Principles of Anatomy and Physiology

Thirteenth Edition

Chapter 22The Lymphatic System and Immunity

Copyright © 2012 by John Wiley & Sons, Inc.

Gerard J. Tortora • Bryan H. Derrickson

(a) Anterior view of principal components of lymphatic system

Palatine tonsil

Submandibular node

Cervical node

Right internal jugular vein

Right lymphatic duct

Right subclavian vein

Lymphatic vessel

Thoracic duct

Cisterna chyli

Intestinal node

Large intestine

Appendix

Red bone marrow

Lymphatic vessel

Left internal jugular vein

Left subclavian vein

Thoracic duct

Axillary node

Spleen

Aggregated lymphatic follicle (Peyer’s patch)

Small intestine

Iliac node

Inguinal node

(b) Areas drained by right lymphatic and thoracic ducts

Area drained byright lymphatic duct

Area drained bythoracic duct

(a) Relationship of lymphatic capillaries to tissue cells and blood capillaries

Venule

Tissue cell

Lymph

Interstitial fluid

Blood

Blood capillary

Arteriole

Lymphatic capillary

Blood

(b) Details of a lymphatic capillary

Lymph

Endothelium of lymphatic capillary

Tissue cell

Interstitial fluid

Anchoring filament

Opening

(a) Overall anterior view

Right internal jugular vein

RIGHT JUGULAR TRUNK

RIGHT SUBCLAVIAN TRUNK

Right subclavian vein

RIGHT LYMPHATIC DUCT

Right brachiocephalic vein

RIGHT BRONCHO-MEDIASTINAL TRUNK

Superior vena cava

Rib

Intercostal muscle

Azygos vein

CISTERNA CHYLI

RIGHT LUMBAR TRUNK

Inferior vena cava

Left internal jugular vein

LEFT JUGULAR TRUNK

THORACIC (LEFT LYMPHATIC) DUCT

LEFT SUBCLAVIAN TRUNK

Left subclavian vein

First rib

Left brachiocephalic vein

Accessory hemiazygos vein

LEFT BRONCHO-MEDIASTINAL TRUNK

THORACIC (LEFT LYMPHATIC) DUCT

Hemiazygos vein

LEFT LUMBAR TRUNK

INTESTINAL TRUNK

(b) Detailed anterior view

Right jugular trunk

Right subclavian trunk

Right lymphatic duct

Right bronchomediastinal trunk

Left jugular trunk

Left subclavian trunk

Thoracic (left lymphatic) duct

Left bronchomediastinal trunk

Lymphatic duct

SYSTEMIC CIRCULATION PULMONARY CIRCULATION

Subclavian vein

Lymphatic vessel

Valve

Lymph node

Lymphatic capillariesSystemic blood capillaries

Arteries

Lymphatic capillaries

Pulmonary blood capillaries

Lymph node

Veins

Heart

Right commoncarotid artery

(a) Thymus of adolescent

Right lung

Thyroid gland

Trachea

Superior vena cava

Thymus

Left lung

Fibrouspericardium

Diaphragm

Brachiocephalic veins

Capsule

(b) Thymic lobules

30xLM

Lobule:

Cortex

Thymic (Hassall’s)corpuscle

Medulla

Trabecula

(c) Details of the thymic medulla

385xLM

T cell

Thymic (Hassall’s)corpuscle

Epithelial cell

(a) Partially sectioned lymph node

Valve

Afferent lymphaticvessel

Afferent lymphatic vessels

Subcapsular sinus

Reticular fiber

Trabecula

Trabecular sinus

Outer cortex:

Germinal center in secondary lymphatic nodule

Cells around germinal centerInner cortexMedulla

Medullary sinus

Reticular fiber

Efferent lymphatic vessels

Valve

Hilum

Capsule

Cells in germinal center of outer cortex

B cells

Follicular dendritic cells

Macrophages

Cells around germinal center of outer cortex

B cells

Cells of inner cortex

T cells

Dendritic cells

Cells of medulla

B cells

Plasma cells

Macrophages

Route of lymph flowthrough a lymph node:

