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Chapter 22
Overview of the Lymphatic System and Immunity
▪Lymphatic System- includes the cells, tissues, and organs responsible for
defending the body against both environmental hazards and internal threats.
▫Lymphocytes are the primary cells of the lymphatic system
▫Innate (Nonspecific) defenses▫Adaptive (Specific) defenses▫Immunity▫All cells and tissues involved with the production of immunity are
sometimes considered to be part of the immune system.
Organization of the Lymphatic System
▪The lymphatic system consists of:
1) lymph2) lymphatic vessels3) lymphoid tissues and organs
primary lymphoid tissuessecondary lymphoid tissues4) lymphocytes and phagocytic cells
▪Functions of the lymphatic system-
▪Lymphatic Vessels▫Lymphatic capillaries▫Small lymphatic vessels-
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▫Major lymph collecting vessels-Superficial lymphatics-Deep lymphatics-Deep and superficial lymphatics merge to form larger lymphatic
trunks, which drain into larger ducts; the right lymphatic duct and
the thoracic duct.
-Right lymphatic duct drains lymph from the right side of the body
superior to the diaphragm.
-Thoracic duct drains lymph from the rest of the body
▪Lymphocytes- account for 20-40% of circulating white blood cell population.
There are three classes of lymphocytes in blood; T cells, B cells, and NK cells
▫There are many types of T cells, including; cytotoxic T cells, helper T
cells, suppressor T cells. They account for about 80% of circulating
lymphocytes.
▫B cells account for about 10-15% of circulating lymphocytes.
-When stimulated, B cells differentiate into plasma cells which are
responsible for production and secretion of antibodies
(immunoglobulins).
▫NK cells, the remaining 5-10% of circulating lymphocytes, are large
granular lymphocytes, attack foreign cells, virus infected, and cancer cells.
▫Lymphocytes are not evenly distributed in the blood, bone marrow, and
lymph tissues and organs
▫Lymphocytes have relatively long life spans, 80% live up to 4 years,
some up to 20 years.
▫Lymphopoiesis (production of lymphocytes) involves the bone marrow,
thymus, and peripheral lymphoid tissues.
-Hemocytoblasts in the red bone marrow produce two types of
lymphoid stem cells.
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-Divisions of T, B, or NK cells can only render daughter cells
of the same type.
▪Lymphoid Tissues▫Lymphoid nodule- lymphocytes are densely packed in an area of areolar
tissue
-MALT- mucosa-associated lymphoid tissue- collection of lymphoid
tissues linked with the digestive system.
-Tonsils- large nodules in the walls of the pharynx, usually 5 of
them
▪Lymphoid Organs▫Lymph Nodes- small oval organs surrounded in a fibrous CT capsule.
-Trabeculae-Afferent lymphatics-Efferent lymphatics-Lymph flow▫Thymus-Capsule divides the thymus into lobes, septa further divide thymus
into lobules.
-Reticular epithelial cells surround clusters of lymphocytes in the
cortex. They maintain the blood-thymus barrier and secrete
thymus hormones.
-Thymosins- name given to the group of hormones produced in the
thymus that function to development and maintenance of T cells
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▫SpleenFunctions of the spleen include:
-Soft organ that’s shape reflects its association with the structures
around it.
-Contains red pulp (large quantities of RBC) and white pulp (similar
to lymphoid nodules)
Nonspecific Defenses
▪Physical Barriers-
▪Phagocytes▫Microphages▫Macrophages-Fixed macrophages-Free macrophages-Both classes of macrophages are derived from monocytes of the
blood.
▫Most phagocytes die before they have engulfed more than 25 bacteria
(about an hour).
▪Immune surveillance▫Abnormal cells contain antigens that are not found on normal cells
▫NK cells respond to a variety of abnormal antigens, and will result in that
cell being attacked, much less selective than B or T cells.
▫NK cells respond immediately on contact, unlike B and T cells which
activation takes a complex, time consuming sequence of events.
