Module 4 Disease Detectives

Investigation 4.1 Epidemiology Basics Investigation 4.2 Immunology Basics Investigation 4.3 Microarray Model

Module 4 Disease Detectives

Investigation 4.1: Epidemiology Basics Activity 1: Nature’s Nanobots- Viruses

Permission http://www.swbic.org/

Materials MedMyst Emerging and Reemerging Diseases magazine handout. Great Background information. Nature’s Nanobots – Viruses- Student Worksheet How do Viruses Recognize Target Cells (Genetic Science Learning Center, Utah) http://learn.genetics.utah.edu/units/genetherapy/print-and-go/viruses.cfm Styrofoam balls, paint, paintbrushes, Velcro, snaps, hot glue gun Toothpicks, marshmallow, yarn

• Option 1 : Make a virus – follow instructions - How do Viruses Recognize Target Cells (Genetic Science Learning Center, Utah) http://learn.genetics.utah.edu/units/genetherapy/print-and-go/viruses.cfm

• Option 2: Build a virus structures using toothpicks and marshmallows • Option 3: Icosahedron virus – composed of 20 facets. Each facet is an

equilateral triangle. Why are viruses called nature’s nanobots?

• Nanotechnology – “nano” means one billionth of a meter. It is a very small measurement! Atoms and molecules range between 0.2 nm - 0.3 nm! An atomic force microscope allows us to view small molecules and atoms and manipulate them into new structures. New tools and techniques have revolutionized science and opened the “nano world.” Creating very small structures to deliver medicines, kill cancer cells, detect disease is a new and revolutionary tool.

• Viruses range in size between 25 nm (nanometer) and 300 nm. They are nature’s “nanobots.” They are not living because they require a host cell to reproduce. They “hijack” the host cell”s DNA and alter how the cell’s functions.

• Viruses do not need food! • Viruses come in various sizes and shapes and are very specific to the

cells they attack (e.g., hepatitis – liver, polio-nerve, influenza-lungs). • Viruses are very simple structurally: protein head (capsid), DNA or

RNA, and various means of attachments to the host cell. Some have an envelope or additional lipid membrane.

• Your immune system is designed to try to fight and destroy attacks by viruses.

• Viruses are being engineered to carry genes or medicines to repair cells. Viruses used in this manner are called gene vectors and are used in gene therapy! The viral genome is replaced with human genes that will be incorporated into the target cells and produce proper cell functioning. One area of research is diabetes.

Head (caspid)

Tail fibers

End plate

Neck

Sheath

DNA

Make Your Own Nanobots Materials Icosahedron template (20 faces, 12 vertices, 30 edges) Scissors Tape Color pencils Straws Yarn (two different colors – DNA and RNA) Pipe cleaners Toothpicks and marshmallows (make your own shape), other assorted materials .

Procedure 1. Cut template and tape each side together. Before you tape the last

edge insert yarn (either DNA or RNA). 2. Tape your straw in place 3. Place pipe cleaners to represent the tail fibers * Make your own virus!

Nature’s Nanobots - Viruses - Student Worksheet

Name ____________________________________________ What are viruses? ____________________________________________________________________________________________________________________________________________________________________________________________________ Are viruses living or non-living? Explain your answer. __________________________________________________________________________________________________ How big are viruses? ________________________________________________ What do viruses look like? Sketch a few viruses? What are the major components that make up a virus? __________________________________________________________________________________________________ How are viruses used as vectors for transferring genes? ___________________________________________________________________________________________________________________________________________________

What are some viruses that cause disease?

Virus Name Disease

How does the immune system fight viruses and other pathogens? _______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Detectives in the Classroom - Investigation 1-1: Why Are These Students Getting Sick?

DZ

DZ

DZ

DZ

Why Are These Students Getting Sick?

