chapt21_immune2

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Chapter 21
Lecture
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Lymphatic and Immune Systems
• immune system – not an organ system, but a
population of cells that inhabit all of our organs
and defend the body from agents of disease
– especially concentrated in the true organ system –
lymphatic system
• network of organs and vein-like vessels that
recover fluid
• inspect it for disease agents
• activate immune responses
• return the fluid to the bloodstream
21-2
Lymphatic and Immune Systems
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Capillary bed
Tissue fluid
Tissue cell
Lymphatic
capillary
Venule
Arteriole
Figure 21.3a
(a)
• maintain fluid balance
• protect body from infection and disease
21-3
Functions of Lymphatic System
• fluid recovery
– fluid continually filters from the blood capillaries into the
tissue spaces
• blood capillaries reabsorb 85%
• 15% enters lymphatic system and is returned to the blood
• immunity
– excess filtered fluid picks up foreign cells and chemicals
from the tissues
• passes through lymph nodes where immune cells stand
guard
• lipid absorption
– lacteals in small intestine absorb dietary lipids that are
not absorbed by the blood capillaries
21-4
Components of the
Lymphatic System
• lymph
– the recovered fluid
• lymphatic vessels
– transport the lymph
• lymphatic tissues
– aggregates of lymphocytes and macrophages that
populate many organs
• lymphatic organs
– defense cells are especially concentrated here
– separated from surrounding organs by connective
tissue capsules
21-5
Lymph and Lymphatic Capillaries
• lymph
– clear, colorless fluid, similar to plasma, less protein
– extracellular fluid
• lymphatic capillaries (terminal lymphatics)
–
–
–
–
penetrate nearly every tissue of the body
sacs of thin endothelial cells - loosely overlap each other
closed at one end
gaps between cells are large enough to allow bacteria
and cells to enter
– valve-like flaps that open when interstitial fluid pressure
is high, and close when it is low
• so no backflow into tissue
21-6
Lymphatic Capillary
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Lymph
Opening
Tissue
fluid
Endothelium
of lymphatic
capillary
Anchoring
filaments
(b)
Figure 21.3b
21-7
Valve in a Lymphatic Vessel
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Lymph
Lymph flows
forward through
open valves
Valve
(a)
(b)
Closed valves
prevent backflow
© The McGraw-Hill Companies, Inc./Dennis Strete, photographer
Figure 21.4a
Figure 21.4b
21-8
The Fluid Cycle
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Lymphatic system
Cardiovascular system
Lymphatic
capillaries
Cervical lymph nodes
Pulmonary
circuit
Lymph nodes
Lymphatic
trunks
Palatine tonsil
L. internal jugular v.
Thoracic duct
R. lymphatic duct
Thymus
Axillary lymph node
Subclavian vein
Collecting
duct
Thoracic duct
Cisterna chyli
Spleen
R. and l. lumbar trunks
Superior
vena cava
Collecting
vessels
Abdominal,
intestinal,
and mesenteric
lymph nodes
Intestinal trunk
Red bone marrow
Inguinal lymph nodes
Blood
flow
Popliteal lymph nodes
Lymph
flow
Systemic
circuit
Lymphatic
capillaries
Figure 21.5
Lymphatic vessels
Figure 21.1
21-9
Mechanisms of Lymph Flow
• Low pressure, no pump
• moved along by rhythmic contractions of lymphatic vessels
– stretching of vessels stimulates contraction
• skeletal muscle pump
• arterial pulsation rhythmically squeezes lymphatic vessels
• thoracic pump aids flow from abdominal to thoracic cavity
• valves prevent backward flow
• rapidly flowing blood in subclavian veins, draws lymph into it
• exercise significantly increases lymphatic return
21-10
Lymphatic Tissue
• lymphatic (lymphoid) tissue – aggregations of
lymphocytes in the connective tissues of mucous
membranes and various organs
• diffuse lymphatic tissue – simplest form
– lymphocytes are scattered, rather than densely clustered
– prevalent in body passages open to the exterior
• respiratory, digestive, urinary, and reproductive tract
• lymphatic nodules
– dense masses of lymphocytes and macrophages that
congregate in response to pathogens
– constant feature of the lymph nodes, tonsils, and appendix
– Peyer patches – dense clusters in the ileum (small
intestine)
21-11
Lymphatic Nodule
