Professional Documents
Culture Documents
Edit
51
Table of Contents
Introduction
Any course on stem cells must include a section on the hematopoietic system, as it was the
first organ system to provide stem cells for therapeutic medicine. Even in 2011-2012, bone
marrow transplants provide a rich source of stem cells used to treat a variety of cancers,
anemias, AIDS, and sickle cell disease.
In order to appreciate the current and potential utility of hematopoietic stem cells (hSC) in
clinical medicine, one must first understand fundamental principles of immunology. This module
provides a brief review of immunology.
Readers first learning about immunology must always keep in mind one of its most basic tenets:
the immune system is designed to destroy the pathogen/tumor and protect the host. Most of
the information contained in this chapter is based on an excellent textbook called Janeway's
Immunobiology: 8th Edition.
Introduction
How does the
Hematopoietic System
Preserve or Protect the
Host?
What Makes our Immune
System so Effective?
Cellular Origins of
Hematopoietic Cells
Innate and Adaptive
Immunity
How does one Classify a
Specific Cell Type?
Immune Recognition of
Foreign vs. Self
Immune Recognition of
Foreign vs. Self
Human Hematopoietic
Stem Cells (hSC)
Conclusion
Test Your Knowledge
References
Generating specific immune cells that have the capacity to destroy pathogens and
tumors and protect the body against toxins;
Disseminating essential nutrients, such as oxygen, to all tissues of the body. Red
blood cells serve as essential cells that transport oxygen from the lungs to all the tissues of the body;
Repairing tissues and maintaining organ system function. Many organs undergo constant repair and maintenance. In the
blood, for example, neutrophils are short lived and must be cleared each day by various macrophages located in vital organs
in the body;
Enabling clotting, a process in which platelets rapidly form a barrier to prevent blood loss and protect the host from
infection.
Before we go into the details of the various functions of immune cells, it is important to define the term immunity. Historically,
immunity was once exclusively used to connote exemption from taxes. It also has a political definition, as in diplomatic immunity
from legal action. Use of the word immunity in biology represents a collective process by which the organism fights pathogens and
diseases.
Return to Top
1/6
/
/
Origins of immunology
429 BC: Thucydides notices that smallpox survivors do not get re-infected.
900 AD: The Chinese were the first to discover and use a primitive form of vaccination called variolation. By inhaling dried
powders derived from the crusts of smallpox lesions or by placing these samples under the skin, people could become
immunized and not become infected with smallpox.
1774: Benjamin Jesty, a farmer who inoculated his wife with the vaccinia virus obtained from farmer Elford of Chittenhall,
near Yetminster. First record of anyone using vaccinia virus to "protect" against smallpox.
1796: British physician Dr. Edward Jenner discovered vaccination in its modern form and proved to the scientific
community that it worked. Jenner received a cash prize of 30,000 pounds and election to nearly all of the learned
societies throughout Europe.
Was Dr. Jenner really a physician? Did he really prove his theory? How many people did he kill before he got it right?
Source: Silverstein AM (2009). A History of Immunology. 2nd Edition Publisher: Elsevier Science
data:text/html;charset=utf-8,%3Cdiv%20class%3D%22ws-menu-bar%20WikiControls%20WikispacesContent%20WikispacesBs3%22%20style%3D%22max-wid
2/6
/
/
Innate immunity, was first characterized by Elie Metchnikoff, involves cells derived from a myeloid progenitor cell and differentiate
into natural killer (NK) cells, mast cells, dendritic cells, neutrophils, and phagocytes. All these cells exhibit a rapid non-specific
response to either foreign cells or to tumor cells. In addition to the white blood cells involved in innate immunity, various secretions,
in saliva, tears, gut, and mucus, as well as cells comprising the skin, gastrointestinal tract, and pulmonary system create a
protective barrier to prevent entry or survival of pathogens such as viruses and bacteria. The innate system represents the first line of
defense against an intruding pathogen.