Activity 2: Disease Detectives Materials and Procedures from: Detectives in the Classroom Montclair State University – permission granted to use and adapt module. http://www.montclair.edu/detectives/

Mark Kaelin -- Project Director Email: kaelinm@mail.montclair.edu Phone: 973-655-7123 EXCITE http://www.cdc.gov/excite/

In Investigation 1-1: Why Are These Students Getting Sick? selected students are given “DZ” (disease) signs that represent a fictitious disease. For example, the teacher may give “DZ” signs to all students wearing sneakers. The students observe how the “DZ” is distributed and develop hypotheses about possible “causes” of “DZ”. Students may hypothesize that fumes from the school’s newly refinished gymnasium floor caused the “DZ”. In Investigation 1-1, students begin to become familiar with the terminology of epidemiology (called "Epi Talk") by using terms such as disease distribution, hypothesis, and disease detectives. (Note: Epi Talk is used throughout the Investigations in all five of the modules.)

EPI TALK

1. Clue - something that helps to solve a problem or mystery.

2. Descriptive Epidemiology - study of the distribution of a disease or other health-related condition. Basis for formulating hypotheses.

3. Disease Distribution - the pattern of how a sickness is spread out among a group of people.

4. Epidemiologist / Disease Detective - an investigator who studies the occurrence of disease in populations of people for the purpose of preventing or controlling health problems.

5. Epidemiology - the study of how and why diseases or other health-related conditions are distributed in a population the way they are, in other words, why some people get sick and others do not.

6. Hypothesis – an educated guess. A problem that can be tested or investigated. At the end of the experiment or study, one accepts or rejects hypothesis.

7. Person, Place, and Time - the three basic categories of clues that can describe the distribution of a disease in a population of people.

8. Population - All the people in a particular group. 9. Stakeholder - someone who represents a group of people and their

interests.

Investigation 1-1: Why Are These Students Getting Sick?

Teacher’s List of Possible Exposures for DZ Cards

Consider using the following exposures as “DZ” sign distributions.

• Student is wearing sneakers • Student is acting in the school play • Student is a female • Student is a male • Student is a member of the school athletic team • Student is a member of the student government • Student is sitting next to a window • Student ate in the cafeteria yesterday • Student is carrying a backpack • Student has a younger brother or sister • Student has long hair • Student has short hair • Student is wearing hightop sneakers • Student lives in a particular neighborhood • Student takes the bus to school • Student is wearing a necklace • Student is wearing a ring • Student is wearing glasses • Student is wearing white sneakers • Blonde hair • Blue eyes • Brown eyes

Detectives in the Classroom Name: __________________________________________ Investigation 1-1: Epi Log Worksheet Date: _____/_____/_____

Hypothesis Chart

DZ DZ Distribution My Hypothesis Other Hypotheses

1

2

3

4

5

6

7

8

9

10

Activity 3: Spread of Infectious Diseases American Social Health Association http://www.iwannaknow.org/ HIV in Action http://www.pbs.org/wgbh/nova/aids/action.html Fight Back Interactive game macrophages and mumps http://www.pbs.org/wgbh/nova/aids/immune.html Centers for Disease Control (CDC) – Disease cards

Materials 0.1M NaOH (4g of NaOH per 1L of H2O) 1% phenolphthalein indicator Test tubes (one for each student) Plastic dropper (one for each student) Spread of Infectious Diseases Student Worksheet

Procedure 1. Each student has one test tube filled with water (only one of the test

tubes contains 0.1M NaOH) 2. A plastic dropper for each student. 3. Remove about 20 -30 drops of the fluid in your test tube and place it

in another test tube. This is our control. 4. Walk around the room carefully and stop when I tell you, One person

fills his/her dropper with fluid and places it inside your partner’s test tube.

5. Mix 6. Your partner takes a sample of his/her fluid and places it back in

your test tube. 7. Mix 8. Walk until I say STOP, Exchange fluids. Repeat one more time. 9. Your instructor will place 2-3 drops of 1% phenolphthalein indicator in

each test tube. 10. A pink color indicates infection.

Spread of Infectious Diseases Student Worksheet

Name ____________________________________________________ Complete the table below. Name of the Disease

What are the Symptoms of the Disease?

