Microbiology 375
FUNDAMENTALS OF
IMMUNOLOGY
(AS INFORMED BY MICROBIAL PATHOGENS)
COURSE INSTRUCTORS:
DR. JOHN MANSFIELD
PROFESSOR OF BACTERIOLOGY and
MEDICAL MICROBIOLOGY & IMMUNOLOGY
DR. JULIA GILDEN
POSTDOCTORAL FELLOW
DEPARTMENT OF MEDICAL MICROBIOLOGY &
IMMUNOLOGY
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
EXPOSURE TO DISEASES ONCE THOUGHT TO BE EXOTIC,
GEOGRAPHICALLY ISOLATED AND ONLY PRESENT
IN OTHER SOCIETAL CULTURES
MONKEYPOX
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?).
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
WHAT IS THE CLASS FORMAT?
• FORMAL LECTURES
• CLASS DISCUSSIONS
COURSE OUTLINE
WEEK 1-OVERVIEW: EVOLUTION OF IMMUNE SYSTEM STRUCTURE AND FUNCTION; COEVOLUTION 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
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
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!
WHAT IS THE IMMUNE SYSTEM?
(AND WHERE IS IT??)
WHAT CELLS MAKE UP THE TISSUES AND
ORGANS OF THE IMMUNE SYSTEM?
THE IMMUNE SYSTEM HAS TWO
FUNCTIONAL COMPONENTS:
•INNATE IMMUNE SYSTEM
•ADAPTIVE IMMUNE SYSTEM
RELATIVE IMPORTANCE OF INNATE vs ADAPTIVE IMMUNITY
SEQUENTIAL INDUCTION OF INNATE AND ADAPTIVE
IMMUNE RESPONSES TO INFECTION
INNATE
RECOGNITION OF
MICROBIAL “DANGER”
SIGNALS (PAMPs)
ADAPTIVE
RECOGNITION OF
SPECIFIC MICROBIAL
ANTIGENS
COMPARISONS OF INNATE vs ADAPTIVE IMMUNITY
LYMPHOCYTES CAN RECOGNIZE AND SPECIFICALLY
RESPOND TO ANY MICROBIAL PATHOGEN!
THE ADAPTIVE IMMUNE RESPONSE REMEMBERS PRIOR
EXPOSURE TO PATHOGENS
Adaptive
Immunity
Innate
GENERALIZED IMMUNE RESPONSE TO
MICROBIAL PATHOGENS
SELECTIVE PRESSURES OF MICROBIAL
INFECTION LED TO THE EVOLUTION AND
DIVERSIFICATION OF THE IMMUNE SYSTEM
BUT…
WITH SUCH AN EFFICIENT AND EFFECTIVE
IMMUNE SYSTEM, WHY DO WE EVER GET
SICK (AND OFTEN DIE) FROM INFECTIONS?
MICROBIAL PATHOGENS HAVE CO-EVOLVED WITH
THE IMMUNE SYSTEM OF ALL ANIMALS
>500 MILLION YEARS
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 frequencydependent 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.
ANTIGENIC VARIATION EVADES HOST
IMMUNE RECOGNITION
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.
OTHER BACTERIAL IMMUNE ESCAPE MECHANISMS
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