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Intestinal villus
Lymphatic
nodule
Custom Medical Stock Photo
Figure 21.8
21-12
Lymphatic Organs
• lymphatic organs have well-defined anatomical
sites
– have connective tissue capsule that separates the
lymphatic tissue from neighboring tissues
• primary lymphatic organs
– red bone marrow and thymus
– site where T and B cells become immunocompetent –
able to recognize and respond to antigens
• secondary lymphatic organs
– lymph nodes, tonsils, and spleen
– immunocompetent cells populate these tissues
21-13
Red Bone Marrow
• involved in hemopoiesis (blood formation)
and immunity
– soft, loosely organized, highly vascular
material
– separated from osseous tissue by endosteum
of bone
– as blood cells mature, they push their way
through the reticular and endothelial cells to
enter the sinus and flow away in the blood
stream
21-14
Histology of Red Bone Marrow
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Sinusoid
Capillary
Adipose cell
Artery
Endothelial cells
Figure 21.9
Reticular cells
Central
longitudinal
vein
Platelets and
blood cell
entering
circulation
Sinusoid
Megakaryocyte
Sinusoid
21-15
Thymus
• thymus – member of the endocrine, lymphatic,
and immune systems
–
–
–
–
–
houses developing lymphocytes
secretes hormones regulating their activity
bilobed organ located between sternum and aortic arch
degeneration or involution with age
fibrous capsule gives off trabeculae (septa) that divide
the gland into several lobes
• lobes have cortex and medulla populated by T
lymphocytes
21-16
Histology of Thymus
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Trabecula
Trabecula
Cortex
Medulla
Lobule
(b)
© The McGraw-Hill Companies/Rebecca Gray, photographer/Don Kincaid, dissections
Figure 21.10b
21-17
Lymph Node
• lymph nodes – most numerous lymphatic organs
– about 450 in typical young adult
– two functions:
• cleanse the lymph
• act as a site of T and B cell activation
• elongated, bean shaped structure
• enclosed with fibrous capsule with trabeculae that divide
interior into compartments
21-18
Lymph Node
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Stroma:
Medullary cords
Capsule
Reticular tissue
Trabecula
Medullary sinus
Macrophage
Trabecula
Cortex
Lymphatic nodule
Reticular fibers
Artery
and vein
(b)
Medulla
Efferent
lymphatic
vessel
Afferent lymphatic
vessels
(a)
Figure 21.12a,b
21-19
Lymph Nodes and Metastatic
Cancer
• metastasis – cancerous cells break free from the
original, primary tumor, travel to other sites in the
body, and establish new tumors.
– metastasizing cancer cells can easily enter the lymphatic
vessels
– tend to lodge in the first lymph node they encounter
– multiply there and eventually destroy the node
– tend to spread to the next node downstream
– treatment of breast cancer is lumpectomy, mastectomy
along with removal of nearby axillary nodes
21-20
Tonsils
• tonsils – patches of lymphatic tissue located at
the entrance to the pharynx
– guard against ingested or inhaled pathogens
– have deep pits – tonsillar crypts lined with lymphatic
nodules
• three main sets of tonsils
– palatine tonsils - posterior margin of oral cavity
– lingual tonsils - root of tongue
– pharyngeal tonsil (adenoid)
21-21
The Tonsils
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Pharyngeal
tonsil
Palate
Palatine
tonsil
Lingual
tonsil
Figure 21.13 a
(a)
21-22
Spleen
• spleen – the body’s largest lymphatic organ
• parenchyma exhibits two types of tissue:
– red pulp - sinuses filled with erythrocytes
– white pulp - lymphocytes, macrophages
surrounding small branches of splenic artery
21-23
Spleen
• functions
– blood production in fetus
– blood reservoir
– ‘erythrocyte graveyard’ - RBC disposal
– white pulp monitors blood for foreign antigens
• spleen highly vascular and vulnerable to trauma
and infection
– ruptured spleen - splenectomy
21-24
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Diaphragm
Spleen
Spleen
Splenic artery
Splenic vein
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Pancreas
Superior
Kidney
Inferior vena
cava
Aorta
Common iliac
arteries
Gastric area
Hilum
(a)
Renal area
Figure 21.14a
Red pulp
Central artery
(branching)
Splenic
vein
Splenic
artery
(b)
White pulp
(c)
© The McGraw-Hill Companies, Inc./Photo by Dr. Alvin Telser
Figure 21.14c
Inferior
Figure 21.14b
21-25
?
