Transcript Lymphatic & Immune System

Lymphatic & Immune System
Dr. Michael P. Gillespie
Important Terminology
 Pathogens – disease producing microbes
such as bacteria and viruses.
 Resistance – the ability to ward off damage
or disease through our defenses.
 Susceptibility – our lack of resistance or
vulnerability.
Types Of Resistance
 Nonspecific resistance – innate defenses.




Present at birth.
Provides immediate, but general protection
against invaders.
Mechanical and chemical barriers of the skin and
mucous membranes (1st line of defense).
Acidity of the gastric juice.
Types Of Resistance
 Specific resistance – immunity.




Develops in response to contact with a particular
invader.
Occurs more slowly than nonspecific resistance.
Involves activation of specific lymphocytes.
The lymphatic and immune system is responsible
for this kind of resistance.
Components
 Lymph fluid.
 Lymphatic vessels.
 Various structures containing lymphatic
tissue.
 Red bone marrow – stem cells develop into
lymphocytes (among other types) here.
Lymph Fluid
 A clear liquid.
 Blood plasma filters through the capillaries
into the interstitial fluid.
 After interstitial fluid passes into lymphatic
vessels it is called lymph.
Lymphocytes In The Immune
Response
 B cells.
 T cells.
Functions Of Lymphatic &
Immune System
 1. Draining excess interstitial fluid.
 2. Transporting dietary lipids and lipid
soluble vitamins (A, D, E, and K).
 3. Carry out immune responses.

Lymphocytes, aided by macrophages, recognize
foreign cells, microbes, toxins, and cancer cells.
T cells destroy the intruders.
 B cells produce antibodies that recognize foreign cells.

Lymphatic Vessels &
Circulation
 Lymphatic vessels begin as lymphatic capillaries.
 Lymphatic capillaries unite to form larger
lymphatic vessels.
 Lymphatic vessels are similar to veins, but have
thinner walls and more veins.
 Lymph flows through lymph nodes (masses of B
cells and T cells).
Lymphatic Vessels &
Circulation
 In the skin, lymphatic vessels generally follow
veins.
 Lymphatic vessels of the viscera generally follow
arteries.
 Avascular tissues lack lymphatic capillaries
(cartilage, epidermis, cornea of the eye).
 The CNS, portions of the spleen, and bone marrow
also lack lymphatic capillaries.
Lymphatic Capillaries
 Slightly larger than blood capillaries.
 Permit fluid to flow into them, but not out.
 Lacteals – specialized lymphatic capillaries
in the small intestine that carry dietary lipids.
Lymph here appears white due to the lipids
and is referred to as chyle.
Lymph Trunks & Ducts
 Lymph vessels merge and unite to form
trunks.
 Principal trunks:

Lumbar, intestinal, bronchomediastinal,
subclavian, and jugular trunks.
 Lymph passes from lymph trunks into two
main channels, the thoracic duct and the right
lymphatic duct.
Thoracic (Left Lymphatic)
Duct
 Begins as a dilation of the cisterna chyli
anterior to the 2nd lumbar vertebra.
 Receives lymph from the left side of the
head, neck and chest, left upper limb, and the
entire body inferior to the ribs.
Thoracic (Left Lymphatic)
Duct
 Drains into the left subclavian vein.
 Drains the following trunks:





Right and left lumbar trunks.
Intestinal trunk.
Left jugular trunk.
Left subclavian trunk.
Left bronchomediatinal trunk.
Right Lymphatic Duct
 Drains lymph from the upper right side of the
body into venous blood via the right
subclavian vein.
 Drains lymph from the following trunks:



Right jugular trunk.
Right subclavian trunk.
Right bronchomediastinal trunk.
Formation & Flow Of Lymph
 Many components of blood plasma freely
flow through the capillaries to form
interstitial fluid.
 More fluid filters out of blood capillaries
than is reabsorbed by them (about 3 liters
more).
Formation & Flow Of Lymph
 The excess fluid drains into lymphatic
capillaries and becomes lymph.
 Lymph returns plasma proteins to the blood
(they cannot be reabsorbed by the blood
capillaries).
 Lymphatic vessels have valves to ensure one
way flow.
Sequence Of Fluid Flow
 Blood capillaries (blood) > interstitial spaces
(interstitial fluid) > lymphatic capillaries
(lymph) > lymphatic vessels (lymph) >
lymphatic ducts (lymph) > subclavian veins
(blood).
Pumps To Return Lymph
 Skeletal muscle pump.
 Respiratory pump.
Edema & Lymph Flow
 Edema – excessive accumulation of interstitial
fluid.
 Edema can be caused by obstruction of lymph flow
due to an infected lymph node or blocked lymphatic
vessel.
 Increased capillary blood pressure can cause edema
by producing accumulation of interstitial fluid
faster than it can flow into the lymphatic vessels.
Elephantiasis
Lymphatic Organs & Tissues
 Primary lymphatic organs – sites where stem
cells divide and become immunocompetent.


