National University

Lymphatic System
Histology
Overview of Lymphatic System

Basic Immunology
Lymphocyte Origins and Differentiation
Thymus
Mucosa-associated Lymphoid Tissue (MALT)
Lymph Nodes
Spleen
Functions of the Lymphatic System

FLUID BALANCE
DIETARY FAT ABSORPTION
DEFENSE
Components of the Lymphatic System
• Primary Lymphoid Organs - produce the cell components of the immune
system
1. Bone Marrow
2. Thymus

• Secondary Lymphoid Organs - the sites where immune responses occur

1. Lymph nodes
2. Spleen
3. Tonsils
4. Aggregates of lymphocytes and antigen-presenting cells in the lung
(bronchial-associated lymphoid tissue, BALT) and the mucosa of the digestive
tract (gut-associated lymphoid tissue, GALT), including Peyer’s patches.
Components of the Lymphatic System
Components of the Lymphatic System

After leaving the two primary organs (bone marrow and thymus),
mature B and T cells circulate in the blood until they reach one of
the various secondary lymphoid organs (lymph nodes, spleen, and
tonsils)
Types of Immunity
Immunity - The reaction of cells and tissues to foreign (nonself) substances or pathogens including
bacterial, viral, and parasite antigens.

1. Innate or Natural Physical Barriers Blood Borne

Immunity 1. Neutrophils
Prevent microorganisms and • Quickly remove Bacteria, fungi, and
parasites that manage to penetrate
• The simplest mechanism of chemicals from entering the body
the physical barriers.
protection. It does not require in two ways:
1. Toll-Like Receptors
previous exposure to a pathogen 1. Skin and mucous
• Leukocytes that allow the
and elicits rapid responses by membranes form barriers recognition and binding of surface
macrophages and dendritic cells. that prevent pathogen entry. components of invaders.

2.Tears, saliva, and urine wash 1. Natural Killer Cells

• destroy various unhealthy host cells,
pathogens from body
including those infected with viruses or
surfaces. bacteria, as well as certain potentially
tumorigenic cells.
Types of Immunity
Innate or Natural Immunity
Chemical Barriers

1. Hydrochloric acid (HCl) and 3.Lysozyme 5. Interferons

organic acids • an enzyme made by • paracrine factors from
• lower the pH locally to either neutrophils and cells of leukocytes and virus-infected
kill entering microorganisms epithelial barriers, which cells that signal NK cells to kill

directly or inhibit their growth. hydrolyzes bacterial cell wall such cells and adjacent cells to

1. Defensins components, killing those cells. resist viral infection.

• short cationic polypeptides 4. Complement

produced by neutrophils and • a system of proteins in blood
various epithelial cells that kill plasma, mucus, and
bacteria by disrupting the cell macrophages that react with
walls. bacterial surface components
to aid removal of bacteria.
Types of Immunity
Adaptive Immunity

T cell immunity
• Uptake of a pathogen by
phagocytes.
acquired gradually by exposure • Cytokine production
to microorganisms, is more • Cellular Mediated Immunity
B cell immunity
specific, slower to respond, and
• Antigen Exposure
an evolutionarily more recent Two types of T cell immunity
• Antibody Production
development than innate 1. Passive immunity
• Humoral immunity
immunity. • transferred from an immunized
individual to another individual
1. Active Immunity
• results from exposure to a pathogen.
Cytokines
• promote inflammation and phagocytosis.
Chemotaxis
• Directed cell movements, toward and cell accumulation
at sites of inflammation
• Ex. Diapedesis

Chemokines
• Are chemotactic cytokines that control the migration and
positioning of immune cells in tissues.
• stimulate the movement of certain types of white blood
cells and attract them to areas of inflammation to help the
body fight infections, inflammatory conditions, and other
diseases.

