Chapter 22 Lymphatic System Power Point

Chapter 22: The
Lymphatic System and

Immunity
Copyright 2009, John Wiley & Son

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Immunity or Resistance
 Ability to ward off damage or disease through our
defenses
 2 types of immunity
 Innate or nonspecific immunity – present at birth
 No specific recognition of invaders, no memory
component
 1st and 2nd line of defenses
 Adaptive or specific immunity
 Specific recognition of invaders with a memory
component

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Lymphatic system structure and
function
 Consists of lymph, lymphatic vessels,
structures and organs containing lymphatic
tissue, red bone marrow
 Functions of the lymphatic system
1. Drain excess interstitial fluid
2. Transport dietary lipid
3. Carry our immune responses

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Components of the
Lymphatic System

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Lymphatic vessels and lymph
circulation
 Vessels begin as lymphatic capillaries
 Closed at one end
 Unite to form large lymphatic vessels

 Resemble veins in structure but thinner
walls and more valves

 Passes through lymph nodes
 Encapsulated organs with masses and B
and T cells

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Lymphatic capillaries
 Slightly large diameter that blood capillaries

 Unique one-way structure
 Permits interstitial fluid to flow in but not out
 Anchoring filaments pull openings wider when
interstitial fluid accumulates
 Small intestine has lacteal for dietary lipid
uptake
 Chyle is lymph with lipids

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Lymphatic Capillaries

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Lymph trunks and ducts
 Vessels unite to form lymph trunks

 Principal trunks are the lumbar, intestinal,
bronchomediastinal, subclavian and jugular
 Passes from lymph trunks into 2 main
channels (thoracic and right lymphatic ducts)
before draining into venous blood

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Routes for drainage of lymph

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Formation and flow of lymph
 More fluid filters out of blood capillaries than

returns to them by reabsorption
 Excess filtered fluid – about 3L/day – drains into
lymphatic vessels and become lymph
 Important function of lymphatic vessels to return
lost plasma proteins to blood stream
 Contain valves
 Same 2 “pumps” aiding venous return also used
 Skeletal muscle pump – milking action
 Respiratory pump – pressure changes during breathing

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Relationship of the Lymphatic
System to the Cardiovascular
System

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Lymphatic tissues and
organs
 2 groups based on function
1. Primary lymphatic organs
 Sites where stem cells divide and become
immunocompetent
 Red bone marrow and thymus
2. Secondary lymphatic organs
 Sites where most immune response occurs
 Lymph nodes, spleen, lymphatic nodules

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Thymus and Medulla
 Thymus
 Outer cortex composed of large number of T cells
 Immature T cells migrate here from red bone marrow where
they proliferate and begin to mature
 Dendritic cells derived from monocytes assist in T cell
maturation
 Specialized epithelial cells help educate T cells through positive
selection – only about 25% survive
 Macrophages clear out dead and dying cells
 Medulla
 More mature T cells migrate here from cortex
 More epithelial cells, dendritic cells and macrophages
 Thymus shrinks with age from 70g in infants to 3g in old age

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Thymus

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Lymph nodes
 Located along lymphatic vessels

 Scattered throughout body
 Stroma – supporting connective tissue
 Capsule, trabeculae, reticular fibers and fibroblasts
 Parenchyma – functional part

 Outer cortex – aggregates of B cells called
lymphatic nodules (follicles) – site of plasma cell

and memory B cell formation
 Inner cortex – mainly T cells and dendritic cells
 Medulla – B cells, antibody producing plasma cells
from cortex, and macrophages

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Structure of a Lymph Node

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Lymph
 Lymph flows through a node in 1 direction only
 Enters through afferent lymphatic vessels
 Directs lymph inward
 Lymph enters sinuses (irregular channels)
 Into medulla
 Medullary sinuses drain into efferent lymphatic vessels
 Conveys lymph, antibodies and activated T cells out of the
node
 Lymph nodes function as a filter
 Foreign substances trapped
 Destroyed by macrophages or immune response of
lymphocytes

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Spleen
 Largest single mass of lymphatic tissue in the
body
 Stroma – capsule, trabeculae, reticular fibers,
and fibroblasts
 Parenchyma
 White pulp – lymphatic tissue (lymphocytes
and macrophages)
 B cells and T cells carry out immune
function
 Red pulp

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Red Pulp
 Red pulp – blood-filled venous sinuses and
splenic (Bilroth’s) cords – red blood cells,
macrophages, lymphocytes, plasma cells, and
granulocytes
 Macrophages remove ruptured, worn out or
defective blood cells
 Storage of up to 1/3 of body’s platelet supply
 Production of blood cells during fetal life

