PowerPoint ® Lecture Slides prepared by Betsy C. Brantley Valencia College C H A P T E R © 2013 Pearson Education, Inc. The Lymphatic System and Immunity

PowerPoint® Lecture Slidesprepared byBetsy C. BrantleyValencia College

C H A P T E R

© 2013 Pearson Education, Inc.

The Lymphatic System and Immunity

13


Chapter 13 Learning Outcomes

• Section 1: Anatomy of the Lymphatic System

• 13.1 • Describe the structure and function of important lymphatic

vessels, their relationship to blood vessels, and how lymph flows in the body.

• 13.2 • Describe the lymph collecting vessels, identify the structures

returning lymph to the venous system, and explain lymphedema.

• 13.3• Define lymphopoiesis, and discuss the classes of lymphocytes,

their importance, and their distribution in the body.• 13.4

• Identify and describe lymphoid tissues and lymphoid organs, and trace the pathway of lymph flow through a lymph node.



• Section 2: Nonspecific Immunity

• 13.5• Explain how physical barriers and phagocytes play a role in

nonspecific defenses. • 13.6

• Explain the significance of inflammation and fever as mechanisms of nonspecific defenses, and summarize nonspecific defenses.

• Section 3: Specific Immunity

• 13.7• Explain how antigens trigger specific defenses and the immune

response.



• 13.8• Discuss the structure of an antibody and the types of antibodies in

body fluids, and explain the primary and secondary responses to antigen exposure.

• 13.9• Explain the mechanisms used by antibodies to destroy target

antigens.• 13.10

• CLINICAL MODULE Define allergies and anaphylaxis and describe the role of antibodies in causing allergic and anaphylactic responses.

• 13.11• CLINICAL MODULE Describe autoimmune disorders, graft rejection,

allergies, immunodeficiency diseases, and age-related changes with respect to excessive or misdirected immune responses or inadequate immune responses.


The Lymphatic System (Section 1)

• Includes cells, tissues, and organs that defend the

body against environmental hazards and internal

threats

• Cells are lymphocytes

• Vessels are lymphatic vessels (or lymphatics)

• Lymphoid tissues and organs are scattered

throughout the body


The Lymphatic System (Section 1)

• Lymphocytes• Primary cells of lymphatic system that respond to:

• Invading pathogens

• Abnormal body cells

• Foreign proteins

• Most produced and stored within lymphoid tissues and organs

• Also produced in red bone marrow

• Surrounded by lymph

• Liquid that resembles interstitial fluid


An overview of the lymphatic system

Figure 13 Section 1-2 2

Lymphatic Vessels and Lymph Nodes

Lymphoid Tissues and Organs

ThymusSpleenMucosa-associated lymphoid tissue(MALT) in digestive, respiratory,urinary, and reproductive tracts

Appendix

Tonsil

Cervical lymph nodesThoracic duct

Right lymphatic ductAxillary lymph

nodesCisterna chyli

Inguinal lymph nodes


Fluid Flow (13.1)

• Lymphatic vessels

• Carry lymph from peripheral tissues to venous system

• Begin with lymphatic capillaries

• Found in almost every tissue and organ

• Closely associated with blood capillaries

• Interstitial fluid flows into lymphatic capillaries

• Fluid inside lymphatic capillaries is called lymph


Arteriole

Endothelial cells

Lymphaticcapillary

Blood capillaries

Looseconnective

tissue

Lymphflow

Interstitialfluid

Venule

Lymphatic capillaries

Figure 13.1 1 1


Lymphatic Capillaries (13.1)

• Lined by endothelial cells

• Incomplete or missing basement membrane

• Differ from blood capillaries

1. Originate as pockets instead of forming continuous

tubes

2. Have larger diameters

3. Have thinner walls

4. Look flattened or irregular in sectional view


One-Way Flow (13.1)

• Overlapping endothelial cells in lymphatic

capillaries

• Act as one-way valve

• Permit entry of fluids and solutes

• Prevent return to intercellular spaces


Sectional view of lymphatic and blood capillaries

Figure 13.1 2 2

Although lymphaticcapillaries are lined byendothelial cells, thebasement membrane isincomplete or missingentirely.

Overlapping endothelialcells act as one-way valve

Lymphflow

Lymphocyte

To largerlymphatics

Looseconnective

tissue

Interstitialfluid

Interstitialfluid

Looseconnective

tissueLymphaticcapillary

Bloodcapillary

Sectional view


Lymphatic Flow (13.1)

• Lymph flows from lymphatic capillaries

• Into larger lymphatic vessels

• Toward body's trunk

• Larger lymphatic vessels contain valves

• Valves close together

• Vessels bulge at each valve

• Series of bulges make vessels resemble string of beads

• Low pressure in lymphatic vessels

• Valves prevent backflow


Lymphatic vessels and valves

Figure 13.1 3 - 4 3 4–

Artery

Vein

Lymphaticvessel

To larger lymphatic vesselsthat deliver lymph to the venous system

From lymphaticcapillaries

Lymphatic valveLymphatic vessel

ArteryVein

Lymphatic valve

Lymphatic vessel

Valve in lymphatic vessel LM x 65


Lymphatic Capillary Locations (13.1)

• Areas without blood supply have no lymphatic

capillaries

• Cornea of eye

• Other areas without lymphatic capillaries

• Red bone marrow

• Central nervous system


Module 13.1 Review

a. What is the function of lymphatic vessels?

b. What is lymph?

c. What is the function of overlapping endothelial

cells in lymphatic capillaries?