21-26
Defenses Against Pathogens
• pathogens – environmental agents capable of
producing disease
– infectious organisms, toxic chemicals, and radiation
• three lines of defense against pathogens:
– first line – external barriers, skin and mucous membranes
– second line – nonspecific defense mechanisms
• leukocytes and macrophages, antimicrobial proteins,
immune surveillance, inflammation, and fever
• effective against a broad range of pathogens
– third line of defense – the immune system
• defeats a pathogen, and leaves the body of a ‘memory’ of it
so it can defeat it faster in the future
21-27
Nonspecific Resistance and
Immunity
• nonspecific resistance – guards equally against a
broad range of pathogens
– effectiveness does not depend on prior exposure
– skin and mucous membranes
– leukocytes and macrophages, antimicrobial proteins,
immune surveillance, inflammation, and fever
• immunity – specific defense because it results
from prior exposure to a pathogen
– usually provides future protection only against that
particular one
21-28
External Barriers
• skin
– mechanically difficult for microorganisms to enter the body
– too dry and nutrient-poor to support microbial growth
– defensins – peptides that kill microbes by creating holes in their
membranes
– acid mantle – lactic acid from sweat - inhibits bacterial growth
• mucous membranes
– digestive, respiratory, urinary, and reproductive tracts
– mucus physically traps microbes
– lysozyme - enzyme destroys bacterial cell walls
• subepithelial areolar tissue
– viscous barrier of hyaluronic acid
21-29
Leukocytes and Macrophages
• phagocytes – cells that “eat” foreign matter
• five types of leukocytes
– neutrophils
– eosinophils
– basophils
– monocytes
– lymphocytes
21-30
Neutrophils
• wander in connective tissue killing bacteria
– phagocytosis and digestion
– produces a cloud of bactericidal chemicals
• create a killing zone
– degranulation
• lysosomes discharge into tissue fluid
– respiratory burst – neutrophils rapidly absorb
.
oxygen and toxic chemicals are created (O2 ,
H2O2, HClO)
– kill more w/ toxic chemicals than phagocytosis
21-31
Eosinophils
• found especially in the mucous membranes
• stand guard against parasites, allergens (allergy
causing agents)
• kill worms by producing superoxide, hydrogen
peroxide, and toxic proteins
• promote action of basophils and mast cells
• phagocytize antigen-antibody complexes
21-32
Basophils
• secrete chemicals that aid mobility and action of
other leukocytes
– leukotrienes – activate and attract neutrophils and
eosinophils
– histamine – a vasodilator which increases blood flow
• speeds delivery of leukocytes to the area
– heparin – inhibits the formation of clots
• lets the leukocytes get there fast
• mast cells also secrete these substances
– type of connective tissue cell very similar to basophils
21-33
Lymphocytes
• three basic categories
• circulating blood contains
– 80% T cells
– 15% B cells
– 5% NK cells
• many diverse functions more later
21-34
Monocytes
• monocytes - move from blood into connective
tissue and transform into macrophages
• macrophage system – all the body’s avidly
phagocytic cells
– wandering macrophages – actively seeking pathogens
• widely distributed in loose connective tissue
– fixed macrophages – don’t move around
• microglia – in central nervous system
• alveolar macrophages – in lungs
• hepatic macrophages – in liver
21-35
?
