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Tetanus

Immunity


Developed by

Parker A. Small, J r, MD
J . Edwin Blalock, PhD
Department of Immunology and
Medical Microbiology
College of Medicine
University of Florida
Gainesville, Florida

Susan M. J ohnson, PhD
College of Pharmacy
University of Florida
Gainesville, Florida















BOOK D










Note to Students The fundamental purpose of all activities in the health-care
professions is to help other people. Like all behavior, helping behavior becomes
more effective and natural with practice. This workbook enables you to practice
by helping your fellow students to learn basic science. Your skill at helping your
fellow students should relate to your ability to help your patients in the future.
This is a Patient-Oriented Problem-Solving ("POPS") workbook designed for four
students. Before beginning this session, you should have (a) reviewed your
immunology lectures given prior to this, (b) taken the pretest, and (c) reviewed
the topics listed at the end of the pretest. Now, each of you should take one of
the four (A, B, C or D) color-coded booklets and follow the directions in it. If your
group has only three students, one of you should take two booklets. Leave the
remainder of the workbook for others in your group until you meet for discussion.

Bring at least one laptop for your group; you will need it for accessing parts of
this exercise.
Tetanus Immunity

Introduction to the Patient-Oriented Problem-Solving
(POPS) System

This is a Patient-Oriented Problem-Solving activity. The purposes are

1. To help you learn how to apply your basic science knowledge to the solution of clinical
problems

2. To help you learn how to better use sources (i.e., textbooks and peers) that will be available to
you throughout your career

This activity consists of four phases. First, you will review the attached set of objectives, do
background reading on the topics to be covered, and complete the pretest on your own. In the
second phase, you will join three other students and review the pretest answers in an "open-book"
discussion. In the third phase, the group will solve patient-oriented problems. Information exchange
and group interaction are keys to the success of this phase. This process will allow you to teach
your fellow students and, at the same time, learn from them. Finally, you will take a posttest,
individually, which will enable you to assess your progress.
Tetanus Immunity

Introduction

This clinical Simulation deals with tetanus, a life-threatening infection. Tetanus is caused by an
exotoxin synthesized by the bacterium Clostridium tetani. The toxin is released after a wound is
infected by this bacterium. This toxin causes muscle spasm, which may lead to death if not treated
correctly. Spasms of the masseter muscles have led to the name lockjaw. Every time a patient with
a wound is examined, the physician must determine the appropriate immunization for the
prevention of tetanus. This simulation will help you understand the different approaches to the
prevention of tetanus as well as the indications for each approach. The immunologic concepts
addressed in this problem are fundamental to the understanding of many other diseases.

When you have completed this activity you should be able to

1) define and give several examples of immunity.

2) compare and contrast the terms antigen and antibody.

3) differentiate between acti ve and passi ve immunization and be able to give examples of each.

4) compare and contrast the primary and secondary (anamnestic) immune responses in terms of
their time course and magnitude.

5) state differences between acquired and innate immunity, as well as between specific and
nonspecific immunity.

6) state which cell types are involved with cell-mediated and antibody-mediated immunity.

7) compare tetanus toxin and tetanus toxoid relative to toxicity and immunogenicity.

8) select the appropriate immunization for a patient with a wound, given his past medical history.






When you have become familiar with the objectives, complete the pretest on the next page.


Tetanus Immunity

Pretest

Instructions: Please mark your answers to the following questions on this exam to facilitate
later discussion and review. If your instructor has provided a separate answer form, please
be sure to fill in the identification section; then answer the questions both on the form and
on this exam.
Choose the one correct or most appropriate answer. If you do not know an answer, leave it
blank. Do not guess. Health professionals who think they know something, but don't, can do
real harm. Those who know they don't know something can get help.
Don't be upset if you don't know all the answers. The purpose of the pretest and objecti ves
is to alert you to important concepts. The posttest will be similar to the pretest.

1. J udging from the following graph, how many days does it take to detect antibody in the serum
after a primary and a secondary immunization, respectively? The arrows above "Ag" indicate
the times when antigen injections were given to the patient. The term "mg% Antibody" refers
to the number of milligrams of antibody detected in 100 mL of the patient's serum.





(A) 15 and 10
(B) 10 and 15
(C) 10 and 4
(D) 4 and 10
(E) 3 and 3

Tetanus Immunity
Pretest (ctd.)