Adaptive immunity, first described by Paul Ehrlich, involves cells derived from the lymphoid progenitor cell and differentiate into
various types of lymphocytes that display a high degree of memory and specificity. While the innate system represents the first line
of defense to an intruding pathogen, the adaptive system exhibits slower temporal dynamics. Additionally, the cells of the acquired
immune system possess a high degree of specificity and evokes a more potent response on secondary exposure to a pathogen. In
1908 Drs. Metchnikoff and Ehrlich shared the Nobel Prize for their pioneering work in immunology.
In addition, both types of immunity can be divided into two humoral and cellular components:
a humoral component consists of the complement system composed of about 30 proteins that can become activated (by
cleaving the proteins into various fragments). These activated biological substances can trigger inflammatory response and
assist neutrophils, monocytes, and macrophages with their task as cellular assassins;
a cellular component that involves the various types of myeloid cells described above.
a humoral or B-cell-mediated immune response that leads to production and release of immunoglobulins (IgM, IgG, IgA, IgE,
IgD);
a cellular or T-cell-mediated immune response that results in production of effector T cells that have the capacity to target and
kill either virally infected cells or cancer cells. T-cells can also be generally divided into two types of cells, helper cells (CD 4)
whose role is to regulate the immune response or cytotoxic CD 8 cells that kill specific target cells.
Clinical or genetic defects in cells involved in either innate or acquired immunity may lead to immunodeficiencies, and may result in
autoimmune diseases, allergies, and tumors.
Return to Top
data:text/html;charset=utf-8,%3Cdiv%20class%3D%22ws-menu-bar%20WikiControls%20WikispacesContent%20WikispacesBs3%22%20style%3D%22max-wid
3/6
/
/
Return to Top
data:text/html;charset=utf-8,%3Cdiv%20class%3D%22ws-menu-bar%20WikiControls%20WikispacesContent%20WikispacesBs3%22%20style%3D%22max-wid
4/6
/
/
Return to Top
The capacity of the immune system to recognize a protein or cell as foreign has tremendous implication for infections, cancerous
tumors, and organ transplantation. Infectious pathogens are often easy to recognize as foreign. The problem for the host is to try to
generate an antibody or cellular response to clear the pathogen. In the case of tumors, the situation is slightly more complex since
tumor cells arise from normal cells and will generally express the same MHC cell surface markers as all other cells of the body.
Tumor cells, however, often express unique tumor-specific proteins on their cell surfaces that can at times generate an immune
response. Some tumors, however, produce tumor-specific proteins that are weak antigens and do not generate a strong
immunological response. As most readers know, many cancers and virus-caused diseases such as HIV/AIDS can fool our
immune system in various ways to avoid detection and elimination (as an evolutionary survival mechanism).
data:text/html;charset=utf-8,%3Cdiv%20class%3D%22ws-menu-bar%20WikiControls%20WikispacesContent%20WikispacesBs3%22%20style%3D%22max-wid
5/6
/
/
remains poorly understood. This is because only a small percent of the bone marrow cells are stem cells, and the lack of methods
to segregate HSCs from multipotent progenitors (MPPs) to obtain pure populations for biological and molecular analysis.
Conclusion
The hematopoietic system is an important source for stem cells. Learning how to manipulate these cells can yield new methods to
create a large variety of differentiated cells. These cells could then be applied clinically to treat diverse illnesses and conditions. In
breast cancer, high dose chemotherapy presents an opportunity to eradicate the tumor but is associated with impairing the immune
system. Autologous bone marrow transplantation in which all the stem cells have been purified and separated from cancer cells that
lodge in the marrow may offer new opportunities to treat this deadly disease. HIV primarily infects and destroys immune cells. We
have already seen that eradicating an AIDS patients immune system, and replenishing it with bone marrow cells derived from
hematopoietic stem cells of an HIV-resistant individual, has been used to cure a patient of HIV infection. Imagine if this experimental
therapy could be scaled up for wide-spread clinical use. Bone marrow transplantation has historically been a viable model for stem
cell replacement therapy and will continue to serve as a clinically useful model to treat disease using stem cells.
References
Garver-Apgar CE, Gangestad SW, Thornhill R, Miller RD, Olp JJ (2006) Major histocompatibility complex alleles, sexual
responsivity, and unfaithfulness in romantic couples. Psychol Sci. Oct;17(10):830-5.
Murphy KM, P Travers, M Walport (Eds.) (2010) Janeway's Immunobiology. 8th Edition. New York:Taylor & Francis, Inc.
Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE (2011). Isolation of single human hematopoietic stem cells
capable of long-term multilineage engraftment. Science Jul 8;333(6039):218-21.
Silverstein AM (2009). A History of Immunology. 2nd Edition. New York: Elsevier Science.
data:text/html;charset=utf-8,%3Cdiv%20class%3D%22ws-menu-bar%20WikiControls%20WikispacesContent%20WikispacesBs3%22%20style%3D%22max-wid
6/6