1.

HISTOLOGY: THE LYMPHATIC SYSTEM 13

NON-IMMUNE RESPONSE (INFLAMMATION)

INTRODUC TION  Triggers…

o Chemotaxins from bacteria
 The body is under constant threat of o Detection of antige n by complement
invasion by diseases causing system (a system of proteins)
microorganisms and other toxic  Production of chemotaxins
substances, so to ward them off, the body  Marking off of bacteria/antigens
employs several lines of defense through  Release of cytokines (proteins that
the Lymphatic System. It’s a network of act as signaling compounds)
tissues and organs whose primary function  Release of other mediators like
is to transport lymph – a fluid containing histamine by mast cells and
infection-fighting white blood cells basophils
throughout the body.  Ne utrophil and macrophages
congregate in injured or invaded area
o Phagocytosis
TABLE OF CONTENTS
o Release cytokines and other chemical
1. Defense Systems of the Body (P.1) mediators
a. Non-Immune Response (P.1)  Attract and activate other
b. Immune Response (P.1) concerned cells
2. Lymphoid System (P.3)  Produce local and systemic signs of
a. Lymphoid Tissue (P.3)
b. Central Lymphoid Organs (P.4) inflammation
c. Peripheral Lymphoid Vessels(P.6)
IMMUNE RESPONSE

 Not innate, must be developed

DEFENSE SYSTEMS OF THE BODY  Antigen-specific, must be developed for
every new antigen
Non-immune Immune o Antigen - any substance that is
(inflammation) perceived by the immune system as
- Immediate - Slow response foreign to the body; elicits an immune
response (minutes) - Antigen-specific response
- Innate (naturally- response o Ellicits an immune response
occurring - Key feature is  Production of chemotaxins
- Localized process memory of  Marking off of bacteria/antigens
- Plays a role in offending substance  Release of cytokines (proteins that
development of act as signaling compounds)
immune response  Release of other mediators like
histamine by mast cells and
basophils
AGENTS
 Ne utrophil and macrophages
Non-immune Immune congregate in injured or invaded area
(inflammation) o Phagocytosis
- Phagocytes - Lymphocytes o Release cytokines and other chemical
 Neutrophils - Macrophages mediators
 Macrophages - Antigen-Presenting  Attract and activate other
- Other cells Cells (APCs) concerned cells
 Eosinophils  Produce local and systemic signs of
 Basophils inflammation
 Mast cells
 NK cells
 T cells