Extracellular Fluid Circulation (13.2)

• Blood confined to vessels of cardiovascular

system

• Water and solutes move from plasma into surrounding

interstitial fluid

• Lymph contained in lymphatic vessels

• Forms as interstitial fluid drains into lymphatic vessels


Fluid Homeostasis (13.2)

• Continuous recirculation of interstitial fluid

1. Helps eliminate local differences in levels of nutrients,

wastes, and toxins

2. Maintains blood volume

3. Alerts immune system to infections in peripheral

tissues


The circulation of extracellular fluid

Figure 13.2 1 1

The Circulation of Extracellular Fluid

StartArteries carry bloodaway from the heartand into the tissuesof the body.

Veins carry bloodfrom capillary beds tothe heart.

Capillaries are the smallest and mostdelicate blood vessels. All exchangebetween the blood and interstitialfluid occurs at capillaries.

At capillary networks, bloodpressure forces water and smallsolutes out of the bloodstream and into the surroundinginterstitial fluid.

Lymph forms as interstitialfluid enters lymphatic vessels.

Lymphatic vessels form anetwork that returns lymph tolarge subclavian veins nearthe heart.

1

2

Heart

Water andsolutes frombloodstream

3

4

56


Lymphatic Drainage (13.2)

• Superficial and deep lymphatics converge to form:• Larger vessels, lymphatic trunks, which empty into:

• Collecting vessels

• Thoracic duct

• Right lymphatic duct

• Cisterna chyli is expanded chamber at base of thoracic duct• Receives lymph from inferior part of abdomen, pelvis,

lower limbs via:

• Right and left lumbar trunks

• Intestinal trunk


Pattern of lymphatic fluid drainage in the body

Figure 13.2 2 2

Drainage ofthoracic duct

Drainage of rightlymphatic duct


Lymphatic Ducts (13.2)

• Thoracic duct

• Collects lymph from:

• Body inferior to diaphragm

• Left side of body superior to diaphragm

• Empties into the left subclavian vein

• Right lymphatic duct

• Collects lymph from:

• Right side of body superior to diaphragm

• Empties into right subclavian vein


Relationship between lymphatic ducts and the venous system

Figure 13.2 3 3

Right Lymphatic Duct

Right subclavianvein

Superior vena cava (cut)

Rib (cut)

Azygos vein

Intestinal trunk

Inferior vena cava (cut)

Right lumbar trunkLeft lumbar trunk

Cisterna chyli

Diaphragm

Parietalpleura (cut)

Thoraciclymph nodes

Thoracic duct

Thoracic Duct

Left jugular trunkLeft subclavian trunkThoracic duct enteringleft subclavian veinLeft bronchomediastinaltrunk

Right internaljugular vein

Brachiocephalicveins

Left internaljugular vein


Lymphedema (13.2)

• Caused by blocked lymphatic drainage

• Interstitial fluid accumulates

• Causes swollen and distended areas

• Usually affects limbs; can affect other areas

• Swelling may become permanent

• Connective tissue loses elasticity

• Stagnant interstitial fluids may accumulate toxins and

pathogens

• Local immune defenses overwhelmed


Lymphedema

Figure 13.2 4 4


Module 13.2 Review

a. Name the two large lymphatic ducts into which

the lymphatic trunks empty.

b. Describe the drainage of the right lymphatic duct

and the thoracic duct.

c. Explain lymphedema.


Lymphocytes (13.3)

• Account for 20–40 percent of circulating

leukocytes

• Circulating lymphocytes are a small fraction of

total lymphocyte population

• Three classes of lymphocytes

1. T cells

2. B cells

3. NK cells


Antigens (13.3)

• All classes of lymphocytes are sensitive to

antigens

• Pathogens, parts or products of pathogens, or other

foreign substances

• Most are proteins

• Some are lipids, polysaccharides, and nucleic acids

• Stimulate an immune response


T Cells (13.3)

• 80 percent of circulating lymphocytes

• Three major categories of T cells1. Cytotoxic T cells

• Attack foreign cells or body cells infected by viruses

• Primary cells involved in cell-mediated immunity

2. Helper T cells

• Stimulate activation and function of T cells and B cells

3. Suppressor T cells

• Inhibit activation and function of T cells and B cells

• With helper T cells, involved in sensitivity of immune response


B Cells (13.3)

• 10–15 percent of circulating lymphocytes

• Differentiate into plasma cells when stimulated

• Produce and secrete antibodies

• Responsible for antibody-mediated immunity

• Some B cells become memory B cells instead of

plasma cells

• Remain in reserve to fight subsequent infections by

same antigen


NK Cells (13.3)