21-36
Antimicrobial Proteins
• proteins that inhibit microbial reproduction
and provide short-term, nonspecific
resistance to pathogenic bacteria and
viruses
• two families of antimicrobial proteins:
– Interferons – used against viruses
– complement system – cause inflammation
and removal or killing of invaders
21-37
Fever
• fever – an abnormal elevation of body temperature
– from trauma, infections, drug reactions, brain tumors, and
other causes
• fever is an adaptive defense mechanism - a moderate fever
is helpful
– promotes interferon activity
– elevates metabolic rate and accelerates tissue repair
– inhibits reproduction of bacteria and viruses
In most cases, there’s no medical need to bring down a
fever
21-38
Reye Syndrome
• Reye Syndrome – serious disorder in children
younger than 15 following an acute viral infection
such as chicken pox or influenza
– fatty infiltration of liver and other viscera
– swelling of brain neurons
• nausea, vomiting, disorientation, seizures and coma
• 30% die, survivors sometimes suffer mental retardation
• can be triggered by the use of aspirin to control
fever
• never give aspirin to children with chickenpox or
flulike symptoms
21-39
Inflammation
•
inflammation – local defensive response
to tissue injury of any kind, including
trauma and infection
•
general purposes of inflammation
– limit spread of pathogens, then destroy them
– remove debris from damaged tissue
– initiate tissue repair
•
four cardinal signs of inflammation
- redness
- swelling - heat
- pain
21-40
Processes of Inflammation
• three major processes of inflammation
– mobilization of body defenses
– containment and destruction of
pathogens
– tissue cleanup and repair
21-41
Mobilization of Defenses
• When tissue is injured - get the defensive leukocytes to the
site quickly!
• local hyperemia – increasing blood flow beyond normal rate
is a way to do this
– local vasodilation due to vasoactive chemicals
• histamine, leukotrienes, and other cytokines
– endothelial cells separate increasing capillary permeability
– fluid, leukocytes, and plasma proteins leave the bloodstream
and go to battle
21-42
Mobilization of Defenses
• basis for the four cardinal signs of inflammation
– heat – results from hyperemia
– redness – due to hyperemia, and RBCs in the tissue
– swelling (edema) – due to increased fluid filtration from
the capillaries
– pain – from direct injury to the nerves, pressure on the
nerves from edema, stimulation of pain receptors by
prostaglandins, bacterial toxins, and a chemical called
bradykinin
21-43
Containment and Destruction of Pathogens
• a priority of inflammation is to prevent the
pathogens from spreading throughout the body
– fibrinogen clots around injury site
• forms a sticky mesh that walls off microbes
– heparin prevents clotting at site of injury
• pathogens are in a fluid pocket surrounded by clot
• attacked by antibodies, phagocytes, and other defenses
21-44
Containment and Destruction of Pathogens
• chemotaxis – attraction to chemicals that guide
WBC’s to the injury site
• neutrophils are quickest to respond
– macrophages and T cells secrete colony-stimulating
factor to stimulate leukopoiesis
21-45
Tissue Cleanup
• monocytes -main agents of tissue cleanup and repair
– arrive in 8 to 12 hours and become macrophages
– engulf and destroy bacteria, damaged host cells, and dead
and dying neutrophils
• edema contributes to tissue cleanup
– swelling compresses veins and reduces venous drainage
– lymphatics collect and remove bacteria, dead cells,
proteins, and tissue debris better than blood capillaries
• pus – accumulation of dead neutrophils, bacteria, cellular
debris, and tissue fluid
– abscess – accumulation of pus in a tissue cavity
21-46
Tissue Repair
• platelet-derived growth factor secreted by blood
platelets and endothelial cells in injured area
• hyperemia delivers oxygen, amino acids, and
other necessities for protein synthesis
• increased heat increases metabolic rate, speeds
mitosis, and tissue repair
• fibrin clot forms a scaffold for tissue
reconstruction
• pain makes us limit the use of a body part so it
has a chance to rest and heal.
