Transcript Ch22

Chapter 22
Lymphatic System and Immunity
THE LYMPHATIC SYSTEM AND IMMUNITY
A human body recognizes anything other than its own as an invader.
When these foreign bodies are capable of living in the human body and are
harmful, they are called pathogens.
The lymph and plasma contains antibodies and special cells which fight against
cells other than its own. These antibodies are formed when the infants are about
three month old. Recall the timing when the blood types were formed.
When the reaction is against each specific foreign body, it is called immune
response or immunity.
The lymphatic system in the body identifies and destroys foreign bodies by their
antibodies.
But, how do we distinguish our own from the others?
1. Organization and functions of the lymphatic
system
In the lymphatic system there are:
(1)
Lymphatic fluid (lymph) that contains
lymphocytes,
(2)
Vessels that transport lymph
(3)
And the sites where large amounts of
lymphocytes are held: Lymph nodes, spleen and
thymus.
(4)
Where are the lymphocytes made?
Lymphatic System
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Lymph
Lymphatic vessels
Lymphatic tissue
Lymphatic nodules
Lymph nodes
Tonsils
Spleen
Thymus
Functions of the Lymphatic System
• Fluid balance
– Excess interstitial fluid enters lymphatic
capillaries and becomes lymph
• Fat absorption
– Absorption of fat and other substances from
digestive tract
• Defense
– Microorganisms and other foreign substances
are filtered from lymph by lymph nodes and
from blood by spleen
Fluid balance. Circulating blood release about 30 L of
fluid into the interstitial space each day. Of which 27 L
are returned to the circulation. Remaining 3 L will
enters the lymphatic system as lymph. The lymph
passes through the lymphatic system and returns to the
blood vessels.
In addition to water, lymph contains substances in
plasma and substances extracted from cells.
Lymphatics spread
out throughout the
body except the
region of central
nervous system.
(Fig. 22-1).
They start from
lymphocyte
producing organs.
There is a major
thoracic duct.
Many lymph nodes in
which nodules are
found.
Lymphatic Vessels
• Lymphatic capillaries join to form
• Lymphatic vessels
– Have valves that ensure one-way flow
• Lymph nodes: Distributed along vessels and filter lymph
• Lymphatic trunks: Jugular, subclavian,
bronchomediastinal, intestinal, lumbar
• Lymphatic ducts: Right and thoracic which connect to
large veins, brachiocephalic veins.
Like blood vessels, they have small vessels called
lymphatic capillaries, which become close to the blood
capillaries. (Fig. 22-2a,b)
Lymph soluble fluid will be picked up through the lymph capillaries
and pushed back to a larger trunk. (Fig. 22-4b) Thelymphatic
system drains into the blood at brachiocephalic veins.
Lymph Drainage Into Veins
They even have valves to control the flow of lymph
through very low pressure of fluid. (Fig. 22-3)
c.
Lymphocytes
They compose the 25% of circulating white cells
and could be up to one Kg in total, but the
majority of lymphocytes remain in peripheral
tissues.
i.
Types of lymphocytes
There are three types of lymphocytes: (Fig. 22-5) They originate
in red bone marrow, but T-cells mature in thymus.
(a)
T cells: 80% of circulating lymphocytes
Lymphoid stem cells in the red bone marrow migrate
to thymus and become mature T-cells.
Cytotoxic T cells attack foreign cells or cells infected
with viruses.
Provides cell-mediated immunity.
Helper T cells stimulate the activities of T cell and B
cells.
Suppresser T cells inhibit T cells and B cells.
(a)
B cells: 10 - 15 %.
Plasma cells produce antibodies (immunoglobulins) and
react antigenic pathogens.
Reside in lymph nodes, the spleen, and other lymphoid
tissues
Antibody-mediated immunity.
(b)
NK cells: The remainder.
Attack foreign cells, normal cell infected with viruses
and cancer cells.
They immunological survey peripheral tissues.
ii.Origin and development of lymphocytes
Lymphocytes travel around the entire body and have
significantly long life span.
80% survive up to 4 years and some to 20 years!