▫Activated NK cells react in a predictable way:
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▪Interferons▫Once an interferon has contacted the surface of a normal cell, it triggers
a second messenger pathway that leads to the production of antiviral
proteins.
▫Antiviral proteins interfere with the viral replication that takes place inside
a cell.
▫There are at least three types of interferons:
-Alpha () interferons-Beta () interferons-Gamma () interferons▪Complement System▫Complement proteins interact with one another in chain reactions, two
types; classical and alternate pathways.
-Classical pathway-
-Alternate pathway-
-Both end with the conversion of C3 to C3b, stimulation of
phagocytosis, and formation of the membrane attack complex
(MAC)
▪Inflammation▫Inflammation produces local sensations of swelling, redness, heat, and
pain.
▫Almost any tissue subjected to physical damage or infection will result in
inflammation.
▫The damage to the tissue changes the chemical make-up in the
interstitial tissue, which initiates the inflammation response.
▫Inflammation has a number of effects:
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▫Inflammation occurs in a series of integrated steps
▪Fever▫Circulating proteins called pyrogens can reset the hypothalamic
thermostat and raise body temperature.
▫Pyrogens can be stimulated by many things; pathogens, bacterial toxins,
antigen-antibody complexes.
▫Within limits, fever can be beneficial.
Specific Defenses: An overview of the Immune Response
▪The basic functional relationship between B and T cells is:
▫T cells are responsible for cell-mediated immunity
▫B cells are responsible for antibody-mediated immunity
▪Both play important roles, but under different circumstances:
▫T cells cannot respond to antigenic materials in solution and activated B
cells cannot cross cell membranes
▪Forms of immunity- immunity is either innate or acquired
▫Innate immunity▫Adaptive immunity-Active immunity:
-Naturally Acquired:
-Artificially Induced:
-Passive immunity:
-Naturally Acquired:
-Artificially Induced:
▪Properties of Immunity- regardless of form, immunity has 4 general properties
1) specificity2) versatility-
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3) memory4) toleranceT Cells and Cell-mediated Immunity
▪Key cells in this immunity are cytotoxic T cells, helper T cells, memory T cells,
and suppressor T cells.
▪Before an immune response can begin, T cells must be activated by exposure to
an antigen, does not occur with direct antigen-lymphocyte contact.
▪Antigen Presentation- T cells recognize antigens only when the antigens are
bound to glycoproteins in cell membranes.
▫Glycoproteins are genetically determined, genes are found on a region of
chromosome 6 called the major histocompatibility complex (MHC), these
proteins are called MHC proteins.
▫There are two major classes of MHC proteins; class I and class II.
-Class I MHC proteins are in the membranes of all nucleated cells,
they are continually be added to the cell membrane
-Class II MHC proteins are present only in the membranes of
antigen-presenting cells (APC) and lymphocytes.
-Antigen-presenting cells include all the phagocytic cells,
Langerhans cells of the skin and dendritic cells of the lymph
nodes and spleen.
▪Antigen Recognition- T cell recognition of a specific antigen presented in an
MHC protein.
▫Inactive T cells have receptors that recognize class I or class II MHC
proteins. These receptors also have binding sites for specific antigens
▫Some T cells respond to antigens bound to class I MHC proteins and
others respond to antigens bound to class II MHC proteins.
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-This recognition depends on the structure of the T cell membrane.
-Membrane proteins involved in this structure are called CD
markers
▫Costimulation-CD8 or CD4 markers are bound to the CD3 receptor complex, this
complex ultimately activates the T cells.
-Appropriate costimulation proteins appear in the presenting cell
only if that cell has engulfed antigens or is infected by viruses
▪Activation of CD8 T Cells- two classes of CD8 T cells are activated by exposure
to antigens bound to class I MHC proteins, quick responding cells that give rise
to cytotoxic T cells and memory Tc cells, and slower responding cells that give
rise to suppressor T cells.
▫Cytotoxic T cells seek out and destroy abnormal and infected cells.
