CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design.

This course will introduce the student to the major concepts of biotechnology. The student will discuss genetic engineering of plants and animals and the current major medical, environmental, and agricultural applications of each. There are also a variety of topics that this course will cover after ranging from nanobiotechnology to environmental biotechnology. Upon successful completion of this course, the student will be able to: identify and describe the fields of biotechnology; compare and contrast forward and reverse genetics and the way they influence biodiversity; compare and contrast systemic studies of the genome, transcriptome, and proteome; explain how genome projects are performed, and discuss the completion and the information processing in these projects; describe and explain the principles of existing gene therapies; design strategies that support genetic counseling; explain and analyze DNA fingerprints, and compare DNA fingerprints to non-DNA biometrics; describe and compare bioremediation technologies in air, water, and soil; design strategies for generating genetically modified organisms, and discuss ethical concerns; discuss emerging fields in biotechnology. (Biology 403)

Covers cells and tissues of the immune system, lymphocyte development, the structure and function of antigen receptors, the cell biology of antigen processing and presentation including molecular structure and assembly of MHC molecules, lymphocyte activation, the biology of cytokines, leukocyte-endothelial interactions, and the pathogenesis of immunologically mediated diseases. Consists of lectures and tutorials in which clinical cases are discussed with faculty tutors. Details of the case covering a number of immunological issues in the context of disease are posted on a student Web site.

Covers cells and tissues of the immune system, lymphocyte development, the structure and function of antigen receptors, the cell biology of antigen processing and presentation including molecular structure and assembly of MHC molecules, lymphocyte activation, the biology of cytokines, leukocyte-endothelial interactions, and the pathogenesis of immunologically mediated diseases. Consists of lectures and tutorials in which clinical cases are discussed with faculty tutors. Details of the case covering a number of immunological issues in the context of disease are posted on a student Web site.

This Web site, created to complement the museum's Epidemic! exhibit, provides an in-depth look at the world of infectious disease. It includes the following sections: Environmental Change looks at how a season of heavy snow and rainfall led to an outbreak of hantavirus in the Four Corners region of the southwestern U.S., and at the different habitat needs of microbes. Long-Term Changes examines how changes to the prehistoric landscape and in our living patterns since the development of agriculture, have made diseases like malaria a major threat in tropical regions. Microbes and Others looks at the three major groups of microbes (viruses, bacteria, and protozoa) and the great variety within each group. Diagnostics and Testing examines how the link between microbes and disease was first made and the many medical advances since then. Infection covers how microbes enter the body and the body's built-in defense mechanisms. Outbreak looks at the different routes microbes use to spread through a population and the work of epidemiologists. Epidemic/Pandemic explores the factors that determine whether an outbreak will become an epidemic or a pandemic. Resources is a list, organized by topic and specific disease, of more than 250 Web sites. Glossary includes nearly 200 infectious disease terms, from AIDS to WHO.

Seminar covering topics of current interest in biology. Includes reading and analysis of research papers and student presentations. Contact Biology Education Office for topics.

The course covers basic concepts of biomedical engineering and their connection with the spectrum of human activity. It serves as an introduction to the fundamental science and engineering on which biomedical engineering is based. Case studies of drugs and medical products illustrate the product development-product testing cycle, patent protection, and FDA approval. It is designed for science and non-science majors.

In this episode of MicrobeWorld Video we ask some leading researchers, education specialists, and public health officials about the state of HIV/AIDS education in America and ideas they have to support the teaching of microbial evolution using the latest HIV/AIDS research all while instilling innovative prevention strategies. Filmed at a forum for educators on February, 11, 2008 at the Koshland Science Museum in Washington, D.C. and at San Diego State University, this episode features the following experts:Roland Wolkowicz, Ph.D., Assistant Professor, Department of Biology, San Diego State University, whose research focus is on the use of random peptide libraries and other chemical genetics approaches for the study of viral pathogenesis and the search of antiviral factors in HIV1 and HCV. Shannon Lee Hader, M.D., MPH, Director of the HIV/AIDS Administration for Washington, D.C., an epidemiologist and public health physician who has worked with HIV-infected children and adults in Brazil, Jamaica, and Zimbabwe. Anila Asghar, Ph.D., Assistant Professor of Education at Johns Hopkins University, whose research focuses on curriculum development and evolution. Educational resources mentioned within the video can be found online at: Koshland Science Museum http://koshlandscience.org/teachers/webquest.jsp NIH Curriculum Guide http://science.education.nih.gov/supplements/nih1/Diseases/default.htm Howard Hughes Medical Institute http://www.hhmi.org/biointeractive/ Please feel free to embed or distribute this video.

In a clinical setting, it is often necessary to examine the cells of the immune system, especially in patients with immune deficiencies. One method takes advantage of the fact that lymphocytes will bind foreign red blood cells to form rosettes which can be enumerated microscopically. Specifically, the Ox49/50 antigen on the rat T lymphocyte surface has been identified as the probable binding site of the sheep rbcs. In this exercise, we will show that the number of antigen-binding lymphocytes increases after immunization.

Immune Attacks content is geared for senior level high school biology and first year university biology. To play the game, users control a microscopic robot and navigate through a first-person 3D body, completing a series of stepwise missions to detect a bacterial infection and activate the appropriate defensive immune cells. These stepwise missions follow the actual biological process that occurs during an infection and how immune cells are stimulated to kill the bacteria.