Interleukins
• A group of cytokines that regulate cell growth,
differentiation, and motility.
• They are particularly important in stimulating immune
responses, such as inflammation.
Antigens and Antibodies
Antigen
• A molecule that is recognized by cells of the adaptive immune system.
• Immune cells recognize and react to small molecular domains of the
antigen known as antigenic determinants or epitopes.
• The immune response to antigens may be cellular, humoral, or both.
• Examples: foreign matter, bacteria. and viruses

Antibodies
• A.K.A immunoglobulin
• Proteins that are produced by plasma cells in response to antigens.
• Part of the body's immune system, which protects it from foreign
substances like bacteria and viruses.
• Examples: IgG, IgA, IgM, IgE, IgD
Classes of Antibodies
Actions of Antibodies
Actions of Antibodies
Antigen Presentation
Major Histocompatibility Complex
• group of genes that code for proteins found on the surfaces of cells that help the immune
system recognize foreign substances.
• proteins were first recognized by their roles in the immune rejection of grafted tissue or organs.
• made in the rough ER and Golgi apparatus.
• Also known as Human Leukocycte Antigen. (HLA)

Two classes of MHC

CLASS 1 CLASS 2

Expression All nucleated cells Antigen presenting cells

CD8 molecule on the surface of cytotoxic CD4 molecule on the surface of helper T
Bound to
T cells. cells

Major Genes HLA-A, HLA-B, and HLA-C, HLA-DP, DQ, and DR

Cells of Adaptive Immunity

Antigen Presenting Cells

• Part of the mononuclear phagocyte system
• an active endocytotic system and expression of MHC class II molecules for presenting peptides
of exogenous antigens.
• An immune cell that detects, engulfs, and informs the adaptive immune response about an
infection.
• Antigen presentation can be done by dendritic cells, macrophages, monocytes and thymic
epithelial cells.
Cells of Adaptive Immunity
Lymphocytes
• Regulate and carry out adaptive immunity
• Located in the bone marrow.
• Reticular connective tissue is filled with large numbers of
lymphocytes.
• Have prominent basophilic nuclei and very little cytoplasm,
lymphoid tissue packed with such cells usually stains dark
blue in hematoxylin and eosin.
• All secondary lymphoid tissue the lymphocytes are
supported by a rich reticulin fiber network of type III
collagen.
Reticular Fibers
Lymphoid Tissue

R = fibroblast-like reticular cells

T = trabeculae
M - macrophages
Specific receptors on T and B lymphocytes.
T lymphocyte
• T cells are long-lived lymphocytes and constitute nearly 75% of the circulating
lymphocytes.
• They recognize antigenic epitopes via surface protein complexes termed T-cell
receptors (TCRs).
• Has two glycoproteins: α and β chains,
• MHC restricted.

Types of Lymphocytes:
1. Helper T cells
• a.k.a CD4 T lymphocytes.
• produces cytokines that promote the differentiation of B cells into plasma cells.
• Activate macrophages to become phagocytic and cytotoxic T lymphocytes (CTLs).
• Activated helper T cells persist as long-lived memory helper T cells.
 T lymphocyte
2. Cytotoxic T cell
• a.k.a as CD8 T cells and killer T cells.
• attach to the cell sources of the antigens and remove them by releasing perforins and granzymes,
which trigger apoptosis.
• Responsible for Cell-Mediated Immunity
• Activation of cytotoxic T cells also results in a population of memory cytotoxic T cells.
3. Regulatory T cells
• a.k.a. Tregs or suppressor T cells and CD4+CD25+
• serve to inhibit specific immune responses. (T regs play an important role in suppressing the immune
response to self-antigens)
• produce peripheral tolerance, which acts to supplement the central tolerance that develops in the
thymus.
4. γδ T lymphocytes
• migrates to the epidermis and mucosal epithelia
• They regulate immunosuppressive functions of Intra Epithelial Lymphocytes and play role in
development of tolerance.
• Promotes tissue repair and cell healing.
Activation of T lymphocyte
B lymphocytes
• B-cell receptors (BCRs) are IgM or IgD antibodies on the cell surface that bind
specific antigens whenever they contact them.
• B and T cells are often activated, proliferate, and begin to function in the
secondary lymphoid organs: the lymph nodes, all MALT, and the spleen.
• In secondary lymphoid tissues, BCRs bind antigen not presented in MHC class II
molecules of another cell, the FDC.
• With cytokines from helper T cells, a FDC-activated B cell proliferates clonally to
produce temporarily a large lymphoid nodule (or follicle), which develops a pale
germinal center.
• From lymphoid nodules cells produced there disperse as plasma cells, various T
cells, and B and T memory cells that respond and proliferate quickly if their
specific antigen reappears.
B lymphocytes
Lymphoid nodules

