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THE LYMPHATIC

SYSTEM

ACHMAD AMINUDDIN
THE LYMPHATIC SYSTEM
• CONSIST OF ;
- LYMPH.
- LYMPHATIC VESSELS.
- ORGANS CONTAINING LYMPHATIC
TISSUE.
- RED BONE MARROW.
LYMPHATIC TISSUE
• IS A SPESIALIZED FORM OF
RETICULAR CONNECTIVE TISSUE
THAT CONTAINS LARGE NUMBERS OF
LYMPHOCYTES.
• TWO TYPE OF LYMPHOCYTES ;
- B CELLS.
- T CELLS.
FUNCTIOS OF THE LYMPHATIC
SYSTEM
• DRAINING EXCESS INTERSTITIAL FLUID.
• TRANSPORTING DIETARY LIPID.
• CARRYING OUT IMMUNE RESPONSES.
- IN CELL-MEDIATED IMMUNE
RESPONSES.
T cells destroy the intruders by
causing them to rupture or by reali-
sing cytotoxic ( cell-killing ) substances.
- IN ANTIBODY-MEDIATED IMMUNE
RESPONSES.
B cells differentiate into plasma cells that protec us
against disease by producing antibody, proteins
that combine with and cause destruction of specific
foreign substances.
LYMPHATHIC ORGAN AND
TISSUE.
• PRIMARY LYMPHATIC ORGANS
- THE SITES WHERE STEM CELLS
DEVIDE AND BECOME IMMUNOCOM-
PETENT, THAT IS CAPABLE OF MOUN
TING AN IMMUNE RESPONSE.
- RED BONE MARROW AND THYMUS.
- PLURIPTENT STEM CELLS IN THE BONE
MARROW GIVE RISE TO MATURE, IMMUNO
COMPETENT B CELLS AND TO PRE-T CELLS
WHICH MIGRATE TO AND BECOME
IMMUNOCOMPETENT T CELLS IN THE
THYMUS.
• SECONDARY LYMPHATIC ORGANS
SECONDARY LYMPHATIC
ORGANS
• ARE THE SITES WHERE MOST
IMMUNE RESPONSES OCCUR.
• INCLUDE
- LYMPH NODES.
- SPLEEN.
- LYMPHATIC NODULES.
THYMUS
• IN THE MEDIASTINUM, BETWEEN THE
STERNUM AND THE AORTA.
• CAPSULE – TRABECULAE – LOBULES.
• LOBULE CONSIST OF CORTEX AND
MEDULLA.
• IN INFANT ABOUT 70 g, AND IN OLD
AGE ABOUT 3 g.
LYMPH NODES
• CAPSULE – TRABECULAE –
COMPARTEMENTS.
• STROMA CONSIST OF CAPSULE,
TRABECULAE, RETICULAR FIBER, AND
FIBROBLASTS.
• PARENCHYMA ;
- CORTEX.
- MEDULLA.
SPLEEN
• LOCATED IN THE LEFT
HYPOCHONDRIAC REGION BETWEEN
THE STOMACH AND DIAPHRAGM.
• STROMA CONSIST OF CAPSULE,
TRABECULAE, RETICULAR FIBERS
AND FIBROBLASTS.
• THE PARENCHYMA CONSIST OF ;
- WHITE PULP.
- RED PULP.
LYMPHATIC NODULES
• SCATTERED THROUGHOUT THE LAMINA
PROPRIA LINING THE GASTROINTESTINAL,
GENITOURINARY AND RESPIRATORY
TRACTS.
• MULTIPLE LARGE AGGREGATION ;
- TONSILS IN THE PHARYNGEAL
REGION.
- PEYER’S PATCHES IN THE ILEUM.
- IN THE APPENDIX.
IMMUNITY
• Specific resistance ; the ability of the body
to defend itself against specific invading
agents such as bacteria, toxin, viruses and
foreign tisue.
• Antigen; substances that are recognized
as foreign and provoke immune responses
MATURATION OF T CELLS AND B
CELLS.