Red bone marrow.
Thymus.
Lymphatic Organs & Tissues
 Secondary lymphatic organs – sites where
most immune responses occur.



Lymph nodes.
Spleen.
Lymphatic nodules (follicles) – these are tissues
not organs because they lack a capsule.
Thymus
 A bilobed organ located in the mediastinum
between the sternum and the aorta.
 The cortex consists of T cells.
Thymus
 Pre-t cells migrate from the bone marrow and
mature into T cells here.
 The medulla consists of more mature T cells
and macrophages.
 The thymus is large in an infant, but begins
to atrophy after puberty.
Lymph Nodes
 Located along the lymphatic vessels.
 There are about 600 bean shaped lymph
nodes.
 They are scattered throughout the body, but
usually occur in groups.
Lymph Nodes
 The outer cortex contains aggregates of B
cells called lymphatic nodules (follicles).
 When B cells encounter a foreign antigen,
they develop into antibody producing plasma
cells or into memory B cells (which persist to
recognize the foreign antigen in the future).
Lymph Nodes
 The inner cortex contains primarily T cells,
which proliferate when exposed to a foreign
antigen. They then migrate to areas of the
body with antigenic activity.
 The medulla contains B cells, antibodyproducing plasma cells, and macrophages.
Lymph Flow
 Lymph flows through the node in only one
direction.
 Afferent (to carry toward) vessels carry
lymph to the node.
 Efferent (to carry away) vessels carry lymp
away from the node.
Lymph Nodes
 Lymph nodes serve to filter lymph.
 Foreign substances are trapped within the
reticular fibers.
 Macrophages destroy foreign substances by
phagocytosis.
 Lymphocytes destroy substances via other
immune responses.
Metastasis
 Metastasis is the spread of disease from one
part of the body to another.
 The blood vessels and lymph nodes serve as
routes for metastasis.
Metastasis
 Cancer cells may travel through the
lymphatic vessels and lodge in a lymph node.
 Cancerous lymph nodes feel enlarged, firm,
non-tender, and fixed to underlying
structures.
 Lymph nodes enlarged due to infection are
soft, movable, and very tender.
Spleen
 The spleen is the single largest mass of
lymphatic tissue.
 It is located in the left hypochondriac region
between the stomach and the diaphragm.
Spleen
 B cells and T cells carry out immune functions in a
similar fashion to lymph nodes.
 Macrophages destroy blood born pathogens by
phagocytosis.
 Blood cell related functions:



Removal of worn out or defective RBCs by
macrophages.
Storage of platelets (1/3).
Hemopoiesis (production of RBCs) during fetal life.
Ruptured Spleen
 The spleen is the most often damaged organ
in cases of abdominal trauma.
 Blows to the left inferior chest can fracture
ribs and rupture the spleen.
 Intraperitoneal hemmorrhage and shock
follow.
Ruptured Spleen
 Splenectomy (removal of the spleen) is
needed to prevent death due to bleeding.
 The red bone marrow and liver take over
many of the functions of the spleen;
However, immune functions are decreased.
Ruptured Spleen
 Sepsis (blood infection) is more likely to
occur due to loss of the filtering and
phagocytosis of the spleen.
 These patient must take antibiotics prior to
any invasive procedures to reduce the risk of
sepsis.
Lymphatic Nodules
 Lymphatic nodules are egg-shaped masses of
lymphatic tissue that are not surrounded by a
capsule.
 The are scattered through mucous
membranes of the GI, urinary, reproductive,
and respiratory systems.
Lymphatic Nodules
 They are referred to as mucosa-associated
lymphatic tissue (MALT).
 Large aggregations of these nodules are
referred to as tonsils (5 of them).

A single pharyngeal tonsil (adenoid), 2 palatine
tonsils, 2 lingual tonsils.
Development Of Lymphatic
Tissues
 Lymphatic vessels develop from lymph sacs
that are derived from mesoderm.
 The jugular lymph sacs appear first, then the
retroperitoneal lymph sac, then the cysterna
chyli, and finally the posterior lymph sacs.
Nonspecific Resistance: Innate
Defenses
 Present at birth.
 Offer immediate protection against a wide
variety of pathogens and foreign substances.
Nonspecific Resistance: Innate
Defenses
 First line of defense: skin and mucous membranes.










