STRUCTURE & FUNCTION

IMMUNE SYSTEM 11

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.22

1.Reticuloendothelial component1.Reticuloendothelial component..

a) Phagocytic cells. a) Phagocytic cells.

b) Plasma cells.b) Plasma cells.

2.Lymphoid component.2.Lymphoid component.

a) Lymphocytes (T & B). a) Lymphocytes (T & B).

b) Plasma cells.b) Plasma cells.

Non specific Immune response

Specific Immune response

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ORIGIN and ORGANIZATION

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MyeloblastsMyeloblasts

MonoblastsMonoblastsMegakaryoblastMegakaryoblast

ProerythroblastProerythroblast

LymphoblastsLymphoblasts

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Production:Production:Yolk sac. Yolk sac.

(Up to 6(Up to 6thth -8 -8thth wks of wks of

gestation) gestation)

Fetal liver. Fetal liver.

Bone marrow. Bone marrow.

(From just before birth)(From just before birth)

Fetal LiverFetal Liver

Bone marrowBone marrow

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Lymphopoiesis Lymphopoiesis in central & Peripheral in central & Peripheral lymphoid organs and mix together constantly to lymphoid organs and mix together constantly to maintainmaintain Lymphocyte traffic Lymphocyte traffic..

Mucosa associated

lymphoid tissue

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Thymus:Thymus: Lymphoepithelial structure.Lymphoepithelial structure.Behind the upper part of Behind the upper part of sternumsternum33rdrd& 4& 4thth pharyngeal pouches pharyngeal pouches at at 66thth week of IUL. week of IUL.Maximum size just before Maximum size just before birth. birth. Atrophied after puberty. Atrophied after puberty.

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T-stem cells T-stem cells migrate migrate into Thymic rudiment into Thymic rudiment(During 3(During 3rdrd month of I U L) month of I U L)

Thymus develop into…………. Thymus develop into…………. Cortex Cortex Medulla Medulla. .

(Immature T-cells) (Mature T- cells )(Immature T-cells) (Mature T- cells )

In In thymic epithelialthymic epithelial cells cells Peptidic hormones. Peptidic hormones.

Thymulin, α & β4 thymosin, Thymulin, α & β4 thymosin, Thymopoietin. Thymopoietin.

Matured into Matured into immuno competent T- cellsimmuno competent T- cells..

Maturation processMaturation process is more vigorous during….. is more vigorous during…..

Fetal age ,Neonatal stage, Puberty. 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 antigen- MHCs 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 marrowBone marrow Some of the lymphoid stem cells Some of the lymphoid stem cells

retained and converted into retained and converted into B – lymphocytesB – lymphocytes. .

by by

Interaction with Interaction with Marrow stromal Marrow stromal cellscells and production of cytokines (IL-7)and production of cytokines (IL-7)..

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Acts as Filters or traps for antigens, become inflamed or enlarged in various conditions

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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

Lymph node is a small ball-shaped organ of the immune system,

13

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.

Clinical significance of lymphnode

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While most of the gut viscera are endodermally the spleen is derived from mesenchymal tissue. The spleen is purple and gray.

The spleen is unique in respect to its development within the gut.

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Area Function Composition

Red pulp Mechanical filtration of red blood cells.

•"sinusoids” which are filled with blood. •"splenic cords" of reticular fibers. •"marginal zone" bordering on white pulp

White pulpActive immune response through humoral and cell-mediated pathways.

•Composed of nodules, called Malpighian corpuscles. These are composed of "lymphoid follicles" , rich in B- cells •“Periarteriolar lymphoid sheaths" (PALS), rich in T-lymphocytes.

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Functions of spleen:

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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.

•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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Effect of Splenectomy on Immune response.

MALT MALT (Mucosa Associated Lymphoid Tissue).(Mucosa Associated Lymphoid Tissue).

Sub epithelial accumulations of lymphoid tissue in Sub epithelial accumulations of lymphoid tissue in

the mucosa of various secretary systems.the mucosa of various secretary systems.

Sites: Sites: Respiratory tract. (BALT)Respiratory tract. (BALT)

Alimentary tract (GALT)Alimentary tract (GALT)

Genitourinary tract Genitourinary tract

Consists of Consists of T & B lymphocytes, T & B lymphocytes, Macrophages.Macrophages.

Produces Produces Ig A , Ig M & Ig E antibodies. Ig A , Ig M & Ig E antibodies.

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Distributed as:

1).Diffuse collections.1).Diffuse collections.

2).Specialized 2).Specialized aggregations aggregations

Lingual, Lingual,

Palatine,Palatine,

Pharyngeal tonsils.Pharyngeal tonsils.

Payer's patches.Payer's patches.

