THE

LYMPHATICS
&
THE
IMMUNE SYSTEM
 LYMPHATIC SYSTEM

 is part of the circulatory system,

comprising a network of lymphatic vessels
 a closed one way system

 allows lymph to flow from tissue spaces

towards heart
 Almost all tissues of the body have lymph
channels
 Works with immune system to remove disease-
causing agents
 LYMPHATIC SYSTEM…
 Collects fluid (lymph)
between cells and returns
it to bloodstream
 Picks up lipids from
digestive organs and
transports them to blood
stream
 Functions to defend the
body against pathogens
Lymphoid
Organs-
➢Thymus
➢Spleen
➢Lymph
nodes
➢Tonsils,
➢Peyer’s
patches,
➢Appendix
FUNCTIONS OF LYMPHATIC SYSTEM
„
lymphatic vessels

 transport fluids that have escaped from

 blood vascular system back to the blood

lymphoid organs
 house phagocytic cells & lymphocytes
 body defence
 resistance to diseases
 LYMPH

➢ Modified Tissue fluid that enters lymphatic

vessels
➢ It is formed from interstitial fluid

➢ Yellowish in color, slightly alkaline

➢ Clots slowly

➢ Has proteins slightly less than plasma

 Lymph of intestines has more fats & is

milky
FORMATION- formed by
trans-capillary exchange i.e.
rapid & continuous
exchange between intra-
vascular & extra-vascular
compartments

Most of the fluid filtered

from blood capillary flow
among the cells & finally
reabsorbed at the venous
end, part of interstitial fluid
which is not reabsorbed
forms LYMPH.
 LYMPHATIC SYSTEM: PATHWAYS
Lymphatic capillaries
 Extend into interstitial
spaces
 Permeable, thin walls pick up
lymph
 Delivers lymph to lymphatic
vessels
Lymphatic vessels
 Deliver lymph to lymph
nodes
 Cells in nodes can remove
pathogens from lymph and
start an immune response
 Leaves nodes through
efferent lymphatic vessels
 LYMPHATIC SYSTEM: PATHWAYS CONTD…
Lymphatic trunks
 Receive lymph from
efferent lymphatic vessels
 Deliver it to Lymphatic
collecting ducts
 Thoracic duct→
Left side of head and neck,
left arm, left side of thorax,
entire abdominopelvic
area, and both legs
 Right lymphatic duct →
 Right side of head and
neck, right arm, and right
side of chest
 Lymph is essentially
recycled blood plasma.

➢ High in nutrients, oxygen, and

small proteins
➢ Flows slowly = 0.5-1ml/min
Flow is maintained by →
1. Contraction of skeletal
muscles against lymphatic
vessels
2. Smooth muscle contraction
3. Valves in lymphatic vessels
4. -ve intrathoracic pressure
during Breathing
5. Peristalsis of GIT
 FUNCTIONS OF LYMPH
1. Exchange of nutrients, wastes & gases
between blood & Interstitial Fluid (IF)
2. „95% plasma proteins that leak from
blood to IF is returned to blood via
lymphatics
3. ensure sufficient blood volume to operate
4. Transport of Fatty Acids& cholesterol from
intestine to blood
5. Transport of RBCs, WBCs & bacteria to
regional LNs.
6. Transport of antibiotics
7. Helps in conc. of urine by maintaining
osmotic gradient between vasa recta &
medullary interstitium.
8. Supplies O2 & nutrients to cornea &
cartilage
9. Continuous movement exposes antigen to
large No. of Lymphocytes.
 LYMPHOID TISSUE
 Fundamental in all types of immune response
 Sites- Bone Marrow, Spleen, Lymph Nodes,