2. A car accident victim, who is 12 years old, suffered severe lacerations when she was thrown
clear of the vehicle and has just been brought into the hospital. Her parents stated that she
has not had previous immunization against tetanus. To provide protection against the
possibility of tetanus now and in the future, which of the following is the preferred method of
treatment?

(A) A mixture of tetanus toxoid and tetanus antitoxin as one injection, thereby causing less
pain and producing an adjuvant effect
(B) A tetanus antitoxin injection this visit
(C) A tetanus toxoid injection this visit, with an injection of tetanus antitoxin approximately
three weeks later
(D) Separate injections of tetanus toxoid and tetanus antitoxin in different sites on this visit
to ensure active and passive immunization
(E) None of the above

3. In which of the following pairs will the first substance function as an antigen to elicit a potentially
beneficial immune response and the second substance function as an antigen to produce a potentially
dangerous immune response? (Homologous means "made in the same species" [e.g., humans],
whereas heterologous means "made in a different species" [e.g., horses].)

(A) Toxin and toxoid
(B) Toxoid and toxin
(C) Heterologous antiserum and toxin
(D) Homologous antiserum and heterologous antiserum
(E) Toxoid and heterologous antiserum

4. Tetanus toxoid
(A) is an active toxin.
(B) cannot react with antibody to tetanus toxin.
(C) retains antigenicity for immunization purposes.
(D) is chemically identical to tetanus toxin.
(E) stimulates antibody formation to the organism Clostridium tetani.

5. You have decided your patient needs passive immunization for snake bite, but the only
available antisera are from horses. The following important aspect must be taken into account
before administering the serum:
(A) The patient's blood type
(B) The patient's history of passive immunizations
(C) The patient's history of active immunizations
(D) The snake's blood type
(E) The half-life of the passive antibody, which is such that passive immunization should be
repeated every six to eight months if protection is to be maintained

6. A typical secondary (anamnestic) response is characterized by a change in antibody level.
The type of change differs from a primary response, since it is usually
(A) neither higher nor faster, but is more prolonged.
(B) higher, but no sooner.
(C) sooner, but no higher.
(D) sooner, higher, and more prolonged.
(E) sooner and higher, but less prolonged.
Tetanus Immunity
Pretest (ctd.)

7. The passive immunity to tetanus provided by antisera is
(A) nonspecific and innate.
(B) acquired and antibody-mediated.
(C) innate and specific.
(D) acquired and cell-mediated.
(E) none of the above.

8. The immunity to many bacteria such as streptococci and staphylococci provided by intact
skin(i.e., bacteria on your skin will not usually produce disease) is
(A) specific and innate.
(B) acquired and antibody-mediated.
(C) innate and nonspecific.
(D) acquired and cell-mediated.
(E) innate and antibody-mediated.

9. Serum sickness can be a serious problem with which of the following procedures?
(A) Active immunization with tetanus toxin
(B) Active immunization with tetanus toxoid
(C) Passive immunization against tetanus using heterologous antiserum
(D) Passive immunization against tetanus using homologous antiserum
(E) None of the above

10. A 25-year-old man who recently sustained a severe, dirty laceration of his right foot is brought
to you. He has never received any immunizations. At age 7 he had tetanus. He was treated
with penicillin and tetanus immune globulin (human). Fortunately, he recovered. Which of the
following would you do to prevent tetanus now?
(A) Immunize with tetanus toxoid, which will stimulate a secondary antibody response.
(B) Administer tetanus immune globulin (human) to passively immunize the patient.
(C) Administer tetanus immune globulin (human) in addition to tetanus toxoid, because you
cannot depend on a secondary immune response after 18 years.
(D) Administer tetanus immune globulin (human) plus tetanus toxoid, because the patient
has absolutely no immunity to tetanus.
(E) Give no injection, because the residual immunity from the clinical tetanus will protect the
patient.

