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Anatomy & Physiology 2e: 21.7 Transplantation and Cancer Immunology

Anatomy & Physiology 2e
21.7 Transplantation and Cancer Immunology
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table of contents
  1. Cover
  2. Title Page
  3. Copyright
  4. Table Of Contents
  5. Chapter 1. An Introduction to the Human Body
    1. 1.0 Introduction
    2. 1.1 How Structure Determines Function
    3. 1.2 Structural Organization of the Human Body
    4. 1.3 Homeostasis
    5. 1.4 Anatomical Terminology
    6. 1.5 Medical Imaging
  6. Chapter 2. The Chemical Level of Organization
    1. 2.0 Introduction
    2. 2.1 Elements and Atoms: The Building Blocks of Matter
    3. 2.2 Chemical Bonds
    4. 2.3 Chemical Reactions
    5. 2.4 Inorganic Compounds Essential to Human Functioning
    6. 2.5 Organic Compounds Essential to Human Functioning
  7. Chapter 3. The Cellular Level of Organization
    1. 3.0 Introduction
    2. 3.1 The Cell Membrane
    3. 3.2 The Cytoplasm and Cellular Organelles
    4. 3.3 The Nucleus and DNA Replication
    5. 3.4 Protein Synthesis
    6. 3.5 Cell Growth and Division
    7. 3.6 Cellular Differentiation
  8. Chapter 4. The Tissue Level of Organization
    1. 4.0 Introduction
    2. 4.1 Types of Tissues
    3. 4.2 Epithelial Tissue
    4. 4.3 Connective Tissue Supports and Protects
    5. 4.4 Muscle Tissue
    6. 4.5 Nervous Tissue
    7. 4.6 Tissue Injury and Aging
  9. Chapter 5. The Integumentary System
    1. 5.0 Introduction
    2. 5.1 Layers of the Skin
    3. 5.2 Accessory Structures of the Skin
    4. 5.3 Functions of the Integumentary System
    5. 5.4 Diseases, Disorders, and Injuries of the Integumentary System
  10. Chapter 6. Bone Tissue and the Skeletal System
    1. 6.0 Introduction
    2. 6.1 The Functions of the Skeletal System
    3. 6.2 Bone Classification
    4. 6.3 Bone Structure
    5. 6.4 Bone Formation and Development
    6. 6.5 Fractures: Bone Repair
    7. 6.6 Exercise, Nutrition, Hormones, and Bone Tissue
    8. 6.7 Calcium Homeostasis: Interactions of the Skeletal System and Other Organ Systems
  11. Chapter 7. Axial Skeleton
    1. 7.0 Introduction
    2. 7.1 Divisions of the Skeletal System
    3. 7.2 Bone Markings
    4. 7.3 The Skull
    5. 7.4 The Vertebral Column
    6. 7.5 The Thoracic Cage
    7. 7.6 Embryonic Development of the Axial Skeleton
  12. Chapter 8. The Appendicular Skeleton
    1. 8.0 Introduction
    2. 8.1 The Pectoral Girdle
    3. 8.2 Bones of the Upper Limb
    4. 8.3 The Pelvic Girdle and Pelvis
    5. 8.4 Bones of the Lower Limb
    6. 8.5 Development of the Appendicular Skeleton
  13. Chapter 9. Joints
    1. 9.0 Introduction
    2. 9.1 Classification of Joints
    3. 9.2 Fibrous Joints
    4. 9.3 Cartilaginous Joints
    5. 9.4 Synovial Joints
    6. 9.5 Types of Body Movements
    7. 9.6 Anatomy of Selected Synovial Joints
    8. 9.7 Development of Joints
  14. Chapter 10. Muscle Tissue
    1. 10.0 Introduction
    2. 10.1 Overview of Muscle Tissues
    3. 10.2 Skeletal Muscle
    4. 10.3 Muscle Fiber Excitation, Contraction, and Relaxation
    5. 10.4 Nervous System Control of Muscle Tension
    6. 10.5 Types of Muscle Fibers
    7. 10.6 Exercise and Muscle Performance
    8. 10.7 Smooth Muscle Tissue