21-47
?
21-48
Specific Immunity
• immune system – composed of a large population of
widely distributed cells that recognize specific foreign
substances and act to neutralize or destroy them
• two characteristics distinguish immunity from nonspecific
resistance
– specificity – immunity directed against a particular
pathogen
– memory – when re-exposed to the same pathogen, the
body reacts so quickly that there is no noticeable illness
21-49
Specific Immunity
• two types of specific immunity
– cellular (cell-mediated) immunity: (T cells)
• lymphocytes directly attack and destroy foreign cells or
diseased host cells
• can attack pathogens that reside inside human cells,
where they are inaccessible to antibodies
– kills cells that harbor them
– humoral (antibody-mediated) immunity: (B cells)
• indirect attack where antibodies assault the pathogen (but
don’t destroy it)
• can only work against the extracellular stage of infectious
microorganisms
21-50
Antigens
• antigen – any molecule that triggers an immune response
– large molecular weights of over 10,000 amu
•
complex molecules with structures unique to the individual
• proteins, glycoproteins, glycolipids
• epitopes (antigenic determinants) – certain regions of an
antigen molecule that stimulate immune responses
• haptens - too small to be antigenic in themselves
– combine with a host macromolecule
– create a unique complex that the body recognizes as foreign
– cosmetics, detergents, industrial chemicals, poison ivy, and
animal dander
21-51
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Lymphocytes
• major cells of the immune system
– lymphocytes
– macrophages
– dendritic cells
• especially concentrated in strategic places like
lymphatic organs, skin, mucous membranes
• three categories of lymphocytes
– natural killer (NK) cells – immune surveillance
– T lymphocytes (T cells)
– B lymphocytes (B cells)
21-53
Life Cycle of T cells
• Stage 1: ‘born’ in the red bone marrow
– released into the blood as still-undifferentiated stem cells that
go to thymus
• Stage 2: mature in thymus
– thymosins stimulate maturing T cells to develop surface
antigen receptors
– with receptors in place, the T cells are now immunocompetent
– capable of recognizing antigens presented to them by APCs
– T cells are tested by presenting ‘self’ antigens to them
– two ways to fail the test:
• don’t recognize the testing cell (not responsive enough)
• reacting to the self antigen - wrong response
21-54
Life Cycle of T cells
– negative selection - T cells that fail either test must be
eliminated
– 2% of the T cells that reach the thymus leave as
immunocompetent T cells
• move to thymus medulla, multiply, and form clones of
identical T cells that respond to a specific antigen
• Stage 3: deployment into body
– naïve T cells leave thymus and colonize lymphatic tissues
and organs everywhere in the body
21-55
B Lymphocytes (B cells)
• site of development
– stem cells remain in bone marrow
– develop into B cells
• B cell selection
– B cells that react to self antigens are destroyed as in T cell
selection
• self-tolerant B cells synthesize antigen surface
receptors, divide rapidly, produce immunocompetent
clones
• leave bone marrow and colonize same lymphatic
tissues and organs as T cells
21-56
Antigen-Presenting Cells (APCs)
• T cells cannot recognize their antigens on their own
• antigen-presenting cells (APCs) are required to help
– dendritic cells, macrophages, reticular cells, and B cells
function as APCs
• function of APCs depends on major histocompatibility
complex (MHC) proteins
– act as cell ‘identification tags’ that label every cell of your
body as belonging to you
– structurally unique for each individual, except for identical
twins
21-57
Antigen-Presenting Cells (APCs)
• antigen processing
– APC encounters antigen
– internalizes it by endocytosis
– digests it into molecular fragments
– displays relevant fragments (epitopes) in the grooves of
the MHC protein
21-58
Antigen-Presenting Cells (APCs)
• antigen presenting
– wandering T cells inspect APCs for displayed antigens
– if APC only displays a self-antigen, the T cell disregards it
– if APC displays a nonself-antigen, the T cell initiates an immune
attack
– APCs alert the immune system to presence of foreign antigens
21-59
Antigen Processing
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1 Phagocytosis
of antigen
Lysosome
Epitopes
MHC protein
2 Lysosome
fuses with
phagosome
3 Antigen and
enzyme mix in
phagolysosome
4 Antigen is
degraded
Phagosome
6 Processed
antigen
fragments
(epitopes)
displayed on
macrophage
surface
Figure 21.21a
5 Antigen
residue is
voided by
exocytosis
(a)
21-60
?