Tonsils, Peyers patches, Appendix, Thymus

Contains 3 types of cells

→Tissue macrophages
→ Lymphocytes ( 90% small, 10% large)
→Plasma Cells
 Tissue macrophages-
 large cells of RE system(MPS)present in
tissues
 are also called fixed histiocytes
 Wandering RE cells are Neutrophils &
Monocytes.
1. Egs-Littoral cells lining blood sinuses in Bone
Marrow
2. Kupfer cells – Liver
3. Reticulum cells- spleen
4. Lymph Nodes-lining lymphatic pathway
5. Osteoclasts-in bone
6. Microglia-in brain
 FUNCTIONS
➢ Phagocytosis
➢ Secretion of bactericidal agents-O2¯,H2O2,
OH¯
➢ Secretion of Interleukins-for maturation &
proliferation of T & B lymphocytes
➢ Destruction of senile RBCs &Hb→ release
bilirubin
➢ Haemopoiesis
➢ Ingest and process antigen→ stimulation of
antibody production from plasma cell
Compensatory hypertropy in case of damage to
some part of RE system
 LYMPHOCYTES develop in lymph nodes (after
they are formed in the bone marrow)
➢ They circulate in blood & lymph

➢ Non Phagocytic

➢ Move in a characteristic way

➢ Do not respond to chemo tactic stimuli

➢ 2 types- →T lymphocytes

→B lymphocytes
➢ Key elements in the production of cellular &
humoral immunity respectively.
 THYMUS
• Bilobed
• most active during youth

– prominent in newborns
– grows until adolescence
begins to atrophy
➢ „ location
– inferior neck
– extends to mediastinum
of superior thorax
 Thymus gland is utmost
essential for development of
lymphocytes.
 Acts on bone marrow to -

1. Promote cell differentiation

from stem cells
2. Migration of lymphocytes to
other lymphoid tissues for
complete development
3. Thymosin conditions the
lymphocytes & makes the
immunologically competent.
 „functions of thymus

➢ strictly in T lymphocyte maturation

➢ does not directly fight antigens

➢ secrete hormones that stimulate

lymphocytes to become immunocompetent.

➢ able to recognize antigens
 Developing & Processing of T Lymphocytes

 T lymphocytes are processed in Thymus mostly

just before birth and few months after birth
 The gland secretes humoral factors like
Thymosin which accelerates the proliferation &
development of T lymphocytes
 Are transformed into 4 types-
→ Helper T cells / CD4+ cells
→ Cytotoxic T cells / CD8+ cells
→ Suppressor T cells
→ Memory T cells
 After transforming , are stored in lymphoid tissues
–LNs, spleen, bone marrow & GIT
 PLASMA CELLS

- Replicated & differentiated B lymphocytes

with a life span of 2-3 days
Circulation of Lymphocytes
Lymphocytes formed in Lymphoid tissues and
released into Lymph,
↓
General Circulation
↓
By Diapedesis enter Tissues
↓
Renters Lymph
Developing & Processing of B Lymphocytes
➢ Discovered in ‘Bursa of Fabricius’ in birds
➢ In humans processing occurs in bone marrow
& liver.
➢ After processing are transformed into
→ Plasma cells
→ Memory cells
➢ After transforming , are stored in lymphoid
tissues –LNs, spleen, bone marrow & GIT
Developing & Processing of Lymphocytes
 It has been estimated that
during our lifetime, we will
encounter a million foreign
antigens capable of causing
disease, and our bodies
need the same amount of
lymphocytes to defend
against them.
 There will always be a
different type of lymphocyte
for each possible antigen.
 SPLEEN

 Not essential for life

 Forms RBCs in intrauterine life

 & in adults if BM not functional

 Forms lymphocyes & plasma cells.

 Destroys all blood cells by its macrophages

 Forms antibodies against toxins & protects the

body
 LYMPH NODES
 „small organs

 „embedded in connective tissue

 „cluster along lymphatic vessels

 large clusters near body surface

 places where lymphatic

vessels converge to form

large trunks
 inguinal region

 axillary region

 cervical region
 function– filter lymph as it is transported
back to bloodstream. Water & electrolytes
are removed .
➢ – phagocytic macrophages remove &
➢ destroy microorganisms & toxic
substances.
➢ activate the immune system
➢ „ fight against antigens
➢ lymphocytes located in lymph nodes
APPLIED PHYSIOLOGY
➢ Infection causes increased activity of the
regional lymph nodes & its swelling .
➢ Swollen LNs are sometimes painful.
WHAT IS IMMUNITY?