    9. 10.8 Development and Regeneration of Muscle Tissue
  15. Chapter 11. The Muscular System
    1. 11.0 Introduction
    2. 11.1 Describe the roles of agonists, antagonists and synergists
    3. 11.2 Explain the organization of muscle fascicles and their role in generating force
    4. 11.3 Explain the criteria used to name skeletal muscles
    5. 11.4 Axial Muscles of the Head Neck and Back
    6. 11.5 Axial muscles of the abdominal wall and thorax
    7. 11.6 Muscles of the Pectoral Girdle and Upper Limbs
    8. 11.7 Appendicular Muscles of the Pelvic Girdle and Lower Limbs
  16. Chapter 12. The Nervous System and Nervous Tissue
    1. 12.0 Introduction
    2. 12.1 Structure and Function of the Nervous System
    3. 12.2 Nervous Tissue
    4. 12.3 The Function of Nervous Tissue
    5. 12.4 Communication Between Neurons
    6. 12.5 The Action Potential
  17. Chapter 13. The Peripheral Nervous System
    1. 13.0 Introduction
    2. 13.1 Sensory Receptors
    3. 13.2 Ganglia and Nerves
    4. 13.3 Spinal and Cranial Nerves
    5. 13.4 Relationship of the PNS to the Spinal Cord of the CNS
    6. 13.5 Ventral Horn Output and Reflexes
    7. 13.6 Testing the Spinal Nerves (Sensory and Motor Exams)
    8. 13.7 The Cranial Nerve Exam
  18. Chapter 14. The Central Nervous System
    1. 14.0 Introduction
    2. 14.1 Embryonic Development
    3. 14.2 Blood Flow the meninges and Cerebrospinal Fluid Production and Circulation
    4. 14.3 The Brain and Spinal Cord
    5. 14.4 The Spinal Cord
    6. 14.5 Sensory and Motor Pathways
  19. Chapter 15. The Special Senses
    1. 15.0 Introduction
    2. 15.1 Taste
    3. 15.2 Smell
    4. 15.3 Hearing
    5. 15.4 Equilibrium
    6. 15.5 Vision
  20. Chapter 16. The Autonomic Nervous System
    1. 16.0 Introduction
    2. 16.1 Divisions of the Autonomic Nervous System
    3. 16.2 Autonomic Reflexes and Homeostasis
    4. 16.3 Central Control
    5. 16.4 Drugs that Affect the Autonomic System
  21. Chapter 17. The Endocrine System
    1. 17.0 Introduction
    2. 17.1 An Overview of the Endocrine System
    3. 17.2 Hormones
    4. 17.3 The Pituitary Gland and Hypothalamus
    5. 17.4 The Thyroid Gland
    6. 17.5 The Parathyroid Glands
    7. 17.6 The Adrenal Glands
    8. 17.7 The Pineal Gland
    9. 17.8 Gonadal and Placental Hormones
    10. 17.9 The Pancreas
    11. 17.10 Organs with Secondary Endocrine Functions
    12. 17.11 Development and Aging of the Endocrine System
  22. Chapter 18. The Cardiovascular System: Blood
    1. 18.0 Introduction
    2. 18.1 Functions of Blood
    3. 18.2 Production of the Formed Elements
    4. 18.3 Erythrocytes
    5. 18.4 Leukocytes and Platelets
    6. 18.5 Hemostasis
    7. 18.6 Blood Typing
  23. Chapter 19. The Cardiovascular System: The Heart
    1. 19.0 Introduction
    2. 19.1 Heart Anatomy
    3. 19.2 Cardiac Muscle and Electrical Activity
    4. 19.3 Cardiac Cycle
    5. 19.4 Cardiac Physiology
    6. 19.5 Development of the Heart
  24. Chapter 20. The Cardiovascular System: Blood Vessels and Circulation
    1. 20.0 Introduction
    2. 20.1 Structure and Function of Blood Vessels
    3. 20.2 Blood Flow, Blood Pressure, and Resistance
    4. 20.3 Capillary Exchange
    5. 20.4 Homeostatic Regulation of the Vascular System
    6. 20.5 Circulatory Pathways