• T CELLS AND B CELLS DEVELOP IN PRIMARY
LYMPHATIC ORGAN ( RED BONE MARROW AND
THYMUS ).
• B CELLS COMPLETE THEIR DEVELOPMENT IN RED
BONE MARROW.
• T CELLS DEVELOP FROM PRE T CELLS THAT
MIGRATE FROM BONE MARROW INTO THE
THYMUS, WHERE THEY MATURE.
• BEFORE T CELLS LEAVE THE THYMUS OR B CELLS
LEAVE RED BONE MARROW, THEY BEGIN TO MAKE
ANTIGEN RECEPTOR THAT ARE INSERTED INTO
THEIR PLASMA MEMBRANE.
TYPES OF IMMUNE RESPOSES

• Cell-mediated immune responses ; CD8 T


cells proliferate into cytotoxic T cells that
directly attack the invading antigen.
• Antibody-mediated immune responses; B
cells transform into plasma cells, which
synthesize and secrete specific protein
called antibodies or immunoglobulin
TYPES OF IMMUNE RESPONSES
• Cell-mediated immunity is particularly effetive
against :
1. Intracellular pathogens, which include
any viruses, bacteria, or fungi.
2. Some cancer cells
3. Foreign tissue tranplants.
• Antibody-mediated immunity work mainly
against :
1. Antigens present in body fluid.
2. Extracellular pathogens, which include any
viruses, bacteria, or fungi
ANTIGEN
• ANTIGEN
- IMMUNOGENICITY is the ability to
provoke an immune response by stimu-
lating the production of specific antibo-
dies, the proliferation of specific T cells
or both.
- REACTIVITY, is the ability of the antign
to react specifically with the antibodies
or cells it provoked.
ANTIGEN
• Epitopes, certain small parts of a large antigem molecule
act as the trigers for immune responses.
• Most antigens have many epitopes, each of which induces
production of a specific antibody or activates a specific T
cell.
• Antigen that get past the nonspecific defenses follow one
of three route ;
1. Most antigens that enter the blood stream are
trapped as they flow through the spleen.
2. Antigens that penetrate the skin enter lymphatic vessel
and lodge in lymph nodes.
3. Antigens that penetrate mucous membranes are
entrapped by mucosa-associated lymphatic tissue.
CHEMICAL NATURE OF
ANTIGENS
• Antigen are large, complex molecules.
• Antigen,they are protein ( most often ),
nucleic acids, lypoproteins, glycoprotein,
and certain large polysacharides.
• T cells respond only to antigen made up of
protein.
• Bcells respond to antigens made up of
protein, certain lipids, carbohydrates and
nucleic acids.
CHEMICALNATURE OF
ANTIGENS
• Complete antigen usually have large
molecular weights of 10.000 dalton or
more. But large molecules that have
simple, repeating subunits – for example
cellulose and most plastics – are not
usually antigen.
• Hapten , a smaller substance that have
reactivity but lacks immunogenicity
CHEMICAL NATURE OF
ANTIGENS
• A hapten can stimulate an immune
respond only if it is attached to a large
carrier molecule.
• Such hapten-stimulated immune
responses are resposible for some allergic
reactions to drugs and other substances.
• Sometimes the immune system fails to
distinguish “ friend “ from “ foe “ ( non self )
EPITOPES
DIVERSITY OF ANTIGEN
RECEPTOR
• The human immune system can recognize and
bind to at least a billion different epitopes .
• The basis for the ability to recognize somany
epitopes is an equally large diversity of antigen
receptors.
• The diversity of antigen receptors in both B cells
and T cells is the result of shuffling and
rearranging a few hundred versuions of several
small gene segments ( genetic recombination ).
• After transcription and translation, the receptor
molecules are inserted into the plasma
membrane.
MAJOR HISTOCOMPTABILITY
COMPLEX ANTIGENS
• MHC antigen molecules mark the surface of each
of the body cells except r.b.c.