Epidermis.
Mucous membranes, mucus, hairs, cilia.
Lacrimal apparatus manufactures and drains tears.
Saliva washes microbes from the teeth.
Flow of urine retards microbial colonization.
Vaginal secretions move microbes out of the body.
Defecation and vomiting expel microbes.
Sebaceous glands secrete sebum which forms a protective film.
Perspiration flushes microbes and contains lysozyme.
Acid gastric juice destroys microbes.
Nonspecific Resistance: Innate
Defenses
 Second line of defense: internal defenses.

Antimicrobial proteins.



Natural killer cells and phagocytes.
Inflammation.



Interferons (IFNs) and transferrins inhibit bacterial growth and
replication.
Redness, pain, heat, swelling.
Emigration of phagocytes.
Fever.

Inhibits the growth of microbes and speeds up body reactions that
aid repair.
Specific Resistance: Immunity
 Specific resistance or immunity is the ability
of the body to defend itself against specific
invading agents such as bacteria, toxins,
viruses, and foreign tissues.
Specific Resistance: Immunity
 Antigens (Ags) are substances that are
recognized as foreign and provoke immune
responses.
 2 properties distinguish immunity from
nonspecific defenses:


1. Specificity.
2. Memory.
Immunocompetence
 Immunocompetence is the ability to carry out
immune responses.
 Lymphocytes called B cells and T cells carry
out immune responses.
Immunocompetence
 Both of these types of cells develop from the
primary lymphatic organs (red bone marrow
and thymus).
 B cells mature in the bone marrow.
 Pre-t cells from the bone marrow migrate to
the thymus where they mature.
Types Of Immune Responses
 Cell-mediated immune responses.

T cells become cytotoxic T cells that attack the
invading antigen directly.
 Antibody-mediated immune responses.

B cells secrete antibodies (abs) or
immunoglobulins. Antibodies bind to and
inactivate specific antigens.
Immune Response & Invader
Types
 Cell-mediated immunity is effective against:

1. Intracellular pathogens that reside within host cells.



Fungi, parasites, and viruses.
2. Some cancer cells.
Foreign tissue transplants.
 Antibody-mediated immunity is effective against:


1. Antigens present in body fluids.
2. Extracellular pathogens in body fluids (bacteria).
 Most pathogens elicit both responses.
Characteristics Of Antigens
 Immunogenicity – the ability to provoke an immune
response by stimulating the production of specific
antibodies.
 Reactivity – the ability of an antigen to react with
specific antibodies.
 Epitopes – the small parts of antigen molecules that
initiate immune responses.
 Entire microbes or parts of microbes may act as
antigens.
Routes Of Antigens Into
Lymphatic Tissue
 Most antigens that enter the bloodstream are
trapped as they flow through the spleen.
 Antigens that penetrate the skin enter
lymphatic vessels and lodge in lymph nodes.
 Antigens that penetrate mucous membranes
are entrapped by mucosa-associated
lymphatic tissue.
Hapten
 A hapten is a smaller substance that has
reactivity, but lacks immunogenicity.
 It can only stimulate an immune response if
it is attached to a larger carrier molecule.
 Poison ivy is an example of a hapten.
Major Histocompatibility
Complex (MHC)
 The major histocompatibility complex (MHC)
antigens are “self antigens”.
 The MHC are located in the plasma membrane of
body cells.
 Unless you have an identical twin, your MHC
antigens are unique.
 These are responsible for identifying a foreign
antigen as not self.
Histocompatibility Testing
 The more similar the MHC antigens, the
greater the histocompatibility.
 Greater histocompatibility leads to a lower
likelihood that the organ or tissue will be
rejected.
Processing & Presenting An
Antigen
 B cells recognize and bind to foreign
antigens; However, T cells only recognize
fragments of antigenic compounds that are
“presented” with the MHC.
Processing Of Exogenous
Antigens
 Exogenous antigens are outside of body
cells.
 Ingestion of the antigen by the antigenpresenting cells (APCs).
Processing Of Exogenous
Antigens
 Digestion of the antigen into peptide fragments.
 Antigen fragments fuse to MHC-II complexes,
which are then inserted into the plasma membrane
of the APC.
 The APCs then migrate to lymphatic tissue where
they “present” the antigen fragment-MHC-ii
complex to T cells to inform them to attack.
Processing Of Endogenous
Antigens
 Endogenous antigens are inside of body
cells.
 The MHC-I complex binds with the antigen
fragments inside infected cells.
 The new antigen fragment-MHC-i complex
moves to the plasma membrane of the cell
for “presentation”.
Cytokines
 Cytokines are small protein hormones that
stimulate or inhibit many normal cell
functions, such as cell growth and
differentiation.
 Cytokine therapy is the use of cytokines to
treat medical conditions.
 Interferons were the first cytokines to be
effective against human cancer.
Cell-mediated Immunity
 A cell-mediated immune response begins
with the activation of a small number of T
cells by a specific antigen.
 Once a T cell has been activated, it
undergoes proliferation and differentiation
into effector cells.
 Effector cells recognize and attack the
specific antigen.
Types Of T Cells
 Helper T (TH) cells {CD4+} – resting
(inactive) TH cells recognize antigen
fragments associated with MHC-II
molecules. When activated, they secrete a
variety of cytokines that attack the invaders.
Types Of T Cells
 Cytotoxic T (TC) cells {CD8+} – recognize
foreign antigens associated with MHC-I
molecules. They are capable of lysing
affected cells.
 Memory T cells – these cells remain from a
proliferated clone after a cell-mediated
response. This allows for a swifter response
with subsequent infection.
Elimination Of Invaders
 Cytotoxic T cells are the soldiers that battle with
foreign invaders.
 Cytotoxic T cells use 2 killing mechanisms:


Perforin forms holes in the plasma membrane of the
target cell, which allows extracellular fluid to flow in
causing the cell to burst (cytolysis).
Lymphotoxin is secreted, which activates enzymes
within the target cell. These enzymes cause the targets
DNA to fragment and the cell dies.
Graft Rejection
 Organ transplantation involves the
replacement of an injured or diseased organ
with an organ donated by another individual..
 Usually, the immune system recognizes the
proteins of the transplanted organ as foreign
and mounts immune responses against them.
 This process is known as graft rejection.
Graft Rejection
 The more closely matched the
histocompatibility, the less likely the organ is
to be rejected.
 Organ recipients receive immunosuppresive
drugs to reduce the risk of rejection.
 This increases the risk of infection by some
diseases.
Antibody-mediated Immunity
 Cytotoxic T cells leave lymphatic tissue to
search out and destroy a foreign antigen;
However, B cells stay put.
 When B cells are exposed to a foreign
antigen, they differentiate into plasma cells
that secrete specific antibodies, which
circulate through lymph and blood to reach
the site of invasion.
Activation, Proliferation, &
Differentiation Of B Cells
 Antigens bind to B cell receptors, which activates
them.
 B cells enlarge, divide, and differentiate into plasma
cells which secrete antibodies.
 Some B cells do not differentiate, but remain as B
memory cells.
 Antibodies enter circulation and form antigenantibody complexes with the antigen that initiated
their production.
Antibodies
 Antibodies (Ab) combine specifically with
the antigen that initiated their production.
Antibody Actions
 Neutralizing antigen – blocks or neutralizing
some bacterial toxins and prevents bacterial
attachment to cells.
 Immobilizing bacteria – some form against
cilia or flagella.
Antibody Actions
 Agglutinating and precipitating antigen –
cause agglutination (clumping together) of
pathogens for easier phagocytosis and
precipitation.
 Activating complement.
 Enhancing phagocytosis – attracts
phagocytes.
Complement System
 The complement system is a defensive
system consisting of plasma proteins that
attack and destroy microbes.
 This system leads to the following events”
inflammation, enhancement of phagocytosis,
and bursting of microbes.
Complement System
 Inflammation increases the permeability of blood
capillaries allow WBCs to emigrate into affected
tissues.
 Opsonization – complement fragment c3b binds to
the surface of the microbe and interacts with
receptors on phagocytes.
 Cytolysis – complement proteins form a membrane
attack complex (MAC) that inserts on the
membrane and forms large holes.
Immunological Memory
 The immune system can remember specific
antigens that have triggered immune responses,
either through antibodies, or long lasting
lymphocytes.
 Immune responses are much quicker and more
intense after a second exposure.
 The antibody titer can be utilized to measure
immunological memory.
 Memory cells may remain for decades.
Self-recognition & Selftolerance
 To function properly T cells must:


Recognize your own major histocompatibility
complex (MHC) proteins (self-recognition).
They must lack reactivity to peptide fragments
from your own proteins (self-tolerance).