GC – germinal centers
M – follicular mantlle
Thymus
 Thymus
• T lymphoblasts, or thymocytes, attach in the thymus to a cytoreticulum composed of interconnected
TECs.
• The TECs also secrete many cytokines, compartmentalize the thymus into a cortex and a medulla, and in
the cortex surround blood vessels in the blood-thymus barrier.
• Developing T cells with nonfunctional TCRs are detected and removed in the thymic cortex by a process
of positive selection; cells with functional TCRs move into the thymic medulla.
• In the thymic medulla T cells whose TCRs bind strongly to “self-proteins,” including proteins of many
nonthymus cell types made by thymic epithelial cells expressing the Aire gene, are induced to undergo
apoptosis there in a process of negative selection.
• This two-stage thymic selection leads to central immune tolerance, producing functional T cells that do
not bind to proteins of the host.
• Peripheral immune tolerance occurs throughout the body when specific immune reactions are suppressed
by regulatory T cells that also originate largely in the thymic medulla.
• Regulatory T cells form in the thymus upon interacting with dendritic cells presenting self-antigens in a
process promoted by cytokines from thymic epithelial cell (TEC) aggregates called Hassall corpuscles,
found only in the thymic medulla.
 Thymus

C - capsule
S – septa
Co – cortex
M – medulla
A – adipose tissue
Cortex of the Thymus
E – thymic epithelial cells
 Medulla of the thymus with Hassall corpuscles.

E – epithelial cells
HC – Hassall corpuscles
Role of the Thymus in
T-Cell Maturation &
Selection
Mucosa- Associated Lymphoid Tissue
• Found in the mucosa of most tracts but is concentrated in the
palatine, lingual, and pharyngeal tonsils, Peyer patches, and the
appendix.
• dispersed aggregates of nonencapsulated organized lymphoid
tissue within the mucosa, which are associated with local immune
responses at mucosal surfaces.

Types of MALT
1. Tonsils
2.Peyer patches
3.Appendix
Tonsils
• large, irregular masses of lymphoid tissue in the mucosa of the posterior oral cavity and nasopharynx where their cells
encounter antigens entering the mouth and nose. LN – lymphoid nodules
E – stratified squamous epithelium
• Can be named by their location: palatine, lingual, and pharyngeal tonsils. CT – connective tissue capsule
GC – germinal centers
C - crypts
Tonsils
Peyer’s Patches
• Peyer's patches are clusters of
subepithelial, lymphoid follicles found in
the intestine. They are oval or rectangular
in shape and found on the antimesentric
wall of the intestine. They are more
prominent in ileum and are characterized
by specialized epithelial cells called M
cells.
• The M cells are compactly arranged with
adjacent absorptive cells and create
hallows that enfold lymphocytes and other
similar defensive components.
Appendix
• short, small-diameter projection
from the cecum.
• mucosa of the appendix is almost
filled with lymphoid tissue, effacing
the glands otherwise found in the
large intestine wall.
Lymph Nodes
Lymph Nodes
• Each lymph node filters lymph and provides a site for B-cell activation and
differentiation to antibody-secreting plasma cells.
• A lymph node has three functional but not physically separate compartments: an outer
cortex, an underlying paracortex, and an inner medulla adjacent to the hilum and
efferent lymphatic.
• Lymphatics enter at the cortex of a node, where B cells encounter antigens, proliferate
in lymphoid nodules, and then move into the deeper regions of the lymph node.
• Most lymphocytes enter at the paracortex of the lymph node via High endothelial
venules (HEVs) located there only; most lymphocytes in this region are T helper cells.
• The medulla has medullary cords containing reticular fibers with many plasma cells,
macrophages, and other leukocytes; between the cords are lymph-filled medullary
sinuses that converge at the efferent lymphatic.
Three Major Region of Lymph Nodes
• An outer cortex containing the nodules;
• the paracortex, which lacks nodules and the deeper extension of the cortex.
• A medulla with prominent draining sinusoids adjacent to the hilum.
Cortex
1. Subcapsular sinus
• sinuses that are lined by a very thin, discontinuous endothelium penetrated by reticulin fibers and processes
of dendritic cells.
• Lymph containing antigens, lymphocytes, and APCs passes through these sinuses and percolates easily into
the surrounding lymphoid tissue.
1. Lymphoid Nodules
• with or without germinal centers, consist largely of developing B lymphocytes and occupy much of the
cortex not filled with helper T lymphocytes.
• Each nodule is organized around the long, interdigitating processes of FDCs, but these are not readily seen
by routine light microscopy.
• Numerous macrophages are also present for removal of newly formed defective B cells that undergo
apoptosis.
Lymph Node Cortex