21-61
Immunity
• there are two kinds: cellular and humoral
• Both occur in three stages:
– recognition
– attack
– memory
• thought of as the ‘three Rs of immunity’
– recognize
– react
– remember
21-62
Cellular Immunity
•
cellular (cell-mediated) immunity –
a form of specific defense in which the
T lymphocytes directly attack and destroy
diseased or foreign cells, and the immune
system remembers the antigens and
prevents them from causing disease in the
future
21-63
Cellular Immunity
•
cellular immunity involves four classes of T cells
–
cytotoxic T (TC) cells – killer T cells (T8, CD8, or CD8+)
•
carry out attack on enemy cells
–
helper T (TH) cells (T4, CD4, CD4+)
•
promote TC and B cell action & nonspecific resistance
–
regulatory T (TR) cells – T-regs
•
limit immune response
–
memory T (TM) cells
•
descend from the cytotoxic T cells
•
responsible for memory in cellular immunity
21-64
T Cell Recognition
1. Antigen Presentation
– APC encounters and processes an antigen
– migrates to nearest lymph node
– displays it to the T cells
– when T cell encounters its displayed antigen on the
MHC protein, they initiate the immune response
21-65
T Cell Recognition
2. T Cell Activation
–
–
•
–
•
•
•
•
TC or TH cell binds to a MHCP displaying an epitope that
the T cell is programmed to recognize
T cell must then bind to another APC protein on same cell
“double checks” to make sure it should respond costimulation
successful costimulation will trigger clonal selection
activated T cell undergoes repeated mitosis
get clones of identical T cells programmed against the
same epitope
some clone cells become effector cells and attack
other cells become memory cells
21-66
21-67
Costimulation
protein
MHC protein
APC
Antigen
T cell
Activation
1 Antigen
recognition
TC or TH
APC
TC or TH
2 Costimulation
TM
TH
TC
or
TC
TC
TH
TM
TH
TM
3 Clonal selection
Memory
T cells
Effector cells
TC
Figure 21.22
4 Lethal hit
Enemy
cell
TH
MHC-I
protein
Destruction of
enemy cell
or
APC
MHC-II
protein
4 Interleukin
secretion
Activity of NK, B, or TC cells
Development of memory T cells
Inflammation and other nonspecific defenses
Attack : Role of Helper T (TH) Cells
• helper and cytotoxic T cells play different roles in the
attack phase
• Helper T cell: central role in coordinating both cellular and
humoral immunity
• when helper T cell recognizes the Ag-MHCP complex:
– secrete interleukins that exert three effects:
• attract neutrophils and NK cells
• attract macrophages, stimulate their phagocytic activity,
and inhibit them from leaving the area
• stimulate T and B cell mitosis and maturation
21-68
Attack : Role of Helper T (TH) Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Macrophage,
B cell, or other
antigen-presenting cell
Helper T (T4) cell
Figure 21.23
Macrophageactivating factor
Other cytokines
Interleukin-2
Other cytokines
Interleukin-1
Other cytokines
Macrophage activity
Leukocyte chemotaxis
Inflammation
Clonal selection
of B cells
Clonal selection of
cytotoxic T cells
Humoral immunity
Cellular immunity
