Chapter 22: The Lymphatic
System and Immunity
Copyright 2009, John Wiley & Sons, Inc.
Immunity or Resistance


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Ability to ward off damage or disease through our
defenses
2 types of immunity
Innate or nonspecific immunity – present at birth
(Table 22.1, p891)


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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
Copyright 2009, John Wiley & Sons, Inc.
Lymphatic system structure and function
Consists of lymph (liquid), lymphatic
vessels, structures and organs containing
lymphatic tissue, red bone marrow
Functions of the lymphatic system
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
1.
2.
3.
Drain excess interstitial fluid
Transport dietary lipid
Carry our immune responses
Copyright 2009, John Wiley & Sons, Inc.
See page
833 for
potential
problem
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Components
of the
Lymphatic
System
Lymphatic vessels and lymph circulation

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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
Copyright 2009, John Wiley & Sons, Inc.
Definitions:

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T Cells = lymphocytes that mediate celluar immunity;
including helper and cytotoxoic (aka T lymphocytes).
Origin – Thymus.
B Cells = (aka B lymphocytes) oversee humoral (fluids)
immunity; their descendants differentiate into antibodyproducing plasma cells. Origin – Red Bone marrow.
Lymphocyte – agranular white blood cell via bone
marrow maturing in lymphoid organs of the body
Pluripotent stem cells - can develop into most of the
specialized cells and tissues of the body, are selfrenewing (see page Blood Chapter)
Antibody (protein), Antigen (foreign substance)
Lymphatic capillaries
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Slightly large diameter than 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
Copyright 2009, John Wiley & Sons, Inc.
Lymphatic Capillaries
**Blood Osmotic Pressure** - High = low blood volume =
via dehydration
Lymph trunks and ducts

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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

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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

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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
Primary lymphatic organs

1.
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Sites where stem cells divide and become
immunocompetent
Red bone marrow and thymus
Secondary lymphatic organs
2.


Sites where most immune response occurs
Lymph nodes, spleen, lymphatic nodules
Copyright 2009, John Wiley & Sons, Inc.
Thymus and Medulla

Thymus

Outer cortex composed of large number of T cells
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Medulla
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Immature T cells migrate here from red bone marrow where
they proliferate and begin to mature
Dendritic cells derived from monocytes (largest WBC) assist in
T cell maturation
Specialized epithelial cells help educate T cells through positive
selection – only about 2% survive
Macrophages (phagocyte derived from monocyte, free or fixed)
clear out dead and dying cells
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

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Located along lymphatic vessels (~600)
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 (one
type of antigen presenting cell)
 Medulla – B cells, antibody producing plasma cells
from cortex, and macrophages
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Lymph

Lymph flows through a node in 1 direction only
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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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Structure of a
Lymph Node
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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. Functions:

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Macrophages breakdown 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
Copyright 2009, John Wiley & Sons, Inc.
Lymphatic nodules
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Not surrounded by a capsule
Scattered throughout lamina propria
(connective tissue) 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

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Provide both physical and chemical barriers
Physical barriers

Epidermis – closely packed, keratinized cells
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Mucous membranes
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Periodic shedding
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
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Lacrimal apparatus of eye
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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
vomiting
Chemicals
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Sebaceous (oil) glands secrete sebum – protective film,
acid
Perspiration, gastric juice, vaginal secretions – all acidic
Copyright 2009, John Wiley & Sons, Inc.
Second line of defenses: Internal defenses

Antimicrobial substances
1. Interferons
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2.
Produced by lymphocytes, macrophages, and fibroblasts
infected by viruses
Prevents replication in neighboring uninfected cells
Complement
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Proteins in blood plasma and plasma membranes
“complement” or enhance certain immune reactions
Causes cytolysis of microbes, promotes phagocytosis,
contributes to inflammation
Copyright 2009, John Wiley & Sons, Inc.
Internal Defenses
3.
Iron-binding proteins

4.
Inhibit growth of bacteria by reducing available
iron
Antimicrobial proteins (AMPs)
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
Short peptides that have a broad spectrum of
antimicrobial activity
Can attract dendritic cells and mast cells that
participate in immune responses
Copyright 2009, John Wiley & Sons, Inc.
Internal Defenses

Natural Killer (NK) cells
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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
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Neutrophils (type of WBC) 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
Plasma
membrane
4 DIGESTION
Digested microbe
in phagolysosome
5 KILLING
Digestive
enzymes
Phases of phagocytosis
Residual body
(indigestible
material)
Inflammation

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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
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Vasodilation and increased blood vessel permeability
Emigration
Tissue repair
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Vasodilation and increased permeability of
blood vessels
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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 – released due to injury via mast cells (cell in areolar
connective tissue), platelets, and Basophil (type of WBC)
Kinins – polypeptides, that VD and promote chemotaxis
prostaglandins (PGs) – chemotaxis and enhance response of 1st two.
leukotrienes (LTs) – chemotaxis, phagocyte attachment, via basophils.
complement - similar to above traits and can also kill some bacteria.
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Inflammation
Emigration of phagocytes
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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
Copyright 2009, John Wiley & Sons, Inc.
Maturation of T cells and B cells

