THE LYMPHORETICULAR SYSTEM

DR J E OKWARA
• The lymphoreticular system consists of the tissues of
• The lymphoid system
• and the mononuclear phagocyte system (reticuloendothelial system)
• The lymphoid system consists of
• The spleen,
• Lymphnodes,
• Lymphatic vessels,
• Thymus,
• Bone marrow
• The lymphoid tissues associated with the GIT-eg tonsils, Payer
patches
Primary and Secondary lymphoid organs
• The bone marrow and the thymus are the primary
lymphoid organs. Site where T and B cells become
immunocompetent:able to recognize and respond to
antigens
• While the spleen and the lymph nodes are the major
secondary lymphoid organs. Immunocompetent cells
populate these tissues
Functions of the LRS
• The functions of these systems include
• Collection and transport of interstitial fluid-Fluid balance
• Fluid continually filters from the blood capillaries into
the tissue spaces
• • Blood capillaries reabsorb 85%
• • 15% (2 to 4 L/day) of the water and about half of the
plasma proteins enter the lymphatic system and then are
returned to the blood
Functions of the LRS
• Transport of fats throughout the body

• Lacteals in small intestine absorb dietary lipids that are

not absorbed by the blood capillaries
Functions of the LRS
• Immunity- defense,
• Excess filtered fluid picks up foreign cells and chemicals
from the tissues

• • Passes through lymph nodes where immune cells stand

guard against foreign matter

• • Activates a protective immune response-cellular and

humoral immunity
Cells of the lymphoreticular system
• Lymphocytes • Antigen presenting cells-
• T-lymphocytes APC
• T-helper • Macrophages
• T-cytotic • Dendritic cells
• T-memory
• T-regulator/suppressor
• Natural killer cells-NKC
• B-lymphocytes
Haematopoietic stem cells in the bone marrow

• The myeloid lineage (progenator stem cells)

• Erythropoiesis-RBC
• Megakariopoiesis-Platelets
• Leucopoiesis-Granulocytes-Neutophyls, Eosinophyls,
Basophyls, monocytes

• The lymphoid lineages (progenator stem cells)

• T-lymphoctes
• B-lymphocytes
• The natural killer cells
HEAMATOPOIESIS
• Three categories of lymphocytes
• – Natural killer (NK) cells (5%): immune surveillance
• – T lymphocytes (T cells) (80%)
• – B lymphocytes (B cells) (15%)

• Three stages in life of T Cell:

• – Produced in bone barrow
• – Educated in thymus
• – Deployed to carry out immune function
Natural killer (NK) cells
• Natural killer (NK) cells are morphologically described as
large granular lymphocytes.
• These cells are called natural killer cells due to their
ability to kill certain virally infected cells and tumor cells
without prior sensitization.
• Their activities are not enhanced by exposure and are not
specific for any virus.
• NK cells comprise approximately 5–10% of peripheral
lymphocytes and are found in spleen and peripheral
blood.
T lymphocytes (T cells)
• Cytotoxic T (TC) cells: killer T cells (T8, CD8, or CD8+)
– “Effectors” of cellular immunity; carry out attack on
enemy cells;
• Helper T (TH) cells:– Help promote TC cell and B cell
action and nonspecific resistance (T4, CD4, CD4+)
• Regulatory T (TR) cells: Also called T-suppressor cells.
T-regs – Inhibit multiplication and cytokine secretion by
other T cells; limit immune response– Like TH cells, TR
cells can be called T4, CD4, CD4+
• Memory T (TM) cells – Descend from the cytotoxic T
cells: – Responsible for memory in cellular immunity
B-Cells
• B cells develop in bone
• – Some fetal stem cells remain in bone marrow and
differentiate into B cells
• • B cells that react to self-antigens undergo either anergy or
clonal deletion, same as T cell selection
• • Self-tolerant B cells synthesize antigen surface receptors,
divide rapidly, produce immunocompetent clones
• • Leave bone marrow and colonize same lymphatic tissues
and organs as T cells
Plasma cells
• Plasma cells originate from terminally differentiated B
cells. Activated B cells
• The main function of the plasma cells is to produce and
secrete all the classes of immunoglobulins·
• They secrete thousands of antibody molecules per
second, which are specific for the epitope of the antigen
for a few days and then die.They have a short lifespan of
30 days during which they produce large quantities of
immunoglobulins.
• They divide very poorly, if at all, and are usually found in
the bone marrow and in the perimucosal lymphoid
Antigen-Presenting Cells-APC
• T cells cannot recognize antigens on their own.
• Antigen-presenting cells (APCs) are required
• Dendritic cells,
• Macrophages,
• Reticular cells,
• and B cells function as APCs
Dendritic cells