As we have already seen, lymphocytes are made in the red
bone marrow and some continue to develop in the thymus.
(Fig. 22-5)
Pre-B cells and pre-T cells are in the red bone marrow. Pre-B
cell mature in the red bone marrow and become B cell.
Pre T-cells move into the thymus and become T-cells. Recall
there are suppressor T-cells and helper T-cell.
A positive selection process keep cells capable of
immune response. Those which are incapable will die.
“A group of B or T cells capable of responding to a
specific antigen is a clone.“
Each clone is capable of responding to a particular
antigen and there are many clones.
When the clones respond to self-antigens, negative
selection eliminates such clones.
If this is done successfully, there will be no auto-immune
response.
These processed will start during the prenatal
development, but may continue throughout life.
d.
Lymphatic organs
i.
Diffuse lymphatic tissue.
Dispersed lymphocytes, macrophages and others. No
clear boundaries (Fig. 22-6a)
• Lymphatic tissue
– Consists mainly of
lymphocytes
– Encapsulated or not
• Lymphatic nodules
– Numerous in loose
connective tissue of
digestive (Peyer’s
patches), respiratory,
urinary, reproductive
systems
Lymphoid
nodules (Fig.
22-6a)
Lymphoid nodules
Packed with lymphocytes.
Flexible in size depending upon the number of
lymphocytes.
Found in the digestive, respiratory and urinary systems.
Peyer’s Patches on the intestine are large number of
aggregated lymph nodules.
There is a germinal center, where lymphocytes divide.
Though filled with lymphocytes, lymphoid nodules could
be infected: tonsillitis, appendicitis.
i.
Tonsils
Large groups of lymphnodules and diffuse lymphatic
tissue located in the oral cavity. (Fig. 22-6b)
Protection against bacteria, etc. in the nose and mouth.
Three types of tonsils.
Enlarged pharyngeal tonsil is called adenoid.
i.
Lymph
nodes (Fig. 22-1
and Fig. 22-7)
Lymph nodes
An encapsulation of lymphocytes, macrophages and
reticular cells with blood vessels.
Found through out the body except the CNS.
1 - 25 mm in diameter and has medulla and cortex.
Act as a sieve and remove 99% of the antigens while
reactivating T cells and B cells.
Lymphocytes division takes place in the nodules of the
lymph nodes
The spleen Fig. 22-9
The spleen
Largest as the lymphatic tissue. 160g.
Found in the upper-left and posterial part of the
abdominal cavity.
Pulps of the spleen.
The red pulp - Red blood cells.
The white pulp - lymphoid nodules.
Removes antigens and damaged blood cells.
Immune response, irons for recycling
The thymus gland (Fig. 22-8)
The thymus gland
Found on top of the heart. (Fig. 22-8)
Lobules consist of cortex and medulla.
T cells are made and mature here.
Becomes large in size during the first or second year.
Intrinsic size is the largest at puberty and then
decreases.
Thymosins are made here, too.
Reticular cells wrap around the capillaries to form the
blood thymic barrier.
1.
Immunity
How the human body defends itself against damages from
foreign substances such as microorganisms and harmful
chemical as toxins..
Two types of immunity are distinguished by the way they
respond to specific stimulations and how they memorize the
events.
Nonspecific immunity: Acts against bacteria in general (nonspecific) and has no-memory. Thus each event is an
independent event.
Specific immunity: Can distinguish among different kinds of
bacteria (pathogens) and has memory. Because of its memory,
the second exposure to the pathogens brings faster and
stronger immune response than the first exposure -- immunity
has been established
1.
Non-specific immunity - general and has no memory
a.
Mechanical Mechanism
Physical barriers, such as the skin and
membranes.
Mechanical Mechanisms and
Chemical Mediators
• Mechanical Mechanisms
– Skin, tears, saliva, mucous
membranes, mucus
• Chemical Mediators
– Complement
• Group of 20 proteins
• Circulate in blood in
inactive form
• Become activated in
cascade form: Classical
or alternative pathway
– Interferons
• Prevent viral replication
b. Chemical Mediators
Molecules which contribute to develop immunity.
