Module 6: The Lymphatic and Immune Systems

Lesson 7: Transplantation and Cancer Immunology

Ghép Tạng Và Miễn Dịch Ung Thư

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Dưới đây là danh sách những thuật ngữ Y khoa của module The Lymphatic and Immune Systems.
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Medical Terminology: The Lymphatic and Immune Systems

active immunity
immunity developed from an individual’s own immune system
acute inflammation
inflammation occurring for a limited time period; rapidly developing
adaptive immune response
relatively slow but very specific and effective immune response controlled by lymphocytes
afferent lymphatic vessels
lead into a lymph node
antibody
antigen-specific protein secreted by plasma cells; immunoglobulin
antigen
molecule recognized by the receptors of B and T lymphocytes
antigen presentation
binding of processed antigen to the protein-binding cleft of a major histocompatibility complex molecule
antigen processing
internalization and digestion of antigen in an antigen-presenting cell
antigen receptor
two-chain receptor by which lymphocytes recognize antigen
antigenic determinant
(also, epitope) one of the chemical groups recognized by a single type of lymphocyte antigen receptor
B cells
lymphocytes that act by differentiating into an antibody-secreting plasma cell
barrier defenses
antipathogen defenses deriving from a barrier that physically prevents pathogens from entering the body to establish an infection
bone marrow
tissue found inside bones; the site of all blood cell differentiation and maturation of B lymphocytes
bronchus-associated lymphoid tissue (BALT)
lymphoid nodule associated with the respiratory tract
central tolerance
B cell tolerance induced in immature B cells of the bone marrow
chemokine
soluble, long-range, cell-to-cell communication molecule
chronic inflammation
inflammation occurring for long periods of time
chyle
lipid-rich lymph inside the lymphatic capillaries of the small intestine
cisterna chyli
bag-like vessel that forms the beginning of the thoracic duct
class switching
ability of B cells to change the class of antibody they produce without altering the specificity for antigen
clonal anergy
process whereby B cells that react to soluble antigens in bone marrow are made nonfunctional
clonal deletion
removal of self-reactive B cells by inducing apoptosis
clonal expansion
growth of a clone of selected lymphocytes
clonal selection
stimulating growth of lymphocytes that have specific receptors
clone
group of lymphocytes sharing the same antigen receptor
complement
enzymatic cascade of constitutive blood proteins that have antipathogen effects, including the direct killing of bacteria
constant region domain
part of a lymphocyte antigen receptor that does not vary much between different receptor types
cytokine
soluble, short-range, cell-to-cell communication molecule
cytotoxic T cells (Tc)
T lymphocytes with the ability to induce apoptosis in target cells
delayed hypersensitivity
(type IV) T cell-mediated immune response against pathogens infiltrating interstitial tissues, causing cellular infiltrate
early induced immune response
includes antimicrobial proteins stimulated during the first several days of an infection
effector T cells
immune cells with a direct, adverse effect on a pathogen
efferent lymphatic vessels
lead out of a lymph node
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
fas ligand
molecule expressed on cytotoxic T cells and NK cells that binds to the fas molecule on a target cell and induces it do undergo apoptosis
Fc region
in an antibody molecule, the site where the two termini of the heavy chains come together; many cells have receptors for this portion of the antibody, adding functionality to these molecules
germinal centers
clusters of rapidly proliferating B cells found in secondary lymphoid tissues
graft-versus-host disease
in bone marrow transplants; occurs when the transplanted cells mount an immune response against the recipient
granzyme
apoptosis-inducing substance contained in granules of NK cells and cytotoxic T cells
heavy chain
larger protein chain of an antibody
helper T cells (Th)
T cells that secrete cytokines to enhance other immune responses, involved in activation of both B and T cell lymphocytes
high endothelial venules
vessels containing unique endothelial cells specialized to allow migration of lymphocytes from the blood to the lymph node
histamine
vasoactive mediator in granules of mast cells and is the primary cause of allergies and anaphylactic shock
IgA
antibody whose dimer is secreted by exocrine glands, is especially effective against digestive and respiratory pathogens, and can pass immunity to an infant through breastfeeding
IgD
class of antibody whose only known function is as a receptor on naive B cells; important in B cell activation
IgE
antibody that binds to mast cells and causes antigen-specific degranulation during an allergic response
IgG
main blood antibody of late primary and early secondary responses; passed from carrier to unborn child via placenta
IgM
antibody whose monomer is a surface receptor of naive B cells; the pentamer is the first antibody made blood plasma during primary responses
immediate hypersensitivity
(type I) IgE-mediated mast cell degranulation caused by crosslinking of surface IgE by antigen
immune system
series of barriers, cells, and soluble mediators that combine to response to infections of the body with pathogenic organisms
immunoglobulin
protein antibody; occurs as one of five main classes
immunological memory
ability of the adaptive immune response to mount a stronger and faster immune response upon re-exposure to a pathogen
inflammation
basic innate immune response characterized by heat, redness, pain, and swelling
innate immune response
rapid but relatively nonspecific immune response
interferons
early induced proteins made in virally infected cells that cause nearby cells to make antiviral proteins
light chain
small protein chain of an antibody
lymph
fluid contained within the lymphatic system
lymph node
one of the bean-shaped organs found associated with the lymphatic vessels
lymphatic capillaries
smallest of the lymphatic vessels and the origin of lymph flow
lymphatic system
network of lymphatic vessels, lymph nodes, and ducts that carries lymph from the tissues and back to the bloodstream.
lymphatic trunks
large lymphatics that collect lymph from smaller lymphatic vessels and empties into the blood via lymphatic ducts