• Dendritic cells are so named because of their many long,

narrow processes that resemble neuronal dendrites,
which make them very efficient at making contacts with
foreign materials.
• They are primarily present in the skin (e.g., Langerhans
cells) and the mucosa, from where they migrate
Dendritic cells

• Four types of dendritic cells are known:

• (i) Langerhans cells,
• (ii) interstitial dendritic cells,
• (iii) myeloid cells, and
• (iv) lymphoid dendritic cells.
• All these cells constitutively express high levels of both
class II MHC molecules
Dendritic cells

• Following microbial invasion or during inflammation,

mature and immature forms of Langerhans cells and
interstitial dendritic cells migrate into draining lymph
nodes, where they make the critical presentation of
antigen to TH cells, which is required for the initiation of
responses by those key cells.
 Macrophages
• The mononuclear phagocytic system consists of monocytes
circulating in the blood and macrophages in the tissues.
• The monocyte is considered a leukocyte in transit through the
blood, which becomes a macrophage when fixed in a tissue.
• Monocytes and macrophages as well as granulocytes are able
to ingest particulate matter (microorganisms, cells, inert
particles) and for this reason are said to have phagocytic
functions.
• The phagocytic activity is greater in macrophages
• Macrophages are 5 to 10 times larger than monocytes
• Macrophages perform threemain functions:
• (a) phagocytosis,
• (b) antigen presentation, and
• (c) cytokine production
• Antigen processing
• – APC encounters antigen
• – Internalizes it by endocytosis
• – Digests it into molecular fragments
• – Displays relevant fragments (epitopes) in the grooves of
the MHC protein
• Antigen presenting
• – Wandering T cells inspect APCs for displayed antigens
• – If APC only displays a self-antigen, the T cell disregards it
• – If APC displays a nonself-antigen, the T cell initiates an
immune attack
• – APCs alert the immune system the presence of foreign antigen
• – Key to successful defense is to quickly mobilize immune cells
against the antigen
• – With so many cell types involved in immunity, they require
chemical messengers to coordinate their activities—interleukins
• Both cellular and humoral immunity occur in three stages
• – Recognition-Recognize
• – Attack– React
• – Memory– Remember

“The three Rs of immunity”

• – Recognize– React– Remember
 THE BONE MARROW
• Bone marrow is a soft, gelatinous tissue
• Present in the central cavity of long bones such as the
femur and humerus.
• Blood cells and immune cells arise from the bone marrow;
• They develop from immature stem cells
(haemocytoblasts), which follow distinct developmental
pathways to form erythrocytes, leucocytes or platelets-
HEMATOPOIESIS
 The Thymus
• The thymus gland is a bi-
lobed, pinkishgrey organ
located just above the heart in
the mediastinum, where it
rests below the sternum
(breastbone).
• Structurally, the thymus
resembles a small bow tie
• Gradually atrophies (shrinks)
with age
Thymic involution
• In pre-pubescents, the thymus is a relatively large and
very active organ that, typically weighs around 40g
• By 20 years of age, the thymus is 50% smaller than it was
at birth,
• By middle-age it may have shrunk sufficiently to be
difficult to locate.
• By 60 years of age it has shrunk to a sixth of its original
size
• This is called thymic involution
Thymus
• Lobules within the lobes have two distinct areas:
• A dense outer cortex that is rich in actively dividing T-
cells
• An inner medulla, which is much paler in colour and
functions as an area of T-cell maturation.
• The thymus has endocrine function by its secretion of a
family of hormones collectively referred to as thymosin,
thymulin, thymopoietin, interleukins, and interferon
• These hormones are essential for normal immune function
and signaling
 Role of THYMUS in T-cell maturation

