fundamentals of immunology (as informed by microbial pathogens) microbiology 375
TRANSCRIPT
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FUNDAMENTALS OF IMMUNOLOGY(AS INFORMED BY MICROBIAL PATHOGENS)
Microbiology 375
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COURSE INSTRUCTORS:
DR. JOHN MANSFIELDPROFESSOR OF BACTERIOLOGY andMEDICAL MICROBIOLOGY & IMMUNOLOGY
DR. JULIA GILDENPOSTDOCTORAL FELLOWDEPARTMENT OF MEDICAL MICROBIOLOGY &IMMUNOLOGY
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WHY HAVE WE DEVELOPED THIS COURSE?
•EXPOSE CURIOUS UNDERGRADUATES TO IMPORTANT ASPECTS OF HUMAN HEALTH AND INFECTIOUS DISEASE
•PROVIDE AN UNDERSTANDING OF HOW THE IMMUNE SYSTEM WORKS AND WHY WE BECOME ILL FROM MICROBIAL INFECTIONS
•RAISE AWARENESS OF GLOBAL IMPACT OF DISEASES
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EXPOSURE TO DISEASES ONCE THOUGHT TO BE EXOTIC, GEOGRAPHICALLY ISOLATED AND ONLY PRESENT
IN OTHER SOCIETAL CULTURES
MONKEYPOX
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Smallpox Vaccination
An Ethiopian baby receives a smallpox vaccination in the mid-1970s, during the latter stages of the World Health Organization's (WHO) eradication effort. By 1980, WHO recommended that countries discontinue vaccination (WHY?).
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WE’LL DISCUSS POPULAR PERCEPTIONS AND POPULAR PRESS ARTICLES THAT ADDRESS IMMUNOLOGY AND HUMAN DISEASE
Also see Penn and Teller “Bullsh*t” Episode on Vaccines
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WHAT IS THE CLASS FORMAT?
• FORMAL LECTURES
• CLASS DISCUSSIONS
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COURSE OUTLINE
WEEK 1-OVERVIEW: EVOLUTION OF IMMUNE SYSTEM STRUCTURE AND FUNCTION; CO-EVOLUTION BY MICROBIAL PATHOGENS OF MECHANISMS TO DEFEAT HOST IMMUNITY
WEEK 2-INNATE IMMUNITY: THE FIRST LINE OF DEFENSE AGAINST INFECTION, AND HOW MICROBIAL PATHOGENS ESCAPE FROM BEING RECOGNIZED
WEEK 3-ADAPTIVE IMMUNITY: B LYMPHOCYTES AND THE ANTIBODY RESPONSE, AND HOW MICROBIAL PATHOGENS EVADE BEING ELIMINATED BY THIS ARM OF THE IMMUNE SYSTEM
WEEK 4-ADAPTIVE IMMUNITY: T LYMPHOCYTE DIVERSITY AND CELLULAR RESPONSES IN HOST IMMUNITY, AND HOW MICROBIAL PATHOGENS INHIBIT THEIR FUNCTIONS
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Continued…
WEEK 5-IMMUNE REGULATION: WHAT REGULATES OR CONTROLS THE EXPRESSION OF IMMUNITY, AND HOW MICROBIAL PATHOGENS ALTER IMMUNE REGULATION FOR THEIR OWN BENEFIT
WEEK 6-OPPORTUNITIES: FURTHER YOUR EDUCATION IN THE FIELD OF IMMUNOLOGY AND PERFORM RESEARCH IN IMMUNOLOGY LABS
WEEK 7-OVERVIEW: COURSE MATERIALS: EMPHASIS ON THE “BIG PICTURE” FUNDAMENTALS OF IMMUNITY AND ELEMENTS OF MICROBIAL PATHOGEN IMMUNE EVASION
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WHAT ARE THE EXPECTATIONS?
