STRUCTURE & FUNCTION
IMMUNE SYSTEM
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WHAT IS THIS ?
Lymphoreticular system;
Complex organization of cells
with different morphology
and distributed in all organs
and tissues of the body and
responsible for immunity.
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1.Reticuloendothelial component.
a) Phagocytic cells.
b) Plasma cells.
2.Lymphoid component.
a) Lymphocytes (T & B).
b) Plasma cells.
Non specific Immune
response
Specific Immune
response
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ORIGIN and ORGANIZATION
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Myeloblasts
Monoblasts
Megakaryoblast
Proerythroblast
Lymphoblasts
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Production:
Yolk sac.
(Up to 6th -8th wks of gestation)
Fetal liver.
Bone marrow.
(From just before birth)
Fetal Liver
Bone marrow
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Lymphopoiesis in central & Peripheral lymphoid organs and
mix together constantly to maintain Lymphocyte traffic.
Mucosa associated
lymphoid tissue
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Thymus:
Lymphoepithelial structure.
Behind the upper part of sternum
3rd& 4th pharyngeal pouches at
6th week of IUL.
Maximum size just before birth.
Atrophied after puberty.
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T-stem cells migrate into Thymic rudiment
(During 3rd month of I U L)
Thymus develop into………….
Cortex
Medulla.
(Immature T-cells)
(Mature T- cells )
In thymic epithelial cells
Peptidic hormones.
Thymulin, α & β4 thymosin,
Thymopoietin.
Matured into immuno competent T- cells.
Maturation process is more vigorous during…..
Fetal age ,Neonatal stage, Puberty.
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Functions of Thymus
 Production, maturation & differentiation of
T – cells.
 Death of T- cells that cannot recognize antigenMHCs and T- cells react with self-antigen-MHC.
•Thymectomised mice: Deficient CMI
Lymphopenia,Deficient Graft rejection
Runting disease.
•Congenital aplasia:
Di-George syndrome (CMI deficient)
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Bone marrow
Some of the lymphoid stem cells
retained and converted into
B – lymphocytes.
by
Interaction with Marrow stromal cells
and production of cytokines (IL-7).
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Lymph node is a small ball-shaped organ of the
immune system,
distributed widely throughout
the body including the armpit
and stomach/gut and linked by
lymphatic vessels.
Garrisons of B, T, and other
immune cells dendritic cells,
macrophages
Acts as Filters or traps for antigens,
become inflamed or enlarged in
various conditions
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Clinical significance of lymphnode
Naive lymphocytes (cells,not yet
encountered an antigen) enter
the node from the bloodstream,
through specialized capillary
venules, known as high
endothelial venules.
After the lymphocytes specialize
they will exit the lymph node
through the efferent lymphatic
vessel with the rest of the lymph.
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The spleen is unique in respect to its
development within the gut.
While most of the gut viscera
are endodermally the spleen is
derived from mesenchymal
tissue.
The spleen is purple and gray.
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Area
Red pulp
White pulp
Function
Composition
Mechanical filtration of
red blood cells.
•"sinusoids” which are
filled with blood.
•"splenic cords" of
reticular fibers.
•"marginal zone"
bordering on white pulp
•Composed of nodules,
called Malpighian
corpuscles. These are
Active immune response
composed of "lymphoid
through humoral and
follicles" , rich in B- cells
cell-mediated pathways.
•“Periarteriolar lymphoid
sheaths" (PALS), rich in
T-lymphocytes.
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Functions of spleen:
It is a part of reticulo endothelial
system.
It synthesizes antibodies in its white
pulp and removes antibody-coated
bacteria along with antibody-coated
blood cells by way of blood and
lymph node circulation.
Removal of aged elements,
elimination of particulate matter
from blood.
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Effect of Splenectomy on
Immune response.
•Depends on age.
•In children : Bacterial sepsis
is common with
Str.pneumoniae,
N.meningitidis, H.influenzae
•In adults : Susceptibility to
Blood borne bacterial
infections.
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MALT (Mucosa Associated Lymphoid Tissue).
Sub epithelial accumulations of lymphoid tissue in
the mucosa of various secretary systems.
Sites: Respiratory tract. (BALT)
Alimentary tract (GALT)
Genitourinary tract
Consists of T & B lymphocytes,
Macrophages.
Produces Ig A , Ig M & Ig E antibodies.
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Distributed as:
1).Diffuse collections.
2).Specialized aggregations
Lingual,
Palatine,
Pharyngeal tonsils.
Payer's patches.
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T cell maturation
T - cell precursors
Migrate in to thymus
Thymic epithelial cells.
( Attains self tolerance , Capacity to recognize Ag- MHC complex
)
Synthesis CD3 & acquire new surface Ag (Thy ag.)
Pre T – cells
With T- cells receptor ( T C R)
Becomes Antigen recognition unit ( I C C ).
(TCR & CD3, Thy proteins)
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Most can be
distinguished by
the presence of either
CD4 or CD8
CD4 (65%):
Perform helper
function;
membrane molecules.
Transformation of B
CD8(35%):
Present in thymic
Cytotoxic activity on
virus- infected cells,
Allograft cells and tumor
cells.
medulla, tonsil and
cells to plasma cells.
blood.
Recognizes Ag by MHC
class II molecules.
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•Immunologically competent cells ( I C C ) :
•Lymphocytes which are educated by central
lymphoid organs.
Recognizing capacity of antigen.
Storage of immunological memory.
Immune response to specific antigen.
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Functional cell
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Regulatory functions of T cells.