TRANSCRIBERS: Group 6A – Steph Bautista, Red Dela Cruz, Rig Es trella, Nica Garcia, Ma ra Mercado, Randell Sioson, Asa Tanaka 1
SUBTRANSHEAD: RJ Beltran
 TYPES OF IMMUNE RESPONSES
1. HUMORAL
 Mediated by antibodies (involves
formation and action of antibodies)
 Function of B cells
 Important in containing viral and
bacterial infections
 Type of response elicited by vaccines
2. CELL-MEDIATED
 Not antibody mediated
 Function mainly of T cells
 Confers immunity to microorganisms
that are located intracellularly and
protected from antibodies
 Also responsible for delayed
hypersensitivity reaction and organ
transplant rejection
CATEGORIES OF IMMUNE RESPONSE
PRIMARY IMMUNE RESPONSE
 Elicited when new antigen enters body
 Long induction phase (takes a while to
develop)
 Takes days to weeks to eliminate antigen
 Key aspect is memory
 ANTIGEN-PRESENTING CELLS (APCs)
o Are all over the body and include:
endothelial cells, NK cells, and other
cells
o Professional APCs able to deliver
antigen signal and co-stimulatory
signal to naïve CD4+T cells =
macrophages, dendritic cells, B cells
 Macrophages – engulf antigen by
endocytosis, and process
antigen, and display and present
antigenic material on their
surfaces to naïve CD4+T cell
 Dendritic ce lls – most potent
APCs, which present antigen to
naïve CD4+T cell the same way
as macrophage.
 Myeloid-related de ndritic
cell (mDC) – Langerhans
cell from Colony-Forming
Unit -Macrophage Dendritic
Cell (CFU-M/DC)
 Lymphoid-re lated
dendritic
(plasmocytoid de ndritic
cell; pDC) – Origin not
definite yet; probably
hemopoietic stem
directly
 B cells – endocytose and present
antigen the same way
TOPIC: 1. THE LYMPHATIC SYSTEM
LECTURER: Dr. E. Gonzales
macrophages and dendritic cells;
binds antigens to their receptors
o Must first present antigen to naïve
CD4+T cells because
 Na ïve B ce lls will not react to
antigen unless activated by T h2
cells
 Na ïve CD8-T cells will not
differentiate into Tc and Ts cells
unless activated by APCs and/or
T h1 cells
 CD4+T cells will not differentiate
into Th1 , T h2, and Th3 cells unless
antigen is presented to them
 They proliferate and
differentiated into T h cells
 In cellular immunity
o Cytokines from Th1 cells activate naïve
CD8+T cells, which then proliferate
and differentiate (effector cells below)
 Tc cells – destroys pathogen,
effector cells
 Memory T cells – responsible for
secondary immune response
(takes a “photograph” of the
pathogen and remembers it)
 Suppressor T cells (Ts cells)
Note: some antigens can be
presented directly to CD8+T cells by
APCs
 In humoral immunity
o Cytokines from T h2 cells activate naïve
B cells, which then proliferate and
progenies differentiate
 Plasma cells – produce antibodies
 Memory B ce lls – responsible for
secondary immune response
Note: some antigens are T
independent. They are able t o
activate naïve B cells on their own
o When T h2 cells encounter naïve B cells
that have the same antigen
Produce cytokines…
Th1 cells Needed for cell-mediated
immunity
Th2 cells Needed for humoral immunity
cell
Th3 cells Mediate inflammatory process
cell
as SECONDARY IMMUNE RESPONSE
2
  Elicited every time same antigen enters the o Hav ing a normal imm une response 
body again immunocompetence
 Rapid and vigorous response (1-2 days)
 Often, antigen eliminated without the
person noticing the event
Types of Diffuse Lymphoid Lymphocytes
 APC present antigen and prime naïve T h
Tissue are…
cell
 Naïve B cell that has the same antigen on Loose Lymphoid Tissue Far apart
its surface encounters primed T h cell Dense Lymphoid Tissue Closely packed
 Activated B cell proliferates and progenies together
differentiate  plasma cells and memory B LYMPHOID TISSUES
cells (see humoral immunity)
 Tissue where parenchyma consists mainly
 Memory T cells and memory B cells
of lymphocytes
o Become activated when they
 Composed of:
encounter antigen in their memory; no
o Stroma (supporting framework)
need for APC
 Reticular connective tissue, except
o Rapidly proliferate and differentiate
in thymus
into effector cells; also renew their
o Parenchyma (functional elements)
numbers
 Mostly lymphocytes
o Pathogenic organisms are eliminated
 Forms of Lymphoid Tissue:
before person presents with symptoms
o Diffuse
o Nodular
CLINICAL CORRELATION

 Upon first contact with an unknown

DIFFUSE LYMPHOID TISSUE
pathogen (Measles Virus). You will elicit
the Primary Immune Response Cascade  Lymphocytes are evenly distributed,
(takes days to weeks) thus you will mostly T cells
experience signs and symptoms of the  Form part of lymphoid organs and
disease. practically all connective tissues
 On the succeeding contact with the same  Prominent in lamina propria and
pathogens the memory cells you have submucosa of Gastrointestinal (GIT),
produced from the first cascade will Respiratory (RT), and Genitaloutinary
immediately determined and your body w ill Tracts (GUT)
be able to do a rapid response.
 The amount of Memory cells diminish over
time thus it is necessary to give booster
shot of vaccines.
 Immunity:
o Active
 Natural - When you are naturally
infected by the live pathogens.
(Getting Mumps).
 Artificial - When you receive
vaccination of live weakened
pathogens.
o Passive
 Natural - When you receive
antibodies e.g Breastfeeding.
 Artificial - When you receive
antibodies from vaccination
shots.