•ABSORB NEW INFORMATION, THINK ABOUT HOST IMMUNITY TO INFECTION, ASK QUESTIONS IN CLASS
•WEEKLY DISCUSSION SESSIONS
•PASS FINAL EXAM THAT TESTS YOU ON THE BASIC FUNDAMENTALS OF IMMUNE SYSTEM FUNCTION THAT YOU HAVE LEARNED IN CLASS
•CONSIDER A COURSE OF STUDY THAT INTEGRATES IMMUNITY AND MICROBIAL PATHOGENESIS
•EDUCATE OTHERS!
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WHAT IS THE IMMUNE SYSTEM?
(AND WHERE IS IT??)
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WHAT CELLS MAKE UP THE TISSUES AND ORGANS OF THE IMMUNE SYSTEM?
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THE IMMUNE SYSTEM HAS TWO FUNCTIONAL COMPONENTS:
• INNATE IMMUNE SYSTEM
•ADAPTIVE IMMUNE SYSTEM
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RELATIVE IMPORTANCE OF INNATE vs ADAPTIVE IMMUNITY
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RECOGNITION OF MICROBIAL “DANGER”
SIGNALS (PAMPs)
RECOGNITION OF SPECIFIC MICROBIAL
ANTIGENS
INNATE ADAPTIVE
SEQUENTIAL INDUCTION OF INNATE AND ADAPTIVE IMMUNE RESPONSES TO INFECTION
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COMPARISONS OF INNATE vs ADAPTIVE IMMUNITY
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LYMPHOCYTES CAN RECOGNIZE AND SPECIFICALLY RESPOND TO ANY MICROBIAL PATHOGEN!
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Innate
AdaptiveImmunity
THE ADAPTIVE IMMUNE RESPONSE REMEMBERS PRIOR EXPOSURE TO PATHOGENS
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GENERALIZED IMMUNE RESPONSE TO MICROBIAL PATHOGENS
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BUT…
WITH SUCH AN EFFICIENT AND EFFECTIVE IMMUNE SYSTEM, WHY DO WE EVER GET SICK (AND OFTEN DIE) FROM INFECTIONS?
SELECTIVE PRESSURES OF MICROBIAL INFECTION LED TO THE EVOLUTION AND
DIVERSIFICATION OF THE IMMUNE SYSTEM
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MICROBIAL PATHOGENS HAVE CO-EVOLVED WITH THE IMMUNE SYSTEM OF ALL ANIMALS
>500 MILLION YEARS
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Figure 1. Evolutionary Alice Through the Looking Glass “The most curious part of the thing was, that the trees and the other things round them never changed their places at all: however fast they went, they never seemed to pass anything. ‘I wonder if all the things move along with us?' thought poor puzzled Alice.” (Carroll, 1872). Originally applied by Van Valen to frequency-dependent coevolution (Van Valen, 1973). In this case, Alice is a metaphor for animals unable to put distance between themselves and their ever-present parasites. Illustration by Kristina Hedrick, Lightray Productions, Los Angeles, California.
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ANTIGENIC VARIATION EVADES HOST IMMUNE RECOGNITION
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The Complement “MAC” kills gram negative bacteria by direct lysis
Immune evasion of Enterococcus faecalis by an extracellular gelatinase that cleaves C3 and iC3b
Shin Yong Park, Yong Pyo Shin, Chong Han Kim, Ho Jin Park, Yeon Sun Seong , Byung Sam Kim , Sook Jae Seo and In Hee Lee
The Journal of Immunology, 2008, 181: 6328-6336.
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OTHER BACTERIAL IMMUNE ESCAPE MECHANISMS
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FUNDAMENTAL #1
ANIMALS HAVE HIGHLY EVOLVED AND COMPLEX INNATE AND ADAPTIVE IMMUNE SYSTEMS THAT FIGHT MICROBIAL PATHOGENS
however…MICROBIAL PATHOGENS HAVE CO-EVOLVED ELABORATE MECHANISMS TO EVADE, INTERFERE AND MANIPULATE THE HOST’S IMMUNITY TO THEIR OWN BENEFIT
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