• NK (natural killer) cells

• 5–10 percent of circulating lymphocytes

• Attack

• Foreign cells

• Body cells infected with viruses

• Cancer cells in normal tissues

• Continuously monitor peripheral tissues

• Immunological surveillance


Classes of lymphocytes

Figure 13.3 1 1

Classes of Lymphocytes

T Cells B Cells NK Cells

CytotoxicT Cells

HelperT Cells

Suppressor T Cells

Plasma Cells

Cytotoxic T cell

Foreign or infected cell


Lymphopoiesis (13.3)

• Lymphocyte production

• Involves:

• Red bone marrow

• Thymus

• Peripheral lymphoid tissues

• Red bone marrow primary in maintaining normal

lymphocyte population


Lymphopoiesis in Red Bone Marrow (13.3)

• Hemocytoblasts generate lymphoid stem cells

• One group of lymphoid stem cells migrates to thymus

• Second group stays in red bone marrow and divides to

produce:

• B cells

• Mature and move into lymph nodes, spleen, other

lymphoid tissue

• NK cells

• Mature and migrate throughout body, patrolling

peripheral tissues


Lymphopoiesis in Thymus (13.3)

• Blood-thymus barrier• Isolates stem cells from general circulation

• Thymic hormones• Stimulate lymphoid stem cells to divide, producing T

cells

• T cells • Produced and differentiate in thymus

• Reenter bloodstream when near mature and travel to:

• Red bone marrow

• Peripheral tissues


The derivation and distribution of lymphocytes

Red Bone Marrow

Lymphoid stem cells

Lymphoid stem cells divide,producing various kinds of Tcells

Thymus

Migrates tothymus

Stays in red bone marrowand divides

Production anddifferentiationof immatureT cells Mature T cell B cells NK cells

As they mature, Bcells and NK cellsenter the bloodstreamand migrate toperipheral tissues.

Peripheral Tissues

When they arealmost mature,T cells reenterthe bloodstreamand either returnto the red bonemarrow or travelto peripherallymphoid tissuesand organs.

Cell-mediatedimmunity

Antibody-mediatedimmunity

Immunologicalsurveillance

Figure 13.3 2 2


Lymphocyte Reproduction (13.3)

• Stem cells in red bone marrow

• Migrated B cells and T cells maintain ability to

divide

• Produce daughter cells of same type

• Crucial to success of immune response


Module 13.3 Review

a. Identify the three main classes of lymphocytes.

b. Which cells are responsible for antibody-

mediated immunity?

c. Which tissues are involved in lymphopoiesis?


Lymphoid Tissue (13.4)

• Connective tissue dominated by lymphocytes

• Lymphoid nodules

• Spherical masses of lymphoid tissue

• Lymphoid organs

• Lymph nodes, thymus, spleen

• Separated from surrounding tissues by fibrous

connective tissue


Lymphoid Nodules (13.4)

• Clusters of lymphoid tissues

• Found in tracts opening to exterior environment

• Deep to epithelia lining passages

• As a group, called mucosa-associated lymphoid

tissue (MALT)


The Tonsils (13.4)

• Three locations of large lymphoid nodules in walls of pharynx

1. Pharyngeal tonsil (or adenoid)

• Located on posterior, superior wall of nasopharynx

2. Palatine tonsils

• Located in posterior, inferior margin of oral cavity along boundary of pharynx

3. Lingual tonsils

• Deep to epithelium covering base of tongue

• Tonsillitis• Swollen tonsils from infection


Lymphoid tissue in the body

Figure 13.4 1 - 2 1 2–

MALT in large intestine

Pharyngeal tonsil

Hard palatePalatine tonsilLingual tonsil


Lymph Nodes (13.4)

• Small, lymphoid organs shaped like a kidney bean

• Function like a water filter

• Purifies lymph before reaching venous circulation

• Removes 99 percent of antigens from lymph

• Immune response stimulated as needed

• Afferent lymphatics bring lymph into lymph node

• Lymph flows through network of fibers and dendritic cells

• Involved in initiation of immune response

• Regions in lymph nodes contain B cells and plasma cells

• Efferent lymphatics carry lymph out of node toward veins


Lymph node structure

Figure 13.4 3 3

Lymph node

Lymphatic vessel

Lymph nodesAfferent lymphatics

Dendritic cells

Regions containingB cells and plasmacells

Efferent lymphatics

Lymph node artery and vein


The Thymus (13.4)

• Produces hormones important to development of

functional T cells

• Several complementary hormones known as

thymosins

• Size and secretory abilities decline with age

• Correlated with increased susceptibility to disease


The thymus

Figure 13.4 4 4

Thyroid glandTrachea

Thymus

Heart

Diaphragm

Rightlung

Leftlung


The Spleen (13.4)

• Contains largest mass of lymphoid tissue in body

• Same function for blood that lymph nodes

perform for lymph

1. Removes abnormal red blood cells by phagocytosis

2. Stores iron recycled from red blood cells

3. Initiates immune response by B cells and T cells


The spleen

Figure 13.4 5 5

Diaphragm

Gastrosplenic ligament

Hilum

Gastric area

Renal area

Lateral surfaceof the spleen

Kidneys

Aorta

Spleen

SpleenSpleen

Pancreas

Rib

Stomach

Lateral surface of spleen

LiverLiver

Inferiorvena cava


Module 13.4 Review

a. Name the lymphoid tissue that protects epithelia

lining the digestive, respiratory, urinary, and

reproductive tracts.

b. Define tonsils, and name the three types of

tonsils.

c. Describe the functions of the spleen.