Afferent lymphatic vessel

Subcapsular sinus

Trabecular sinus

Efferent lymphatic vessel

Medullary sinus

Capsule

(b) Portion of a lymph node

40xLM

Subcapsular sinus

Outer cortex

Trabecular sinus

Germinal center in secondary lymphatic nodule

Trabecula

Inner cortex

Medullary sinus

Medulla

(c) Anterior view of inguinal lymph node

Efferent lymphaticvessels

Nerve

Skeletal muscle

Lymph node

Afferent lymphaticvessels

(a) Visceral surface

Splenic vein

SUPERIOR

POSTERIOR ANTERIOR

Colic impression

Hilum

Renal impression

Splenic artery

Gastric impression

(b) Internal structure

Splenic artery

Splenic vein

White pulp

Red pulp:

Venous sinus

Splenic cord

Central artery

Trabecula

Capsule

(c) Portion of the spleen

25xLM

Capsule

Red pulp

Trabecula

Central artery

White pulp

Internal jugular vein

Subclavian vein

Inferior vena cava

Jugular lymph sac

Thoracic duct

Cisterna chyli

Retroperitoneal lymph sac

Posterior lymph sac

CHEMOTAXIS Microbe

ADHERENCE

Pseudopod

Phagosome

Lysosome

Plasma membrane

Digestiveenzymes

INGESTION

DIGESTION

KILLING

Phagocyte

Digested microbein phagolysosome

Residual body(indigestiblematerial)

1

2 3

4

5

(a) Phases of phagocytosis

Phagocyte

Microbe

(b) Phagocyte (white blood cell) engulfing microbe

1800xSEM

Chemotaxis Microbe

PhagocytesEmigration

Vasodilationand increasedpermeability

Tissue injury

Phagocytes migrate from blood to site of tissue injury

Primary lymphaticorgans Red bone marrow

Thymus

Pre-T cells

Mature T cells Mature B cells

CytotoxicT cell

HelperT cell B cell B cell

Antigenreceptors

CD4proteinActivation ofhelper T cell

Formation of helper T cell clone:MemoryhelperT cells HelpHelp

Active helperT cells

Activation ofcytotoxic T cell

Activation ofB cell

Formation of B cell clone:

Formation of cytotoxic T cell clone:

Active cytotoxicT cells

MemorycytotoxicT cells

Antibodies

Plasma cells

MemoryB cells

Antibodies bind to and inactivate antigens in body fluids

Active cytotoxic T cells leave lymphatic tissue to attack invading antigens

Secondary lymphatic organs and tissues

CD8protein

CELL-MEDIATED IMMUNITYDirected against intracellular pathogens, some cancer cells, and tissue transplants

ANTIBODY-MEDIATED IMMUNITYDirected against extracellular pathogens

Epitopes

Antigen

Exogenousantigen

1

2

3

4

5

Phagosomeor endosome

Digestion ofantigen intopeptide fragmentsAntigen-presenting

cell (APC)Packaging of MHC-IImolecules into a vesicle

Synthesis of MHC-II molecules

Vesicles containing antigen peptide fragments and MHC-II molecules fuse Antigen peptide

fragments bind to MHC-II molecules

Vesicle undergoesexocytosis and antigen–MHC-II complexes are inserted into plasma membrane

Endoplasmicreticulum

Key:

Antigenpeptidefragments

MHC-IIself-antigen

Phagocytosis or endocytosis of antigen

6

7

APCs present exogenous antigens in association with MHC-II molecules

1

2

3

4

Endogenousantigen

Digestion of antigeninto peptide fragments

Antigen peptide fragmentsbind to MHC-I molecules

Synthesis of MHC-I molecules

Endoplasmicreticulum

Packaging ofantigen–MHC-Imolecules into a vesicle

Vesicle undergoes exocytosis and antigen–MHC-I complexes are inserted into plasma membrane

Infected bodycell

Key:

Antigenpeptidefragments

MHC-Iself-antigen

5

Infected body cells present endogenous antigens in association with MHC-I molecules

Antigen-presentingcell (APC)

CostimulationAntigen recognition

InactivehelperT cell

ActivatedhelperT cell

Formation of helper T cell clone:

Clonal selection(proliferation anddifferentiation)

Active helper T cells (secreteIL-2 and other cytokines)

Memory helper T cells(long-lived)