• Important role in transplantation.
• Help T cells recognize that an antigen is foreign,
not self.
• Two types ;
- class I MHC ( MHC I ) molecules
are built into the plasma membrane
of all body cells, except r.b.c cells.
- class II MHC ( MHC II ) molecules
appear on the surface of antigen-presenting
cells ( dendritic cells,macrophages,Bcells )
PATHWAYS OF ANTIGEN
PROCESSING
• For an immune response to occur, B cell
and T cells must recognize that a foreign
antigen is present.
• B cells can recognize and bind to antigen
in lymph, interstitial fluid or blood plasma.
• T cells only recognize fragment of
antigenic proteins that are processed and
presented in certain way
PROCESSING OF EXOGENOUS
ANTIGENS
COMBATIVE ACTION
• After APC cells processing an antigen.
• APC cells migrates to lymphatic tissue to
present the antigen to T cells.
• Within the lymphatic tissue, a small
number of T cells that have compatibly
shaped receptors recognize and bind to
antigen fragment-MHC II complex ,
triggering either a cell-mediated or an
antibody-mediated immune response.
PROCESSING OF ENDOGENOUS
ANTIGENS
• Endogenous antigens ; foreign antigen that are
synthesized inside body cells
• Fragments of endogenous antigens associate
with MHC I molecules inside infected cells.
• The resulting endogenous antigen fragment –
MHC I complex then move to the plasma
membrane, where it is presented at the surface
of the cell.
• Most cells of the body can process and present
endogenous antigens.
• The dysplay of an endogenous antigen bound to
an MHC – I molecule signals that a cells has
been infected and needs help.
CYTOKINES
• Cytokines,are small protein hormones that
stimulate or inhibit many normal cell
functions, such as cell growth and
differentiation.
• Lymphocytes and APC cells secrete
cytokines, as do fibroblasts, endothalial
cells, monocytes, hepatocytes and kidney
cells
CELL-MEDIATED IMMUNITY
• A cell-mediated immune response begins with
activation of a small number of T cell by specific
antigen.
• Once a T cell has been activated, it undegoes
proliferation and differentiation into a clone of
effector cells, a population of identical cells that
can recognize the same antigen and carry out
some aspect of the immune attack.
• Finally, the immune response result in
elimination of the intruder.
ACTIVATION, PROLIFERATION,
DIFFERENTIATION OF T Cells
• At any given time, most T cells are inactive
• T-cell receptors, recognize and bind to specific
foreign antigen fragments that are presented in
antigen-MHC complex.
• Antigen recognition also involves CD4 or CD8
proteins. These proteins interact with the MHC
antigen and help maintain the TCR-MHC
coupling.
• First signal in activation of a T cell; antigen
recognition by a TCR with coreceptors ( CD4 or
CD8 )
ACTIVATION,PROLIFERATION,
DIFFERENTIATION OF T Cells
• A T cell become activated only if it binds to the
foreign antigen and at the samr time receives a
second signal,a process known as costimulation.
• Constimulators ;
- interleukin-2
- plasma membrane molecules on the
surface of the T cell, and on the surface
of an antigen presenting cell.
ACTIVATION, PROLIFERATION,
DIFFERENTIATION OF T cells
• An activated T cell enlarges and begins to
proliferate and to differentiate.
• The result is identical cells, called a clone, that
can recognize the same specific antigen.
• Before the first exposure to a given antigen, only
a few cells might be able to recognize, but once
an immune response has begun, there are
thousands.
• Activation, proliferation and differentiation of T
cells occur in the secondary lymphatic organs
and tissues.
TYPES OF T CELS
• HELPER T Cells
- T cells that display CD4 --- CD4 Tcells.
• CYTOTOXIC Cells
- T cells that display CD8 ---- CD8 cells.
• MEMORY T Cells
- T cells that remain from a proliferated
clone after a cell-mediated immune
response.
HELPER T Cells
• T cells that display CD4 develop into
helper T cells also known as CD4 T cells.