-Highly mobile cells that roam throughout injured tissue
-Once bound to its target antigen presented on a class I MHC
protein, it will immediately destroy that cell, by one of 3 different
ways:
1)
2)
3)
-Takes about 2 days or more from the presence of an antigen to
high enough concentrations of cytotoxic T cells to be effective.
▫Memory Tc cells ensure there will be no delay in the response if that
specific antigen reappears.
-If the antigen appears again, the memory cells will immediately
differentiate into cytotoxic T cells.
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▫Suppressor T cells suppress the responses of other T cells and B cells by
secreting suppression factors.
▪Activation of CD4 T Cells- Upon activation, CD4 T cells undergo a series of
divisions that produce helper T cells and memory TH cells.
▫The memory TH cells remain in reserve
▫Helper T cells secrete a variety of cytokines that coordinate specific and
nonspecific defenses and stimulate cell-mediated and antibody-mediated
immunities:
1)
2)
3)
4)
B Cells and Antibody-Mediated Immunity
▪B cells are responsible for launching a chemical attack on antigens by producing
appropriate antibodies
▪B Cell Sensitization and Activation
▫Each kind of B cell carries its own particular antibody molecules in its cell
membrane
▫Sensitization-
▫B cells have class II MCH proteins, integrating antigens onto the surface,
this activates the B cell, but needs to be “O.K’d” by a helper T cell.
▫Once a sensitized B cell makes contact with a helper T cell, it binds to the
MCH complex, recognizes the antigen, then begins secreting cytokines
that promote B cell activation.
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▫When B cells have been activated, they begin dividing, producing plasma
cells and memory B cells.
*see fig. 22-22 to visualize this process*
▪Antibody Structure
▫An antibody consists of two parallel pairs of polypeptide chains: one pair
of heavy chains and one pair of light chains, both containing constant
segments and variable segments
▫There are five types of constant segments:
▫The antigen binding site▫When an antibody binds to its corresponding antigen molecule, an
antigen-antibody complex is formed.
▫Antigenic determinant sites▫Complete antigen-
▫There are 7 ways in which the antigen may be eliminated:
1)
2)
3)
4)
5)
6)
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7)
*look over table 22-1 for descriptions of the classes of antibodies*
▪Primary and Secondary Responses to Antigen Exposure
▫Primary responses-
▫Antibody titer-
▫If the exposure ends, the antibody concentration declines because:
1)
2)
▫Two types of antibodies are involved in the primary response, IgM, IgG
▫Secondary responses-
▫If a second exposure takes place, the memory cells immediately start
dividing into plasma cells, which secrete massive quantities of antibodies
▫The antibody titer of a secondary response rises quicker and higher than
in the primary response
Normal Resistance and Abnormal Resistance
▪Immunological competence-
▪Immune Disorders▫Autoimmune disorders-
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-Autoantibodies- antibodies released from B cells that target normal
body cells and tissues.
-For unknown reasons, the risk of autoimmune problems increases
if an individual has an unusual type of MHC proteins.
▫Immunodeficiency diseases- can result from:
1) problems with the embryological development of lymphoid
organs and tissues
2) an infection with a virus that depresses the immune function
3) treatment with, or exposure to, immunosuppressive agents
SCID- severe combined immunodeficiency disease- genetic disorder
where individual fails to develop either cellular or anti-body
mediated immunity.
-AIDS is an immunodeficiency disease that targets helper T cells
▫Allergies-Immediate hypersensitivity- anaphylaxis▪Stress and the Immune Response
▫Long-term secretion of glucocorticoids, GAS, can inhibit the immune
response and lower resistance to disease. Glucocorticoids have the
following effects on tissues which can alter the effectiveness of specific
and nonspecific defenses:
1) depress the inflammatory response
2) reduce the activities and numbers of phagocytes in peripheral
tissues
3) inhibition of interleukin secretion.
Aging and the Immune System
▪With age, T cells become less responsive to antigens
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▪B cells are less active due to the decrease in helper T cells, antibodies are not
produced as quickly
▪Increases an individual’s susceptibility to viral and bacterial infection.
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