BIO 447: Immunobiology Introduction to Immunobiology and Immunology in Health and Medicine
Folder Title: 447Intro Updated: August 20, 2014 Filename: 447Intro
(WithTP Questions; edited using TP5)
Course Web-Site and Presentations
The Power-Point Presentations are available on the course web-site at tpfondy.syr.edu/bio447 in the table link called “Course Schedule and Graphics” http://tpfondy.syr.edu/bio447 (Turning Point question slides are not included until after the presentation)
Textbook and Teaching Assistant
Textbook: Kuby, Immunology, 7th Edition by Owen, Punt, & Strandford
Yifan Gong: Teaching Assistant EMail:
[email protected]
To Enter your name on your NXT Response Transmitter (Revised August 20, 2014)
Participant List Monday August 25th, 8 PM:
For NXT Transmitter (Off-white) Press grey button with white oval in the middle Get screen with a wrench on it Press upper right button (square with two bubbles) “Find Channel”. Use Channel 41 Press Left Arrow next to grey button once to get to “Your ID” (Your Name goes here) Grey Button (Left arrow under abc will clear characters) Enter your name (first five letters OK) using the letters shown on each key. If you want a “c”, hit the abc key three times in quick succession. When your name is entered hit the grey button. You will get a smiley face.
To Respond to Turning Point Questions in Class: Using the NXT Transmitter (Revised August 20, 2014)
1. Put your last name onto your NXT transmitter under “Your ID” 2. If you borrow a transmitter from us, fill out an index card so we get your name, take instruction form, please leave bio1, 2, 3, 4, 5, or 6 on the borrowed NXT transmitters 3. We are using Channel 41 in this room. NXT should find Channel 41 when you hit “Find Channel”. You get a smiley face. 4. With the NXT transmitter you have to hit the square response button in the upper left below the screen in order to get to the blank screen that is presentation mode. 5. Screen will show whether your response has been received. Your device will also show a check when your name (or the bio number) has been received. 6. If there is a problem, we will provide a back-up form for you to hand in your response. Back-up responses must be handed in while the question is open on the screen. Elisabeth will give back-up forms and collect them. Back-up forms should be a rarity. If you forget your transmitter you can borrow one from us at the start of class.
I am here!
(Testing your Turning Point Transmitter)
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Yes No
Be sure that your name is entered under “Your ID” in your NXT Device Unless you have a borrowed Bio NXT transmitter We are using channel 41 Response Counter
For Off-White NXT Device Enter your name under “Your ID” Hit Grey Circular button with white oval Get a wrench icon Hit square split screen button in upper right “Find Channel” Hit grey button again. Enter Channel Number 41 Hit grey button again “Channel Changed”. Get Smiley Face. Should see “41” Hit grey button again. Hit the square button at the top left under the screen Get blank screen. Enter your response
Single Word (Fill in the blank) response (I hope) What day of the week is today? Please use three-letter abbreviations to get uniform responses (sun, mon, tue, wed, thr, fri, sat) Rank 1 2
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Course Evaluation, Grading, and Maintenance of Standards Three In-Class Exams, 100 Pts Each Exams only for those who actually come to class based on responses received from NXT transmitters. Exam 1 TBA; Exam 2 TBA; EXAM 3 Last Day of Class (No Final Exam) Class Participation Components: Based on Responses Using Turning Point NXT Transmitters Number of responses is matched to the number of persons in class 200 Points Maximum Possible (40% of Course Grade) 500 Points for the entire course: Graded based on standing in the class of 108 students
Course Evaluation and Maintenance of Standards No Make-Ups for scheduled exams. Medical excuses are required for illness causing absence from an exam. (See Verification of Medical Conditions, University Policy, February 25, 1993) Dean's office confirmation required for personal emergencies. Exam contents cover only what is actually presented in class, whatever parts of the textbook directly pertain to what is covered in class, hand-outs given in class, or whatever is specifically assigned in class. Course organized based on Immunology by Janis Kuby and later Authors: Prior editions 1, 2, 3, 4, 5 and 6. 7th Edition Currently in Use (Required Textbook)
Course Evaluation and Maintenance of Standards Class Participation: 200 Points In-class Quizzes using Turning Point NXT Transmitters 10 Points Each Start of Class, End of Class, or In-Between Will Give 26 - Count 20 (will assign your average quiz grade for any quizzes legitimately excused) Course Total: 500 Points
Course Grading
Done strictly on a comparative basis by determining standing in the class. Therefore: Rigorous honesty is essential! (Don’t cheat and don’t assist anyone else in cheating) NXT Transmitter, also called “Response Card” used for all classes. Procedures for use sent to Class via Blackboard and given in earlier slides
No cell phones or other electronic devices other than the NXT transmitters are permitted in class, during quizzes, or during exams. If you wish to record a class because of limitations with your comprehension of English, or for problems with hearing, You can place your recording device on the front desk.