LYMPHOID SYSTEM Figure 1. Loose Lymphoid Tissue

Lamina Propria, Trachea, x400
 Organs (lym phoid organs) and tissues
(lymphoid tissues) concerned with immune
response

TOPIC: 1. THE LYMPHATIC SYSTEM 3

LECTURER: Dr. E. Gonzales
 Figure 3. Primary Lymphoid Nodule
Figure 2. Dense Lymphoid Tissue
Submucosa, Colon, x100
Lamina Propria, Ileum, x100
 Secondary
o Germinal or reaction center
NODULAR LYMPHOID TISSUE  Pale central area
 Many mitotic figures; larger,
 Clustered lymphocytes from discrete younger lymphocytes
masses or lymphs called lymphoid  Area where B lymphocytes are
nodules (lymphoid follicles; lymphatic proliferating
follicles – see types below) o Corona
 Lymphocytes mostly B cells but scattering  Darker peripheral region
of T cells and APCs  Older, smaller lymphocytes
 Generally ovate in shape  Nuclei is closer together  darker
 Begin to appear only at birth (not present area
in utero)
 Interspersed in areas of diffuse lymphoid
tissue in
o Spleen
o Lymph nodes
o MALT

TYPES OF LYMPHOID NODULES

 Primary
o Cells are evenly distributed throughout
nodule
o Small lymphocytes with no mitotic
figures visible

Figure 4. Secondary Lymphoid Nodule

Lymph node, x100

CENTRAL LYMPHOID ORGANS

 Where T and B stem cells transform into

mature, immunocompetent but still naïve T
and B cells
o BONE MARROW
o THYMUS

TOPIC: 1. THE LYMPHATIC SYSTEM 4

LECTURER: Dr. E. Gonzales
 THYMUS  Very little connective tissue
 CAPSULE
 In superior mediastinum, just above the o Dense irregular connective tissue that
heart envelopes lobes
 Derived from the third branchial pouch  TRABECULAE
 At birth, weighs 10-35g; maximu m weight o Incompletely subdivide lobes into
(at about puberty) is 30-50g then unequal lobules
gradually involutes o Secondary septa arise from trabeculae
 In adults - two pyramidal lobes that are  LOBULE
fused together o CORTEX
 In elderly - mass of connective tissue with o – peripheral dark-staining region
small amount of functioning parenchyma (darker than the medulla because cells
 Also involutes in individuals who are are numerous and packed);
subjected to severe stress, serious illness, Parenchymal cells
or ionizing radiation  T Lymphocytes
 Nurture and process T cells from stem  T stem cells f rom bone
cells to mature, immunocompetent marrow settle here
cells that are self-tolerant  Transform to lymphoblasts
 Produce cytokines that regulate T ce ll and proliferate
proliferation, maturation, and function  T cells move to this area
in thymus and other organs from the outer cortex as
 Lymphocytes, called thymocytes small lymphocytes
 Acquire receptors; those
In adults In children unable to do so die by
- Almost exclusively T - May have small apoptosis
lymphocytes population of B cells
- Not a site of - Even occasional  Macrophages
antibody production lymph nodule  Phagocytose cells that die by
- Devoid of lymphoid apoptosis
nodules

o MEDULLA – central, light-staining

HISTOLOGICAL ORGANIZATION OF THYMUS region
o Medullae are interconnected because
trabeculae do not extend to medulla
 Thymic Interdigitating Cells
 Dendritic cells in the medulla
 Presents self-antigens to T
cells
 To prevent autoimmunity,
reactive T cells are induced
to undergo apoptosis and
phagocytosed by
macrophages
 T cells
 Join the “reticulating pool” by
entering blood and lymphatic
vessels of the medulla
 Only 10-30% of cells
generated in the cortex leave
the thymus – as mature,
immunocompetent, “self-
tolerant”, but naïve T cells
 Thymic corpuscles (Hassal’s
bodies or corpuscles)
 Most distinctive feature
 Core of hyaline material
Figure 5. Thymus surrounded by layers of
flattened epitheloid cells

