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Host Defenses

Ali Sultan,M.D., Ph.D., Course Director
Samar Al Amad, Basic Science Curriculum Coordinator

The Host Defenses course will introduce the principles of general pathology, immunology, microbiology and pharmacology in such a manner that the student can appreciate the individual disciplines, yet also see how they are integrated in the context of disease. Each week the PBL case introduces the theme of the week, which will include topics from the 4 core disciplines. These topics will then be developed and expanded upon by each discipline in lectures, lab and small group discussions.

Pathology is the study of disease. The study of pathology includes: the cause of disease (etiology), the mechanisms by which a causative agent leads to disease (pathogenesis), structural and functional consequences of disease. General pathology, the subject of this course, details the basic reactions of cells and tissues, which are common to all diseases. Each week basic pathological principles will be presented in the context of the PBL case, an overview lecture and histopathology laboratory. The histopathology laboratory exercises expand upon the pathological principles, which are either integral or related to the week’s PBL case. These laboratory exercises are intended to extend the students knowledge of pathology by demonstrating additional examples and by comparing and contrasting the PBL case material to other pathologic conditions. The laboratory exercises will usually not present the PBL case materials, which the students are expected to explore on their own, but will build upon that knowledge base. Microscopic slides and computer images, derived from representative pathologic specimens, will be examined in the context of new clinical scenarios. Students are expected to examine both slides and computer images prior to lab. Active participation is expected.

In this course, the students are expected to acquire and integrate the basic mechanisms and functions of the immune system. They are also expected to understand in principle how the immune system has evolved phylogenetically and evolves ontogenetically in response to infectious agents. Topics presented and/or discussed will encompass the cells, molecules and organs of the immune system. The principles of the innate (natural) and the adaptive (learned) immune response to infections and tumors will be explored. The students will learn the differences between humoral and cellular immune responses, how they are triggered in response to bacterial, viral and tumor antigens, and how they mature and evolve such that effector cells are generated and immune memory is established.

Lectures have been selected to provide a backbone of information. The first three weeks of the course outline the elements and principles of the innate immune system and the maturation of adaptive immunity, via T and B lymphocytes. In the remaining weeks, students are expected to understand the regulation of the immune system, the role of antibodies, cytokines, and effectors T cells in the immune response. The Immunology lectures will provide students with the basic tools to handle immunological issues of the PBL cases.

The microbiology section of the host defenses course is designed to expose students to the basics of bacteriology, mycology and virology in the context of case presentations, lectures and laboratories. In the second year you will build on the foundation that we have established in Host Defenses. This course is biased towards bacteriology. The emphasis on bacteriology is based on several reasons including clinical occurrence, the clinically treatable nature of bacterial infections and the diversity of disease associated with bacterial infections. Virology is presented towards the end of the course with an emphasis on understanding viruses and host interactions. Fungal infections are presented at the very end of the course as a survey of fungal infections. The PBL cases are used to present common types of bacterial or viral infections in a background of human disease. The lectures are organized to combine basic science in lecture format followed by a more clinically relevant view of disease cause by bacterial infections. Because of the need to address a broad scope of infectious agents, there will be times when the lecture material will focus on organisms that are distinct from those being presented in the PBL cases. The laboratories will use additional cases to augment those presented in the PBL, and will involve wet lab exercises to complement the lectures and the PBL case. The laboratory sessions in microbiology are primarily oriented around bacterial pathogens involved in human disease. The labs are an opportunity to learn basic bacteriology. The reading material assigned each week complements lecture, PBL, and laboratory. During each laboratory we will be working toward the characterization of unknown samples identifying the presumptive pathogen responsible for the disease presented in each week’s case(s). The cases presented are intended to expand the students’ exposure to bacterial pathogens while complementing the week’s PBL case. Before lab starts, it is expected that each student will have studied the cases, the lab material for the week and read relevant text. Lab will begin by a student presentation of the unknown cases followed by a discussion of the lab strategy for characterization of the target pathogens. Each case has a number of study questions that are relevant to the cases as well as the general pathogens associated with the cases. Students should arrive at independent answers to these questions that can then be discussed in the lab.

The Pharmacology component is part of the Host Defense course for two reasons. First, just as the immune system constitutes the body's main internal host defense system, drugs constitute our external host defense system for responding to disease and other disturbances of normal function. Second, the mechanisms the body has in place to limit the effects of drugs and their potential toxicities, i.e. the development of specific drug metabolizing enzymes, constitute a parallel host defense system to the immune system, for protecting the body against foreign chemicals. Our goal for the pharmacology component of this course is to teach you the fundamental principles of pharmacology upon which all drug prescribing is based. We hope to provide you with a framework that you can apply in making prescribing decisions. There are thousands of drugs available for drug bacterial infections. Because of the need to address a broad scope of infectious agents, there will be times when the lecture material will focus on organisms that are distinct from those being presented in the PBL cases. The laboratories will use additional cases to augment those presented in the PBL, and treatment, and drug companies are constantly bombarding physicians with new drugs with marketing claims of superiority to older drugs. If you are to be a good physician you will need to know not only which drugs to use but also how to distinguish drugs and to evaluate new marketing claims. These daunting tasks can be made much simpler if you have in your mind a group of rational principles that you can apply to evaluating drugs and make distinctions among them.

Pharmacology is governed by a group of rational principles. If you master them you can develop a systematic approach to acquiring the key information you need to have about any drug. One of the main principles is that every drug can become a toxic agent depending on dose. The following statement of Paracelsus (1493-1541) is as true today as in his time: “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy”. Each lecture in the pharmacology section of this course will be devoted to one or more general principles: i.e. Dose-response, selective toxicity, drug metabolism, induction and inhibition, pharmacokinetics, tolerance, maternal-fetal interactions and principles of antineoplastic therapy. Small group conferences will reinforce your understanding of these principles using cases and problem solving.

Our main goal in this course is to teach you principles of pharmacology and not the specific pharmacology of any particular drugs or drug classes. That will take place in other courses. However, we will use the PBL cases to apply the principles of pharmacology to two specific drugs per case. Each of the drugs selected will be a prototype of a major class of medications. Also, in lectures and conferences we will try to use specific examples of drugs that relate to other aspects of the course or to the PBLs. Therefore by the end of the course you can expect to have also learned some specific drug-related pharmacology along the way. Below is an outline of the kind of framework required for thoughtful drug prescribing, which you should apply to your evaluation of specific drugs in relation to the PBLs.

• Generic name of drug (brand names)
• Pharmacological effects of drug including putative mechanism of therapeutic action
• Pharmacokinetics (drug absorption, distribution, metabolism and excretion)
• Indications for therapeutic use(s)
• Contra-indications
• Adverse effects and overdose toxicity
• Conditions that require modifications of usual therapeutic dose (such as renal failure, old age, etc.) (For the purpose of this course, you are not expected to know the dose itself, only what conditions require modifications of the standard adult dose.)
• Medically important drug interactions

Quizzes will usually be given each week on Sunday (except for holidays). The quizzes will cover the material covered during the previous week including lectures, labs, small group conferences and the drug facts from the PBL cases. The quizzes are meant to serve as a means for both the students and faculty to assess competence.

Your overall evaluation in this course will be derived as follows:

• Knowledge Base Quizzes 55%
• Professional Performance 35%
• PBL
• Lab Reports
• Triple Jump Exam 10%