    7. 20.6 Development of Blood Vessels and Fetal Circulation
  25. Chapter 21. The Lymphatic and Immune System
    1. 21.0 Introduction
    2. 21.1 Anatomy of the Lymphatic and Immune Systems
    3. 21.2 Barrier Defenses and the Innate Immune Response
    4. 21.3 The Adaptive Immune Response: T lymphocytes and Their Functional Types
    5. 21.4 The Adaptive Immune Response: B-lymphocytes and Antibodies
    6. 21.5 The Immune Response against Pathogens
    7. 21.6 Diseases Associated with Depressed or Overactive Immune Responses
    8. 21.7 Transplantation and Cancer Immunology
  26. Chapter 22. The Respiratory System
    1. 22.0 Introduction
    2. 22.1 Organs and Structures of the Respiratory System
    3. 22.2 The Lungs
    4. 22.3 The Process of Breathing
    5. 22.4 Gas Exchange
    6. 22.5 Transport of Gases
    7. 22.6 Modifications in Respiratory Functions
    8. 22.7 Embryonic Development of the Respiratory System
  27. Chapter 23. The Digestive System
    1. 23.0 Introduction
    2. 23.1 Overview of the Digestive System
    3. 23.2 Digestive System Processes and Regulation
    4. 23.3 The Mouth, Pharynx, and Esophagus
    5. 23.4 The Stomach
    6. 23.5 Accessory Organs in Digestion: The Liver, Pancreas, and Gallbladder
    7. 23.6 The Small and Large Intestines
    8. 23.7 Chemical Digestion and Absorption: A Closer Look
  28. Chapter 24. Metabolism and Nutrition
    1. 24.0 Introduction
    2. 24.1 Overview of Metabolic Reactions
    3. 24.2 Carbohydrate Metabolism
    4. 24.3 Lipid Metabolism
    5. 24.4 Protein Metabolism
    6. 24.5 Metabolic States of the Body
    7. 24.6 Energy and Heat Balance
    8. 24.7 Nutrition and Diet
  29. Chapter 25. The Urinary System
    1. 25.0 Introduction
    2. 25.1 Internal and External Anatomy of the Kidney
    3. 25.2 Microscopic Anatomy of the Kidney: Anatomy of the Nephron
    4. 25.3 Physiology of Urine Formation: Overview
    5. 25.4 Physiology of Urine Formation: Glomerular Filtration
    6. 25.5 Physiology of Urine Formation: Tubular Reabsorption and Secretion
    7. 25.6 Physiology of Urine Formation: Medullary Concentration Gradient
    8. 25.7 Physiology of Urine Formation: Regulation of Fluid Volume and Composition
    9. 25.8 Urine Transport and Elimination
    10. 25.9 The Urinary System and Homeostasis
  30. Chapter 26. Fluid, Electrolyte, and Acid-Base Balance
    1. 26.0 Introduction
    2. 26.1 Body Fluids and Fluid Compartments
    3. 26.2 Water Balance
    4. 26.3 Electrolyte Balance
    5. 26.4 Acid-Base Balance
    6. 26.5 Disorders of Acid-Base Balance
  31. Chapter 27. The Sexual Systems
    1. 27.0 Introduction
    2. 27.1 Anatomy of Sexual Systems
    3. 27.2 Development of Sexual Anatomy
    4. 27.3 Physiology of the Female Sexual System
    5. 27.4 Physiology of the Male Sexual System
    6. 27.5 Physiology of Arousal and Orgasm
  32. Chapter 28. Development and Inheritance
    1. 28.0 Introduction
    2. 28.1 Fertilization
    3. 28.2 Embryonic Development
    4. 28.3 Fetal Development
    5. 28.4 Maternal Changes During Pregnancy, Labor, and Birth
    6. 28.5 Adjustments of the Infant at Birth and Postnatal Stages
    7. 28.6 Lactation
    8. 28.7 Patterns of Inheritance
  33. Creative Commons License
  34. Recommended Citations
  35. Versioning