How is the Disease Transmitted?

Name the Pathogen that causes the Disease.

How do you cure the Disease?

How do you Prevent the Disease?

Activity 4: MedMyst

• Excellent Online Activity about Disease and Pathogens – Mission 1

http://medmyst.rice.edu/index.html

Investigation 4.2: Immunology Basics Activity 1: Online Immune System Review Immune System Defending Our Bodies Nobel Prize Organization –games and teacher resources http://nobelprize.org/educational_games/medicine/immunity/ How the body protects itself form disease. National Institute of Allergies and Infectious Diseases http://www.niaid.nih.gov/final/immun/immun.htm#Defense PPT HHMI Outreach Harvard – Excellent Overview of the Immune System File Format: Microsoft Powerpoint - View as HTML Immune System Animation Links through Anatomy & Physiology Groups; http://science.nhmccd.edu/biol/ap2int.htm; Pier,G. , Lyczak,J., Wetzler,L; Immunology, ... outreach.mcb.harvard.edu/teachers/Summer04/PatriciaLafleur/Immunology.ppt - Similar pages Animation Very good http://www.learner.org/channel/courses/biology/archive/animations/hires/a_hiv1_h.html

antibody

antigen

Activity 2: Antigen/Antibody Balloon Activity Adapted from David Scott, Ph.D. American Red Cross Rockville, MD http://www.aai.org/educating/

Materials Large plastic garbage bag

15 yellow balloons with air

15 red balloons with air

Procedure Place all the balloons in the plastic bag.

Have 6-8 student volunteers catch as many balloons as they can.

Have students keep only the balloons they are holding in each hand.

If the balloons are of different colors, have students exchange balloons so that each student is holding 2 of the same colored balloons.

Explain the terms antigen and antibody.

Immunology Terms

1. antigen – any substance that elicits an immune response. For example, a virus or bacteria contain foreign proteins or other molecules causing our immune system to make antibodies to fight against them. Sometimes certain foods or metals, like silver will elicit an immune response.

2. antibody (also known as immunoglobulin) – is specific to the antigen (foreign molecules) and binds to the antigen at specific sites.

3. Monoclonal antibodies – same kind of antibody that binds to one antigen. 4. serum (antiserum) – blood from an immunized animal in which the red blood

cells and platelets (clotting proteins)have been removed. 5. adaptive immunity – acquired after birth. The body

builds a memory library of antigens and the antibodies it produces.

• Just like your brain is able to learn and remember events, the body’s immune system has its own way to learn and remember when it has been attacked.

6. lymphoctes- one of the 5 different types of white blood cells in our blood. Lymphocytes are the cells important in our immune response. Because they can live for a long time, they can remember when a foreign antigen has attacked. If we are exposed again it remembers and antibodies fight the antigens. This is why we don’t get chickenpox or measles again.

• B lymphocytes – made in the bone marrow and produce antibodies • T lymphocytes – mature in the thymus and destroy foreign cells and

help the B lymphocytes produce antibodies (Killer T cells, Helper T cells)

7. vaccine – a weakened or inactive foreign body that elicits an immune response

• Edward Jenner – first vaccine against smallpox. Excellent information on the history of the first vaccine.

Biology Project http://www.biology.arizona.edu/ Click on immunology, click on Introduction to Immunology, click on Introduction

What are Monoclonal Antibodies (MAB)?

• Mono – means one • Clonal – from the same • Antibody – a molecule that binds to a specific antigen or part of a cell

Inject antigen into mouse

Collect blood serum and check for antigens and antibodies.

B-lymphocytes make many different kinds of antibodies (polyclonal).

Clone the cell with the antibody desired. These antibodies can be used for treatment or diagnosis.

Monoclonal Antibody with Cancer Cell

Monoclonal Antibodies

• Monoclonal antibodies are considered targeted therapies because they act primarily on cancer cells.

• CD20 antigen is present on the cancer cells of many patients with NHL.