C – capsule
S – subcapsular sinuses
N – lymphoid nodules
Three Major Region of Lymph Nodes
Paracortex
• region between the cortex and medulla.
• does not have precise boundaries but can be distinguished from the outer cortex by its lack of
nodules.
• contains lymphoid tissue rich in T cells distinguishable by immunohistochemistry.
• Contains specialized post-capillary venules called high endothelial venules (HEVs)
representing an important entry point for most (90%) circulating lymphocytes into lymph
nodes. Endothelial cells of these vessels become unusually enlarged or cuboidal and express
specific apical surface glycoproteins that mediate the tethering and diapedesis of B and T cells
from the blood into the paracortex of the lymph node
• HEVs also occur in large accumulations of MALT
High endothelial venules
Three Major Region of Lymph Nodes
Medulla
1. Medullary cords
• are branched cordlike masses of lymphoid tissue extending from the paracortex.
• They contain T and B lymphocytes and many plasma cells.

2. Medullary sinuses
• dilated spaces lined by discontinuous endothelium that separate the medullary cords.
• include a meshwork of processes from reticular cells, which represent a final lymph filter.
These sinuses contain many macrophages and sometimes neutrophils if the lymph node is
draining an infected region.
• They are continuous with the cortical sinuses and converge at the hilum as the efferent
lymphatic vessel.
 Medulla of Lymph Node

MS – Medullary sinuses
MC – medullary cords
 Regions of Lymph Node

C – cortex
P – paracortex
M – medulla
CT – connective tissue of the capsule
T – trabeculae
LN – lymphoid nodules
MS – medullary sinuses
MC – medullary cords
Spleen
• The spleen is a large lymphoid organ without a cortex/medulla structure; instead, it has two
intermingled but functionally different regions: white pulp and red pulp.
• White pulp, only 20% of the spleen, is secondary lymphoid tissue associated with small central
arterioles that are also enclosed by (Periarteriolar lymphoid sheaths) PALS of T cells.
• Red pulp, which filters blood, removes defective erythrocytes, and recycles hemoglobin iron,
consists of splenic cords with macrophages and blood cells of all kinds and splenic sinusoids.
• The splenic sinusoids are lined by unusual endothelial cells called stave cells, which are
elongated and aligned parallel to the blood flow, with open slits between the cells.
• Blood flow in red pulp is either a closed circulation, moving from capillaries into the venous
sinusoids, or an open circulation, with capillaries opening directly into the splenic cords.
• Blood filtration in the open circulation involves interaction with splenic cord macrophages,
which remove old, swollen RBCs unable to slip between stave cells to reenter the venous blood
flow.
Spleen
C - capsule
T – trabeculae
R – red pulp
W – while pulp
White pulp of the Spleen
Red pulp of the Spleen
Splenic Sinusoids
Blood flow in the Spleen
Blood flow through the splenic red pulp

1. Closed Circulation
• capillaries branching from the penicillar arterioles connect directly to the sinusoids
and the blood is always enclosed by endothelium.
1. Open Circulation
• capillaries from about half of the penicillar arterioles are uniquely open-ended,
dumping blood into the stroma of the splenic cords
• In this route plasma and all the formed elements of blood must reenter the vasculature
by passing through narrow slits between the stave cells into the sinusoids.
Erythrocyte removal by splenic macrophages.
Important histologic comparisons of the major lymphoid organs.
Thank you