TOPIC: 1. THE LYMPHATIC SYSTEM 5

LECTURER: Dr. E. Gonzales
  Up to 100 micra meter LYMPHATIC VESSELS IN THE THYMUS
 Increase in number with
advancing age  No afferent lymphatic vessels
 Effe rent vessels start as blind
 EPITHELOID CELLS (EPITHELIAL capillaries
RETICULAR CELLS)  Bigger vessels follow course of veins
o Comprise stroma
o Look like reticular cells but they arise
BLOOD-THYMUS BARRIER
from the endoderm and do not
produce reticular fibers  In cortex
o Stellate cells/cytoplasmic processes  “Protects” thymocytes from exposure to
attached to neighboring epitheloid cells circulating antigens
by desmosomes  Consists of:
o Produce most of thymic cytokines o Capillary wall - with thick basal
o Some in cortex – called nurse cells lamina and non-fenestrated
 Envelope multiple lymphocytes endothelium
 Promote proliferation and o Perivascula r space - containing
differentiation of lymphocytes macrophages and fluid
o 6 types distinguishable in EM o Epitheloid space and their basal
lamina
BLOOD VESSELS IN THE THYMUS

PERIPHERAL LYMPHOID TISSUES AND

ORGANS

 Generate lymphocytes needed to effect an

immune response (Lymphocytes wait until
they’re called upon)
o LYMPH NODES
o SPLEEN
o MUCOSA-ASSOC IATED LYMPHOID
TISSUES (MALT)
 Tonsils
 Other nonencapsulated lymphoid
tissues in GIT, RT, and GUT

LYMPH NODE
 Branches of several arteries
 Bean-shaped organ
o Internal thoracic
 Along course of lymphatic vessels
o Anterior intercostal
 Encapsulated collection of lymphoid tissue
o Inferior thyroid
 Size: pinhead to 3cm in diameter
 Penetrate capsule and ramify in trabeculae
 Number: 500-600
and septa
 Filters lymph for pa rtic ulate matter
 At corticomedullary junction, break up into
and microorganisms
capillaries:
o Macrophages
o Supply cortex and medulla
o APCs
o Anastomose extensively
 Site of lymphopoiesis
 Capillaries of cortex drain into post -
o Activated B and T cells proliferate and
capillary venules w hich unite with those in
differentiate into various functional
medulla
types in organ
 Post-capillary venule of medulla is where T
 Parts of the Lymph Node
cells join in recirculating pool
o HILUS
 Medullary venules unite int o bigger veins
 Indented area
that follow septa and trabeculae  exit at
 Entry and exit point of blood
capsule.
vessels
 Exit point of efferent lymphatic
vessel
TOPIC: 1. THE LYMPHATIC SYSTEM 6
LECTURER: Dr. E. Gonzales
 o CONVEX SIDE  Dendritic cells with
 Entry point of afferent lymphatic polymorphic nuclei and
vessels processes that interdigitate
o MEDULLA
HISTOLOGICAL ORGANIZATION OF LYMPH  Inner region
NODE  Deeper paler area
 Dense lymphoid tissue arranged in
strands (medullary cords)
 Between cords are
medullary sinuses
 Seldom have lymphoid nodules,
but cells are mostly B cells a nd
plasma cells