• T-cells originate as haematopoietic stem cells from the red bone

marrow.
• A population of these haematopoietic stem cells infiltrate the
thymus, dividing further within the cortical regions of the lobules then
migrating into the medullary regions to mature into active T-cells
• This process of T-cell maturation is controlled by the hormone
thymosin.
• A proportion of these mature T-cells continually migrate from the
thymus into the blood and other lymphoid organs (spleen and lymph
nodes), where they play a major role in the body’s specific immune
responses
T-cells programming-thymic education
• One of the most important functions of the thymus is
programming T-cells to recognise ‘self ’ antigens
through a process called thymic education
• This process allows mature T-cells to distinguish foreign,
and therefore potentially pathogenic, material from
antigens that belong to the body.
• It has been demonstrated that removal of the thymus may
lead to an increase in autoimmune diseases, as this
ability to recognise self is diminished
Thymic education
• Within the thymus
• – Reticular epithelial (RE) cells release chemicals that
stimulate maturing T cells to develop surface antigen
receptors
• – With receptors, the T cells are now immunocompetent:
• capable of recognizing antigens presented to them
Thymic education
• RE cells test T cells by presenting self-antigens to them;
• T cells can fail by:
• • Being unable to recognize the RE cells at all
• • Would be incapable of recognizing foreign attack
• • Reacting to the self-antigen
• • Would attack one’s own tissues
• • T cells that fail are eliminated by negative selection
Clonal deletion—self-reactive T cells die and macrophages
phagocytize them
Anergy—self-reactive T cells remain alive but unresponsive
Thymic education
• Negative selection leaves the body in a state of self-tolerance
• The surviving T cells respond only to
• suspicious antigens (ignoring the body’s own proteins)
• – Only 2% of T cells pass the test
• • In thymus medulla, surviving T cells undergo positive selection:
• they multiply and form clones of identical cells programmed to respond to
a specific antigen
• • Naive lymphocyte pool: immunocompetent T cells that have not yet
encountered foreign antigens
• • Deployment
• – Naive T cells leave thymus and colonize lymphatic tissues and organs
everywhere in the body
THE SPLEEN
• The spleen and lymph nodes are two major secondary
lymphoid organs that play key roles in:
• Filtering out and destroying unwanted pathogens;
• Maintaining the population of mature lymphocytes (which
are white blood cells) to enable the adaptive immune
response to begin
THE SPLEEN
• The spleen is the largest lymphoid organ.
• Situated in the upper left hypochondriac region of the
abdominal cavity,
• Between the diaphragm and the fundus of the stomach
• Primarily functions as a filter for the blood, bringing it into
close contact with scavenging phagocytes (white blood
cells in the spleen that will seek out and ‘eat’ any
pathogens in the blood) and lymphocytes.
• The spleen is made up of
two regions:
• Stroma – comprising the
dense outer capsule with its
trabeculae, some fibres and
fibroblasts (cells that
secrete connective tissue
collagen)
• Parenchyma – composed
of two types of intermingling
tissue called white pulp
and red pulp
• White pulp is a mass of germinal centres of
dividing B-lymphocytes (B-cells),
surrounded by T-cells and accessory cells,
including macrophages and dendritic cells
• These cells are arranged as lymphatic nodules
around branches of the splenic artery.
• As blood flows into the spleen via the splenic
artery, it enters smaller, central arteries of the
white pulp, eventually reaching the red pulp.
• The red pulp is a spongy tissue, accounting for
75% of the splenic volume
• It consists of blood-filled venous sinuses and
splenic cords
THE SPLEEN

• When foreign antigens reach these organs, they initiate

lymphocyte activation and subsequent clonal
expansion and maturation of these important white
blood cells.
• Mature lymphocytes can then leave the secondary organs
to enter the circulation, or travel to other areas, and target
foreign antigens
THE SPLEEN
• Due to its extensive vascularisation
• The spleen is a dark-purplish oval-shaped organ
• In adults it is approximately 12cm long, 7cm wide
• Weighs around 150g
Spleen functions
• The spleen has three major functions:
• To mount an immune response and remove micro-
organisms from circulation;
• To destroy damaged and worn-out red blood cells;(RBC
GRAVE YARD)
• To store platelets (and blood).
• The spleen also plays a minor role in haematopoiesis:
usually occuring in foetuses of up to five months’
gestation
• As the spleen is the largest collection of lymphoid tissue in the
body, infections that cause white blood cell proliferation and
antigenic stimulation may cause germinal centres in the organ
to expand, resulting in its enlargement (splenomegaly).
• This happens in many diseases –
• Malaria, cirrhosis and leukaemia.
• The spleen is not usually palpable,
• But an enlarged spleen is palpable during deep inspiration.
• Enlargement may also be caused by any obstruction in blood
flow, for example in the hepatic portal vein.
LYMPH NODE