Kill bacteria: lysozyme, sebum mucus
Others: Histamine and kinins by vasodilation; interferon
production, etc.
Complement: A group of about 20 proteins in plasma activated in
the form of cascade and provide protection by attacking the
bacterial membrane to cause lysis. (Fig. 22-12)
Interferons: Interferon is an example of cytokine (cell to cell
communication). They are small proteins released from
lymphocytes, macrophages and tissue that are infected with
viruses. Arriving at the normal cell membrane they bind to the
receptor and trigger the production of antiviral proteins in the
cytoplasm and inhibit the production viruses.
a.
Cells for non-specific immunity
Review the major functions of neutrophils, macrophages,
monocytes, basophils, mast cell, eosinophils, and natural
killer cells. (Table 22.2 of Seeley)
c. Innate Immunity: Cells
• White blood cells
– Most important cellular
components of immune
system
– Methods
• Chemotaxis
• Phagocytosis
• Neutrophils
– Phagocytic and first
cells to enter infected
tissue
• Macrophages
– Monocytes that leave
blood, enter tissues
– Large phagocytic cells
• Basophils and mast cells
– Promote inflammation
• Eosinophils
– Reduce inflammation
• Natural killer cells
– Lyse tumor and virusinfected cells
NK cells in action (Fig. 22-11): NK cells recognizes unusual
cells (immunological surveillance) and make contact. Its
Golgi apparatus releases enzymes to lyses cells.
Inflammatory Response
• Tissue injury regardless of type can cause
inflammation
• Response initiated by chemical mediators that
produce vasodilation, chemotactic attraction,
increased vascular permeability
• Types
– Local: Symptoms are redness, heat, swelling, pain, loss of
function
– Systemic: Symptoms are increase in neutrophil numbers,
fever and shock
e.
Fever
Body temperature higher than 37.2˚C (99˚F).
Pyrogen that unlocks the homeothermic body
temperature regulation in the hypothalamus is
released by pathogens, bacterial toxins, etc.
The pyrogen released by active macrophages is
called interleukin-1.
High body temperature inhibits virus and
bacterial activities, while increasing the host’s
body metabolism for recovery.
1. Specific immunity – specific
immunity with memory Overview –
types of immunity (Fig. 22-14)
a.
Introduction
Substances to stimulate specific immunity, i.e. formation of
antibodies, are antigens, of which molecular weights could be as
large as Mr = 10,000 or more.
A small molecule may become antigenic upon binding with other
molecules. For example, Haptens are small molecules capable
of combining with larger molecules to stimulate adaptive immune
response.
Two types of antigens: Foreign antigens are from outside of the
body, and self antigens are molecules of its own body.
For example, allergic reaction is by foreign antigens, while
autoimmune disease is from self antigens.
Immunity has been divided into two types: Humoral (body fluid)
immunity and cell mediated immunity.
Specificity: Recognition of antigens
The specificity is established because of the specific receptors
located on the surface of the T and B lymphocyte cells.
Versatility: There are many types of lymphocytes.
Responding to many antigens many types of lymphocytes are
formed to fight against each antigen.
Memory: The specific immune system has memory. With the presence of a
foreign body, the lymphocytes respond by initiating cell divisions and:
Active and memory cells are made.
The active cells respond to the antigens immediately, while the
dormant memory cells wait until the next onslaught of antigens.
In this manner, the second response to the same antigens will be fast
and stronger
Tolerance: Self vs. non-self cells.
Introduction to immune response see Fig. 22-15
i.
T-cells and cell mediated immunity
T-cells are made in response to a specific
antigen and in a large quantity
(a)
Antigenic
determinants and
antigen receptors
An antigen may have many
antigenic determinants
(epitope)
Each antigenic determinant
can activate a specific
lymphocyte.
Thus it is possible that an
antigen with many epitopes
can activate many different
lymphocytes.
Each lymphocyte from the same clone will have the
same antigen receptors.
For example, a membrane bound T-cell receptor has
variable and constant regions. (Fig. 22.13). The
variable region, which is outside the membrane, will
have a specific antigen binding site. Thus a clone of Tcells, having the same receptor, will bind only a specific
antigenic determinant of an antigen. The other T-cells
may have different antigen binding sites.
