Download Lymphatics

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o
Lymphatic System – General:

Consists of :
o Cells
o Tissues
o Organs

Fxn:
o Monitor body surfaces and internal fluid compartments
o React to the presence of potentially harmful substances
Introduction to Cells of the Lymphatic System:
o Supporting Cells - organized into loose meshworks: reticular cells & reticular fibers

Monocytes

Macrophages

Neutrophils

Basophils

Eosinophils

Reticular cells

Dendritic cells

Follicular dendritic cells

Langerhans’ cells

Epithiliolreticular cells
o Lymphocytes:

Circulating lymphocytes are the chief cellular constituents of lymphatic tissue

They are the “effector” cells in immune response to harmful substances

Lymphocytes are “educated” (maturation & differentiation) in bone marrow (B cells) &
thymus (T cells) to become immunocompetent cells (discussed later)
o Summary of Cell Types/Subtypes:
o Legend:

Th = T-Helper

BCR = B-Cell Recepter

IL = Interleukin

IFN = Interferon

TNF = Tumor Necrosis Factor

CD = “Cluster of differentiation” = cell “marker”

Basically, when there are morphologically similar cells (i.e. they look the same
microscpically), cell surface “markers” or CD’s (i.e. cell surface components =
proteins?...Ag’s?) that are expressed enable us to differentiate the different
immune system cells “histochemically” (i.e. test for presence or absence of
chemical reaction with certain reagents)

Therefore, CD’s or “markers” used to I.D. diff’t types of lymphatic cells
BOLDED CD’s in chart are ones that Dr. O’Sullivan specifically said to remember!

CELL
T Lymphocytes (60 –80%)
(Cell-Mediated response)
o
FUNCTION/Other
Helper

Th1
Fxn: Help T lymphocyte produce cell-mediated (no Ab’s)
immune responses that control intracellular pathogens

Th2
Fxn: Help B lymphocytes produce humoral (Abmediated) immune responses to control extracellular
pathogens
o
Cytotoxic
o
Gamma/Delta

B Lymphocyte (20 – 30%)
(Humoral response)

Natural Killer (NK) Cells
(5-10%)
SYNTHESIS
EXPRESSES
CD2
CD3
CD7
TCR’s
IL-2,
IFN- γ
TNF-α
IL-4
IL-5
IL-10
IL-13
CD4+
Mature in Thymus
Fxn: Kill target cells infected w/ intracellular pathogens
or transformed cells (virus-infected or tumor)
Reside in various epithelial tissues; do not recirculate; 1st
line of defense
Develop in bone marrow
Fxn: produce & secrete Ig’s (def = circulating Ab’s);
BCR’s (def = membrane-bound Ig’s) bind Ag’s
Do NOT mature in the Thymus
Fxn: Programmed to recognize transformed cells (virusinfected & tumor cells)
CD4+
CD8+
CD9
CD19
CD20
CD24
CD16
CD56
CD94
o
Immune Responses:

Innate (“built-in”)/1st line of defense /Non-specific

Not long-lasting

May trigger Complement System (cascade event)

Defenses:
o Physical barriers (skin, mucous membranes)
o Chemical barriers (low pH)
o Secretory substances [thiocyanate (saliva), interferons….I didn’t get the rest]
o Phagocytic cells

Adaptive/2nd line of defense /Specific (B & T Lymphocytes)
o Long-lasting; targets specific invaders (Ab do NOT kill invader, they simply “tag” them)
o Introduction: Antigen (Ag)

Definition = any substance that can induce a specific immune response

Examples:

Soluble substances

Infectious microorganisms

Foreign tissue

Transformed tissue

Most Ag’s must be “processed” by cells of the immune system before other cells can
mount an immune response (i.e. before they can be recognized)
o Proliferation & Differentiation = Ag-independent

Proliferation occurs in the bone marrow (B & T cells)

Differentiation Location = 1o (or central) lymphatic organs
o Bone marrow (B cells)
o Thymus (T cells)

Immunocompetent lymphocytes
o Definition: genetically programmed to recognize a single Ag out of
an infinite # of possible Ag’s
o Lymphocytes are “educated” (maturation & differentiation) in bone
marrow (B cells) & thymus (T cells; Thymic “education”) to become
immunocompetent cells:

Recognize & destroy specific Ag’s

Distinguish “self” & “non-self”

Enter blood or lymph & are transported throughout body &
“seed” in the lymphoid tissue awaiting an antigenic
challenge
o Activation = Ag-dependent activation (antigenic challenge)

T & B cells undergo Ag-dependent activation into effector cells and memory cells

Location: 2o (or periphery) lymphatic tissues & organs

Definition: 2o (periphery) lymphatic organs = group of cells that organize around
reticular cells & their reticular fibers

Group of Cells:

Immunocompetent lymphocytes

Plasma Cells

Macrophages

Dendritic cells

2o lymphatic or periphery organs:

“Diffuse” lymphatic tissue  GALT (Gut-Assoc. Lymphatic Tissue)

Lymphatic Nodules:
o Tonsils
o Peyer’s patches – ileum
o Vermiform appendix

Lymph nodes

Spleen

Inflammatory Response – initial response to an Ag 
3 possible fates:

Sequester the Ag

Digestion of Ag by neutrophilic enzymes

Phagocytosis & degradation of Ag by macrophages which may lead to
subsequent presentation (via MHC II molecules) to immunocompetent
lymphocytes (CD4+)  discussed later

“Specific” Immune Response Classifications
o Cellular Immune response (Cell-mediated)

Specific T lymphocytes destroy virus-infected or foreign cells

NO Ab’s involved

Major Histocompatibility Complexes (MHC) display peptides on cell
surfaces
o General details:

MHC molecules are products of the “supergene”
(chromosome 6)

Inside the cell, small fragments (Ag) of digested “self”, &
when present, foreign proteins, bind with the MHC
molecule = Ag—MHC complex

The Ag—MHC complex is transported to the cell surface

Protein fragments, ie Ag (“self” & foreign--when present)
are displayed on outside of cell surface
o Types:

MHC I

Expressed in ALL nucleated cells and platelets

All endogenous (“self”) peptides are bound by
MHC I & displayed on ALL cell PM’s

H/w viral or cancer-specific peptides (i.e Ag’s)
are also bound by MHC I ( = Ag—MHC I
Complex) & the Ag is displayed ONLY on
“infected” or “transformed” cell’s surface

MHC II

Expressed by antigen-presenting cells (APC’s =
Ag Presenting Cell)
o Mononuclear phagocytotic system APC

Macrophages

Perisinusoidal macrophages
(kupffer cells)

Langerhans’ cells (epidermis)

Dendritic Cells (spleen,
lymph nodes, mucosal
surfaces)
o B Lymphocytes APC

Type II & Type III
epithelioreticular cells
(thymus)

APC’s endocytose the Ag & break it down into 8
to 10 a.a. peptides

In the APC endosomal compartments, the a.a.
peptides bind to MHC II molecules
( = Ag—MHC II Complex)

Ag—MHC II Complex is translocated to the
APC PM

Ag is displayed on cell surface

T-cell receptors (TCR) on T lymphocytes recognize & bind “displayed”
Ag (from Ag—MHC cmplx)
= TCR—Ag—MHC Complex (“triplex” required for immune response)
o T lymphocyte TCR’s ONLY recognize Ag when it is attached to a
major histocompatibility complex (MHC)

Cytotoxic (CD8+) T Lymphocyte TCR’s are MHC I restricted:
they can ONLY recognize Ag when presented by MCH I
(transformed or virus-infected, i.e “non-self” cells)

TCR—Ag—MHC I Complex forms

CD8+ releases cytokines (biological modulators)

Ctyokines  CD8+ proliferation

Other Cytokines  cell apoptosis/lysis
o Lymphokines
o Perforins
o Fragmentins

o
Helper (CD4+) T lymphocytes are MHC II restricted:
they can ONLY recognize Ag when it presented by MHC II (APC’s)

TCR—Ag—MHC II Complex forms

CD4+ releases interleukins (a specific CD4+ cytokine)

Interleukins 
o Proliferation

T cells (bone marrow)

B cells (bone marrow)

NK cells (?)
o Differentiation

T cells (thymus)

B cells (bone marrow)

NK cells (?)