Immunobiology: Why Do We Want to Know? Why Does it Matter?
What’s special about immunology and the immune response system?
Why does Syracuse University have an Immunology Policy?
Why did we all get this mailing here at SU a few years ago? See next three slides…
SU NEWS ALERT: Flu Information for the Fall Semester August 26, 2009: Syracuse University continues to monitor developments related to the spread of flu—both the common seasonal flu and the H1N1 flu virus (popularly known as “swine flu”). The University’s goal is to work with all members of the community to reduce the effects of flu and flu-like illness, while maintaining the academic mission and business functions of the campus. Members of SU’s multi-departmental Pandemic Flu Preparedness Task Force convene regularly on flu planning, and task force representatives met recently with Onondaga County Health Department officials for the latest in an ongoing dialogue. In addition, last week the Centers for Disease Control and Prevention issued new guidance for colleges and universities (http://www.cdc.gov/h1n1flu/schools/) that is currently being reviewed by University officials for possible modifications to the University’s flu strategies.
Widespread flu-like illness is expected over the next several months, with H1N1 flu intermingling with seasonal (“regular”) flu during 2009-10. Based on current information from health officials, H1N1-specific testing will not be routinely available, so it is unlikely that health professionals will know whether a specific individual with flu-like symptoms is ill with seasonal flu or H1N1. Based on the current behavior of H1N1 in the Southern Hemisphere, H1N1 is expected to cause mild to moderate (rather than severe) illness in most persons infected with this virus in the United States this fall. All students, faculty and staff are encouraged to receive the seasonal flu vaccine (a “flu shot”). Opportunities to obtain the flu vaccine will be available on and off campus beginning in early fall and continuing while supplies last. Information on vaccine availability will be posted on the Syracuse University Preparing for the Flu website (http://sunews.syr.edu/h1n1flu/index.html). When H1N1 vaccine becomes available, the University anticipates it will be administered on campus to eligible (based on criteria established by the CDC) students. Opportunities for faculty and staff to receive the vaccine will be available in the community.
All persons 50 years and older, and persons younger than 50 years who have certain medical conditions, should receive the Pneumovax 23 vaccine from their health care provider (if they have not already done so) to reduce the risk of pneumonia following infection with H1N1. Persons who are ill with flu-like symptoms will typically be advised to stay at home or in their residence hall room until 24 hours after fever (100 degrees Fahrenheit or 38 degrees Celsius) symptoms abate without the aid of fever-reducing medications. Individuals with flu-like symptoms may be advised to wear a mask when it is necessary to be in public places, such as a dining hall. At this time, the University does not anticipate closure or severe disruption of the academic year due to H1N1, although planning is taking place to diminish the impact of potential interruptions of work or services due to faculty and staff illness, the necessity for faculty and staff to care for ill family members, and similar situations. All members of the University community should practice good hygiene such as proper hand washing, cough etiquette and other flu mitigation strategies. Individuals are also encouraged to take personal responsibility for the sanitization of frequently/commonly used surfaces such as doorknobs, keyboards, copiers, remote controls and desks within their personal living, learning and work areas to minimize the transmission of virus. Hand sanitizing products are available for purchase by schools/colleges/departments from Materials Distribution through the Materials Distribution Online Ordering System (http://mdoos.syr.edu/). In addition, students should ask instructors about class attendance policies, and faculty and staff should work with their school/college/department to review policies regarding flexible work, paid time off, leaves of absence, and expectations for continuity of operations and services.