When you have completed the pretest, consult your study materials. Try to identify the
correct answers and understand the concepts that make them correct. The list of objectives
may be used as a guideline for your studies. When your group meets, you will have the
responsibility of explaining some of the correct pretest answers to the others. Please bring
your textbook and pretest to the group meeting.
Tetanus Immunity

Pretest Correct Answers

You have the answers to the ten pretest questions. First, study the answers in your booklet
and then EXPLAIN them to your group. Please don't just read them to your classmates, and
don't let your classmates read their answers to you. In explaining something to another
person, most people gain a better understanding of it and often transmit a better
understanding. The pretest discussion and patient-oriented problem-solving parts of this activity
are "open book" Be sure to refer to textbooks, notes, and other written resources whenever
questions arise.

3. The correct answer is E. Toxoid will stimulate the production of antitoxin, which will be
protective. Heterologous antiserum will stimulate the production of antibody to the foreign
protein; this response can lead to serum sickness. Toxin is lethal at doses below those
required to stimulate antibody formation, so it will not produce an immune response but
obviously will produce a very harmful nonimmune response (i.e., toxin will kill the first time a
person is exposed to it).

There is a very important implication to the fact that it takes more toxin to stimulate the
antibody production than to kill a person; unlike most diseases, someone recovering from
tetanus (a very rare event if untreated) will not have developed immunity.

Homologous antiserum may, on some occasions, elicit antibody responses in certain situations
(different allotypes or idiotypes). but these are neither beneficial nor dangerous.

7. The correct answer is C. Immunity means lack of susceptibility to a disease. Immunity can be innate or
acquired, as shown in the diagram below. Innate immunity is present from birth and is independent of
the life experiences of the person, whereas acquired immunity arises only after an infection or
immunization and hence is acquired during life. Acquired immunity is specific for the infecting organism
or immunizing antigen. Thus, a chickenpox infection protects specifically against reinfection by
chickenpox virus but does not protect against measles virus infection. Innate immunity is usually
nonspecific. For example, stomach acid destroys many different bacteria and viruses in food and thereby
protects us from infection nonspecifically. Lysozyme in tears digest the cell wall of many bacteria and in
so doing nonspecifically prevent conjunctivitis.

IMMUNITY
INNATE ACQUIRED
(USUALLY NON-SPECIFIC) (USUALLY SPECIFIC)
ACTIVE PASSIVE ACTIVE ADOPTIVE
ANTIBODY- CELL-
MEDIATED MEDIATED


Specific acquired immunity is further subdivided into "antibody-mediated" or "cell-mediated," depending on
whether antibody alone provides the protection or whether T-lymphocytes alone provide the protection. Do
not be confused by the fact that antibody is synthesized in cells (B-lymphocytes); the origin of the molecules
is not relevant to how protection is provided.
Tetanus Immunity

9. One injection of a heterologous serum, such as horse serum, may stimulate production of antibody to
the foreign proteins. The foreign proteins may persist in the body long enough (seven to 14 days) to
react with the newly formed antibody. Antibody-antigen complexes form in the blood and are deposited
in various tissues, producing pathologic changes in those tissues. More specifically, deposition of
immune complexes in the renal glomeruli leads to glomerulonephritis, and deposition in synovial
membranes leads to arthritis. This process produces the disease called serum sickness. C is therefore
correct.















Remainder of the exercise would be done when you meet as a group.

Discuss the pretest answers with the members of your group.

When your group has finished discussing the pretest, you should read the " Instructions for the
Clinical Problem" on the next page of your booklet.
Tetanus Immunity

Instructions for the Clinical Problem

The purpose of this exercise is to allow you to apply your knowledge of active Vs passive
immunization and primary Vs secondary (or anamnestic) immune response to a common medical
problem.

Each of the four group members has a different case history First, deal with your own patient. After
reading your patient's case history, decide the therapy you would use, the reasons for the choice,
and the consequences of alternative therapy. Next, fill out your answer sheet concerning your
patient. After everybody has finished his/her problem, the group member with the first patient
should present that case history to the other three group members and allow them time to
individually decide therapy, the reasons for their choice, and the consequences of alternative
therapy. They should then fill out their answer sheets for that patient (i.e., commit themselves to
therapy before the group discussion). The group member who has the first patient should then
present his/her choice of therapy to the group and defend it. Members who disagree with this
choice, the reasons for it, or consequences of it should present their ideas and defend them. After
discussion of the first patient is completed, compare your answers with those on the correct answer
sheet for each patient.

This process will then be repeated for the other three cases. Patients should be presented in
numerical order. At first glance, the patients' cases seem repetitious, but there are subtle and
important differences!