lymphocytes
white blood cells characterized by a large nucleus and small rim of cytoplasm
lymphoid nodules
unencapsulated patches of lymphoid tissue found throughout the body
macrophage
ameboid phagocyte found in several tissues throughout the body
macrophage oxidative metabolism
metabolism turned on in macrophages by T cell signals that help destroy intracellular bacteria
major histocompatibility complex (MHC)
gene cluster whose proteins present antigens to T cells
mast cell
cell found in the skin and the lining of body cells that contains cytoplasmic granules with vasoactive mediators such as histamine
memory T cells
long-lived immune cell reserved for future exposure to a pathogen
MHC class I
found on most cells of the body, it binds to the CD8 molecule on T cells
MHC class II
found on macrophages, dendritic cells, and B cells, it binds to CD4 molecules on T cells
MHC polygeny
multiple MHC genes and their proteins found in body cells
MHC polymorphism
multiple alleles for each individual MHC locus
monocyte
precursor to macrophages and dendritic cells seen in the blood
mucosa-associated lymphoid tissue (MALT)
lymphoid nodule associated with the mucosa
naïve lymphocyte
mature B or T cell that has not yet encountered antigen for the first time
natural killer cell (NK)
cytotoxic lymphocyte of innate immune response
negative selection
selection against thymocytes in the thymus that react with self-antigen
neutralization
inactivation of a virus by the binding of specific antibody
neutrophil
phagocytic white blood cell recruited from the bloodstream to the site of infection via the bloodstream
opsonization
enhancement of phagocytosis by the binding of antibody or antimicrobial protein
passive immunity
transfer of immunity to a pathogen to an individual that lacks immunity to this pathogen usually by the injection of antibodies
pattern recognition receptor (PRR)
leukocyte receptor that binds to specific cell wall components of different bacterial species
perforin
molecule in NK cell and cytotoxic T cell granules that form pores in the membrane of a target cell
peripheral tolerance
mature B cell made tolerant by lack of T cell help
phagocytosis
movement of material from the outside to the inside of the cells via vesicles made from invaginations of the plasma membrane
plasma cell
differentiated B cell that is actively secreting antibody
polyclonal response
response by multiple clones to a complex antigen with many determinants
positive selection
selection of thymocytes within the thymus that interact with self, but not non-self, MHC molecules
primary adaptive response
immune system’s response to the first exposure to a pathogen
primary lymphoid organ
site where lymphocytes mature and proliferate; red bone marrow and thymus gland
psychoneuroimmunology
study of the connections between the immune, nervous, and endocrine systems
regulatory T cells (Treg)
(also, suppressor T cells) class of CD4 T cells that regulates other T cell responses
right lymphatic duct
drains lymph fluid from the upper right side of body into the right subclavian vein
secondary adaptive response
immune response observed upon re-exposure to a pathogen, which is stronger and faster than a primary response
secondary lymphoid organs
sites where lymphocytes mount adaptive immune responses; examples include lymph nodes and spleen
sensitization
first exposure to an antigen
seroconversion
clearance of pathogen in the serum and the simultaneous rise of serum antibody
severe combined immunodeficiency disease (SCID)
genetic mutation that affects both T cell and B cell arms of the immune response
spleen
secondary lymphoid organ that filters pathogens from the blood (white pulp) and removes degenerating or damaged blood cells (red pulp)
T cell
lymphocyte that acts by secreting molecules that regulate the immune system or by causing the destruction of foreign cells, viruses, and cancer cells
T cell tolerance
process during T cell differentiation where most T cells that recognize antigens from one’s own body are destroyed
T cell-dependent antigen
antigen that binds to B cells, which requires signals from T cells to make antibody
T cell-independent antigen
binds to B cells, which do not require signals from T cells to make antibody
Th1 cells
cells that secrete cytokines that enhance the activity of macrophages and other cells
Th2 cells
cells that secrete cytokines that induce B cells to differentiate into antibody-secreting plasma cells
thoracic duct
large duct that drains lymph from the lower limbs, left thorax, left upper limb, and the left side of the head
thymocyte
immature T cell found in the thymus
thymus
primary lymphoid organ; where T lymphocytes proliferate and mature
tissue typing
typing of MHC molecules between a recipient and donor for use in a potential transplantation procedure
tonsils
lymphoid nodules associated with the nasopharynx
type I hypersensitivity
immediate response mediated by mast cell degranulation caused by the crosslinking of the antigen-specific IgE molecules on the mast cell surface
type II hypersensitivity
cell damage caused by the binding of antibody and the activation of complement, usually against red blood cells
type III hypersensitivity
damage to tissues caused by the deposition of antibody-antigen (immune) complexes followed by the activation of complement
variable region domain
part of a lymphocyte antigen receptor that varies considerably between different receptor types
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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.
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 1). This disease occurs when people negative for Rh antigen have multiple Rh-positive children. During the birth of a first Rh-positive child, the birth parent makes a primary anti-Rh antibody response to the fetal blood cells that enter the pregnant person’s bloodstream. If the same parent 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 birth parent, and thus the parent is capable of mounting an immune response against it. This disease is treated with antibodies specific for Rh factor. These are given to the pregnant person during the first and subsequent births, destroying any fetal blood that might enter their system and preventing the immune response.
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 1 and Table 2). 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.