Following are contacts that are available to respond to flu-related questions on specific topics:
General health care and flu prevention: SU Health Services, 443-9005,
[email protected] On-campus residence halls and apartments: Bill Longcore, Office of Residence Life, 443-3637,
[email protected] Off-campus and commuter students: Darya Rotblat, Off-Campus and Commuter Services, 443-5489,
[email protected] International students: Lillian and Emanuel Slutzker Center for International Services, 443-2457,
[email protected] Academic policy topics: Sandra Hurd, Academic Programs, 443-1899,
[email protected] Academic personnel topics: Kal Alston, Academic Administration, 443-5525,
[email protected] Staff human resources: Jack Matson, Human Resources, 443-5461,
[email protected] Parent/family concerns: Colleen O’Connor Bench, Parents Office, 443-1200,
[email protected] Additional information on seasonal flu and the H1N1 flu virus will be provided to the University community via email, the Web (http://sunews.syr.edu/h1n1flu/index.html) and other forms of communication as the information becomes available. Sincerely,
Dr. James R. Jacobs, M.D., Ph.D., FACEP Director of University Health Services Co-chair, Pandemic Flu Preparedness Task Force
University Immunization Policy (from Schedule Book ~1990)
Vaccines in Human Health
Re-emergence of Infectious Measles Cases in Texas: Refusal of Vaccination See Chris Hayes, MNNBC, August 27, 2013 Comments on “Herd Immunity” by Arthur Kaplan
Vaccines We Don’t Have: Malaria World-wide: 2010 Caused by Plasmodium falciparum parasite Transmitted by Mosquito vector Infected: Killed:
220,000,000 (assume at any one time?) 660,000 (of those infected?)
Mostly children
Experimental vaccines use immature form of Plasmodium falciparum (sporozoite) See Science, 9 August 2013, p.605, Vol. 341
Why Does Immunobiology Matter? Some Stories: The Boy Policeman from Raleigh, North Carolina http://abclocal.go.com/wtvd/story?section=news/local&id=7531763 http://www.msnbc.msn.com/id/26184891/vp/38084943#38084943
Killer Disease on Campus: NOVA Video on Meningitis (See Slide 54 later) 2-year-old Boy with Fanconi’s Anemia as Best Man for His Parents’ Wedding (Links to Logon Stevenson and Dana Farber Children’s Hospital sent via Blackboard, August 19th http://www.cbsnews.com/8301-201_162-57597155/logan-stevenson-2year-old-pa-boy-dies-after-serving-as-parents-best-man/
Influenza: Types A, B, and C What Is Type A Flu Virus? Type A flu or influenza A viruses are capable of infecting people as well as animals; although it is more common for people to suffer the ailments associated with this type of flu. Wild birds commonly act as the hosts for this flu virus. Type A flu virus is constantly changing and is generally responsible for the large flu epidemics. What Is Type B Flu Virus? Unlike type A flu viruses, type B flu is found only in humans. Type B flu may cause a less severe reaction than type A flu virus, but occasionally, type B flu can still be extremely harmful. Influenza type B viruses are not classified by subtype and do not cause pandemics. How Is Type C Flu Virus Different From the Others? Influenza C viruses are also found in people. They are, however, milder than either type A or B. People generally do not become very ill from the influenza type C viruses. Type C flu viruses do not cause epidemics.
What’s the Big-Deal About “H5N1” or “H7N9”?
H =Hemagglutinin variant N = Neuraminidase variant Different isoforms of proteins and enzymes needed for Viral attachment to target cells entry into the cells and for viral release from infected cells. Are present on viral envelop .
Are specific antigens that can generate a protective immune response if the antibodies are present ahead of time. Basis for specific prophylatic vaccines (Prophylactic = protective, preventative rather than therapeutic)
Current Flu Vaccine at Rite-Aid
Trivalent Vaccine: A - H1N1 A - H3N2 B – MA 02/2012
See Chapter One: Kuby Edition 7
Overview of the Immune System: How does it work? pp. 1 to 10 What does it do? pp. 11 to 18 What can go wrong? pp. 19 to 22
What’s Special about the Immune Response? What it has to do?
Distinguish pathogenic threat from symbiotic beneficial organisms, and from non-pathogenic elements. Distinguish Self from Non-Self.