Nonspecific defense
21-69
Attack : Cytotoxic T (TC) Cells
•
cytotoxic T cells (TC) - only T cells that directly
attack other cells
when TC cell recognizes a complex of ag-MHC
protein on a diseased or foreign cell it ‘docks’ on
that cell
•
–
–
delivers a lethal hit of toxic chemicals
goes off in search of another enemy cell while the
chemicals do their work
21-70
Cytotoxic T Cell Function
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
T cell
T cell
Cancer cell
Dying cancer cell
(a)
10 µm
(b)
Dr. Andrejs Liepins
Figure 21.24 a-b
• cytotoxic T cell binding to cancer cell
21-71
Memory
• immune memory follows primary response
• following clonal selection, some TC and TH cells
become memory cells
– long-lived
– more numerous than naïve T cells
– fewer steps to be activated, so response is faster
• T cell recall response
– if re-exposed to same pathogen later, memory cells
launch quick attack - no noticeable illness occurs
– the person is immune to the disease
21-72
Humoral Immunity
• humoral immunity is a more indirect method of
defense than cellular immunity
• B lymphocytes of humoral immunity produce
antibodies that bind to antigens and tag them
for destruction by other means
– cellular immunity attacks the enemy cells directly
• works in three stages like cellular immunity
– recognition
– attack
– memory
21-73
Humoral Immunity
1. recognition
– immunocompetent B cell has thousands of surface
receptors for one antigen
– activation begins when an antigen binds to several of these
receptors
• links them together
• taken into the cell by receptor-mediated endocytosis
• antigen is digested and epitopes displayed on the cell
surface
– usually B cell response goes no further unless a helper T
cell binds to this Ag-MHCP complex
• bound TH cell secretes interleukins that activate B cell
21-74
Humoral Immunity
1. recognition
– triggers clonal selection
• B cell mitosis gives rise to an entire battalion of identical
B cells programmed against the same antigen
• most differentiate into plasma cells
– secrete antibodies at a rate of 2,000 molecules per
second during their life span of 4 to 5 days
• antibodies travel through the body in the blood or other
body fluids
2. attack
– antibodies bind to antigen, render it harmless, ‘tag it’ for
destruction
3. memory
– some B cells differentiate into memory cells
21-75
Antigen
Receptor
Lymphocyte
1 Antigen recognition
Immunocompetent B cells
exposed to antigen. Antigen
binds only to B cells with
complementary receptors.
Humoral
Immunity Recognition
Figure 21.25
2 Antigen presentation
B cell internalizes antigen
B cell
and displays processed
epitope. Helper T cell binds
to B cell and secretes
interleukin.
Helper T cell
Epitope
MHC-II protein
Interleukin
3 Clonal selection
Interleukin stimulates
B cell to divide repeatedly
and form a clone.
4 Differentiation
Some cells of the
clone become
memory B cells.
Most differentiate
into plasma cells.
5 Attack
Plasma cells synthesize
and secrete antibody.
Antibody employs various
means to render antigen
harmless.