• Lymph nodes vary in size

and shape, but are typically
bean-shaped structures
• Clustered at specific
locations throughout the
body.
• Although their size varies,
each node has a
characteristic internal
structure
LYMPH NODE

• Most numerous lymphatic organs

• – About 450-600 in typical young adult
• – Serve two functions
• • Cleanse the lymph
• • Act as a site of T and B cell activation
LYMPH NODE

• The central portions of the lymph node are essential to its

function; here, there are large numbers of fixed
macrophages
• Phagocytose foreign material such as bacteria on contact,
and populations of B- and T-cells. Lymph nodes are
crucial to most antibody-mediated immune responses
• When the phagocytic macrophages trap pathogenic
material, that material is presented to the lymphocytes so
antibodies can be generated.
LYMPH NODE

• Cervical lymph nodes

• – Deep and superficial group in the neck
• – Monitor lymph coming from head and neck

• • Axillary lymph nodes

• – Concentrated in armpit
• – Receive lymph from upper limb and female breast
• • Thoracic lymph nodes
• – In thoracic cavity, especially embedded in mediastinum
• – Receive lymph from mediastinum, lungs, and airway
LYMPH NODE

• Abdominal lymph nodes

• – Occur in posterior abdominopelvic wall
• – Monitor lymph from the urinary and reproductive
systems
• • Intestinal and mesenteric lymph nodes
• – Found in the mesenteries, adjacent to the appendix and
intestines
• – Monitor lymph from the digestive tract
LYMPH NODE
• • Inguinal lymph nodes
• – In the groin and receive lymph from the entire lower limb
• • Popliteal lymph nodes
• – Occur on the back of the knee
• – Receive lymph from the leg proper
LYMPH NODE
• A healthy, fully functioning node removes the majority of
pathogens from the lymph before the fluid leaves via one
or more efferent lymphatic vessels.
• In addition to its lymphatic supply, each lymph node is
supplied with blood via a small artery
• The artery delivers a variety of leucocytes, which populate
the inner regions of the node.
LYMPH NODE
• When infection is present, the lymph nodes become increasingly
metabolically active and their oxygen requirements increase.
• A small vein carries deoxygenated blood away from each node
and returns it to the major veins.
• In times of infection, this venous blood may carry a variety of
chemical messengers (cytokines) that are produced by the
resident leucocytes in the nodes.
• These cytokines act as general warning signals, alerting the
body to the potential threat and activating a variety of specific
immune reactions
• Swollen lymph nodes and a fever are sure signs that the
body is mounting an effective immune response against
an offending pathogen
• When a lymph node is under challenge by an antigen
• – Lymphadenitis: swollen, painful node responding to
foreign antigen
• – Lymphadenopathy: collective term for all lymph node
diseases
• During infection, antibody-producing B-cells begin to
proliferate in the germinal centres, causing the affected
lymph nodes to enlarge and become palpable and tender.
• Some of the cytokines released are pyrogenic (meaning
they cause fever) and act directly on the thermoregulatory
centre in the hypothalamus to increase body temperature
 Lymph nodes and metastasis
• • Metastasis—cancerous cells break free from original tumor,
travel to other sites in the body, and establish new tumors
• – Metastasizing cells easily enter lymphatic vessels– Tend to
lodge in the first lymph node they encounter
• – Multiply there and eventually destroy the node
• • Swollen, firm, and usually painless
• – Tend to spread to the next node downstream
• – Treatment of breast cancer is lumpectomy, mastectomy,
along with removal of nearby axillary nodes
 Other lymphatic tissues
• Other types of lymphatic tissue also exist.
• Mucosa-associated lymphoid tissue (MALT) positioned to
protect the respiratory and gastrointestinal tracts from
invasion by microbes.
• The following are made up of MALT:
• Gut-associated lymphoid tissue;
• Bronchus-associated lymphoid tissue;
• The palatine, lingual and pharyngeal(adenoids) tonsils
TONSILS
• Three main sets of tonsils
• – Palatine tonsils
• • Pair at posterior margin of oral cavity
• • Most often infected
• – Lingual tonsils
• • Pair at root of tongue
• – Pharyngeal tonsil (adenoids)
• • Single tonsil on wall of nasopharynx
 TONSILS