The B-cell receptor is similar, but larger.
(b)
Major histocompatibility complex antigens
Most lymphocyte activation involves glycoproteins on the
surface of cells called the major histocompatibility complex
(MHC) molecules. All the cell membranes have MHC.
–Class I molecules display antigens on the surface of
nucleated cells, resulting in destruction of the cells, if the
antigens are foreign.
–Class II molecules display antigens on the surface of
antigen-presenting cells, resulting in activation of
immune cells
MHC class I molecules: (Fig. 22-16a)
(i) MHC class I molecules: (Fig. 22-16a)
On nucleated cells.
Foreign or self proteins are fragmented in the nucleated
cells and become antigens.
They combine with MHC class I molecule in the cell and
the complexes are transported on the surface of the
cell.
The antigens will be presented on the surface of
membrane and attract T-cells only to the foreign
antigens and the infected cells will be destroyed.
If it had also attracted to the self antigen, the autoimmune disease might occur. (Transplant)
MHC class II molecules (Fig. 22-16b)
(2) MHC class II molecules (Fig. 22.16b)
These molecules are found in antigen-presenting cells,
such as B-cells, macrophages, monocytes and dendritic
cells.
Antigen-presenting cells phagocytically ingest
unprocessed antigens, process them and let them
combine with MHC II molecules. Note the vescicles.
The complex will be presented on the surface of the cells.
They stimulate the other immune cells to divide leading to
destruction of antigen presenting cells.
(c )
Antigen recognition and Costimulation (Fig 22-17)
Inactive T-cells have receptors that recognize Class I and II MHC
proteins (Fig. 22-17).
The receptors also have binding sites that detect the presence of
specific bound antigens presented by MHC proteins.
If these antigens are not the target of the T cell receptor, the T cell
remains inactive.
If it is one of the target antigen, there will be a binding between the
infected cell and T cell. This is antigen recognition.
The cluster of differentiation (CD) marker proteins are bound on the
membrane of T-cell (Fig. 22-17). More than 70 CDs have been
identified and they are given numerical ID.
All the T cells have CD3.
CD8 markers are on cytotoxic T cell and suppressor T
cells. – CD8 T cells. CD8 T cells respond to antigens
presented by class I MHC proteins.
CD4 markers are found on help T cell – CD4 T cells. CD4
T cells respond to antigens presented by Class II MHC
proteins.
Both CD8 and CD4 make a complex with CD3 receptor
complex.
After the antigen recognition, and interaction of CD, the
secondary binding process, costimulation, must take place
before activation of T cells. (Fig. 22-17) Costimulation
proteins are similar to cytokinins.
(d) Activation of CD8 T cells for Class I
MHC proteins
Cytotoxic T Cells or Killer T cells
Highly mobile killer T cells destroy abnormal and infected
cells in the three different manners shown in Fig. 22-17.
Release of lymphotoxin, cytokine and perforin.
Usually requires a secondary activation of T-cells, thus
taking a week to be effective. (Fig. 22-24)
(c )
Antigen recognition and Costimulation (Fig 22-17)
Memory T cells (Fig. 22-17)
Some of the T cells after activation and cell
division, they become memory cells and do not
participate in destruction of other cells.
The number of memory cells are large enough to
respond quickly and in a large quantity when the
second round of antigenic attack takes place.
Suppressor T Cells
Suppress the responses of other T cells and B
cells by secreting suppression factors –
inhibitory cytokines.
Slow in action
(e) Activation of CD4 T Cells for Class II MHC
Activation is similar to CD8, but possible without
costimulation.
Upon activation and cell division, memory T cells and
helper T cells are made. (Fig. 22-18)
The helper T cells secrete a variety of cytokines and
coordinate specific and nonspecifice defenses and
stimulate cell mediated and antibody-mediated
immunities.
Fig 22-18
Helper T cells
Fig. 22-19 summarizes the pathways of T cell activation
(ii) B Cells and Antibody-Mediated
Immunity
(a) B-cell Sensitization and activation (Fig. 22-20).