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T cell maturation T cell maturation

T - cell precursors T - cell precursors

Migrate in to thymus Thymic epithelial Migrate in to thymus Thymic epithelial cells.cells. ( Attains ( Attains self tolerance , Capacity to recognize Ag- MHC self tolerance , Capacity to recognize Ag- MHC

complex complex ))

Synthesis Synthesis CD3CD3 & acquire new surface Ag & acquire new surface Ag ((ThyThy ag.)ag.)

Pre T – cells Pre T – cells

With T- cells receptor With T- cells receptor ( T C R)( T C R)

Becomes Becomes Antigen recognition unit ( I C C )Antigen recognition unit ( I C C ). .

(TCR & CD3, Thy proteins)(TCR & CD3, Thy proteins)

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Most can be Most can be distinguished by distinguished by

the presence of the presence of either either CD4 or CD8 CD4 or CD8

membrane membrane molecules.molecules.

CD4 (65%):CD4 (65%):

Perform helper Perform helper

function; function;

Transformation of B Transformation of B

cells to plasma cells to plasma cells.cells.

Present in thymic Present in thymic

medulla, tonsil and medulla, tonsil and

blood. blood.

Recognizes Ag by Recognizes Ag by MHC MHC

class II molecules. class II molecules.

CD8(35%):CD8(35%):

Cytotoxic activity on Cytotoxic activity on virus- infected cells, virus- infected cells, Allograft cells and Allograft cells and tumor cells. tumor cells.

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•Immunologically competent cells ( I C C ) :Immunologically competent cells ( I C C ) :

•Lymphocytes which are educated by Lymphocytes which are educated by

central central

lymphoid organs.lymphoid organs.

Recognizing capacity of antigen.Recognizing capacity of antigen.

Storage of immunological memory.Storage of immunological memory.

Immune response to specific antigen. Immune response to specific antigen.

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Functional cell

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Regulatory functions of T cells.Regulatory functions of T cells. Regulation of antibody production by Regulation of antibody production by

B- cells.B- cells.

Stimulation of helper and cytotoxic T Stimulation of helper and cytotoxic T

cells to participate in CMI by the cells to participate in CMI by the

production of IL-2.production of IL-2.

Imbalance betweenImbalance between T4 T4 and and T8T8 cells cells

results in Autoimmunity or results in Autoimmunity or

immunodeficiency. immunodeficiency.

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Effector functions:Effector functions:

Cytotoxicity of CD8 cells. Cytotoxicity of CD8 cells.

Activates macrophages to mediate delayed Activates macrophages to mediate delayed

hypersensitivity. hypersensitivity.

To produce memory T cells.To produce memory T cells.

Destroy the virus- infected cells. Destroy the virus- infected cells.

Graft rejection, tumor destruction. Graft rejection, tumor destruction.

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Cells, with ability to Cells, with ability to

respond rapidly for respond rapidly for many many

years after the initial years after the initial

exposure to an exposure to an antigen.antigen.

Characteristic features:

Live for many years.

Enhanced secondary

response.

Activated by small quantity of antigen.

Activated memory cells

produce large quantities of interleukins.

Memory cellsMemory cells

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Ag + MHC protein on Ag + MHC protein on

APC TCR on T-cell APC TCR on T-cell

Production of Production of IL-1IL-1 from from macrophages.macrophages.

T-cell activationT-cell activation

B7 protein on APC + CD28 B7 protein on APC + CD28 on helper T-cell on helper T-cell

Production of Production of IL-2IL-2 from from

T4 - cells.T4 - cells.IL-2 is responsible for regulatory,effector and memory functions of t4 cellsIL-2 is responsible for regulatory,effector and memory functions of t4 cells

Responsible for regulatory ,

effector and memory

functions of T-cells.

CTLA-4 (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 homeostasisMutant T-cells which lack CTLA-4 & responsible for autoimmune disease.

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B – cell maturationB – cell maturationPro – B cellPro – B cell ( From Lymphoid progenitor) ( From Lymphoid progenitor)

Pre – B cellPre – B cell

Mature B – Cell Mature B – Cell (Virgin B-cell)(Virgin B-cell) Migrate Migrate to peripheralto peripheral lymphoid tissue lymphoid tissue

Transformed into Transformed into PLASMA CELLPLASMA CELL

Contact with AntigenContact with Antigen

Rearrangement of DNARearrangement of DNA .Express Express receptors for IgM, IgG, IgA, IgE &receptors for IgM, IgG, IgA, IgE & for hormones.for hormones. .

Self Self tolerancetolerance..