• The tonsils are aggregates of lymphatic tissue strategically

located to prevent foreign material and pathogens from
entering the body.
• The palatine tonsils are in the pharynx, the lingual tonsils
in the oral cavity and the pharyngeal tonsils (adenoids) are
at the back of the nasal cavity
• As a result of this, the tonsils themselves are at high risk of
infection and inflammation (tonsillitis)
LYMPHADENOPATHY
• There are several potential causes of lymphadenopathy,
• MALIGNANCY
• AUTOIMMUNITY
• INFECTION
• MEDICATION
• Malignancy:,
• Metastatic breast cancer,
• Kaposi sarcoma,
• Leukemias,
• Lymphomas-Hodgkin’s and non-Hodgkin’s lymphomas
• Metastatic disease (i.e., gastric cancer),
• Malignant disorders of the skin.
• Autoimmunity
• Several conditions that are characterized by a highly
active immune system may result in lymph node
abnormalities
• Dermatomyositis,
• Kawasaki disease,
• Rheumatoid arthritis,
• Sarcoidosis,
• Sjogren syndrome,
• Still disease,
• Systemic lupus erythematosus
LYMPHADENOPATHY
• Infection
• There is a wide range of infectious etiologies, including
bacterial, fungal, viral, mycobacterial, spirochetal, and
protozoal organisms.
• Bacterial: brucellosis, cat-scratch disease, bacterial
pharyngitis, syphilis, tuberculosis, tularemia, typhoid fever
• Viral: cytomegalovirus, hepatitis, herpes simplex, HIV,
mononucleosis, rubella, viral pharyngitis.
• Other: bubonic plague, blastomycosis, occidioidomycosis,
cryptococcosis, histoplasmosis, toxoplasmosis
• Medications: Often, medical therapies may incite the
benign growths of lymph nodes.
• allopurinol, atenolol,
• captopril, carbamazepine,
• cephalosporins, gold,
• hydralazine, penicillin,
• phenytoin, primidone,
• pyrimethamine, quinidine,
• sulfonamides, and sulindac
CLASSIFICATION OF LYMPADENOPATHY
• Depending upon the involvement of the lymph nodes,
lymphadenopathy is classified into 2 groups,

• Generalized and

• Localized:
CLASSIFICATION OF LYMPADENOPATHY
• Localized lymphadenopathy:Localized
lymphadenopathy: due to localized spot of asault
• Occurs in contiguous groupings of lymph nodes.
• In discrete anatomical regions, lymph nodes are
distributed, and their enlargement represents their
location's lymphatic drainage.
• 75% of all lymphadenopathies are localized
• Over 50% seen in the region of the head and neck.
• Generalized lymphadenopathy:
• Involves lymphadenopathy in 2 or more non-contiguous
sites
• Due to generalized infection all over the body e.g.
influenza : due to systemic infection.
• In some cases, it may persist for prolonged periods
possibly without an apparent cause- Persistent
generalized lymphadenopathy (PGL)
•
• Malignant or Benign lymphadenopathy
• Malignant types which mainly refer to lymphomas
• Metastatic or non- metastatic.

• Size, where lymphadenopathy in adults is often defined

as a short axis of one or more lymph nodes is greater
than 10mm.
• Location:
• Tracheobronchial lymph nodes.
• Mediastinal lymphadenopathy
• Bilateral hilar lymphadenopathy
• Dermatopathic lymphadenopathy: lymphadenopathy
associated with skin disease. Tangier disease (ABCA1
deficiency) may also cause this.
TWO TYPES OF IMMUNITY
• – Cellular (cell-mediated) immunity:
• • Lymphocytes directly attack and destroy foreign cells
• or diseased host cells
• • Rids the body of pathogens that reside inside human
• cells, where they are inaccessible to antibodies
• • Kills cells that harbor them
• Humoral (antibody-mediated) immunity:
• • Mediated by antibodies that do not directly destroy a
pathogen but tag it for destruction
• • Many antibodies are dissolved in body fluids (“humors”)
• • Can only work against the extracellular stages of
infections by microorganisms
THANK YOU