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Structure of the Spleen

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Lymphatic nodules
 Not surrounded by a capsule

 Scattered throughout lamina propria of
mucous membranes lining GI, urinary,
reproductive tract
 Mucosa-associated lymphatic tissue (MALT)
of respiratory tract
 Most small and solitary
 Some larger – tonsils, Peyer’s patches,
appendix

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Innate immunity
 First line of defenses: Skin and mucous
membranes
 Provide both physical and chemical barriers
 Physical barriers
 Epidermis – closely packed, keratinized cells
 Periodic shedding
 Mucous membranes
 Mucus traps microbes and foreign substances
 Nose hairs trap and filter
 Cilia of upper respiratory tract propel trapped particles
up and out

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Innate Immunity
 Fluids
 Lacrimal apparatus of eye
 Washing action of tears
 Lysozyme breaks down bacterial cell walls – also present
in saliva, perspiration, nasal secretions, and tissue fluids
 Saliva washes mouth
 Urine cleanses urinary system
 Vaginal secretions, defecation and vomiting
 Chemicals
 Sebaceous (oil) glands secrete sebum – protective film,
acid
 Perspiration, gastric juice, vaginal secretions – all acidic

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Second line of defenses:
Internal defenses
 Antimicrobial substances
1. Interferons
 Produced by lymphocytes, macrophages, and fibroblasts
infected by viruses
 Prevents replication in neighboring uninfected cells
2. Complement
 Proteins in blood plasma and plasma membranes
 “complement” or enhance certain immune reactions
 Causes cytolysis of microbes, promotes phagocytosis,
contributes to inflammation

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Internal Defenses
3. Iron-binding proteins
 Inhibit growth of bacteria by reducing available
iron
4. Antimicrobial proteins (AMPs)
 Short peptides that have a broad spectrum of
antimicrobial activity
 Can attract dendritic cells and mast cells that
participate in immune responses

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Internal Defenses
 Natural Killer (NK) cells
 Lymphocyte but not a B or T cell
 Ability to kill wide variety of infected body cells and
certain tumor cells
 Attack any body cell displaying abnormal or unusual
plasma membrane proteins
 Can release perforin (makes perforations) or granzymes
(induce apoptosis)
 Phagocytes
 Neutrophils and macrophages (from monocytes)
 Migrate to infected area
 5 steps in phagocytosis

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Phagocytosis of a microbe

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1 CHEMOTAXIS Microbe
Phagocyte
2 ADHERENCE 3 INGESTION
Pseudopod
Lysosome 4 DIGESTION
Digested microbe
Plasma in phagolysosome
membrane Residual body
5 KILLING (indigestible
material)
Digestive
enzymes
Phases of phagocytosis
Inflammation
 Nonspecific, defensive response of body to tissue

damage
 4 signs and symptoms – redness, pain, heat and
swelling
 Attempt to dispose of microbes, prevent spread,
and prepare site for tissue repair
 3 basic stages
 Vasodilation and increased blood vessel permeability
 Emigration
 Tissue repair

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Vasodilation and increased
permeability of blood vessels
 Increased diameter of arterioles allows more
blood flow through area bringing supplies and
removing debris
 Increased permeability means substances
normally retained in the blood are permitted to
pass out – antibodies and clotting factors
 Histamine, kinins, prostaglandins (PGs),
leukotrienes (LTs), complement

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Inflammation

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Emigration of phagocytes
 Depends on chemotaxis
 Neutrophils predominate in early stages but
die off quickly
 Monocytes transform into macrophages
 More potent than neutrophils
 Pus – pocket of dead phagocytes and

damaged tissue

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Adaptive immunity
 Ability of the body to defend itself against

specific invading agents
 Antigens (Ags) – substances recognized as
foreign and provoking an immune response
 Distinguished from innate immunity by
 Specificity
 Memory

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Maturation of T cells and B cells
 Both develop from pluripotent stem cells

originating in red bone marrow
 B cells complete their development in red bone marrow
 T cells develop from pre-T cells that migrate from red
bone marrow to the thymus
 Helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T
cells)
 Immunocompetence – ability to carry out adaptive
immune response
 Have antigen receptors to identify specific antigen

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Cell-mediated and antibody-
mediated immunity

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2 types of adaptive immunity
 Cell-mediated
 Cytotoxic T cells directly attack invading antigens
 Particularly effective against intracellular pathogens, some
cancer cells and foreign tissue transplants
 Antibody-mediated
 B cells transform into plasma cells making antibodies (Abs) or
immunoglobulins
 Works against extracellular pathogens in fluids outside cells
 Helper T cells aid in both types
 2 types of immunity work together