(a) B-cell Sensitization and activation (Fig. 22-20).
Before B-cells to be activated, they must also have
processed the antigen, which is presented by a class II
MHC.
The helper T-cell recognizes it and forms a bond to
activate the B-cell.
The activated B-cell begins to be proliferated and the
daughter cells make antibodies or become memory B
cells.
(b) Antibody Structure
Antibodies are produced in B-cells in response to an
antigen and found in plasma.
Plasma proteins have four major components: Albumin,
and alpha, beta and gamma globulins.
Antibodies are found in gamma globulin group, thus
sometime called gamma globulins or immunoglobulins (Ig)
There are 5 types of immunoglobulins (Table 22-1)
IgG, IgM, IgA, IgE, and IgD.
They all consist of 4 peptides. (Fig. 22-21a,b)
Connected with disulfide bonds and have
constant regions and antigen binding variable
regions.
The constant regions attach to cells, such as
macrophages, basophil, B-cells, etc.
Also recall antigen, antibody and antigenic
determinants and role of hapten (Fig. 22-21 c,d)
(c)
Action of antigen-antibody complex
The function of antibody is to find antigen and destroys it.
Neutralization, agglutination and precipitation, activation of
complement, attraction of phagocytes, enhancement of
phagocytosis, and stimulation of inflammation.
Antibodies can counteract the action of antigens in several ways.
(Fig. 22.19 of Seeley)
(1) Upon binding with an antigen, the antibody inactivates the
antigen.
(2) Inactivation may lead to co-precipitation of antigens and
antibodies.
(3) Binding of too may stimulates phagocytic activities.
Actions of Antibodies
(d) Primary and Secondary
Responses to Antigen Exposure
Fig. 22-22 Primary
and secondary
immune responses
Antibody Production
(1)
The primary response
The first encounter with an antigen, a B-cell divides and
differentiate leading to antibody production. (Fig. 22-22a)
Antibodies, IgM and IgD, are on the surface of B-cells.
B-cells, which are small lymphocytes, activated by antigen
starts cell divisions.
Some become large plasma cells, which produce antibodies.
And the others become small memory B-cells.
The primary process takes 3 - 14 days,
The antigen may cause tissue damage during this period.
(2)
The secondary, or memory, response
When the immune system is exposed to the same
antigen after the primary response, the memory cells
quickly divide to produce plasma cells and large quantity
of antibody is released, providing quick immune
protection. (Fig. 22-22b)
The response is quick, hours to a few days, and the
quantity of antibody production is large.
Good defense against the disease.
The memory cells, which may survive for years, are also
formed.
5.
Su
mmary
(Fig. 2223, 24)
6.
Immune disorders
• Hypersensitivity reactions
• Autoimmune disease
• Severe combined immunodeficiency disease
(SCID)
• Transplantation
– Acute rejection
– Chronic rejection
i.
Auto-immune disorders
Identify own body cells as antigens and B-cells make
autoantibodies.
May be due to a reduction in suppressor T cell
activity, excess stimulation of of helper T cells.
Rheumatoid arthritis, IDDM, thyroiditis etc.
Some viruses, measles and influenza, have a
sequence similar to those of myelin proteins. Thus,
antibodies which attack viruses may also attack
myelin sheath.
Unusual types of MHC proteins.
ii.
Iimmunodeficiency Diseases
Trouble with the embryological development of
lymphoid organs and tissues
Viral infection that leads to immuno depression
Exposure to immuno suppressive agents, such as
radiation, drugs etc.
Severe combined immunodeficiency diseases (SCID)
fail to develop antibodies.
AIDS – viral infection that targets helper T cells.
iii.
Allergies
Excessive immune responses to antigens,
allergens.
iv.
Stress can reduce the immune response.
iii. Effects of Aging
• Little effect on lymphatic system
• Decreased ability of helper T cells to
proliferate in response to antigens
• Decreased primary and secondary antibody
responses
• Decreased ability of cell-mediated
immunity to resist intracellular pathogens
Ways to Acquire
Adaptive Immunity