• Inactive gelper T cells recognize antigen
fragments associate with MHC-II
molecules at the surfaceof of an APC.
• With the aid of the CD4 protein, the helper
T cell and APC interact with each other
( antigenic recognition ).
HELPER T Cells
• With costimulation, the helper T cell
becomes activated.
• Within hours after costimulation, activated
helper T cell start secreting a variety of
cytokines.
• Different subset of helper T cells
specialize in the production of particular
cytokines
CYTOTOXIC T cells
• Tcells that display CD8 develop into
cytotoxic cells also termed CD8 cells.
• Cytotoxic cells recognize foreign antigen
combined with MHC-I molecules on the
surface of ;
1. body cels infectef by microbes.
2. some tumor cells.
3. cells of a tissue transplant.
CYTOTOXIC T Cells
• Recognition requires the TCR and CD8
protein to maintain the coupling with
MHC-I.
• Costimulation occurs. In order to become
activated, cytotoxic cells equire
costimulation by IL2 or other cytokines
produced by helper T cells
MEMORY T Cells
• T cells that remain from a proliferated clone after
cell-mediated immune response.
• Should a pathogen bearing the same foreign
antigen invade the body later, thousands of
memory cells are available to initiate a far swifter
reaction than occured during the first invasion.
• The second response usually is so fast and so
vigorous that the pathogens are distroyed before
any signs or symptom of disease can occur.
CELL-MEDIATED IMMUNITY
ELIMINATON OF INVADERS
• Cytotoxic cels are the soldier that march
forth to do battle with foreign invaders.
• They leave the secondary lymphatic organ
and tissue and migrate to seek out and
destroy infected target cells, cancer ells
and transplanted cells.
• The cytotoxic cells recognize and attach to
target cells, and then deliver a “ lethal hit “
that kill target cels.
ANTIBODY-MEDIATED IMMUNITY
ANTIBODIES
• AB can combine specifically with the
epitope on the antigen.
• The AB‘s structure matches its antigen
much as a lock accepts a specific key.
• Plasma cels could secrete as many
different antibodies as there are different
B-cell receptors.
ANTIBODY STRUCTURE
• Most AB conain 4 polypeptide chain
- 2 heavy ( H ) chain.
- 2 light ( L ) chain.
• Variable ( V ) region
- At the tip of the H and L chain.
- Constitute the antigen-binding site.
- Is the part that recognize and attaches
specifially to a particular antigen
• Constant ( C ) region
ANTIBODY STRUCTURE
• Constant ( C ) region
- At the tip of the H and L chain.
- Responsible for the type of antigen-anti-
body reaction.
- The C region of the H chain differs from
one classof antibody to another, and its
structure serves as a basic for distingui-
shing five different classes, designated
IgG , IgA , IgM , IgI and IgE.
ACTIONS OF ANTIBODIES

• NEUTRALIZING ANTIGEN.
• IMMOBILIZING BACTERIA.
• AGGLUTINATING AND PRECIPITATING
ANTIGEN.
• ACTIVATING COMPLEMENT.
• ENHANCING PHAGOCYTOSIS.
CLASSES OF IMMUNOGLOBULIN
COMPLEMENT SYSTEM IN
IMMUNITY
• C3 can be activated in three ways
• 1. The classical pathway
Starts when antibodies bind to antigen.
The antigen-antibody complex binds
and activates C1, eventually C3 is actvd
• 2, The alternative pathway
Initiated by an interaction between lipid-
carbohydrate complexes on the surface of
microbes and complement protein factors B, D
and P. This interaction activates C3
• 3. The lectin pathway
COMPLEMNT SYSTEM IN
IMMUNITY
• C3 can be activated in three ways
• 3. The lecitin pathway
Macrophage that digest microbes
release chemicals that cause the liver
produce lectins.
Lectin bind to the carbohydrates on the
surface of microbes, ultimatelly causing
the activation of C3.
COMPLEMENT