Distinguish Normal Self from Pathological Self. Remember what it has seen. Turn on when needed, turn off when no longer needed. Be controllable when we don’t want a response.
What if those elements of the Immune Response Don’t Work Correctly?
Failure to Recognize? Immune deficiency diseases. Attacking Self? Allergy, hypersensitivity, auto-immunity Failure to Distinguish Self from Altered Self: Cancer Immune Evasion. Failure to Remember what it has seen: Immune-unresponsiveness; Vaccine Immunology
Failure to Turn-off: Inflammation, Hypersensitivity Need to control when we don’t want a response: Transplantation Medicine
What’s Special about the Immune Response? How does it do what it has to do?
Cell Sociology in Metazoan Evolution How do cells “talk” to each other from a distance? How does an organ system work when the system is discontinuous? Cell signaling in multicellular organisms How do cells “remember” stuff?
Self and Non-Self Recognition in Biology Species Specific Sperm and Egg Recognition Maternal - Fetal Recognition Kin and Group Recognition Self-Recognition in Plants Innate Natural Immune Response Self-Recognition and Self-Awareness in Neurobiology (See Science, April 12, 2002, Reflections on Self)
Immunity is part of self, non-self, altered-self, and damaged-self recognition in multi-cellular organisms
Host Responses to External and Internal Agents and Events Vision: Ocular and Neurological Response Air and Water-pressure Changes: Auditory Responses Chemical concentration and identity: Olfactory Responses Blood Pressure: Cardiovascular Response Sexual Attraction: Hormonal Response Avoidance Behavior: Hormonal Response
Non-Immunological Responses Response1
Host Responses to External and Internal Agents and Events Distinguishing Cell, Tissue, and Molecular Self from Non-Self Distinguishing Normal Self from Pathological Self Distinguishing Normal Self from Damaged Self Distinguishing Beneficial Organism and Agents from Pathological ones “Remembering” pathogenic challenges
Immunological Responses
What’s Special about the Immune Response? What it has to do? How it does what it has to do? How it is set up?
Questions: Where is the heart? Where is the liver? Where is the digestive system? Where is the respiratory system? Where is the immune response system? More Questions: Where is the nervous system? Where is the circulatory system? Where is the lymphatic drainage system? What happens if they aren’t continuous?
What’s Special about the Immune Response? How can a discontinuous system work?
Inter-cellular communication and cell signaling: Notions of “Biocomplexity”
Keeping a discontinuous system functioning normally. What can go wrong.
Immunology in Human and Animal Health and Disease Why do we want to know about Immunology? What does it tells us about ourselves and about biology? What can it do for us? As a tool in biomedical research? As a diagnostic and therapeutic modality in clinical and veterinary medicine?
What can it do to us, as a source of pathology? InHealth
Immunology in Human and Animal Health and Disease
What Can We Make it Do For Us? ImmUse
BIO 447 Immunobiology: First Third: August 27 to Oct. 8th What Immunology Is What It Can Do in the Host Beneficial Deleterious
What Does the Immunological Response Recognize and Respond to? What Does It Respond With? How Can It Possibly Recognize and Respond to so Much Diversity? 1st3rd
Please send us your Last name and your NXT Device ID
KEY FEATURES OF SPECIFIC ADAPTIVE IMMUNITY IN HISTORY Freedom from Plague after Surviving First Exposure
Immunity Exists
Susceptibility to Other Diseases Even After Surviving Plague
Immunity is Specific
Deliberately Induce Small-pox to Protect Against Later Exposure
Immunity has Memory
Induce Non-pathogenic Cow-pox to Protect Against Virulent Small-pox (Vaccination)
Related Antigens are Cross-Reactive
Resistance to Chicken Cholera after Surviving Exposure to Weakened Chicken Cholera Bacilli (Attenuated Vaccines)
Antigens can be separated from pathogenic features
ImHistry
Some Comments About What Immunology Teaches Us About the Vulnerability of Our Civilizations and Who is looking out for us.
History of the Second Millennium AD Smallpox Bubonic Plague Cholera Tuberculosis Syphilus Influenza Pneumonia Child-bed Fever
Variola major small pox. 30% Death rate.