Immunity (Section 2)

• Ability to resist infection and disease

• Two forms that work independently and together

1. Nonspecific (innate) immunity

• Does not distinguish one type of pathogen from another

• Response is the same regardless of invading agent

• Present at birth (innate)

• Provide nonspecific resistance

2. Specific (adaptive) immunity


Nonspecific Defenses (Section 2)

• Physical barriers

• Phagocytes

• Immunological surveillance

• Interferons

• Complement system

• Inflammatory response

• Fever


Specific Defenses (Section 2)

• Protect against particular pathogen

• Depend on activities of specific lymphocytes

• Produce state of protection known as specific

resistance


Overview of immunity

Figure 13 Section 2

Immunity

Nonspecific (Innate) Defenses Specific (Adaptive) Defenses Physical barriers

Phagocytes

Immunological surveillance

Interferons

The complement system

The inflammatory response

Fever

Destructionof abnormal

cells

Inflammation


The Integumentary System (13.5)

• Provides major physical barrier to invasion by pathogens• Glands

• Sebaceous and sweat gland secretions flush surface• Wash away microorganisms and chemical agents• May contain bactericidal chemicals, destructive enzymes, and

antibodies

• Hair• Protects against mechanical abrasion• Often prevents hazardous material or insects from contact with skin

• Epithelial covering• Multiple layers• Keratinized cells in outer layers• Network of desmosomes locks adjacent cells together


Integumentary system as a physical barrier to the external environment

Figure 13.5 1 1

Duct ofsweat gland

Hair Secretion

Epithelium

Sebaceousgland

KeratinizedcellsDesmosomes


Epithelial Barriers (13.5)

• Line "tracts" (digestive, respiratory, urinary, and reproductive)

• Provide physical barrier

• Secretions contain enzymes, antibodies, or acid• Acid in stomach destroys many pathogens

• Mucus in respiratory tract traps pathogens

• Urine flushes urinary passageways

• Glandular secretions in reproductive tract flush tract

• MALT provides nonspecific defense


Mucous membranes as a nonspecific defense barrier

Figure 13.5 2 2

Mucus

Mucouscell

Tight junctions

Basementmembrane

Epithelial cell

Epithelial cellstied together bytight junctions


Phagocytes (13.5)

• "First line of cellular defense"

• Found in peripheral tissues

• Remove cellular debris

• Respond to invasion by foreign compounds or pathogens

• Can attack and remove microorganisms before lymphocytes detect presence

• Different types target different threats

• All function in same basic way


Micrograph of phagocyte engulfing bacteria

Figure 13.5 4 4

Phagocyte (yellow)engulfing bacteria (orange)

SEM x 2900


Types of Phagocytes (13.5)

• Neutrophils

• Abundant, mobile, fast-acting

• Phagocytize cellular debris or invading bacteria

• Eosinophils

• Less abundant than neutrophils

• Phagocytize foreign compounds or pathogens that have been

coated with antibodies

• Monocyte–macrophage system

• Macrophages derived from monocytes

• Fixed macrophages scattered among connective tissue

• Free macrophages travel throughout body


Types of phagocytes

Figure 13.5 3 3

Types of Phagocytes

12 µm 8–10 µm Monocyte–macrophage system

Neutrophils Eosinophils

Fixed macrophages Free macrophages


Functional Characteristics of Phagocytes (13.5)

• Can leave capillaries by squeezing between adjacent endothelial cells• Process called diapedesis

• May be attracted to or repelled by chemicals in surrounding fluids• Phenomenon called chemotaxis• Particularly sensitive to chemicals released by body cells or

pathogens

• Receptors on plasma membrane of phagocyte bind to surface of target• First step in phagocytosis

• After attaching, phagocyte either destroys target itself or promotes its destruction by activating specific defenses


Module 13.5 Review

a. How does the integumentary system protect the

body?

b. Identify the types of phagocytes in the body, and

differentiate between fixed macrophages and

free macrophages.

c. Define chemotaxis.


Inflammation (13.6)

• Localized tissue response to injury

• Produces swelling, redness, heat, and pain

• Caused by various stimuli that kill cells, damage connective tissue fibers, or injure tissue

• Result is altered chemical composition of interstitial fluid• Prostaglandins, proteins, potassium ions released

• Foreign proteins or pathogens introduced

• Changes trigger inflammation process

Chemical changein interstitial fluid

TissueDamage


Inflammation and the steps in tissue repair

Figure 13.6 1 1

Slide 1


Mast cellsreleasehistamine andheparin

Mast Cell Activation

TissueDamage



Figure 13.6 1 1

Slide 2


Phagocytes,especiallyneutrophils, areattracted to area

Blood vesselsdilate, bloodflow increas-es, vessel be-comes morepermeable

Clot forms(temporaryrepair)