Interaxn of a B lymphocyte w/ TCR—Ag—MHC
II cmplx activates B lymphocyte & t/f Humoral
Immune Response
Humoral Immune response (Ab-mediated)

Activated by Cellular Immunity (B-cell Ab + TCR—Ag—MHC II cmplx)

Activated B cells transformimmunoblasts that proliferate/differentiate
o Plasma Cells: synthesize & secrete a specific Ab
o Memory B Cells: respond quicker to next encounter w/ same Ag

Ab’s produced by B cells or plasma cells act directly on invading agent
o Primary Response:

Lag period of several days before Ab’s or specific
lymphocytes are detected

Memory lymphocytes remain in circulation
o Secondary Response:

More rapid and more intense due to memory cells

Basis of most immunizations

Plasma cell Ab’s binds the stimulating Ag  Ag—Ab complex

Complexes eliminated in a variety of ways:
o NK cell destruction; macrophage & eosinophil phagocytosis
o NK cells act in concert with other cells to induce the lysis Ag cells
o If Ag is a bacterium, the Ag—Ab cmplx may activate the
complement system (cascade event of plasma proteins), which may
cause foreign cells to lyse
Pluripotential Stem Cell
(bone marrow)
Multipotential Myeloid Cell
RBC’s
(bone marrow)
Multipotential Lymphoid Cell
B Cells
(bone marrow)
Plasma Cells
T Cells
(Thymus)
T-helper (CD4+)
Cytotoxic (CD8+)

Lymphatic Tissues and Organs
o Lymphatic Vessels - route for cells & lg molecules to pass from tissue spaces to blood

Begin as networks of blind capillaries in LCT

Most numerous beneath skin & mucous membrane epithelium

More permeable than blood capillaries

Lymph

Substances & fluid removed from extracellular spaces

Lymph flow is one-directional due to valves

Lymph passes thru lymph nodes which fxn as filters

Ag’s conveyed in lymph are trapped by follicular dendritic cells (FDC)

Ag exposed on FDC surface can be processed by APC’s present w/in the lymph node

Lymphocyte Circulation:

Lymphocytes in lymph enter lymph nodes by afferent lymphatic vessels

Lymphocytes from blood enter the node through the walls of postcapillary
venules, known as high endothelial venules (HEV)

B & T Cells migrate to diff’t regions in the lymph node

Some lymphocytes pass thru the lymph node & leave via the efferent lymphatic
vessels

Efferent lymphatic vessels lead to either:
o Right lymphatic trunk
o Thoracic duct (left)

Both efferent lymphatic vessels empty into blood circulation at the jxn of the
IJV & sublclavian veins at the base of the neck
o Diffuse Lymphatic Tissue & Lymphatic Nodules - Initial immune response site

Guard the body against pathogenic substances

Found in lamina propria (LP) of the

Alimentary canal

Respiratory passages

Genitourinary tract

Also called gut-associated lymphatic tissue (GALT)

NOT enclosed by a capsule

The cells are positioned to intercept Ag’s & initiate immune responses

After Ag contact the cells travel to the lymph nodes where they undergo proliferation &
differentiation

Progeny of these cells return to the LP as effector B & T lymphocytes

Presence of lg #’s of plasma cells indicates local Ab secretion

Presence of lg #’s of eosinophils indicates chronic inflammation & hypersensitivity rxns

Lymphatic Nodules (lymphatic follicles)

Discrete, localized [ ]’s of lymphocytes contained in a meshwork of reticular
cells

Located in walls of:
o Alimentary canal
o Respiratory passages
o Genitourinary tract

Sharply defined surface, but not encapsulated

Classification:
o Primary (1o) – consists chiefly of sm. lymphocytes
o Secondary (2o) – most nodules are 2o

Germinal center

Located in central region

Lightly stained due to:
o Lg. immature lymphoblasts
o Plasmablasts

Develops when a B lymphocyte that has
recognized Ag returns to a 1o nodule &
proliferates

Mantle zone – outer ring of sm. lymphocytes that encircles
the germinal center

o
Lymphatic nodules are usually found in structures associated with the
alimentary canal, such as:
o Tonsils:

Squamous epithelium forms the surface of the tonsil and
dips into the CT to form the tonsillar crypts

Crypt walls contain numerous lymphatic nodules

Tonsils do NOT possess afferent lymphatic vessels

Lymph drains via efferent lymphatic vessels

Examples:

Waldeyer’s Ring – ring of lymphatic tissues at
the entrance of the oropharynx

Pharyngeal (adenoids), palantine, lingual
o Peyer’s patches

Located in the ileum

Aggregated nodules

Specialized epithelial cells for Ag uptake (M cells?)
o Vermiform appendix

Arises from the cecum of large intestine

LP is heavily infiltrated with lymphocytes & contains
numerous lymphatic nodules
Lymph Nodes

Sm. bean-shaped encapsulated organs that fxn as lymph filters, located along the pathway
of lymphatic vessels

Supporting elements:

Capsule: DCT surrounding the node

Trabeculae: DCT extends into the node

Reticular tissue: reticular cells & reticular fibers

Lymphatic vessels

Afferent
o Transport lymph toward the node
o Enters at the capsule

Efferent
o Transports lymph away from the node
o Leaves at the Hilum

Reticular meshwork:

Cells – stellate or elongated cells w/ an oval euchromatic nucleus & sm. amt. of
acidophilic cytoplasm
o Reticular Cells

Mesenchymal

Indistinguishable from typical fibroblasts

Secrete

Type III collagen (reticular fibers)

Ground substance (forms the stroma)

Cytoplasmic processes surround bundles of reticular fibers,
isolating them from the lymphoid tissues

Secretes chemokines that attract

T cells

B cells

Dendritic cells
o Dendritic Cells (DC)

V. efficient bone marrow-derived APC’s

Express high levels of MHC II & co-stimulatory molecules

Localized in the T cell areas
o Macrophages

Bone marrow-derived

Express MHC I, MHC II and co-stimulatory molecules
(lower levels than DC)

Immense capacity for endocytosis & digestion of
internalized materials
Follicular Dendritic (FDC’s)

Multiple, thin, branching cytoplasmic processes that
interdigitate b/w B cells in germinal centers

Trap Ag-Ab complexes

Retain Ag on its surface for weeks, months or years

Lack MHC II molecules
General Lymph Node Architecture:

Superficial Cortex
o 1o Nodules: chiefly sm. lymphocytes (B cells)
o 2o Nodules: germinal centers are present

Deep Cortex (Paracortex)
o Free of Nodules
o T Cell area
o High endothelial venules (HEV)

Medulla
o Medullary Cords:

Reticular Cells

Lymphocytes

Macrophages

DC’s

Plasma Cells
o Medullary Sinuses:

Converge near the Hilum

Drain into efferent lymphatic vessels

Sinuses
o Subcapsular sinus (cortical sinus)
o Trabecular sinuses
o Medullary sinuses
o Endothelium

Adjacent to CT = continous

Adjacent to parenchyma = discontinous
o Lumens are spanned by macrophage processes and reticular fibers
(mechanical filter)

High Endothelial Venules (HEV)  afferent (relative to lymph node)
o Lined by cuboidal or columnar endothelial cells
o Transport fluid and electrolytes from the lymph to the blood
o Most lymphocytes enter lymph nodes (LNs) via HEV
o Lymphocytes cross HEV by diapedesis
o T cells remain in the deep cortex
o B cells migrate to the follicles in the superficial cortex
o Lymphocytes leave the LN by entering the lymphatic sinuses then the
efferent lymphatic vessel

Other
o Lymph Node is an important site for phagocytosis & initiation of
immune responses
o Ag is concentrated in LNs
o Trapped on FDC
o Processed by APC’s
o B cells activated & differentiate into plasma cells and memory B
cells
o Plasma cells migrate to the medullary cords and secrete Ab’s into
lymph
o Memory B cells leave LN and circulate throughout the body
o Reactive LN’s often enlarge
o

o
Thymus







Lymphoepithelial organ located in the superior mediastinum
Bilobed, situated on top of the heart
Multipotentail lymphoid stem cells (CFU-L) invade the epithelial rudiment
1o lymphoid organ where T lymphocytes develop
Fully formed and fxn’l at birth
Involution at puberty w/ most of the tissue replaced with adipose tissue
Can be re-stimulated



Structure:

Capsule = thin CT
o Trabeculae extend into parenchyma and establish thymic lobes
o Capsule and trabeculae contain:

Blood vessels

Efferent (not afferent) lymphatic vessels

Nerves

Plasma Cells

Granulocytes

Lymphocytes

Mast Cells

Adipose Cells

Macrophages

Cortex
o Markedly basophilic in H&E preparations
o Developing T lymphocytes (thymocytes) occupy spaces within a
meshwork of epithelioreticular cells
o Epithelioreticular cells have features of epithelial cells (intercellular
jxn, intermediate filaments)
o Epithelioreticular cells have features of reticular cells (provide a
framework for developing T lymphocytes)
o Reticular CT cells and their fibers are not present – thymocytes that
do not fulfill thymic “education” requirements (about 98%) die by
apoptosis and are phagocytosed by cortical macrophages
o Macrophages in the cortex can be I.D.’d by a positive periodic acidSchiff rxn (PAS)

Medula
o Contains lg # of epithelioreticular cells and loosely packed, mostly lg.
lymphocytes
o Ligher staining than the cortex—in some instances staining may
resemble germinal centers (NOTE: there are no germinal centers in
the thymus)
o Thymic (or Hassall’s corpuscles) are a distinguishing feature of the
thymic medulla
o Mature T cells leave the thymus & enter the blood circulation
Blood-Thymus barrier

The blood-thymus barrier protects developing lymphocytes in the thymus from
exposure to Ag’s

Consists of (inner/lumen  outer):
o Endothelium (continuous w/ occluding jxns)
o Endothelial BL (& occasionally pericytes)
o CT (macrophages)
o Epithelioreticular cell BL
o Epithelioreticular cell (occluding jxn)
Thymus is the site of T cell “education”

Stem cell maturation & differentiation into immunocompetent T cells is called
thymic education

The process is promoted by substances secreted by epithelioreticular cells (IL4, IL-7, colony stimulating factors, and IFNγ)

NO reticular cells; NO type III collagen
o
Spleen – not essential for human life

Fxn: Filters blood & monitors blood (reacts immunologically to bloodborne Ag’s)

Components:

Lymphocytes

Vascular spaces

Reticular cell/fibers meshwork

Macrophages

Dendritic cells

Histology:

DCT capsule

Trabeculae

Myofibroblasts provide contractile ability

Hilum: passage of the splenic artery, vein, nerves & lymphatic vessels

Splenic Pulp
o White Pulp

Thick accumulation of lymphocytes surrounding a central artery

Basophilic appearance in H&E

Splenic artery branches travel through the capsule & trabeculae then
enter the white pulp (= central artery)

Lymphocytes aggregated around central artery = periarterial
lymphatic sheath (PALS)

PALS contains mostly T lymphocytes

Splenic nodules consist of B lymphocytes and usually contain
germinal centers
o Red Pulp

Contains lg #’s of red blood cells that it filters & degrades

Red appearance (fresh & stained) consists of splenic sinuses
separated by 
splenic cords:

Loose meshwork of reticular cells & fibers

Contains large numbers of:
o RBC’s
o Macrophages – phagocytose damaged RBC’s
o Lymphocytes
o Dendritic cells
o Plasma cells
o Granulocytes

Splenic or Venous Sinuses

Special sinusoidal vessels lined by long, rod-shaped endothelial cells that run longitudinal
(parallel to sinus)

Few contact points b/w cells  produces large intercellular spaces

Blood cells pass into & out of sinuses

Processes of macrophages extend into the lumen of the sinuses to monitor passing blood
for foreign Ag’s

Perisinusoidal loops of basal lamina

Blood fills both sinuses and cords of the red pulp

Circulation within red pulp allows macrophages to screen for Ag’s in blood

Closed / Open circulation (only):
o Splenic a.  central a.  marginal sinuses  penicillar arterioles  sheathed
capillaries  reticular meshwork of the splenic cords  splenic sinus
trabecular v.  splenic v.  circulation

Immune System Functions:

Ag presentation by APC’s

Activation & proliferation of B & T lymphocytes

Production of Ab’s against blood Ag’s

Removal of macromolecular Ag’s from the blood

Hemopoietic Functions:

Removal & destruction of senescent, damaged, & abnormal RBC’s & platelets

Retrieval of iron from RBC’s Hb; formation of RBC’s during early fetal life

Storage of blood, especially RBC’s in some species