Beneficial Protective Immune Responses Recognition and Response to External Organisms and Agents: Antimicrobial and Anti-parasitic Immunity (Chapter 17) Molecular Pathogens Viruses, Bacteria, Fungi, Molds Single Celled Eucaryotes Multi-cellular Organisms
Induction of Protective Immunity: Vaccines (Chapter 17) Recognition and Response to Internal Pathology: (Chapter 19)
Tumor Immunology Recognition and Response to Transformed Self
Deleterious Immune Responses and Immunopathology Allergy and Hypersensitivity (Chapter 15) Organ and Tissue Transplantation Rejection (Chapter 16) Self-Reactivity: Loss of Tolerance ; Autoimmunity (Chapter 16) Immune Stimulation of Tumor Growth, Invasion, and Metastasis (Chapter 19) Immunodeficiency Diseases (Chapter 18)
Congenital Acquired
What the Immune Response Has to Do: Recognize and respond to external pathogens. Recognize and respond to infected cells. Recognize and respond to transformed self (cancer) cells. Participate in tissue remodeling and senescence. Know where the challenge is. Know how to mount an effective response. Know how to get the effector response to the right place. Respond without damaging normal cells and tissues. Know how much response is needed. Shut down when the response is completed. Remember previous response and respond more quickly effectively the next time around. Do not react against normal self. (no autoimmunity). Do not react against something that is in fact not a problem until the immune responds reacts (no allergies). Accept medically needed transplants
Infection in thumb: That there is a peripheral challenge It’s in the thumb! Which thumb? (Where the challenge is located?) What is the challenge? What do I need to respond with? How do I get it there? How much response do I need? When should I shut it down? What do I do if it comes back? What if I don’t pick up the signals? What if I get it wrong and respond incorrectly? How is the Immune response set-up to do all of these things? How does the immune response know where the problem is? Cytokines, Chemokines, Receptors (Chapter 4) See Appendix I, Pages A1 to A29, 540 CD Antigens See Appendix II, Cytokines, Pages B1 to B6, 58 Cytokines Appendix III, Chemokines and Receptors, p. C1, about 30 chemokines and related receptors.
What is an example of a deleterious immune response? (one word or short phrase. Don’t worry about spelling)
Non-Specific Host Defenses, and Non-Specific and Specific Host Immunity Non-Immunological Host Defenses Innate, Natural, Non-Specific Immune Responses (Chapter 5) Specific, Adaptive, Acquired Immune Responses (Chapter 3 and others) CD Antigens (Constellation of Differentiation Antigens, see Table A1 to A29, 540 CD Antigens!)
Non-Specific Host Defenses, and Non-Specific Immunity Anatomical Barriers
Skin Mucous Membranes; Epithelial Linings
Chemical and Physical Barriers
Temperature pH Enzymes, Cytokines, Chemical Mediators Bathing fluids (e.g. eye), oils
Cellular Barriers
Leucocytes: Neutrophils (Polymorpho-nuclear leucocytes or PMNs) Eosinophils, Basophils Monocytes & Macrophages
Non-Specific Cellular Barriers: Innate, Natural Immune Response Cellular Barriers
Leucocytes: Neutrophils (Polymorpho-nuclear leucocytes or PMNs) Eosinophils, Basophils Monocytes & Macrophages Dendritic Cells Natural Killer Cells (NK Cells)
Inflammatory Responses
Enzymes, Cytokines, Chemical Mediators Elevated Temperature
Specific, Adaptive, Acquired Immune Response Humoral Immunity Antibodies (Immunoglobulins) Involves Cell-free, Specific Antibodies in Serum and Other Body Fluids Produced by B-Cells (B-Lymphocytes or Bone-marrow Derived Lymphocytes) Can use the Complement System (Chapter 6) Cellular Immunity Involves Specific T-Cells (T-Lymphocytes or Thymusderived Lymphocytes) Involves Cytokines (Inter-cellular Protein Signal Molecules Produced by Cells) SpecImm1
Malaria World-wide: 2010 Caused by Plasmodium falciparum parasite Transmitted by Mosquito vector
Infected: Killed:
220,000,000 (assume at any one time?) 660,000 (of those infected?)