Phagocyte Attraction

TissueDamage

Redness, Swelling, Heat, and Pain



Figure 13.6 1 1

Slide 3


Release of cytokines(chemical messengers

affecting immunedefenses)

Neutrophils andmacrophagesremove debris;fibroblasts arestimulated

Specificdefensesareactivated







TissueDamage




Figure 13.6 1 1

Slide 4




Pathogensare removed,clot erodes,scar tissueforms

Tissue Repair





Release of cytokines(chemical messengers

affecting immunedefenses)

Neutrophils andmacrophagesremove debris;fibroblasts arestimulated

Specificdefensesareactivated

TissueDamage




Figure 13.6 1 1

Slide 5


Fever (13.6)

• Rise in body core temperature above 37.2ºC

• Pyrogens (circulating proteins) reset temperature

thermostat in hypothalamus

• Can be beneficial within limits

• Inhibits some viruses and bacteria

• Increases body metabolism

• Quicker mobilization of tissue defenses

• Accelerated repair process


Summary of Nonspecific Defenses (13.6)

• Physical barriers• Keep hazardous organisms and materials outside body

• Phagocytes• Engulf pathogens and cellular debris

• Immune surveillance by NK cells• Monitor peripheral tissues

• Release perforins that destroy abnormal cell's membrane

• Interferons• Released by lymphocytes, macrophages, or virus-infected cells

• Trigger production of antiviral proteins

• Stimulate macrophages and NK cells


Summary of Nonspecific Defenses (13.6)

• Complement system

• Group of circulating proteins that help antibodies

destroy pathogens

• Inflammation (inflammatory response)

• Localized, tissue-level response to limit spread of injury

or infection

• Fever

• Accelerates body metabolism and defense activity


Summary of Nonspecific Immunity

Figure 13.6 3 3

Physical Barriers

Prevent approach ofand deny access topathogens

Duct ofsweat gland

Secretions

Epithelium

Hair

Phagocytes

Remove debrisand pathogens

Neutrophil Eosinophil MonocyteFree

macrophageFixed

macrophage

Immune Surveillance by NK cells

Continuously monitornormal tissues anddestroy abnormal cells Natural killer cell Lysed abnormal cell

Interferons

Increase resistance ofcells to viral infection;slow the spread ofdisease

Complement System

When activated, attacks and breaksdown the surfaces of cells, bacteria,and viruses; attracts phagocytes;stimulates inflammation Complement

Lysedpathogen

Inflammation (Inflammatory Response)

Multiple effects makenonspecific and specificdefenses more effective

• Blood flow increased• Phagocytes activated• Damaged area isolated by clotting reaction• Capillary permeability increased• Complement activated• Regional temperature increased• Specific defenses activated

Fever

Mobilizes defenses;accelerates repairs;inhibits pathogens

Body temperature rises above 37.2°C inresponse to pyrogens

Mast cell

100

80

60

40

20

0


Module 13.6 Review

a. What is the result of mast cell activation?

b. Summarize the body's nonspecific defenses.

c. A rise in the level of interferons in the body

suggests what kind of infection?


Specific Immunity (Section 3)

• Protects against specific pathogens

• Coordinated activity of T cells and B cells provides

specific defenses

• T cells primarily responsible for cell-mediated

immunity

• Defends against abnormal cells and pathogens inside

cells

• B cells provide antibody-mediated immunity

• Defends against antigens and pathogens in body fluids


Types of Specific Immunity (Section 3)

• Active immunity

• When body develops antibodies in response to antigen

• Passive immunity

• When receive antibodies from another source

• Both can be naturally acquired or artificially

acquired


Forms of immunity

Figure 13 Section 3-1 1

Immunity

The ability to resistinfection and disease

Specific immunity is not present at birth;you acquire immunity to a specific antigenonly when you have been exposed to thatantigen or receiveantibodies fromanother source.

Specific (Adaptive) Immunity Nonspecific(Innate) Immunity

Present at birth—anatomical andother defensemechanisms

Active Immunity Passive Immunity

Produced by trans-ferring antibodiesfrom another source

Develops inresponse toantigen exposure

Naturally acquiredactive immunity

Artificially inducedactive immunity

Naturally acquiredpassive immunity

Artificially inducedpassive immunity

Conferred by admin-istering antibodies tocombat infection

Conferred bytransferringmaternal antibod-ies acrossplacenta or inbreast milk

Develops afteradministeringan antigen toprevent disease(as in a vaccine)

Develops afterexposure toantigens inenvironment


Specific Properties of Specific Immunity (13.7)

• Specificity

• Each T cell or B cell has receptors that bind to one specific antigen,

but ignore all others

• Response of activated T cell or B cell specific only to that antigen

• Versatility

• Millions of different lymphocyte populations, each sensitive to

different antigen

• When activated, appropriate lymphocyte divides, producing more of

same lymphocyte type

• All cells produced by the division of activated lymphocyte

constitute a clone


Specific Properties of Specific Immunity (13.7)

• Immunological memory

• Activated lymphocytes produce two groups of cells

• Group that attacks invader immediately

• Group that remains inactive unless exposed to same antigen later

• Memory cells that enable immune system to "remember" antigens

and launch faster, stronger, longer-lasting counterattack when

exposed again

• Tolerance

• Immune response ignores "self" but targets abnormal and foreign

("non-self")

• Can develop over time in response to chronic exposure to antigen


Specific Defenses – Triggers (13.7)

• Exposure to antigen activates phagocytes, which

stimulate:

1. Cell-mediated defenses involving attacks by T cells

2. Antibody-mediated defenses

• First step is antigen presentation


Overview of the immune response

Figure 13.7 1 1

Cell-MediatedImmunity

Specific Defenses

Antigen presenta-tion triggers spe-cific defenses, or animmune response.