 Immunity is the body's ability to fight off

harmful micro-organisms –PATHOGENS &
their TOXIC PRODUCTS

 Theimmune system produces antibodies

or cells that can deactivate pathogens.
 Immune system
 includes all parts of the
Protects the body body that help in the
against recognition and
Bacteria
destruction of foreign
materials.
Viruses
 White blood cells,
Fungi
phagocytes and
Toxins
lymphocytes, bone
Parasites marrow, lymph nodes,
Cancer tonsils, thymus, and
spleen are all part of the
immune system.
 IMMUNITY

The ability of the body to resist the entry of

different pathogens like bacteria , virus,
toxic substances etc.
Is of 2 types
1. Innate Immunity(Natural)/ Non- Specific

2. Acquired Immunity/ Specific

Natural Artificial
- Active - Active
- Passive - Passive
INNATE / NON-SPECIFIC IMMUNITY
 It is also called NATURAL IMMUNITY
 Inborn capacity of the body to resist the
pathogens

 If the organisms enters the body per chance,

innate immunity eliminates them before the
development of any disease.

 This represents the first line of defense

against any type of pathogens.
DEFENCE MECHANISMS
 DEFENSE MECHANISM:-

 GIT- lysozymes in saliva destroy bacteria

- acid in stomach &
various digestive juices destroy the toxic
substances & organisms in food

 RESP. SYSTEM- antimicrobial peptides in

epithelial cells of air passage
- Neutrophils, lymphocytes, macrophages
& Natural Killer cells present in lungs acts
against bacteria & virus

 UROGENITAL SYSTEM- acidity in urine &

vaginal fluid destroys bacteria
 SKIN - keratinized stratum corneum of
epidermis protects against toxic chemicals
- lysozymes secreted in skin destroy bacteria
 PHAGOCYTIC CELLS- Neutrophils, lymphocytes
macrophages ingest & destroy micro-organisms
& foreign bodies by phagocytosis
 INTERFERONS- inhibit the multiplication of
viruses, parasites &cancer cells
 COMPLEMENT PROTEINS- accelerate the
destruction of micro-organisms
 2ND LINE OF DEFENCE
• Phagocytic cells (WBCs)
- N L M E B
- Natural Killer (NK) Cells: attack virus
infected cells
• Inflammatory Response
• Antimicrobial proteins
- Lysozymes
- Interferons
 INFLAMMATORY RESPONSE
 Redness (Rubor) - due to capillary dilation
resulting in increased blood flow
 Heat (Calor) - due to capillary dilation resulting in
increased blood flow
 Swelling (Tumor)– due to passage of plasma from
the blood stream into the damaged tissue
 Pain(Dolor)– due mainly to tissue destruction and,
to a lesser extent, swelling.

Phagocytes
Histamine & Capillaries dilate Chemotactic consume
prostaglandins Clotting begins factors attract pathogens & cell
released phagocytic cells debris
 Natural humoral response
 These are by soluble factors in serum & body
fluids
 1.Complement system

 2.C reactive proteins

 3.Interferons

 4.Natural killer cells

 Complement system
 Cell killing effect of circulating antibodies &
humoral immunity are mediated by a system of
plasma enzymes called complement system
 Plasma Enzymes are C1 to C9
 C1 is made up of 3 subunits C1q , C1r , C1 s
 So 11 proteins in this system
 Activation of this system triggers a sequence of
cascade reactions that activates other
components of the system
 This system is activated by two pathways
 CLASSICAL PATHWAY
 ALTERNATIVE OR PROPERDIN
 Histamine—Dilates blood vessels & Increases
capillary permeability
 C5b , C6, C7 are chemotactic & attract
leucocytes to the site of ag-ab reaction
 C5 to C9 cause holes to appear in the cell
membranes of foreign invaders & results in its
destruction
 C Reactive Proteins
 Entry of foreign invaders--Activates PP esp CRP
 (c reactive)—which coats the invaders
 CRP coated invaders---Activates complement
system—Facilitates phagocytosis

 INTERFERONS
 Virally infected cells –release interferons
 Which form a protective ring & prevents the spread
of infection
 As inhibits protein synthesis & inhibits replication of
viruses
 Natural killer cells
 These are special type of cytotoxic cells.known as
non –T ,non –B Lymphocytes
 Combating the spread of disease while more
specific T & B lymphocytes are being activated
These are large lymphocytes(10-15%of circulating
agranulocytes)
 These kill the cells without prior sensitization
 These destroy the malignant cells
 These kill antibody coated viruses
 Their activity is increased by IL-2
 These are natural first line line of defense against
viral infections
 Natural cell mediated response
 Neutrophils-First line of defense