BLOOD VESSELS OF LYMPH NODE

o Form capillary plexus around lymph

nodules
o Main branch to cortex
o Give off branches to supply medulla
o Breaks up into branches that proceed
to trabeculae
o Artery enters at hilus

Figure 6. Lymph node

 CAPSULE
o Dense connective tissue
 TRABECULAE
o From capsule
o Incompletely subdivide organ into
compartments
 STROMA
o From supporting meshwork for interior
of organ
o Reticular fibers and reticular cells
 PARENCHYMA
o OUTER CORTEX
 Composed mostly of lymphoid
nodules (primary and
secondary) imbedded in dense o Post-capilla ry venules – drain
lymphoid tissue capillaries of cortex
 Mostly B cells o Medulla ry venules – drain capillaries
 Follicular dendritic cells of medullary cords
 Dendritic cells in outer cortex o Trabeculae venules – Union of post-
 Large, pale, nucleus capillary venules and medullary
 Indistinct cell borders with venules
long cytoplasmic processes, o Vein leaves at hilus
which are linked by
desmosomes with those of
neighbors Note: Lymphocytes enter lymph node
o INNER (DEEP) CORTEX mainly through vessels in inner cortex (T
 Consists of dense lymphoid rich area) to ensure that B cells entering
tissue will interact with T cells
 Mostly T cells
 Interdigitating dendritic cells

TOPIC: 1. THE LYMPHATIC SYSTEM 7

LECTURER: Dr. E. Gonzales
 SPLEEN  Reddish brown substance
 Bulk of parenchyma
 Largest lymphoid organ in the body  Consists of sple nic cords
(7cm x 12cm) (of Billroth) (strands of
 Soft and freely movable structure on upper reticular tissue) and
left quadrant of abdomen sinusoids in between
 HILUS splenic cords
o Notch on medial surface  White pulp
o Site of entry and departure of splenic  Small masses of grayish
vessels white material scattered in
 Filters blood red pulp
o Enormous number of macrophages  Lymphoid nodules –
o Destroys foreign substances, imbedded in dense lymphoid
microorganisms, and abnormal cells tissue; with germinal centers
that are present in the blood  Dense lymphoid tissue –
 Removes and destroys damaged a nd organized to form sleeves
old red blood cells and platelets around arteries
o Recycles iron that’s contained in the  Aside from lymphocytes –
RBCs macrophages, dendritic cells
 Act as a storage area for blood (splenic dendritic cells)
 Lymphopoiesis  Marginal zone – transitional area
between white and red pulp
 Lymphocytes from
HISTOLOGIC ORGANIZATION OF THE
“recirculating pool” leave
SPLEEN
blood in this area to reside
 CAPSULE temporarily in spleen
o Lined externally by mesothelium
o Dense collagenous connective tissue
 TRABECULAE
o Incompletely divide parenchyma into
compartments
 STROMA
o Forms internal framework of organ
o Reticular fibers and cells