21.7 Transplantation and Cancer Immunology

Learning Objectives

By the end of this section, you will be able to:

  • Explain why blood typing is important and what happens when mismatched blood is used in a transfusion
  • Describe how tissue typing is done during organ transplantation and the role of transplant anti-rejection drugs
  • Show how the immune response is able to control some cancers and how this immune response might be enhanced by cancer vaccines

The immune responses to transplanted organs and to cancer cells are both important medical issues. With the use of tissue typing and anti-rejection drugs, transplantation of organs and the control of the anti-transplant immune response have made huge strides in the past 50 years. Today, these procedures are commonplace. Tissue typing is the determination of MHC molecules in the tissue to be transplanted to better match the donor to the recipient. The immune response to cancer, on the other hand, has been more difficult to understand and control. Although it is clear that the immune system can recognize some cancers and control them, others seem to be resistant to immune mechanisms.

The Rh Factor

Red blood cells can be typed based on their surface antigens. ABO blood type, in which individuals are type A, B, AB, or O according to their genetics, is one example. A separate antigen system seen on red blood cells is the Rh antigen. When someone is “A positive” for example, the positive refers to the presence of the Rh antigen, whereas someone who is “A negative” would lack this molecule.

An interesting consequence of Rh factor expression is seen in erythroblastosis fetalis, a hemolytic disease of the newborn (Figure 21.7.1). This disease occurs when mothers negative for Rh antigen have multiple Rh-positive children. During the birth of a first Rh-positive child, the mother makes a primary anti-Rh antibody response to the fetal blood cells that enter the maternal bloodstream. If the mother has a second Rh-positive child, IgG antibodies against Rh-positive blood mounted during this secondary response cross the placenta and attack the fetal blood, causing anemia. This is a consequence of the fact that the fetus is not genetically identical to the mother, and thus the mother is capable of mounting an immune response against it. This disease is treated with antibodies specific for Rh factor. These are given to the mother during the subsequent births, destroying any fetal blood that might enter her system and preventing the immune response.

This figure shows the progression of thedisease called erythroblastosis fetalis. The top panel shows the umbilical artery and vein and the placenta. The center panel shows the response in the immune system of a first Rh+ infant. The bottom panel shows the response in the case of a second exposure for a Rh+ infant.
Figure 21.7.1 – Erythroblastosis Fetalis: Erythroblastosis fetalis (hemolytic disease of the newborn) is the result of an immune response in an Rh-negative mother who has multiple children with an Rh-positive father. During the first birth, fetal blood enters the mother’s circulatory system, and anti-Rh antibodies are made. During the gestation of the second child, these antibodies cross the placenta and attack the blood of the fetus. The treatment for this disease is to give the mother anti-Rh antibodies (RhoGAM) during the first pregnancy to destroy Rh-positive fetal red blood cells from entering her system and causing the anti-Rh antibody response in the first place.

Tissue Transplantation

Tissue transplantation is more complicated than blood transfusions because of two characteristics of MHC molecules. These molecules are the major cause of transplant rejection (hence the name “histocompatibility”). MHC polygeny refers to the multiple MHC proteins on cells, and MHC polymorphism refers to the multiple alleles for each individual MHC locus. Thus, there are many alleles in the human population that can be expressed (Table 21.8 and Table 21.9). When a donor organ expresses MHC molecules that are different from the recipient, the latter will often mount a cytotoxic T cell response to the organ and reject it. Histologically, if a biopsy of a transplanted organ exhibits massive infiltration of T lymphocytes within the first weeks after transplant, it is a sign that the transplant is likely to fail. The response is a classical, and very specific, primary T cell immune response. As far as medicine is concerned, the immune response in this scenario does the patient no good at all and causes significant harm.

Partial Table of Alleles of the Human MHC (Class I) (Table 21.8)
Gene# of alleles# of possible MHC I protein components
A21321527
B27982110
C16721200
E113
F224
G5016
Partial Table of Alleles of the Human MHC (Class II) (Table 21.9)
Gene# of alleles# of possible MHC II protein components
DRA72
DRB1297958
DQA14931
DQB1179128
DPA13618
DPB1158136
DMA74
DMB137
DOA123
DOB135

Immunosuppressive drugs such as cyclosporine A have made transplants more successful, but matching the MHC molecules is still key. In humans, there are six MHC molecules that show the most polymorphisms, three class I molecules (A, B, and C) and three class II molecules called DP, DQ, and DR. A successful transplant usually requires a match between at least 3–4 of these molecules, with more matches associated with greater success. Family members, since they share a similar genetic background, are much more likely to share MHC molecules than unrelated individuals do. In fact, due to the extensive polymorphisms in these MHC molecules, unrelated donors are found only through a worldwide database. The system is not foolproof however, as there are not enough individuals in the system to provide the organs necessary to treat all patients needing them.

One disease of transplantation occurs with bone marrow transplants, which are used to treat various diseases, including SCID and leukemia. Because the bone marrow cells being transplanted contain lymphocytes capable of mounting an immune response, and because the recipient’s immune response has been destroyed before receiving the transplant, the donor cells may attack the recipient tissues, causing graft-versus-host disease. Symptoms of this disease, which usually include a rash and damage to the liver and mucosa, are variable, and attempts have been made to moderate the disease by first removing mature T cells from the donor bone marrow before transplanting it.

