Kent T. HayGlass, Ph.D. Canada Research Chair in Immune Regulation Professor and Head, Department of Immunology

Why would a pharmacist study immunology? A. You might flunk this course if you don’t B. It is very exciting C. It will be your partner for your entire professional life

Immunology and Pharmacy Value of Pharmaceuticals in isolation? AIDS: triple therapy Pharmaceuticals are an adjunct to the immune system

Module Objectives Overview of key characteristics of innate vs acquired immunity Who are the players? Key cells How is immunity activated? Applied systems of direct relevance to pharmacists Essential notes: U of M website (Medicine.. Immunology.. Teaching )

Class notes will be available for download from:

Your goal Develop a basic overview of how immune defenses operate so you can understand the rest of the curriculum Our problem Wide variation in prior experience Immunology jargon, “too much” progress. Solution Glossary of terms on web page; powerpoint presentations Focus on the big picture–not the details. Make noise when you get lost. Keep up.

Today Identify the major principles of the human immune response Introduce the two main forms of immune response. What they are and how do they relate to one another ?

The perfect world

The real world

Bacteria, Fungi, Parasites, Viruses FUNGUS - Epidermophyton floccosum (causes athlete’s foot) VIRUS- Polio BACTERIA - Clostridium difficile (causes antibiotic- associated colitis & antibiotic- associated diarrhea) PARASITE - Tapeworm

Antigen: (Ag) something that stimulates an immune response ~ 10 amino acids long. Can be any molecule: components of bacterial cell walls to exotic chemicals like poison ivy sap to your own proteins Antibody (Ab): a family of defensive proteins your body makes when it is stimulated by Ag. Ab contains a receptor that specifically binds one Ag and not another. Example : IgG Essential definitions

What are the key characteristics of an effective defense system? Not looking for CTL, NK cells, ADCC

Self non-self discrimination Specificity A way of amplifying selectively particular immune responses Diversification: converting one response into multiple types Turning responses off so that they don’t get out of control Memory Redundancy The ability to respond to a changing environment by inventing new Ag receptors Essential characteristics of an immune response

One component that is quick to develop and Ag non-specific to contain the pathogen initially: INNATE IMMUNITY A second component that is Ag specific to allow you to select the most appropriate of the ~30 different types of immune responses you have available, keep them highly targeted, exhibit memory...: ADAPTIVE IMMUNITY The optimal immune response

The innate immune response Characteristics: Quick to develop Ag non-specific Goal: contain the pathogen in the initial hours and days of infection, giving more sophisticated defenses time to expand and be deployed. Develop a system that can respond virtually instantly to readily identifiable potential pathogens

Main Assets: Rapid (minutes to hours for full activation), covers the 4-10d for a primary response to develop Intense (essential role in inducing a strong inflammatory response) Main liabilities: No adaptability, hence no protection from novel pathogens (new flu variants) No memory (an innate immune response is the same speed, type and intensity on the first or 10 th exposure to a pathogen) Innate Immunity

1. Constitutive 2. Activated by danger signals (ie LPS) Generation of the inflammatory response. Major components Cell mediated: Phagocytic cells (macrophages,neutrophils) NK cells (natural killer) Humoral Complement Acute phase proteins How does it work?

Highly targeted, specialized host defenses adapted for specific types of threats: Ag specific The capacity to remember previous encounters with a given Ag results in ability to mount faster, stronger and more effective responses during subsequent encounters: Immunological memory The capacity to co-evolve with pathogens, by generating a virtually infinite number of new Ag receptors to counter newly evolved viruses and bacteria: Adaptability The specific immune response (adaptive)

Concealed Ag (bacteria) Shed Ag (parasites) Changing Ag (flu) Manufacture immunosuppressive molecules (pox viruses) Evading the immune response: Dirty tricks

Key characteristics: Specificity Memory Adaptability Adaptive/ Acquired/ Specific Immunity

1. Inflammation brings Ag specific cells to the site, promoting expansion of the Ag-specific component of the response and targeting it. 2. Ab bind to several types of immune cells to confer specificity on Ag non-specific cells 3. The activities of the innate response help determine the type of specific response that develops (enhancing Ab production vs stimulating more cytotoxic cells) Integration of innate and adaptive immunity to form a more effective defense system

inducing and maintaining desirable specific immunity: (vaccines…) coping with immune disorders (ie allergic disease, autoimmunity, cancer). Attempts to manipulate the immune response for specific practical purposes (ie transplantation, prevention of Rh disease) also important for small subsets of the population. Two main applied aspects of immunology of concern to Canadian pharmicists

Passive immunity: transfer of Ab Advantages: intense, immediately effective. Disadvantages: Short duration. Does not activate the host’s own immune response, so no memory develops. Active vs. Passive Specific immunity

Active immunity Results from natural (or vaccine induced) exposure to a pathogen. Advantages: stronger, more diverse response, longer lasting, memory develops Disadvantages: takes several days to months to fully mature.