Topic 2 Cells and Organs of the Immune System

Topic 2 Cells and Organs of the Immune System

Introduction

In this section, we examine the structure of the major lymphoid organs of the body. In these organs the cellular interactions that lead to the immune response occur. Carried within the blood and lymph and populating the various organs are a variety of white blood cells, or leukocytes, that participate in development of the immune response. You will be introduced to various cells of the immune system and learn about the process of hematopoiesis. The organs in which lymphocytes develop are called primary lymphoid organs. These include the thymus, the bursa of Fabricius, and some Peyer’s patches in the intestine. The organs in which mature lymphocytes reside and in which they encounter antigen are called secondary lymphoid organs. The secondary lymphoid organs include lymph nodes, spleen, tonsils and lymphoid tissue in the intestine, the lungs, and other body surfaces. We will learn how the structure of lymphoid organs relates to their function. This section offers a strong basis for further studies in immunology. In order to understand cellular interactions involved in immune responses, it is crucial that you know the structure and developmental origins of the immune system. This part of the lesson examines the architecture and the developmental biology of the immune system.

Objectives

On completion of this section and the required reading, you should be able to:

n describe the life history of leukocytes;

n construct a table to compare and contrast B Lymphocytes and T lymphocytes with respect to structures, roles in immunity, origin, maturation and location

n differentiate among helper T cells, Cytotoxic T cells and regulatory T cells

n describe macrophages in terms of their origin, location, nomenclature and their role in immunity

n describe the role and characteristics of dendritic cells and NK (Null cells)

n describe the role of NK cells (Null cells) in Immunity

n locate the different types of lymphoid tissues in the body

n differentiate between the following:

n draw and label diagrams of the structure of the thymus, lymph node, and spleen

n The immune system is a network of cells, tissues and organs. The organs of the immune system provide the appropriate environment for the proliferation, maturation and differentiation of the cells that provide the immune response.

n The cells of the immune system have individual identifiable marker molecules and receptors that are related to the role each cell plays in the immune response.

n All immunologically related cells arise from stem cell precursors in the bone marrow.

Below is a case study describing a patient with immunological disorder. This example is designed to put the basic immunological mechanism into a clinical perspective. In most textbooks of basic science it may seem inappropriate and difficult to use clinical case studies as illustrative material. However, immunology is relevant and indeed central to many disease processes in both animals and humans, thus supporting this approach. We hope that case studies will provide you with a further perspective on the wide variety of immune-related diseases since most basic immunological mechanisms are already described in your textbook.

This and the example that follows have been designed to help you see the significance of the thymus and the consequences of its lack in humans and animals.

David was born at term after an uneventful pregnancy. At birth he was cyanosed and required oxygen from the first few minutes of life. He was born with abnormal external features including micrognathia, large slanted eyes, and low set prominent ears with notched pinnae. Within the first 36 hours of life he had episodes of muscle tetany. His parathyroid hormone assay was negative. Chromosomal analysis by in situ hybridization of gene probes demonstrated a sub-microscopic deletion of the proximal long arm of chromosome 22. A diagnosis of DiGeorge syndrome was made and David’s management was continued in a special care baby unit. The tetanic episodes were initially treated with intravenous calcium gluconate and were followed up with a low phosphorus diet, calcium supplements, and high doses of vitamin D.

At two months David had failed to thrive and had persistent candidiasis and diarrhoea. A decision was taken to perform a fetal thymus transplant as soon as a donor became available. The thymus was obtained form a 12-week old fetus, which was removed as an ectopic tubal pregnancy. The tissue was dissected under sterile conditions and cut into several pieces before being transplanted peritoneally within two hours. A white cell count taken some weeks later showed an increase in cell numbers, but at three months he developed Pneumocystis carrinii pneumonia, which proved fatal. An autopsy examination confirmed an absent thymus and right sided aortic arch.

Case Studies in Immunology. I. M. Roitt, J. B. Brostoff, D. K. Male, A. Gray. Mosby-Wolfe Ed. 1994 Times Mirror International Publishers Limited

Ordinarily, an individual is born with a full complement of organs and tissues. Assuming that there are no associated organic, or other, disorders this individual can be expected to display all normal physiological functions. Nevertheless, from time to time, individuals are born displaying one defect or another in function. These are sometimes traced to genetic alterations or deficiencies. One instance of a genetic defect with far-reaching consequences for immunological function has emerged. This is the genetically defective nude, or hairless, mouse. They are characterized by: absence of a thymus, failure of hair growth and endocrine abnormalities. The nude mouse provides a natural experiment that mimics conditions seen by neonatal thymectomy. Since full immunological competence does not exists at birth (at least not in mice), neonatal thymectomy leads to impairment of immune function because of a failure of the T cell component of the immune system to function. A similar situation is expected in nude mice. Nonetheless, nude mice have a T cell population, yet these cells fail to differentiate into functionally active, mature T cells. Moreover, these mice possess a B cell component and display effective humoral immunity. Accordingly, nude mice provide an excellent model for studying T cell function. Studies have found that some of the functions of the thymus can be restored to nude, or thymectomized, mice by the administration of extracts of thymus tissue, which consists of hormones and thymic factors. This enables investigators to explore factors that are involved in the regulation of T cell commitment and differentiation. In addition, nude mice can be used to propagate certain human cancer cells that otherwise would be destroyed readily in normal mice. Thus the unique deficiencies displayed by athymic mice provide a convenient natural laboratory in which to explore several aspects of immunological function. Of particular significance are questions of B/T cell dichotomy and environmental influences on the maturation and differentiation of T cell.

Fundamental Immunology. 2^nd Edition. R. M. Coleman, M. F. Lombard, R.E. Sicard. Wm. C. Brown Publishers, 1992

Review questions at the end of the Chapter 3. The answers with explanations are available at the end of the textbook. Before reviewing answers, take the time to complete the review questions.

2. Multiple Choice Questions. (Answers can be found in the separate Answer Key.)

2. Macrophages can be cytotoxic for other target cells as a result of the release of

2. Briefly describe the specific roles of helper and cytotoxic T cells in normal immunity. Correlate these roles with CD4+ T cells and CD8+ T cells.

3. Unlike B cells and T cells, macrophages are neither clonally restricted nor antigen specific. Explain.

5. Name four morphological areas of the lymph node and give the cellular composition of each.

Once you have completed the review, take some time and complete the objectives. If you are having trouble with any of the concepts, contact your instructor.

It is important that you get clarification on any of the topics or concepts that you are having difficulty with as soon as they arise. Many of the concepts build on each other so it is vital that you not only keep up with the schedule, but clear up any questions or problems as they arise.

Remember to regularly check your Assignment and Information provided by your instructor for assignments and due dates for completing them.

When you are confident that you can complete the objectives, proceed to the next topic.