• Rituxan™ is an FDA approved monoclonal antibody with CD20 specificity that is used for treatment of lymphoma.

• Other monoclonal antibodies for treating lymphoma are currently being tested in clinical trials.

The Wellness Community http://www.thewellnesscommunity.org/programs/frankly/lymphoma/PPT/RIT_Slide_S

How Radioimmunotherapy Works

• Technique begins with a monoclonal antibody, as described previously, and attaches a radioactive molecule, such as iodine131, or yttrium90 to the antibody.

• Once this combination has been infused into the person, the monoclonal antibody delivers the treatment primarily to the cancer cells.

• The radiation dose is concentrated primarily in those areas where the cancer exists, resulting in fewer effects on normal cells, and thus fewer side effects, such as hair loss.

How Radioimmunotherapy Works

Cancer Cell Radioactive Antibodies

How Radioimmunotherapy Works

Cancer Cell Radioactive Antibodies

Immunity Antigen/Antibody ELISA (Enzyme Linked Immunosorbent Assay) http://www.biology.arizona.edu/immunology/activities/elisa/main.html ELISA is used in immunology to detect the presence of antibodies or antigens in a sample. It can be used to detect HIV, pregnancy, food allergies.

Investigation 4.3: Microarray Model DNA Microarray Methodology Animation

• Simple flash animation http://www.bio.davidson.edu/Courses/genomics/chip/chip.html

What is a Microarray? A microarray is an orderly sequence of areas that can hold DNA, RNA or proteins. Known gene sequences are placed (or fixed) on a glass or plastic slide. Samples to be tested are marked and labeled with fluorescent dyes. If a gene is expressed, it will bind (hybridize) to the area on the microarray and fluoresce the tagged color. A cancer cell makes different proteins or variations of proteins than those found in healthy cells. A test to detect the proteins (antigens) produced by cancer cells could be a very useful diagnostic tool. A computer will scan the slide and produce an image indicating presence and expression level of a gene. Increase number of areas of one color means the presence of cancer proteins.

Procedure 1. Use color pencils to color antigen/antibody binding locations on the

microarray grid provided. 2. Cancer cell proteins are marked with red fluorescent dye and bind to

antibodies in the following cells of the microarray: • A-1, A-4, A-7, B-3, B-7, B-8, C-2, C-3, C-5, D-1, D-2, D-7, D-8

3. Healthy cell proteins are marked green fluorescent dye and bind to antibodies in the following cells of the microarray: • A-3, A5, B-1, B-2, C-1, C-7, D-4

4. Yellow fluorescent dye shows where both cancer and healthy cell proteins bind. • A-2, A-6, A-8, B-4, B-6, C-6, C-8, D-5

5. Black areas represent absence of both types of proteins

Microarray Student Worksheet Name _____________________________________________

1. What is a microarray? 2. A patient’s microarray shows a high density or number of red areas, what

conclusion can you make?

1 2 3 4 5 6 7 8

A

B

C

D

Websites/References MedMyst- Interactive website, Teacher Resources (MedMyst Magazines available online) http://medmyst.rice.edu/ Genetic Science Learning Center – How Do Viruses Recognize a Target Cell http://gslc.genetics.utah.edu/ Detectives in the Classroom - Disease Detectives http://www.montclair.edu/Detectives/ Immune System Defending Our Bodies Nobel Prize Organization –games and teacher resources http://nobelprize.org/educational_games/medicine/immunity/ Biology Project - Immunology – History of Vaccines http://www.biology.arizona.edu/ DNA Chip Explanation and animation http://www.sumanasinc.com/webcontent/anisamples/majorsbiology/dnachips.html CDC –EXCITE – Disease Detectives Event Updated February 4, 2005 http://www.cdc.gov/excite/disease_detectives/index.htm Heaphy Shawn, “Virus Structure” http://www.tulane.edu/~dmsander/WWW/224/Structure224.html A Science Primer http://www.ncbi.nlm.nih.gov/About/primer/microarrays.html