Communicationand feedback

Phagocytesactivated

T cellsactivated

Direct Physical andChemical Attack

Activated T cellsfind the pathogensand attack themthrough phagocy-tosis or therelease of chemi-cal toxins.

Attack by CirculatingAntibodies

Antibody-MediatedImmunity

Activated Bcells giverise to cellsthat pro-duce anti-bodies.

Destroyantigens

Bacterium

Virus

1

2


Antigen-Presenting Cells (13.7)

• Specialized cells

• Monocytes, macrophages, and dendritic cells

• Engulf a pathogen

• Digest pathogen to produce antigenic fragments

• Bind those fragments to proteins

• Display antigenic fragments on plasma membrane


Antigen-presenting cells

Figure 13.7 2 2

Plasmamembrane

Phagocytic APCsengulf an extracel-lular pathogen.

Lysosomal actionproduces antigenicfragments.

Antigenicfragments arebound to theseproteins.

Antigenic fragmentsare displayed on theplasma membrane.

The rough endoplasmicreticulum producesproteins that will be incorporated into the phagocyticcell’s plasmamembrane.

Endoplasmicreticulum

NucleusNucleusLysosome

Phagocytic cell

1

2

3

4

5


Defenses against Pathogens (13.7)

• Defenses against bacterial pathogens

• Usually initiated by active macrophages

• Followed by antigen presentation by macrophage

• Defenses against viruses involve:

• Direct contact with virus-infected cells

• Antigen presentation by antigen-presenting cells

(APCs)

• Release of interferons


Defenses against bacterial and viral pathogens

Figure 13.7 3 - 4 3 4–

BACTERIA

Macrophageactivation

Antigenpresentation

Contact with activeAPCs activatescytotoxic T cells.Activated T cells divideto produce morecytotoxic T cells andinactive memory TC

cells.

Contact with thesurface of an activeAPC activates helperT cells. These cellsdivide to produceadditional activatedhelper T cells andmemory TH cells.

Contact with activatedhelper T cells activatesB cells. ActivatedB cells divide toproduce active plasmacells and inactivememory B cells.

Destroy bacteria by celllysis or phagocytosis

Plasma cells produceantibodies

VIRUSES

Infection of or uptakeby APCs

Infection oftissue cells

Release ofinterferons

Appearance of antigenin plasma membrane Antigen presentation

Contact with thesurface of an activeAPC activates helper T cells. These cellsdivide to produceadditional activatedhelper T cells andmemory TH cells.

ActivationofcytotoxicT cells

Contact withsurfaces ofinfected cellsstimulates NKcells.

Increasedresistance to viral infectionand spread

Destroyinfected cells

Contact with activatedhelper T cells activatesB cells. ActivatedB cells divide toproduce active plasmacells and inactivememory B cells.

Destroy viruses orprevent viruses fromentering into cells

Plasma cells produceantibodies


Memory Cells (13.7)

• No role in initial infection

• Dramatically reduce response time for

subsequent infection by same pathogen

• Upon secondary exposure, differentiate into:

1. Cytotoxic T cells (memory TC cells)

2. Helper T cells (memory TH cells)

3. Plasma cells (memory B cells)

• Rapid and effective response


Module 13.7 Review

a. Describe antigen presentation.

b. Which cells can be activated by direct contact

with virus-infected cells?

c. Which cells produce antibodies?


Antibodies (13.8)

• Antibody molecule composed of:

• Two parallel pairs of polypeptide chains

• One pair heavy chains

• One pair light chains

• Each chain has:

• Constant segments

• Variable segments

• Constant segments of heavy chains form base of

molecule


Antigen Binding Sites (13.8)

• Free tips of two variable segments

• Can interact with antigen similar to enzyme

interaction with substrate

• Differences in variable segment structure affect

shape of binding site

• Antibodies specific for different antigens

• Variation occurs during production, division, and

differentiation of B cells


Antibody structure

Figure 13.8 1 1

Antigenbinding

site

Heavy chain

Disulfidebond

Variablesegment

Constantsegments

of lightand heavy

chains

Antigen binding sites

Light chain

Binding sites that can activate the complementsystem are covered when the antibody is secretedbut become exposed when the antibody binds toan antigen.

Binding sites may also be present that attach the secreted antibody to the surfaces of macrophages, basophils, or mast cells.