Plasma cells
Antibody
Memory
B cell
21-76
B cells and Plasma cells
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Rough endoplasmic
Mitochondria reticulum
Nucleus
(a) B cell
2 µm
(b) Plasma cell
2 µm
© Dr. Don W. Fawcett/Visuals Unlimited
Figure 21.26 a-b
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Antibodies
• immunoglobulin (Ig) – an antibody is a defensive gamma
globulin (protein)
– found in the blood plasma, tissue fluids, body secretions, and
some leukocyte membranes
• antibody monomer – the basic structural unit of an antibody
– composed of four polypeptide chains
– two heavy chains plus two light chains about half as long
– variable (V) region in all four chains
• gives the antibody its uniqueness
– antigen binding site – V regions of the heavy and light chains
on each arm
– constant (C) region has the same amino acid sequence within
one person
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Antibody Structure
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Disulfide
bonds
Antigenbinding
site
Light chain
Variable
(V) regions
Hinge region
Complement-binding site
Constant
(C) regions
Heavy chain
(a)
Figure 21.27a
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Humoral Immunity - Attack
• neutralization
– antibodies mask pathogenic region of antigen
• complement fixation
– antigen binds antibody, antibody changes shape, initiates
complement binding
– primary defense against foreign cells, bacteria, and
mismatched RBCs
• agglutination
– antibody has 2-10 binding sites; binds to multiple enemy cells
immobilizing them from spreading
• precipitation
– antibody binds antigen molecules (not cells); creates antigenantibody complex that precipitates, phagocytized by
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eosinophils
Agglutination and Precipitation
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Antibodies
(IgM)
(a)
Figure 21.28 a-b
Antigens
(b)
Antibody
monomers
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Humoral Immunity - Memory
• primary immune response – immune reaction brought about by
the first exposure to an antigen
– protective antibodies appear in 3 to 6 days as naïve B cells
multiply and differentiate into plasma cells
– as plasma cells produce antibodies, the antibody titer (level
in the blood plasma) rises
– primary response leaves immune memory of the antigen
• during clonal selection, some of the clone becomes
memory B cells
• found mainly in germinal centers of the lymph nodes
• very quick secondary response
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Humoral Immunity - Memory
• secondary response – if re-exposed to the same
antigen
– plasma cells form within hours
– response is so rapid that the antigen has little chance to
exert a noticeable effect on the body
– no illness results
– IgG antibodies remain elevated for weeks to years
• long-lasting protection
• memory does not last as long in humoral immunity as in
cellular immunity
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Humoral Immunity Responses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Secondary response
Serum antibody titer
Primary response
IgG
IgG
IgM
0
IgM
5
10
15
20
25
Days from first exposure
to antigen
0
5
10
15 20
25
Days from reexposure
to same antigen
Figure 21.29
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?
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Immune System Disorders
• immune response may be:
– too vigorous
– too weak
– misdirected against wrong targets
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Hypersensitivity
• hypersensitivity – an excessive immune reaction against
antigens that most people tolerate
• includes:
– alloimmunity - reaction to transplanted tissue from another
person
– autoimmunity - abnormal reactions to one’s own tissues
– allergies – reactions to environmental antigens (allergens) –
dust, mold, pollen, vaccines, bee venom, poison ivy, foods
such as nuts, milk, eggs, and shellfish, drugs such as
penicillin, tetracycline, and insulin
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Autoimmune Diseases
• autoimmune diseases - failures of self-tolerance
• immune system fails to distinguish self-antigens from foreign ones
– produces autoantibodies that attack the body’s own tissues
• 3rd most common class of diseases in U.S. - affect 5-8% of pop.
–
–
–
–
–
–
–
79% of those affected are women
Graves’ Disease
Insulin-dependent diabetes
pernicious anemia
rheumatoid arthritis
thyroiditis
vitiligo
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Autoimmune Diseases
• three reasons why self-tolerance breaks down
– cross-reactivity
• some antibodies against foreign antigens react to similar
self-antigens
• rheumatic fever - streptococcus antibodies also react
with heart valves
– abnormal exposure of self-antigens in the blood
• some of our native antigens are not exposed to blood sperm
– changes in structure of self-antigens
• viruses and drugs may change the structure of selfantigens or cause the immune system to perceive them
as foreign
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Immunodeficiency Diseases
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• immune system fails to
react vigorously enough
• Severe Combined
Immunodeficiency
Disease (SCID)
– hereditary lack of T and B
cells
– vulnerability to opportunistic
infection and must live in
protective enclosures
© Science VU/Visuals Unlimited
Figure 21.30
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Immunodeficiency Diseases
• Acquired Immunodeficiency Syndrome (AIDS) –
nonhereditary diseases contracted after birth
• group of conditions that involve and severely depress
the immune response
• caused by infection with the human immunodeficiency
virus (HIV) – invades helper T cells
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END
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