Remember, this is an "open-book" activity, and you should consult your textbooks about any point
you don't understand.
Tetanus Immunity

Fourth Patient: Alice Wipple

A 35-year-old migrant worker arrives at your office with a three-inch jagged wound on her head.
She was hit with a brick. Ten years ago she fell off a tractor while tilling a field and received a
six-inch laceration of her left thigh. At that time, she was given tetanus antitoxin (equine) because
she had never been immunized against tetanus. She and her fellow migrant workers left town
before her physician could immunize her with tetanus toxoid. What do you do to prevent tetanus?
Indicate your therapy on the Tetanus Immunity Clinical Problem Answer Sheet (instructions on the
next page and treatment options for Alice on the bottom of the following page).
Tetanus Immunity

Clinical Problem Answer Sheet

Check the box(es) that indicate(s) the preferred therapy for each patient. Then briefly write the
reasons for your choice in the space provided. Finally, describe the consequences of each of the
other therapies in the space provided under each therapy. Commit yourself in writing before the
discussion begins. The answer sheet will not be collected.

Joe Alsop (First Patient)

1. Give tetanus toxin.

2. Give tetanus toxoid.

3. Give tetanus antitoxin (equine).

4. Give tetanus immune globulin (human).

Lester Williams (Second Patient)

1. Give tetanus toxin.

2. Give tetanus toxoid.

3. Give tetanus antitoxin (equine).

4. Give tetanus immune globulin (human).

Tommy Criton (Third Patient)

1. Give tetanus toxin.

2. Give tetanus toxoid.

3. Give tetanus antitoxin (equine).

4. Give tetanus immune globulin (human).

Alice Wipple (Fourth Patient)

1. Give tetanus toxin.

2. Give tetanus toxoid.

3. Give tetanus antitoxin (equine).

4. Give tetanus immune globulin (human).

Tetanus Immunity

Correct Answer for Joe Alsop (Patient #1)

You will be given the answers when you have discussed the case with the other members of your
group and compared your answers. Ask for a password for accessing the answer from your
facilitator.

Tetanus Immunity

Summary of Major Concepts of Tetanus Immunity and Boosters

Primary Immunization should be given to everybody to prevent tetanus. The precise ages at which
diphtheria, pertussis, and tetanus (DPT) shots are given are listed in any pediatrics textbook and
are best learned when you are studying pediatrics. In general, however, children receive three
doses in the first six months of life and boosters at ages 1 and 5. These injections stimulate
lymphocytes to produce antibody. These IgG antibody molecules have a half-life of three weeks,
just like passively administered human IgG, but the "antibody factories" continue to turn out more
antibody so it persists in high enough concentrations to provide protection for five to ten years (see
Table 1). The injections also produce memory lymphocytes that, unlike the antibody, persist
throughout life and are ready to rapidly produce antibody the next time the antigen, tetanus toxoid,
is administered.

Booster immunization with tetanus toxoid can lead to the production of adequate amounts of
protective antibody within three to five days (even when there is little or no circulating antibody) if
there are memory lymphocytes primed by a previous tetanus toxoid injection. Remember: Previous
disease will not stimulate the immune system in patients with tetanus, but it does in patients with
most other infectious diseases.

Passive, immunization with tetanus immune globulin (human) will provide instantaneous immunity,
but antibodies disappear with a half-life of three weeks and memory lymphocytes are not produced
to help the next time. It should never be the sole therapy in normal patients. Consult Table 1 for the
appropriate treatment. Tetanus antitoxin (equine) should be used only when human antiserum is
not available and passive immunization is imperative. When tetanus immune globulin (human) or
tetanus antitoxin (equine) and tetanus toxoid are given at the same time, each should always be
injected at different sites.

TABLE 1. Guide to tetanus prophylaxis in wound management
(Modified from Morbidity and Mortality Weekly Report 30:392-396, 401-407, 1981.)

Td =tetanus toxoid TIG =tetanus immune globulin (human)

History of Clean, minor
All other
tetanus wounds
wounds
immunization
(doses) Td TIG Td TIG

Uncertain Yes No Yes Yes
0-1 Yes No Yes Yes
2 Yes No Yes No*
3 or more No No No No
* Unless wound more than 24 hours old
Unless more than 10 years since last dose
Unless more than 5 years since last dose

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