Figure 8. Red and white pulp of the spleen

BLOOD VESSELS OF THE SPLEEN

 SPLENIC ARTERY
o Branch of celiac artery
o Divides as it approaches spleen
o Branches enter spleen at hilus
o Traverses capsule and give rise to
trabecular arteries
 TRABECULAR ARTERY
Figure 7. Spleen x40 o Muscular artery (medium-sized)
o Gives off branches to white pulp
(central artery)
 PARENCHYMA
 CENTRAL ARTERY or ARTERY OF
o Splenic pulp
WHITE PULP
 Red pulp
TOPIC: 1. THE LYMPHATIC SYSTEM 8
LECTURER: Dr. E. Gonzales
 o Tunica adventitia replaced by sleeve of o Usually loose or dense diffuse
dense lymphoid tissue (PALS; lymphoid tissue with occasional
periarterial; lymphoid sheath solitary nodule
o Gives off follicular arte ries that o Sometimes, nodules form aggregates
supply white pulp as in Peyer’s Patches in ileum
o Terminates by entering marginal zone o Form a ring (Waldeyer’s ring) around
and sending branches to red pulp entrance to respiratory and digestive
(arteries of red pulp; penicillar tracts
arteries; penicilli)
 PENICILLAR ARTERIES OR PENICILLI TONSILS
o Gives off sheathed arteries or ellipsoid
 Covered by concentric layers of
reticular cells (sheath of
Schweigger-Seidel)
 Surrounded by macrophages –
filtering starts at this level
o Penicillar arteries drain into splenic
sinusoids – how?
 Closed circulation theory
 Capillaries from penicillar
arteries are continuous with
venous sinusoids
 Open circulation theory
 Better developed in children than in adults
 Favored by evidence;
 Start to involute at about age 15
 Capillaries from penicillar
 In old people, largely atrophied
arteries open at their ends to
 Histologically:
interstitial spaces among
O ncomplete capsule
reticular cells of splenic cords
O Separated from underlying structures
(of Billroth) then percolates
by a layer of dense connective tissue
into sinusoids.
O Dense lymphoid tissue w here lymphoid
 SPLENIC SINUSOIDS
nodules are embedded
o Interconnect with each other and
O Nodules may have germinal centers
separated only by cords of Billroth
o Fill red pulp
o Large irregular lumens (up to 40 µm)
o Very thin walls.
o Endothelial cells
 fusiform
 rest on discontinuous basal lamina
 limited phagocytosis
o Perisinusoidal macrophages
 External to endothelial cells
 Processes extend to lumen of
sinusoids.
o Collecting veins – drain sinusoids
o Trabecular veins - drain collecting
veins
o Splenic veins - union of trabecular
veins; exit at hilus

Figure 9. Palatine tonsil x40

MUCOSA-ASSOCIATED LYMPHOID ORGANS
(MALT)
 PALATINE TONSILS
 NON-ENCAPSULATED LY MPHOID O epithelium
TISSUES in mucosa and submucosa of  Nonkeratinized stratif ied squamous
GIT, RT, and GUT epithelium
 Deep, branching invaginations
(tonsillar crypts)

TOPIC: 1. THE LYMPHATIC SYSTEM 9

LECTURER: Dr. E. Gonzales
  Tonsillar crypts often with
dead epithelial cells,
lymphocytes, other cells that
reach the surface by passing
through epithelium
O Capsule
 Incomplete
 Connective tissue beneath
epithelium
 Trabeculae incompletely subdivides
organ to several parts.
O In connective tissue
 Lymphocytes
 Mast cells
 Plasma cells Figure 11. Pharyngeal tonsil
 Neutrophils

 PHARYNGEAL TONSILS
O Central area of posterior and superior
nasopharynx
O When enlarged, it’s called adenoid
O Epithelium
 Respiratory epithelium with
patches of nonkeratinized
stratified squamous
 Forms shallow folds.

Figure 10. Lingual tonsil

 LINGUAL TONSILS
o Several on dorsum of tongue; 2-3 mm Figure 12. Tubal tonsil
diameter each
O Also covered by nonkeratinized
 TUBAL TONSILS
stratified squamous epithelium
o Masses of lymphoid tissue in
O May have one deep crypt which
contains dead epithelial cells and nasopharynx near openings of
lymphocytes. Eustachian tube
o Extensions of pharyngeal tonsil
o Covered by respiratory epithelium.

TOPIC: 1. THE LYMPHATIC SYSTEM 10

LECTURER: Dr. E. Gonzales
 Notes:

1. Don’t rely solely on trans, read the book as well

(in case we missed something)
2. Happy studying!

REFERENCES:

1. Dr. Gonzales’ lecture (recordings)

2. Powerpoint
3. Esteban and Gonzales’ Textbook of
Histology

Index. Primary Immune Response

TOPIC: 1. THE LYMPHATIC SYSTEM 11
LECTURER: Dr. E. Gonzales