Inactive helperT cell

MHC-II

AntigenTCR

CD4protein

Infectedbody cell Helper T

cell

Costimulationby IL-2

Antigenrecognition

Inactive cytotoxic

T cell

ActivatedcytotoxicT cell

Clonal selection(proliferation anddifferentiation)

Formation of cytotoxic T cell clone:

Inactive helperT cell

MHC-IIAntigen

TCR

CD8protein

Active cytotoxic T cells (attack infected body cells)

Memory cytotoxic T cells (long-lived)

ActivatedcytotoxicT cell

ActivatedcytotoxicT cell

Recognitionand attachment

Microbe

Infectedbody cell

Infected body cellundergoing apoptosis

Microbe

Phagocyte

Granzymes Recognitionand attachment

Infectedbody cell

Infected body cellundergoing cytolysis

(b) Cytotoxic T cell destruction of infected cell by release of perforins that cause cytolysis; microbes are destroyed by granulysin

Granulysin

Perforin

Channel

Key:

CD8 protein

Antigen-MHC-Icomplex

TCR

(a) Cytotoxic T cell destruction of infected cell by release of granzymes that cause apoptosis; released microbes are destroyed by phagocyte

B-cellreceptor

InactiveB cell

Microbe

MicrobeMicrobe

ActivatedB cell

ActivatedB cell

HelperT cell

B cellrecognizingunprocessedantigen

Costimulationby several interleukins

B cell displaying processedantigen is recognizedby helper T cell, whichreleases costimulators

Clonal selection(proliferation anddifferentiation)

Formation of B cell clone:

AntibodiesPlasma cells(secrete antibodies)

Memory B cells(long-lived)

Light chains

Carbohydratechain

Heavy chains

Antigenbinding site

Antigenbindingsite

(a) Model of IgG molecule

Heavy (H) chain

Hinge region

Carbohydratechain

Light (L) chain

Antigenbinding

sites

Stemregion

(b) Diagram of IgG heavy and light chains

VH

CH

CL

VL

VH

CH

CH

CHCH

CH

CL

VL

IgG

IgA

IgM

IgD

IgE

PHAGOCYTOSIS:Enhancement of phagocytosisby coating with C3b

Mic

robe

Microbe

C3

C3b C3a

C5

C5b C5a

C6

C7C8

C9

C6 C5b Channel

Membrane attack complex forms channel

CYTOLYSIS:Bursting of microbe due to inflow of extracellular fluid through

channel formed by membrane attack complex C5–C9

Microbialplasmamembrane

Microbe

INFLAMMATION:Increase of blood vessel permeability and chemotactic attraction of phagocytes

Mast cell

Histamine

C7C8 C9

12

3

4

Primary response Secondary response1000

100

10

1

0.1

Ant

ibod

y ti

ter

(arb

itra

ry u

nits

)

IgG

IgM

0 14 28 42 56

First exposure Second exposure

Days

Death of cells that cannotrecognize self-MHC molecules

NoYes

Does immature T cell recognize self-MHC proteins?

(b) Selection of T cells after they emerge from the thymus

Mature T cell inlymphatic tissue

Deletion (death) of B cellin bone marrow

Does immature B cell in bone marrow recognize self- MHC molecule or other selfantigens?

(c) Selection of B cells

Cell survival or activationCell death or anergy (inactivation)

Key:

Yes

No Mature B cellrecognizes antigen(first signal)

Costimulation(second signal)

NocostimulationAnergy (inactivation) of Bcell in secondary lymphatictissues and blood

Activation of B cell, which proliferates and differentiates into clone of plasma cells

Activation of T cell, which proliferates and differentiates

Survival of T cells that can recognize self-MHC proteins but not self-peptides

Deletion (death) of T cell

Anergy (inactivation) of T cell

Anergy (inactivation) of T cell

Death of T cell

Positiveselection

Is TCR capable of binding to and recognizing self-peptides?

Negativeselection

Antigen recognition with costimulation

Antigen recognition without costimulation

Deletion signal (?)

No

Yes

Yes

(a) Positive and negative selection of T cells in the thymus

Negativeselection

Glycoproteins

Human immunodeficiency virus (HIV)

Lipidbilayer

Protein coat (capsid)

Reverse transcriptase

RNA (single stranded)

Envelope

100–140 nm