FUNDAMENTALS OF IMMUNOLOGY(AS INFORMED BY MICROBIAL PATHOGENS)

Microbiology 375

COURSE INSTRUCTORS:

DR. JOHN MANSFIELDPROFESSOR OF BACTERIOLOGY andMEDICAL MICROBIOLOGY & IMMUNOLOGY

DR. JULIA GILDENPOSTDOCTORAL FELLOWDEPARTMENT 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; 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

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

RECOGNITION OF MICROBIAL “DANGER”

SIGNALS (PAMPs)

RECOGNITION OF SPECIFIC MICROBIAL

ANTIGENS

INNATE ADAPTIVE

SEQUENTIAL INDUCTION OF INNATE AND ADAPTIVE IMMUNE RESPONSES TO INFECTION

COMPARISONS OF INNATE vs ADAPTIVE IMMUNITY

LYMPHOCYTES CAN RECOGNIZE AND SPECIFICALLY RESPOND TO ANY MICROBIAL PATHOGEN!

Innate

AdaptiveImmunity

THE ADAPTIVE IMMUNE RESPONSE REMEMBERS PRIOR EXPOSURE TO PATHOGENS

GENERALIZED IMMUNE RESPONSE TO MICROBIAL PATHOGENS

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

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 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.

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