Immune Responses Against Cancer

It is clear that with some cancers, for example Kaposi’s sarcoma, a healthy immune system does a good job at controlling them (Figure 21.7.2). This disease, which is caused by the human herpesvirus, is almost never observed in individuals with strong immune systems, such as the young and immunocompetent. Other examples of cancers caused by viruses include liver cancer caused by the hepatitis B virus and cervical cancer caused by the human papilloma virus. As these last two viruses have vaccines available for them, getting vaccinated can help prevent these two types of cancer by stimulating the immune response.

This photograph shows lesions on the surface of skin.
Figure 21.7.2 Karposi’s Sarcoma Lesions. (credit: National Cancer Institute)

On the other hand, as cancer cells are often able to divide and mutate rapidly, they may escape the immune response, just as certain pathogens such as HIV do. There are three stages in the immune response to many cancers: elimination, equilibrium, and escape. Elimination occurs when the immune response first develops toward tumor-specific antigens specific to the cancer and actively kills most cancer cells, followed by a period of controlled equilibrium during which the remaining cancer cells are held in check. Unfortunately, many cancers mutate, so they no longer express any specific antigens for the immune system to respond to, and a subpopulation of cancer cells escapes the immune response, continuing the disease process.

This fact has led to extensive research in trying to develop ways to enhance the early immune response to completely eliminate the early cancer and thus prevent a later escape. One method that has shown some success is the use of cancer vaccines, which differ from viral and bacterial vaccines in that they are directed against the cells of one’s own body. Treated cancer cells are injected into cancer patients to enhance their anti-cancer immune response and thereby prolong survival. The immune system has the capability to detect these cancer cells and proliferate faster than the cancer cells do, overwhelming the cancer in a similar way as they do for viruses. Cancer vaccines have been developed for malignant melanoma, a highly fatal skin cancer, and renal (kidney) cell carcinoma. These vaccines are still in the development stages, but some positive and encouraging results have been obtained clinically.

It is tempting to focus on the complexity of the immune system and the problems it causes as a negative. The upside to immunity, however, is so much greater: The benefit of staying alive far outweighs the negatives caused when the system does sometimes go awry. Working on “autopilot,” the immune system helps to maintain your health and kill pathogens. The only time you really miss the immune response is when it is not being effective and illness results, or, as in the extreme case of HIV disease, the immune system is gone completely.

Everyday Connection – How Stress Affects the Immune Response: The Connections between the Immune, Nervous, and Endocrine Systems of the Body

The immune system cannot exist in isolation. After all, it has to protect the entire body from infection. Therefore, the immune system is required to interact with other organ systems, sometimes in complex ways. Thirty years of research focusing on the connections between the immune system, the central nervous system, and the endocrine system have led to a new science with the unwieldy name of called psychoneuroimmunology. The physical connections between these systems have been known for centuries: All primary and secondary organs are connected to sympathetic nerves. What is more complex, though, is the interaction of neurotransmitters, hormones, cytokines, and other soluble signaling molecules, and the mechanism of “crosstalk” between the systems. For example, white blood cells, including lymphocytes and phagocytes, have receptors for various neurotransmitters released by associated neurons. Additionally, hormones such as cortisol (naturally produced by the adrenal cortex) and prednisone (synthetic) are well known for their abilities to suppress T cell immune mechanisms, hence, their prominent use in medicine as long-term, anti-inflammatory drugs.

One well-established interaction of the immune, nervous, and endocrine systems is the effect of stress on immune health. In the human vertebrate evolutionary past, stress was associated with the fight-or-flight response, largely mediated by the central nervous system and the adrenal medulla. This stress was necessary for survival. The physical action of fighting or running, whichever the animal decides, usually resolves the problem in one way or another. On the other hand, there are no physical actions to resolve most modern day stresses, including short-term stressors like taking examinations and long-term stressors such as being unemployed or losing a spouse. The effect of stress can be felt by nearly every organ system, and the immune system is no exception (Table 21.10).