Antigenic Determinant Sites (13.8)

• Antibody binds to antigen to form antigen-antibody

complex

• Binding between antibody and antigenic determinant

sites

• Specific portions of exposed antigen surface

• Bacteria may contain millions of antigenic determinant

sites


Types of Antigens (13.8)

• Complete antigen• At least two antigenic determinant sites

• Partial antigen (or hapten)• Does not ordinarily activate B cells

• Can attach to carrier molecules and function as complete antigen

• Antibodies will attack hapten and carrier molecule

• If carrier molecule is normally found in tissues:

• Antibodies may attack normal cells

• Basis for drug reactions like allergy to penicillin


Formation of antigen-antibody complex

Figure 13.8 2 2

Antigenic determinant sites

Antibody

Antigen-antibodycomplex

Complete antigen

Carriermolecule

Partial antigen(hapten)

Antibody

Partial antigen32

1


Antigen

Antigenicdeterminant sites Antibodies

Antibodies bind to antigenic determinant sites

Figure 13.8 3 3


Classes of Antibodies (13.8)

• Five classes of antibodies or immunoglobulins (Igs)

• Determined by differences in structure of heavy-chain

constant segments

1. IgG

2. IgE

3. IgD

4. IgM

5. IgA

© 2013 Pearson Education, Inc. Figure 13.8 4 4

IgG antibodies are responsible for resis-tance against many viruses, bacteria, and bacterial toxins. They account for 80 percent of all antibodies.

IgE attaches to basophils and mast cells, releasing histamine and speeding up inflammation.

IgD is an individual molecule on the surfaces of B cells, where it can bind antigens in the extra-cellular fluid. This binding can play a role in sensitizing the B cell.

IgM is the first class of antibody secreted after an antigen is encountered. IgM concentration declines as IgG production accelerates. The anti-A and anti-B antibodies responsible for the agglutination of incom-patible blood types are IgM antibodies.

IgA is found primarily in glandular secretions such as mucus, tears, saliva, and semen. These antibodies attack patho-gens before they gain access to internal tissues.


Primary Response to Antigen Exposure (13.8)

• Primary response is initial response to exposure

• Takes time to develop

• Antigen activates B cells

• Differentiate into plasma cells

• Secrete antibodies

• Antibody titer (concentration) peaks one to two weeks

after exposure then declines if no longer exposed to

antigen


Secondary Response to Antigen Exposure (13.8)

• Secondary response triggered when antigen

encountered again

• More extensive and lasts longer than primary

• Antibody titer increases rapidly and to much higher

levels

• Result of immediate response by memory B cells

• Appears even if second exposure is years after first

• Memory cells survive 20 years or more


The primary and secondary responses in antibody-mediated immunity

Figure 13.8 5 - 65 6–

Primary response

IgMIgG

Time (weeks)

An

tib

od

y ti

ter

in p

las

ma

1 2 3 4 1 2 3 4Time (weeks)

IgG

IgM

Secondaryresponse


Module 13.8 Review

a. Define antigenic determinant site.

b. Describe the structure of an antibody.

c. Name the five classes of immunoglobulins and

cite a function of each.


Antibody Mechanisms (13.9)

• Seven different mechanisms for eliminating

antigens

1. Neutralization

2. Prevention of pathogen adhesion

3. Activation of complement

4. Opsonization

5. Attraction of phagocytes

6. Stimulation of inflammation

7. Agglutination



1. Neutralization

• Bacteria and viruses must bind to plasma membrane of body cells

before they can enter cells

• Antibodies attach to binding sites on bacteria or toxins

• Neutralizes binding ability of bacteria and toxins

• No binding sites available now for attachment to body cells

2. Prevention of pathogen adhesion

• Antibodies part of saliva, mucus, tears, and perspiration

• Coating of antibodies creates barrier

• Difficult for pathogens to adhere to body surfaces



3. Activation of complement

• Binding to antigen changes antibody molecule shape

• Exposed area binds to complement proteins, activating

complement system

4. Opsonization

• Coating of antibodies and complement makes surfaces of

bacteria less slick

• Phagocytes can bind more easily

5. Attraction of phagocytes

• Neutrophils, eosinophils, and macrophages attracted to antigens

coated with antibodies



6. Stimulation of inflammation

• Antibodies stimulate release of heparin and histamine from

basophils and mast cells

• Promotes inflammatory response

7. Agglutination

• Antibodies can bind to antigenic determinant sites on adjacent

antigens

• Large numbers of antigens together create immune complex

• Formation of immune complex from surface antigens called

agglutination

• For example, clumping of erythrocytes in transfusion reaction


Mechanisms antibodies use to destroy target antigens

Figure 13.9

Neutralization Prevention of Pathogen Adhesion Activation of Complement

Opsonization

Agglutination

ImmuneComplex

Antigenicdeterminant

sites

Stimulation of Inflammation

Attraction ofPhagocytes


Module 13.9 Review

a. Describe the ways that antigen-antibody

complexes can destroy target antigens.

b. Define opsonization.

c. Which cells are involved in inflammation?