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Clonal selection
 Process by which a lymphocyte proliferates and

differentiates in response to a specific antigen
 Clone – population of identical cells all recognizing the same
antigen as original cell
 Lymphocyte undergoes clonal selection to produce
 Effector cell – active helper T cell, active cytotoxic T cell,
plasma cell, die after immune response
 Memory cell – do not participate in initial immune response,
respond to 2nd invasion by proliferating and differentiating into
more effector and memory cells, long life spans

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Antigens
 Antigens have 2
characteristics
 Immunogenicity – ability to
provoke immune response
 Reactivity – ability of
antigen to react specifically
with antibodies it provoked
 Entire microbes may act as
antigen
 Typically, just certain small
parts of large antigen
molecule triggers response
(epitope or antigenic
determinant)

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Diversity of antigen
receptors
 Human immune system able to recognize and bind to at
least a billion different epitopes
 Result of genetic recombination – shuffling and rearranging
of a few hundred versions of several small gene segments
 Major Histocompatibility Complex Antigens
 MHC or human leukocyte antigens (HLA)
 Normal function to help T cells recognize foreign or self
 Class I MHC (MHC-I) – built into all body cells except RBCs
 Class II MHC (MHC-II) – only on antigen presenting cells

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Pathways of antigen processing
 B cells can recognize and bind to antigens

 T cells must be presented with processed
antigens
 Antigenic proteins are broken down into peptide
fragments and associated with MHC molecules
 Antigen presentation – antigen-MHC complex
inserted into plasma membrane
 Pathway depends on whether antigen is outside or
inside body cells

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Exogenous and Endogenous
Antigens
 Exogenous antigens – present in fluid outside
body cells
 Antigen-presenting cells (APCs) include dendritic
cells, macrophages and B cells
 Ingest antigen, process, place next to MHC-II
molecule in plasma membrane, and present to T
cells
 Endogenous antigens – antigens inside body
cells
 Infected cell displays antigen next to MHC-I

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Exogenous Antigens

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Key:
5 Vesicles containing antigen Antigen
peptide fragments and peptide
1 Phagocytosis or MHC-II molecules fuse fragments
Exogenous 6 Antigen peptide
endocytosis of
antigen antigen fragments bind to MHC-II
MHC-II molecules self-antigen
Phagosome
or endosome
7 Vesicle undergoes
2 Digestion of exocytosis and
antigen into antigen–MHC-II
peptide fragments 4 Packaging of MHC-II complexes are inserted
Antigen-
presenting molecules into a vesicle into plasma membrane
cell (APC)
Endoplasmic
reticulum
3 Synthesis of MHC-II molecules
APCs present exogenous antigens in association with MHC-II molecules

Endogenous Antigens

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Cell-mediated immunity
 Activation of T cells
 First signal in activation
 T-cell receptors (TCRs) recognize and bind to a specific
foreign antigen fragments that are presented in antigen-MHC
complexes
 CD4 and CD8 proteins are coreceptors
 Second signal required for activation
 Costimulation – 20 known substances (cytokines, plasma
membrane molecules)
 May prevent immune response from occurring accidentally
 Anergy – recognition without costimulation (in both B and T
cells) leads to prolonged state of inactivity

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Activation and clonal selection
of helper T cells
 Most that display CD4 develop into helper T cells (CD4 T
cells)
 Recognize exogenous antigen fragments associated with
MHC-II molecules on the surface of an APC
 After activation undergoes clonal selection
 Makes active helper T cells and memory helper T cells
 Active helper T cells secrete variety of cytokines
 Interleukin-2 (IL-2) needed for virtually all immune responses
 Memory helper T cells are not active cells – can quickly
proliferate and differentiate if the antigen appears again

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of a helper T cell

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of cytotoxic T cells
 Most that display CD8 develop into cytotoxic T
cells (CD8 T cells)
 Recognize antigens combined with MHC-I
 Maximal activation also requires presentation of
antigen with MHC-II to cause helper T cells to
produce IL-2
 Undergoes clonal selection
 Active cytotoxic T cells attack body cells
 Memory cytotoxic T cells do not attack but wait for
a antigen to appear again