Effects of Stress on Body Systems (Table 21.10)
SystemStress-related illness
Integumentary systemAcne, skin rashes, irritation
Nervous systemHeadaches, depression, anxiety, irritability, loss of appetite, lack of motivation, reduced mental performance
Muscular and skeletal systemsMuscle and joint pain, neck and shoulder pain
Circulatory systemIncreased heart rate, hypertension, increased probability of heart attacks
Digestive systemIndigestion, heartburn, stomach pain, nausea, diarrhea, constipation, weight gain or loss
Immune systemDepressed ability to fight infections
Male reproductive systemLowered sperm production, impotence, reduced sexual desire
Female reproductive systemIrregular menstrual cycle, reduced sexual desire

At one time, it was assumed that all types of stress reduced all aspects of the immune response, but the last few decades of research have painted a different picture. First, most short-term stress does not impair the immune system in healthy individuals enough to lead to a greater incidence of diseases. However, older individuals and those with suppressed immune responses due to disease or immunosuppressive drugs may respond even to short-term stressors by getting sicker more often. It has been found that short-term stress diverts the body’s resources towards enhancing innate immune responses, which have the ability to act fast and would seem to help the body prepare better for possible infections associated with the trauma that may result from a fight-or-flight exchange. The diverting of resources away from the adaptive immune response, however, causes its own share of problems in fighting disease.

Chronic stress, unlike short-term stress, may inhibit immune responses even in otherwise healthy adults. The suppression of both innate and adaptive immune responses is clearly associated with increases in some diseases, as seen when individuals lose a spouse or have other long-term stresses, such as taking care of a spouse with a fatal disease or dementia. The new science of psychoneuroimmunology, while still in its relative infancy, has great potential to make exciting advances in our understanding of how the nervous, endocrine, and immune systems have evolved together and communicate with each other.

Chapter Review

Blood transfusion and organ transplantation both require an understanding of the immune response to prevent medical complications. Blood needs to be typed so that natural antibodies against mismatched blood will not destroy it, causing more harm than good to the recipient. Transplanted organs must be matched by their MHC molecules and, with the use of immunosuppressive drugs, can be successful even if an exact tissue match cannot be made. Another aspect to the immune response is its ability to control and eradicate cancer. Although this has been shown to occur with some rare cancers and those caused by known viruses, the normal immune response to most cancers is not sufficient to control cancer growth. Thus, cancer vaccines designed to enhance these immune responses show promise for certain types of cancer.

Review Questions

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An interactive H5P element has been excluded from this version of the text. You can view it online here:
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Critical Thinking Questions

1. Describe how stress affects immune responses.

References

Robinson J, Mistry K, McWilliam H, Lopez R, Parham P, Marsh SG. Nucleic acid research. IMGT/HLA Database [Internet]. 2011 [cited 2013 Apr 1]; 39:D1171–1176. Available from: http://europepmc.org/abstract/MED/21071412

Robinson J, Malik A, Parham P, Bodmer JG, Marsh SG. Tissue antigens. IMGT/HLA Database [Internet]. 2000 [cited 2013 Apr 1]; 55(3):280–287. Available from: http://europepmc.org/abstract/MED/10777106/reload=0;jsessionid=otkdw3M0TIVSa2zhvimg.6

Glossary

erythroblastosis fetalis
disease of Rh factor-positive newborns in Rh-negative mothers with multiple Rh-positive children; resulting from the action of maternal antibodies against fetal blood
graft-versus-host disease
in bone marrow transplants; occurs when the transplanted cells mount an immune response against the recipient
MHC polygeny
multiple MHC genes and their proteins found in body cells
MHC polymorphism
multiple alleles for each individual MHC locus
psychoneuroimmunology
study of the connections between the immune, nervous, and endocrine systems
tissue typing
typing of MHC molecules between a recipient and donor for use in a potential transplantation procedure

Solutions

Answers for Critical Thinking Questions

  1. Stress causes the release of hormones and the activation of nerves that suppress the immune response. Short-term stress has little effect on the health of an already healthy individual, whereas chronic stress does lead to increases in disease in such people.

Annotate

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Anatomy and Physiology
Copyright © 2019 by Lindsay M. Biga, Sierra Dawson, Amy Harwell, Robin Hopkins, Joel Kaufmann, Mike LeMaster, Philip Matern, Katie Morrison-Graham, Devon Quick & Jon Runyeon

Anatomy & Physiology by Lindsay M. Biga, Sierra Dawson, Amy Harwell, Robin Hopkins, Joel Kaufmann, Mike LeMaster, Philip Matern, Katie Morrison-Graham, Devon Quick & Jon Runyeon is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, except where otherwise noted.

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