Mostly children
Experimental vaccines use immature form of Plasmodium falciparum (sporozoite) See Science, 9 August 2013, p.605, Vol. 341
Question from Tuesday’s Class
Properties of the Specific, Adaptive, Acquired Immune Response Recognizes Specific Biochemical Structures:
Antigens Inducible by Antigen-Exposure Exhibits Memory Response Discriminates between Self and Non-Self Involves Specific Cellular Responses: T-Cells Involves Specific Humoral Responses: Antibodies
Non-Specific, Innate, Natural Immune Responses (See Chapter 5) Responds to Non-Self Cell-Surface Structures: PAMP (Pathogen-associated Molecular Patterns) including TLR’s (Toll-like Receptors). or to the Absence of Self ("password") Signals Non-Antigen Specific Discriminates between Self- and Non-Self. Less Specific than the Adaptive Immune Response. No Immunological Memory Response. Inherently Present; Does not have to be induced. Can be induced by cytokines and various other agents Uses Non-Antigen-Specific Cells and Soluble Factors in Humoral Fluids, but not Antibodies or T-Cell Receptors Involved in Inherent Resistance to Infectious and Neoplastic Disease Probably to earliest form of immune response in evolution Se Plant Innate Immunity, pages 178-179
Pathogen-associated Molecular Pattern (PAMP) Receptors and Toll-Like Receptors in the Innate Natural Immune Response
Figure 5-10a, 7th Edition
Phagocytic macrophage ingesting mycobacterium tuberculosum
Interaction Between Natural Immunity and Specific Adaptive Immune Response
Interaction Between Innate Natural Immune Response And the Specific Adaptive Immune Response
T-Helper Cell
Macrophage Macrophage-Helper-T-Cell Interaction
In the picture the macrophage is activating a specific T-cell in their membrane-to-membrane contact by performing a crucial molecular function. What is the macrophage doing in molecular terms?
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Humoral and Cell-Mediated Immunity
Hum&Cell
Humoral and Cell-Mediated Immunity
Hum&Cell
Innate Immunity and Specific Adaptive Immunity Walking along the Quad. See people running out of a building. This is unusual. Something it wrong (Pattern Recognition). Smell smoke. Think “Fire” (Pathogen associated molecular receptors). Run in and grab a fire extinguisher. (effector response) Not good enough. Recognize this is Bowne Hall-Chemistry Building. Don’t know where they store flammable solvents. Don’t know where the peroxides, azides, and other explosives are. Call 911. Professional Fire-Fighters Arrive. They know this is the Chemistry Building. They have details of the lay-out. They have special equipment for managing chemical and electrical fires. This is not the first time they have responded to the Chemistry Building. They put out the fire. They don’t set up a back-fire or burn the building down to contain the original fire.
One major arm of the immune response is the innate natural immunity. What is the other major arm of the immune response?
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The Specific Adaptive Immune Response and
Clonal Selection, Expansion, and Memory
Membrane-bound Antibodies & T-Cell Receptors
See Figure 1-5, p. 11 Kuby 4th Edition
See Figure 1-10, p. 17 Kuby, 4th Edition
Clonal Generation, Antigen Selection, Expansion
Figure 1-12, p. 17 Kuby, 6th Edition
Cellular and Non-Cellular Components for the Immune Response
Morphology and Staining Characteristics of Blood Cells Kuby, 3rd Edition Figure 3-1
CellMorf
Hematopoiesis: Where blood cells come from and what they look like.
From Stem Cell Technologies Wall-Chart on Hematopoietic and NonHematopoietic Stem Cells
A Specific target for an Antibody is an _ _ _ _ _ _ _. Rank 1 2 3
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What is this graphic showing?
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The pluripotent stem cell produces partially committed stem cells in two different hematopoietic lineages. One of these is the myeloid or myelogenous lineage. What is the other lineage? 17%
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Innate Natural Immunity and Systemic Sepsis: NOVA Video on Meningitis (Meningococcal Meningitis, Endotoxin, and Systemic Sepsis)
http://www.pbs.org/wgbh/nova/meningitis/
Has video links to steps in meningococcal sepsis “Amy’s Story” and related NOVA Stories
Whooping Cough Infection and Transmission Whooping Cough Vaccine Today Show, 12/2/04
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What is the reddish object in this photo?
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What is the green stuff in this photo?