This course is an advanced undergraduate seminar based upon discussions and critical analysis of primary literature in the field of immunology. Every infection consists of a battle between the invading pathogen and the resisting host. To be successful, a pathogen must escape the many defenses of the host immune system until it can replicate and spread to another host. A pathogen must prevent one of three stages of immune function: detection, activation, or effector function. Examples of disease specific immune evasion and the mechanisms used by pathogens to prevail over their host's immune systems are discussed. What these host-pathogen interactions reveal about the normal function of the immune system and about basic cell biological processes, such as protein maturation and degradation, are also considered.

This exercise presents the concepts of immunology from biochemical, evolutionary, and adaptive standpoints. While all organisms have developed some mechanism of defense against external agents, vertebrates have the most complex immune responses capable of exquisite specificity and long duration. This affords a distinct advantage to species with a relatively long life span and low fecundity. This exercise explores the relationship between immunologic stimulation of the host with foreign antigens and antibody production. The principles of species specificity, primary and secondary immune responses, cross-reactivity, and complement-mediated cell lysis are demonstrated using the red cell agglutination assay. Agglutination occurs when a single antibody molecule binds simultaneously to a surface antigen on two red cells a principle used daily in the diagnosis of viral infections and blood groups incompatibility in humans and other animals.

Immunology is the study of our immune system, a highly sophisticated system that defends us against all disease-causing invaders by identifying and neutralizing such threats. As with any system in our body, when the immune system malfunctions, disease can result. In this course the student will take a look at what happens when an inappropriate immune response takes place. (Biology 407)

General Learning Objectives for Immunology

1. To understand the structural and genetic basis of diversity and specificity of immunoglobulins and T cell receptors.
2. To understand the utility of antibodies in many clinical tests for proteins, hormones, etc.
3. To understand the events that hallmark the antigen-independent and antigen-dependent phases of B cell differentiation.
4. To understand the diversity of MHC molecules, and how that diversity differs from immunoglobulin and T cell receptor diversity.
5. To understand how MHC molecules present antigens, and how antigens are processed to before presentation.
6. To understand positive and negative T cell selection in the thymus, and how those events influence the final T cell repertoire.
7. To understand the requirements for T cell activation by antigen, and how the nature of the antigen presenting cell influences the outcome of antigen recognition.
8. To understand that transplantation reactions are mainly the result of T cell recognition of allogeneic MHC molecules.
9. To understand how the effector functions of antibodies, T cells, macrophages, neutrophils, and NK cells can eliminate pathogens or lead to pathology.
10. To understand the function of CD4+ Th1, CD4+ Th2 cells, and CD8+ cytotoxic T cells in the immune response.
11. To appreciate the multiple roles of cytokines and chemokines in mediating interactions between leukocytes and other leukocytes and between leukocytes and other types of cells.
12. To understand how cells in both innate and acquired immunity can encounter a pathogen first at one site, and then fight an infection at some distal site.

Cell biology, immunology, neurobiology, and an exploration into current research in cancer, genomics, and molecular medicine.

The MIT Biology Department core courses, 7.012, 7.013, and 7.014, all cover the same core material, which includes the fundamental principles of biochemistry, genetics, molecular biology, and cell biology. Biological function at the molecular level is particularly emphasized and covers the structure and regulation of genes, as well as, the structure and synthesis of proteins, how these molecules are integrated into cells, and how these cells are integrated into multicellular systems and organisms. In addition, each version of the subject has its own distinctive material.

The MIT Biology Department core courses, 7.012, 7.013, and 7.014, all cover the same core material, which includes the fundamental principles of biochemistry, genetics, molecular biology, and cell biology. Biological function at the molecular level is particularly emphasized and covers the structure and regulation of genes, as well as, the structure and synthesis of proteins, how these molecules are integrated into cells, and how these cells are integrated into multicellular systems and organisms. In addition, each version of the subject has its own distinctive material. 7.014 focuses on the application of the fundamental principles toward an understanding of human biology. Topics include genetics, cell biology, molecular biology, disease (infectious agents, inherited diseases and cancer), developmental biology, neurobiology and evolution.

The MIT Biology Department core courses, 7.012, 7.013, and 7.014, all cover the same core material, which includes the fundamental principles of biochemistry, genetics, molecular biology, and cell biology. Biological function at the molecular level is particularly emphasized and covers the structure and regulation of genes, as well as, the structure and synthesis of proteins, how these molecules are integrated into cells, and how these cells are integrated into multicellular systems and organisms. In addition, each version of the subject has its own distinctive material. 7.014 focuses on the application of these fundamental principles, toward an understanding of microorganisms as geochemical agents responsible for the evolution and renewal of the biosphere and of their role in human health and disease.

The MIT Biology Department core courses, 7.012, 7.013, and 7.014, all cover the same core material, which includes the fundamental principles of biochemistry, genetics, molecular biology, and cell biology. Biological function at the molecular level is particularly emphasized and covers the structure and regulation of genes, as well as, the structure and synthesis of proteins, how these molecules are integrated into cells, and how these cells are integrated into multicellular systems and organisms. In addition, each version of the subject has its own distinctive material.7.014 focuses on the application of the fundamental principles toward an understanding of human biology. Topics include genetics, cell biology, molecular biology, disease (infectious agents, inherited diseases and cancer), developmental biology, neurobiology and evolution.