 Monocytes -2nd line of defense

 If fails---fixed macrophages in liver spleen

,lymph nodes & other body tissues
 ACQUIRED / SPECIFIC IMMUNITY
➢ If invaders overcome the natural immune
system then acquired comes into play
➢ It is the resistance developed in the body
against any specific foreign body like
bacteria, viruses, toxins, vaccines or
transplanted tissue mechanism.
➢ It is the most powerful immune mechanism.
➢ LYMPHOCYTES are responsible for
acquired immunity.
➢ Immune System Response to Antigens is of
2 types
→ Cellular Immunity (T lymphocytes)
→ Humoral Immunity (B lymphocytes)
 Cytotoxic & Suppressor T cells have on their
surface the glycoprotein CD8 (cluster of
differentiation) so are called T8 cells
 Helper cells are called T4 Cells
 CD8 & CD4 are coreceptors for major
histiocompatability complex(MHC)
 Helper & Suppressor T cells –Involved in
regulation of antibody production by B
lymphocytes
 2 types of helper cells
 TH 1-Secrete IL-2 & γ Interferon for cellular
immunity
 TH -2-Secrete IL-4 &IL-5 for humoral immunity
 Cytotoxic T cells- are responsible for
 Delayed allergic response
 Rejection of transplant of foreign tissues
 Lysis of tumour cells
 These cause destruction of target cells by
inserting perforins
 Memory B & T Cells –These have been exposed
to an antigen & are readily converted to effector
cells by a later encounter with the same antigen
 These persist in body for months or years or life
long(immunity to measles)

 Primary antibody response
 When antigen eg microorganisms are encountered
for the first time there is primary response-low level
of antibody in blood after 2 wks
 Response limits the antigen, antibody level then
falls

 2ND exposure to same antigen produces secondary

response-
 Marked increase in antibody production
 Decline more slowly
 Seconary response provides Acquired antibody
mediated immunity
 This principle is used in active immunization
against infectious diseases
 HOW BODY RECOGNIZES SO MANY DIFFERENT
ANTIGENS(CLONAL SELECTION THEORY)
 Stem cells differentiate into many million T & B
lymphocytes, each with the ability to respond to
the particular antigen
 When antigen first enters the body it is
processed by ag binding cells & binds to the
appropriate lymphocyte,these cells then divide
to form clone of cells that respond to
antigen(CLONAL SELECTION)
 cells of specific immunity
 T lymphocytes-cell mediated immunity
→ Helper T cells / inducer T cells- activate all
other type of T & B cells & regulate the
immune response
→ Cytotoxic T cells / Killer T cells- kill

→ Altered cells, infected with viruses,

tumor cells, transplanted tissues
→ Suppressor T cells- suppress the activity of
killer T cells & prevent them from destroying
body’s own tissues
→ Memory T cells- are inactivated cells but
remain in lymphoid tissue. Activate other cells
on 2nd exposure of same antigen.
 B lymphocytes (produce antibodies)
→Plasma cells- destroy the foreign
organisms by producing antibodies
(globulin in nature) & releasing into
circulation
→Memory B cells- occupy the lymphoid
tissue in inactive condition. 2nd exposure
of same antigen produces more potent
antibodies & at faster rate.
This phenomenon forms the basic principle
of vaccination against infections
 Antigens are macromolecules that elicit an
immune response in the body. The most common
antigens are proteins and polysaccharides.
 Antigens can enter the body from the environment.
 antigens can be generated within the cells of the
body.