Antibody Overreactions (13.10)

• Allergies

• Inappropriate or excessive immune responses to

antigens

• Sudden increase in cellular activity and antibody titers

• Neutrophils or cytotoxic T cells may destroy normal cells

in addition to antigen

• Antigen-antibody complex may trigger inflammation

• Antigens triggering allergic reactions called allergens


Allergic Responses (13.10)

• Initial exposure to allergen

• Causes sensitization

• Production of large quantities IgE

• Immediate hypersensitivity

• Rapid, severe response to antigen

• Example is allergic rhinitis (includes hay fever)

• Inflammation of nasal membrane

• Hypersensitivity reaction

• May be limited to body surface or can be systemic


Seasonal allergies

Figure 13.10


Anaphylactic Shock (13.10)

• Allergen can trigger systemic response

• Anaphylaxis

• Circulating allergen stimulates histamine release from

mast cells throughout body

• Can cause extensive peripheral vasodilation

• Extreme drop in blood pressure leading to circulatory

collapse

• Anaphylactic shock


Mechanism of anaphylaxis

Figure 13.10

First ExposureAllergen fragment

AllergensMacrophage TH cell activation

B cell sensitizationand activation

Plasma cell

IgE antibodies

SubsequentExposure

AllergenIgE

Granules

Massivestimulation of mast cellsand basophils

Sensitization ofmast cells andbasophils

Release of histaminesand other chemicals that

cause pain and inflammation

Localized Allergic Reactions Systemic Allergic Reactions

If the allergen is at the body surface: localized inflamma-tion, pain, and itchingExample: allergic rhinitis

If the allergen is in the bloodstream: itching, swelling, and difficulty breathing (due to constricted airway)Example: anaphylaxis


Module 13.10 Review

a. Define allergy and allergen.

b. What is anaphylaxis?

c. Which chemicals do mast cells and basophils

release when stimulated in an allergic reaction?


Immune Disorders (13.11)

• Can be excessive or misdirected immune

response

• Autoimmune disorders

• Graft rejection

• Allergies

• Can be inadequate immune response

• Immunodeficiency diseases

• Age-related reductions in immune activity


Autoimmune Disorder Process (13.11)

• Immune system attacks body's own tissue

• Malfunction of "self" antigen recognition system produces

autoantibodies

• Affects about 5 percent of adults in North America and

Europe

• Many caused by similarities in proteins

• Protein associated with measles, Epstein–Barr, influenza, and

other viruses has the same amino acid sequence as myelin

proteins

• Antibodies targeting these pathogens may also attack myelin

sheaths

• Likely mechanism responsible for multiple sclerosis


Autoimmune Disorders (13.11)

• Thyroiditis

• Inflammation from release of autoantibodies against

thyroglobulin

• Rheumatoid arthritis

• Autoantibodies attack connective tissue in joints

• Cause inflammation and destruction of joints

• Type I diabetes

• Autoantibodies attack insulin-producing cells in

pancreatic islets


Autoimmune disorders

Figure 13.11


Graft Rejection (13.11)

• Occurs after organ transplant

• Recipient's T cells activated by donated tissue

attack and destroy foreign cells

• Transplant success improved by

immunosuppression

• Reducing sensitivity of immune system

• Cyclosporin A (CsA)

• Suppresses immune response by inhibiting helper T cells

while not affecting suppressor T cells


Inadequate Immune Response (13.11)

• Immunodeficiency diseases

• Result from:

1. Embryological development problems with lymphoid

organs and tissues

2. Infection with virus that depresses immune function

3. Treatment with or exposure to immunosuppressive

agents

• Age-related reductions in immune activity


Immunodeficiency Diseases (13.11)

• Acquired immune deficiency syndrome (AIDS) • Most common immunodeficiency disease

• Caused by human immunodeficiency virus (HIV)

• Virus binds to CD4 proteins and infects helper T cells

• Infected cells synthesize and release new viral proteins

• Infected helper T cells destroyed by virus or immune defenses

• Impairs cell-mediated and antibody-mediated responses

• Suppressor T cells not affected by virus

• Body vulnerable to microbial invaders, opportunistic infections, cancer

• Spread by contact with body fluids (blood, semen, vaginal secretions)

• Infects 33 million people worldwide with 2 million deaths each year


Immunodeficiency diseases

Figure 13.11

HIV (green) budding from an infected TH cell SEM x 40,000


Age-Related Reductions in Immune Activity (13.11)• Immune system is less effective with age

• Thymus shrinks and thymic hormones decrease

• Increased susceptibility to viral and bacterial infections• T cells less responsive to antigens

• Fewer cytotoxic T cells respond to infection

• Number of helper T cells reduced

• B cells less responsive

• Antibody levels slower to rise after antigen exposure

• Vaccinations (flu, pneumonia) strongly recommended

• Increased incidence of cancer• Declining immune surveillance and elimination of tumor cells


Age-related reductions in immune activity

Figure 13.11


Module 13.11 Review

a. Define autoimmune disorders.

b. Describe immunosuppression.

c. Provide a plausible explanation for the increased

incidence of cancer in the elderly.

Documents

PowerPoint ® Lecture Slides prepared by Betsy C. Brantley Valencia College C H A P T E R © 2013 Pearson Education, Inc. The Lymphatic System and Immunity