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of a cytoxic T cell

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Elimination of invaders
 Cytotoxic T cells migrate to seek out and destroy infected

target cells
 Kill like natural killer cells
 Major difference is T cells have specific receptor for
particular microbe while NK cells destroy a wide variety of
microbe-infected cells
 2 ways to kill cells
 Granzymes cause apoptosis
 Perforin and/ or granulysin causes cytolysis
 Immunological surveillance
 Tumor antigens displayed on cancerous cells targeted by
cytotoxic T cells, macrophages and natural killer cells

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Activity of cytoxic T cells

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Antibody-mediated immunity
 Activation and clonal selection of B cells
 During activation, antigen binds to B cell receptor (BCRs)
 Can respond to unprocessed antigen
 Response much more intense when B cell processes
antigen
 Antigen taken into B cell, combined with MHC-II, moved to
plasma membrane, helper T cell binds and delivers
costimulation (interleukin-2 and other cytokines)
 B cell undergoes clonal selection
 Plasma cells secrete antibodies
 Memory B cells do not secrete antibodies but wait for
reappearance of antigen

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of B cells

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Antibodies (Ab)
 Can combine specifically with epitope of the antigen that

triggered its production
 Belong to group of glycoproteins called globulins
 Ab are immunoglobulins (Igs)
 4 polypeptide chains – 2 heavy (H) chains, 2 light (L)

chains
 Hinge region – antibody can be T shape or Y shape
 Variable (V) region at tips of each H and L chain
 2 antigen-binding sites - bivalent
 Constant (C) region – remainder of H and L chain

 Same in each 5 classes – determines type of reaction

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Chemical structure of the
immunoglobin (IgG) class of
antibody

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Antibody actions
 Neutralizing antigen
 Immobilizing bacteria
 Agglutinating and precipitating antigen
 Enhancing phagocytosis
 Activating complement
 Defensive system of over 30 proteins
 Destroy microbes by causing phagocytosis, cytolysis, and
inflammation
 Acts in a cascade – one reaction triggers another
 3 different pathways ass activate C3
 C3 then begins cascade that brings about phagocytosis,
cytolysis, and inflammation

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Complement activation and
results of activation

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C3
1
Mic 2
ro be C3b C3a
Histamine
C5
e
3
b
cro
Microbe
C5b C5a
Mi
4 C6
PHAGOCYTOSIS:
Enhancement of phagocytosis Mast cell
C7
by coating with C3b C8 INFLAMMATION:
Increase of blood vessel
C9 permeability and chemotactic
attraction of phagocytes
C5b C6 C7 C8 C9
Channel
Membrane attack
Microbial complex forms
plasma channel
membrane
CYTOLYSIS:
Bursting of microbe due to
inflow of extracellular fluid
through channel formed by
membrane attack complex
C5-C9
Immunological memory
 Thousands of memory cells

exist after initial encounter
with an antigen
 Next time antigen appears
can proliferate and
differentiate within hours
 Antibody titer measure of
immunological memory
 Amount of Ab in serum
 Primary response
 Secondary response faster
and stronger

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Self-recognition and self-
tolerance
Your T cells must have
 Self-recognition – be able to recognize your own MHC
 Self-tolerance – lack reactivity to peptide fragments from
your own proteins
 Pre-T cells in thymus develop self-recognition via
positive selection – cells that can’t recognize your
own MHC undergo apoptosis
 Self-tolerance occurs through negative selection in
which T and B cells that recognize self peptide
fragments are eliminated
 Deletion – undergo apoptosis
 Anergy – remian alive but are unresponsive

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Development of self-recognition
and self-tolerance

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End of Chapter 22
Copyright 2009 John Wiley & Sons, Inc.
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Chapter 22: The

Lymphatic System and

Copyright 2009, John Wiley & Son

Copyright 2009, John Wiley & Son

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 Unite to form large lymphatic vessels

walls and more valves

Copyright 2009, John Wiley & Son

 Slightly large diameter that blood capillaries

Copyright 2009, John Wiley & Son

Copyright 2009, John Wiley & Son

 Vessels unite to form lymph trunks

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Copyright 2009, John Wiley & Son

 More fluid filters out of blood capillaries than

Copyright 2009, John Wiley & Son

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Copyright 2009, John Wiley & Son

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 Located along lymphatic vessels

 Parenchyma – functional part

lymphatic nodules (follicles) – site of plasma cell

 Medulla – B cells, antibody producing plasma cells

from cortex, and macrophages

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Copyright 2009, John Wiley & Son

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 Not surrounded by a capsule

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 Nonspecific, defensive response of body to tissue

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 Pus – pocket of dead phagocytes and

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 Ability of the body to defend itself against

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 Both develop from pluripotent stem cells

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 Process by which a lymphocyte proliferates and

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 B cells can recognize and bind to antigens

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