 An antibody is a
protein produced in
response to an
antigen.
 IMMUNOGLULINS
 These contain 4 polypeptides chains linked together
by disulphide bonds
 There are 2 identical light chains & 2 identical heavy
chains
 Both heavy & light chains are divided into constant &
variable regions
 Amino acid sequence in constant region of different
immunoglobulins are very similar but in variable
region are distinct for each immunoglobulin.This
allows large number of unique antibodies each with
specific affinities for different antigens
 Only 2 types of light chains ie λ (lambda)& К (kappa)
 TYPES OF ANTIBODIES
Five classes depending upon difference in heavy chains
Ig G(immunoglobulin) - Antibodies of secondary immune
response
Active in blood against bacteria and viruses
 Most common antibody in the blood
• Crosses blood vessels
• Crosses placenta (passive immunity to fetus)

IgM- antibody of primary immune response

Reacts with certain antigens, usually on first exposure
Helps activate complement
Helps phagocytes eliminate antigens

IgA- most common in mucosa

Are also secreted in tears, saliva, intestinal juices
respiratory secretions & colostrum
Can’t cross placenta
 IgD and IgE are rare in blood
IgE- is involved in
 Allergic reactions,
 Parasitic infestations &
 Anaphylactic type of immediate hypersensitivity disorders
sticks to mast cells, which release inflammatory substances

IgD-
is usually found on B cells (not released)
may be involved in B cell activation
 Cells of inflammation
 Neutrophils- leave blood and enter site of
 injury- kill and phagocytose microbes
 Macrophages- also phagocytes
 Mast cells- release inflammatory
substances
 Complement proteins- contribute to
inflammation
 Lymphocytes may be activated, too
 These cells involved in immune response
communicate through
interleukins,cytokines,complement system
& natural killer cells
 What do these cells do, when exposed to
antigen?

 Proliferate (divide rapidly)

 Produce “effector molecules”

 B cells- antibodies
 helper T cells- cytokines
 cytotoxic T cells- cytotoxic granule
 Macrophages, dendritic cells- present antigen
to T cells
 WHAT IS A CYTOKINE
 Low molecular weight proteins
 regulate immune responses

 Cytokines can activate many cells

 Ex. Cytokines secreted by T helper cells &can

affect B-cells,
 Interleukins, monokines, lymphokines,
chemokines, term CYTOKINE includes all of
them
Cytokines Are Involved In
1. Hematopoiesis
2. Adaptive Immunity
3. Innate Immunity
4. Inflammation
 INTERFERONS (IFN)
Interferons are proteins
The name originates from the fact that they
interfere with viral infection
Interferons Provide First Line of Defense
Against Viral Infection
Interferon release is part of innate immunity
1. Block viral mRNA synthesis
2. Block translation of viral mRNA
Viruses tend to evade Interferon Response
 Regulation of immune response
 Local factors
 Antigen-As long as ag persists ,response
continues
 The response-2 major immune systems ie
cellular & humoral regulate their own
responses through feedback mechanisms
 Eg. IgM Antibodies exert negative feedback
thus preventing uncontrolled population of one
type of abs
 Suppressor T cells dampen the immune
response of T & B cells so turn off the helper
cells
 General factors
 1.Effect of hormones on immune response

 INHIBIT STIMULATE
 GC Growth hormones
 Estrogens,Androgens Thyroxine
 Progesterone Insulin

 2.Genetic factors.Genetic tendency of poor

immune response –susceptible to infections
 IMMUNOLOGICAL TOLERANCE(RECOGNITION OF
SELF)
 Why animals don,t usually make an immunological
response to their own proteins or tissue cells
although these are excellent antigens in other
species
 The capacity to make immunological response to
foreign antigens develop late in foetal life or even
after birth
 All the antigens with which the cells are in contact
during the period of immunological immaturity are
recognized as self
 After this period- nonself—will evoke immunological
response
 The ability to recognize self Is due to
 1.Clonal anergy (immunological silence) -
mechanism preventing destruction of self
 When T & B Lymphocytes in foetal life are
exposed to antigenic material, they are
subsequently unable to make a specific
immune response to these materials & enter
prolonged hypo responsive state(clonal anergy
or immunological silence)
 Thus all antigenic materials encountered in
foetal life whether self or non self elicit no
response then or subsequently as long as it
persists in tissues
 2.Clonal Abortion-Many of the T lymphocytes are
eliminated in the thymus during their early
development
 3.Suppressor T cells keep a check on non self
antibodies
 APPLIED