Regulation of antibody production by
B- cells.

Stimulation of helper and cytotoxic T cells
to participate in CMI by the production of
IL-2.

Imbalance between T4 and T8 cells
results in Autoimmunity or
immunodeficiency.
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Effector functions:
Cytotoxicity of CD8 cells.
Activates macrophages to mediate delayed
hypersensitivity.
To produce memory T cells.
Destroy the virus- infected cells.
Graft rejection, tumor destruction.
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Memory cells
Characteristic features:
Cells, with ability to
respond rapidly for many
years after the initial
exposure to an antigen.
Live for many years.
Enhanced secondary
response.
Activated by small quantity
of antigen.
Activated memory cells
produce large quantities
of interleukins.
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T-cell activation
Ag + MHC protein on
APC
TCR on T-cell
Production of IL-1 from
macrophages.
Responsible for regulatory ,
effector and memory functions
of T-cells.
CTLA-4
B7 protein on APC + CD28 on
helper T-cell
Production of IL-2 from
T4 - cells.
(Cytotoxic T-lymphocyte antigen-4
)
protein
appears on T-cell surface and binds
to B7 by displacing CD28 , results
in inhibition of IL-2 production.
T-cell homeostasis
IL-2 is responsible for regulatory,effector and memory functions of t4 cells
Mutant T-cells which lack CTLA-4 & responsible for autoimmune disease.
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B – cell maturation
Pro – B cell ( From Lymphoid progenitor)
Pre – B cell
Rearrangement of DNA .Express
receptors for IgM, IgG, IgA, IgE &
for hormones. .
Self tolerance.
Mature B – Cell (Virgin B-cell)
Migrate to peripheral lymphoid tissue
Contact with Antigen
Transformed into PLASMA CELL
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PLASMA CELLS:
Antibody secreting cell(Ig factory)
Usually found in the Bone Marrow,
Perimucosal lymphoid tissue.
Life span 30 days.
Some B-cells express T- cell
marker (CD5) on their surface – B1 cells.
Responsible for T -independent antibody”
production in neonates.
Responsible for Autoimmune diseases.
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1). Location :
2).
3).
4).
5).
6).
7).
T – Cell
Thoracic duct
Thymus.
96%
Production, maturation: BM, Thymus
Thy antigen
+
CD3 receptor
+
Surface Ig
S RBC rosette
+
E A C rosette
Blast transformation with
anti – CD3
+
anti – Ig
Endotoxin
-
B – Cell
Spleen
55 – 60%
BM
+
+
+
+
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NULL CELLS (Natural killer cells).
Large granular lymphocytes,
Lack CD3, surface
immunoglobulin markers & TCR
Constitutes 3-5% of
peripheral lymphocytes
Thymus not required for
development.
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Functions:
Kills malignant cells & virus infected cells by
apoptosis.
Cytotoxicity is not M H C restricted.
Mechanism of killing is by cytotoxins like perforins
and granzymes.
Active in severe combined immunodeficiencies.
Activated
by IL-2 and Interferons.
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Antigen Presenting Cells (APC)
1.Macrophages:
Blood: Monocytes.
Tissues: Lungs - Alveolar macrophages.
Liver- Kupffer cells
Skin- Langerhans cells
Spleen- Sinusoidal cells.
Brain - Microglial cells.
Joints - Synovial cells.
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IL-1, IL-8 & TNF
IL-1
CENTRAL ROLE OF MACROPHAGE
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Dendritic cells.
Another variety of
antigen presenting
cells to T – cells.
Derived from BM.
Present in
1.Peripheral blood.
2.Lymph node.
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Granulocytes (Microphages)
Neutrophil:
Phagocytic role in acute inflammation
Eosinophil:
Phagocytic & motile.
Parasite killing with
hydrolytic enzymes.
Basophil:
Blood and tissues(Mast cells)
Not phagocytic.
Receptors for Fc portion of Ig E .
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HLA complex
TCR are unable to recognize free antigens.
To be cleaved into small peptides and must
be embedded within a specific
“molecular
groove” (located on MHC molecule) for T-cell
response…..MHC restriction.
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HLA complex located on
short arm of chromosome-6
Molecules coded by MHC
are classified into three
groups Class I,II and III.
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1.MHC class I molecules
Fibroblasts, Hepatocytes
Lymphocytes, Neuron
2.MHC class II molecules
Stromal cells in BM
Dendritic cells,Macrophages
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Cytokines:
Non antibody molecules.
Produced by ……
Lymphocytes, monocytes, keratinocytes,
Endothelial cells and thymic epithelial cells.
Glycoproteins.
Target cells : Neutrophils
Macrophages
Lymphocytes
Endothelial cells
Fibroblasts.
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Types:
Interleukins
TNF
Interferons
Colony stimulating factors.
Functions:
Control of lymphocyte growth.
Activation of innate immunity.
Control of hemopoiesis.
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Further proceed to
understand the basis of
immune response
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