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.
It is clear that with some cancers, for example Kaposi’s sarcoma, a healthy immune system does a good job at controlling them (Figure 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.

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.

OpenStax. (2022). Anatomy and Physiology 2e. Rice University. Retrieved June 15, 2023. ISBN-13: 978-1-711494-06-7 (Hardcover) ISBN-13: 978-1-711494-05-0 (Paperback) ISBN-13: 978-1-951693-42-8 (Digital). License: Attribution 4.0 International (CC BY 4.0). Access for free at openstax.org.

Erythroblastosis fetalis (hemolytic disease of the newborn) is the result of an immune response in an Rh-negative person who has multiple children with an Rh-positive person. During the first birth, fetal blood enters the pregnant person’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 carrier anti-Rh antibodies (RhoGAM) during the first pregnancy to destroy Rh-positive fetal red blood cells from entering their system and causing the anti-Rh antibody response in the first place.

Gene# of alleles# of possible MHC I protein components
A21321527
B27982110
C16721200
E113
F224
G5016
Gene# of alleles# of possible MHC II protein components
DRA72
DRB1297958
DQA14931
DQB1179128
DPA13618
DPB1158136
DMA74
DMB137
DOA123
DOB135

(credit: National Cancer Institute)

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Script:
  1. Blood transfusion and organ transplantation both require an understanding of the immune response to prevent medical complications.
  2. Blood needs to be typed so that natural antibodies against mismatched blood will not destroy it, causing more harm than good to the recipient.
  3. Transplanted organs must be matched by their major histocompatibility complex (or MHC) molecules.
  4. And, with the use of immunosuppressive drugs, transplantation can be successful even if an exact tissue match cannot be made.
  5. Another aspect to the immune response is its ability to control and eradicate cancer.
  6. 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.
  7. Thus, cancer vaccines designed to enhance these immune responses show promise for certain types of cancer.
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