 Immune tolerance sometimes fails & allows the

production of abs against animal,s own tissues-
AUTO IMMUNIZATION OR AUTO SENSITIZATION &
antibodies are called auto- antibodies
 Deficiency of suppressor T cells Is probably the
cause of auto immune diseases
Auto immune diseases Auto antibodies are
formed against
IDDM- Type –I Pancreatic islets β cells

Myosthenia Gravis Nicotinic cholinergic

receptor
Mutiple sclerosis Myelin basic protein

Hashimoto,s thyroiditis Thyroid gland cells

Grave,s disease TSH receptors

Rhumatoid arthritis Collagen tissues

 Tissue Transplant/Graft
 Types of Grafts
 Heterograft-Graft from one animal species to
another
 Homograft(Allograft) Graft from one person to
another
 Autograft-Graft from one site to another with in the
same person
 When skin,kidney or heart are transplanted from
donor to recipient of same species
 --Transplants take & function for first few days
 Become necrotic & are rejected after a week
As recipient develops immune response
(T lymphocytes are responsible for transplant rejection
 How transplant is rejected
 Some of T lymphocytes possess recognition sites for
foreign transplantation antigens
 Contact with antigens causes lymphocytes to divide &
form daughter lymphocytes with similar recognition sites
 These immunologically activated lymphocytes leave the
lymphoid tissues & enter the blood
 On reaching transplanted tissue,react with it ,reduce its
blood supply & destroy it(Homograft reaction)
 After first graft rejection, if 2nd graft from same donor,
tissue transplant rejection is speeded up & sloughed off in
3-4 days
 THIS 2ND set reaction is due to rapid invasion by
lymphocytes, plasma cells & polymorphs
 IDENTICAL TWIN TRANSPLANTS ARE NEVER REJECTED
 Prevention of rejection of tissue transplant
 A.Identical twins (Homozygotic)
 B.Immuno-suppressive agents

 1. X ray radiation to destroy most of T lymphocytes

 2 Antimetabolic drugs eg Azathioprine kills T lymphocytes

 3. Steriods & Glucocorticoids inhibit production of IL-2 by T4

cells

 4. Anti lymphocytic serum (ALS) Or Anti lymphocytic

globulin(ALG) ie antibodies against T lymphocytes

 5. Drugs which bind with immunosuppressant binding

proteins(Immunophilins)eg Cyclosporin A
 FK-506
 Rapamycin
 CLINICAL ASPECT
 Di george syndrome
 Congenital absence of thymus
 T cells & so cellular immunity is absent
 Humoral immunity is present
 Agammaglobinemia
 Congenital disorder T cells with abnormal helper
& suppressor T Cells
 Deficiency of B cells, absence of plasma cells &
marked reduction of Ig G levels
 Child susceptible to bacterial infection
 Relatively resistant to viral & fungal infections
 Most cases of CLL –due to uncontrolled
proliferation of B lymphocytes
 ALL- T lymphocyte malignancies

 Mutiple Myeloma—Due to malignant

transformation of clones of mature plasma cells
 AIDS- caused by HIV virus-

 HIV binds to CD4----loss of helper T cells-Failure

of proliferation of T8 & B lymphocytes-Loss of
immune functions- Death from infections or
cancer
MECHANISM OF PHAGOCYTOSIS
➢ The circulatory system processes an average of
20 litres of blood per day through capillary
filtration which removes plasma while leaving
the blood cells
➢ Roughly 17 litres of the filtered plasma actually
get reabsorbed directly into the blood vessels,
while the remaining 3 litres are left behind in the
interstitial fluid.
➢ The primary function of the lymph system is to
provide an accessory route for these excess 3
litres per day to get returned to the blood.
Antigen can also be processed or presented to
T4 cells by
 B lymphocytes

 Langerhan cells of skin

 Dendritic cells in the lymph nodes & spleen


 DEVELOPMENT OF T - CELL MEDIATED
IMMUNITY
 Immunity that develops by cell mediated response
 Does not involve antibodies

 Involves several types of cells-macrophages, T

lymphocytes, NK cells.

 Is major defenseTB bacillus

 mechanism against Viruses, fungi &
 Is responsible for
 Delayed allergic reactions
 Rejection of transplanted tissue.
 Lysis of tumour cells
M