIA: common respiratory and sexually transmitted infections
• RICKETTSIA: agents for typhus are rarer severe infections

• CAPSULE AND SLIME LAYER
• A polysaccharide layer external to the cell wall
• Hard = capsule, soft = slime layer (biofilm)
• Most important virulence factor
• Protect from phagocytosis and antibiotics
• Only capsulated S. pneumonia can cause a fatal infection
• LIPOPOLYSACCHARIDE (LPS)
• A surface antigen that can strongly stimulate inflammation
• Endotoxin found only in gram negative bacteria
• Protects from complement-mediated lysis
• Causes septic shock (systemic blood vessel expansion/blood pressure drop)
• FIMBRIAE OR PILI
• More rigid than flagella
• Function in attachment to other bacteria (sex pili) or host cells (common pili)
• Adherence to host involves specific interactions (eg. E. coli is normal flora in gut, but causes UTI in urethra)
• May prevent phagocytosis
• FLAGELLA
• Allow for movement
• Polar monotrichous: single flagellum on one side
• Polar lophotrichous: multiple flagella on one side
• Amphitrichous: flagella/um on both sides
• Peritrichous: flagella all over
• Flagellins (the monomer) are STRONGLY antigenic
• H antigens (flagellar) are important targets of antibody response
• SPORES
• highy resistant endospores in response to adverse conditions
• Allow extended survival (dormant for millions of years)
• Clostridium and Bacillus spores are responsible for tetanus and anthrax