Both develop from pluripotent stem cells
originating in red bone marrow
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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
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2 types - 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
Copyright 2009, John Wiley & Sons, Inc.
Mechanisms of Antigen Entrance

Enters Skin - Lymph vessels – L. Nodes
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Lymph nodules
Enter mucus membrane – M.A.L.T.
Enters blood – Spleen
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Cell-mediated
and antibodymediated
immunity
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2 types of adaptive immunity

Cell-mediated
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Cytotoxic T cells directly attack invading antigens
Particularly effective against intracellular pathogens, some
cancer cells and foreign tissue transplants
Antibody-mediated (B cells stay in secondary LT)
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B cells transform into plasma cells making antibodies (Abs) or
immunoglobulins
Works against extracellular pathogens in fluids outside cells
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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

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Clone – population of identical cells all recognizing the same
antigen as original cell
Lymphocyte undergoes clonal selection to produce
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Effector cell – active helper T cell, active cytotoxic T cell,
plasma cell; all 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 (decades)
Copyright 2009, John Wiley & Sons, Inc.
Antigens

Antigens have 2
characteristics
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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
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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
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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
(APC)
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Pathways of antigen processing
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B cells can recognize and bind to antigens
T cells must be presented with processed
antigens
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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
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Antigen-presenting cells (APCs) include dendritic
cells, macrophages and B cells to…
Ingest antigen, process, place next to MHC-II
molecule in plasma membrane, and present to T
cells
Endogenous antigens – antigens inside any
body cells

Infected cell displays antigen next to MHC-I
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Exogenous
Antigens
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Key:
1 Phagocytosis or
endocytosis of
antigen
Exogenous
antigen
5 Vesicles containing antigen
peptide fragments and
MHC-II molecules fuse
6 Antigen peptide
fragments bind to
MHC-II molecules
Phagosome
or endosome
Antigenpresenting
cell (APC)
2 Digestion of
antigen into
peptide fragments
4 Packaging of MHC-II
molecules into a vesicle
7 Vesicle undergoes
exocytosis and
antigen–MHC-II
complexes are inserted
into plasma membrane
Endoplasmic
reticulum
3 Synthesis of MHC-II molecules
APCs present exogenous antigens in association with MHC-II molecules
Antigen
peptide
fragments
MHC-II
self-antigen
Endogenous Antigens
Cell-mediated immunity

Activation of T cells
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First signal in activation
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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

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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
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Most that display CD4 develop into helper T cells (aka 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
(which triggers t-cell proliferation) via positive feedback
Memory helper T cells are not active cells – can quickly
proliferate and differentiate if the antigen appears again
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Activation and clonal
selection of a helper
T cell
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Activation and clonal selection of
cytotoxic T cells
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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 (cause apoptisis) attack
body cells
Memory cytotoxic T cells do not attack but wait for
a (of the same) antigen to appear again
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Activation and
clonal selection of a
cytoxic T cell
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Elimination of invaders

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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
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Phagocytes then destroy the invading microbes
Perforin and / or granulysin causes cytolysis of the
microbe
Immunological surveillance

Tumor antigens displayed on cancerous cells targeted by
cytotoxic T cells, macrophages and natural killer cells
Activity of
cytoxic
T cells
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Antibody-mediated immunity

Activation and clonal selection of B cells
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During activation, antigen binds to B cell receptor (BCRs)
B Cell can respond to unprocessed antigen (no APC)
Response much more intense when B cell processes
antigen from APC
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
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
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
Plasma cells secrete antibodies
Memory B cells do not secrete antibodies but wait for
reappearance of antigen
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Activation and clonal
selection of B cells
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Chemical structure of the immunoglobin
(IgG) class of antibody
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Antibodies

There are 5 classes of antibodies:
• IgG – a monomer with two antigen-binding sites
 Comprises 80% of total antibody
 Only class able to cross the placenta
 Provides long-term immunity against bacteria and
viruses, by enhancing phagocytosis, neutralizing
toxins, and triggers compliment systems
•
IgA – a dimer with four antigen-binding sites
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prevalent in body secretions like sweat, tears, saliva, breast
milk and gastrointestinal fluids
Provides localized protection of mucous membranes
against B and V
See Table 22.3
Antibody actions

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Neutralizing antigen – stops bacterial toxins or viral adhesion
Immobilizing bacteria – cilia or flagella
Agglutinating and precipitating antigen
Enhancing phagocytosis
Activating complement

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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 to 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
2
C3b
C3a
Histamine
C5
3
C5b
4
PHAGOCYTOSIS:
Enhancement of phagocytosis
by coating with C3b
Microbe
C5a
C6
Mast cell
C7
C8
INFLAMMATION:
Increase of blood vessel
permeability and chemotactic
attraction of phagocytes
C9
C5b
C6
C7
C8
C9
Channel
Membrane attack
complex forms
channel
Microbial
plasma
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

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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 – remain alive but are unresponsive
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Development of self-recognition and selftolerance
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Nova Science Now

http://www.pbs.org/wgbh/nova/body/replacing
-body-parts.html
Thymus
Copyright 2009, John Wiley & Sons, Inc.
Lymph node
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Spleen
Copyright 2009, John Wiley & Sons, Inc.