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PLASMA CELLS:PLASMA CELLS:

Antibody secreting cellAntibody secreting cell(Ig (Ig factory)factory)Usually found in the Usually found in the Bone Bone Marrow, Marrow,

Perimucosal lymphoid Perimucosal lymphoid tissuetissue. . Life span 30 days. 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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T – CellT – Cell B – CellB – Cell 1). 1). LocationLocation:: Thoracic ductThoracic duct Spleen Spleen Thymus. Thymus. 55 – 60% 55 – 60%

96% 96%

Production, maturation: BM, ThymusProduction, maturation: BM, Thymus B M B M 2). Thy antigen2). Thy antigen + + - - 3). CD3 receptor3). CD3 receptor + + - - 4). Surface Ig4). Surface Ig - - + + 5). S RBC rosette5). S RBC rosette + + - - 6). E A 6). E A CC rosette rosette - - + + 7). Blast transformation 7). Blast transformation with with

anti – CD3anti – CD3 + + - - anti – Ig anti – Ig - - + +

EndotoxinEndotoxin - + - + 3131

NULL CELLSNULL CELLS ((Natural killer Natural killer cells). cells).

Large granular lymphocytes, Large granular lymphocytes,

Lack CD3, surface Lack CD3, surface

immunoglobulin markers & immunoglobulin markers & TCRTCR

Constitutes 3-5% of Constitutes 3-5% of

peripheral lymphocytesperipheral lymphocytes

Thymus not required for Thymus not required for

development.development.

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Functions:Functions: Kills malignant cells & virus infected cells by Kills malignant cells & virus infected cells by apoptosis.apoptosis.

Cytotoxicity is not M H C restricted. Cytotoxicity is not M H C restricted.

Mechanism of killing is by cytotoxins like Mechanism of killing is by cytotoxins like perforins perforins and granzymes.and granzymes.

Active in severe combined Active in severe combined immunodeficiencies.immunodeficiencies.

Activated by IL-2 and Interferons. Activated by IL-2 and Interferons. 3333

Antigen Presenting Cells (APC)Antigen Presenting Cells (APC)

1.Macrophages:1.Macrophages:

Blood: Monocytes. Blood: Monocytes.

Tissues: Lungs - Alveolar macrophages. Tissues: Lungs - Alveolar macrophages.

Liver- Kupffer cells Liver- Kupffer cells

Skin- Langerhans cells Skin- Langerhans cells

Spleen- Sinusoidal cells. Spleen- Sinusoidal cells.

Brain - Microglial cells. Brain - Microglial cells.

Joints - Synovial cells. Joints - Synovial cells.

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CENTRAL ROLE OF MACROPHAGE

IL-1, IL-8 & TNF

IL-1

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Another variety of Another variety of

antigen presenting antigen presenting

cellscells to T – cells. to T – cells.

Derived from BM.Derived from BM.

Present in Present in

1.Peripheral blood.1.Peripheral blood.

2.Lymph node.2.Lymph node.

Dendritic cells.

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Granulocytes Granulocytes (Microphages)(Microphages)

Neutrophil: Phagocytic role in acute inflammationrole in acute inflammation

Eosinophil:Phagocytic & motile. Parasite killing with

hydrolytic enzymes. Basophil:

Blood and tissues(Mast cells) Not phagocytic.

Receptors for Fc portion of Receptors for Fc portion of Ig Ig EE . .

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TCR are unable to recognize free TCR are unable to recognize free

antigens.antigens.

To be cleaved into small peptides and To be cleaved into small peptides and

must must

be embedded within a specific be embedded within a specific

“molecular “molecular

groove”groove” (located on MHC molecule) for T- (located on MHC molecule) for T-

cell cell

response…..response…..MHC restriction.MHC restriction.

HLA complex

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HLA complex located on HLA complex located on

short arm of short arm of chromosome-6chromosome-6Molecules coded by MHC Molecules coded by MHC

are classified into three are classified into three

groups Class I,II and III.groups Class I,II and III.

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1.MHC class I molecules1.MHC class I molecules

Fibroblasts, Fibroblasts,

HepatocytesHepatocytes

Lymphocytes, Lymphocytes,

NeuronNeuron

2.MHC class II molecules2.MHC class II molecules

Stromal cells in BMStromal cells in BM

Dendritic Dendritic

cells,Macrophagescells,Macrophages 4040

Cytokines:Cytokines:Non antibody molecules.Non antibody molecules.Produced by ……Produced by ……

Lymphocytes, monocytes, keratinocytes,Lymphocytes, monocytes, keratinocytes,

Endothelial cells and thymic epithelial cells.Endothelial cells and thymic epithelial cells.Glycoproteins.Glycoproteins.Target cellsTarget cells : Neutrophils : Neutrophils

MacrophagesMacrophages

LymphocytesLymphocytes

Endothelial cells Endothelial cells

Fibroblasts.Fibroblasts.

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Types:Types:

InterleukinsInterleukins

TNFTNF

InterferonsInterferonsColony stimulating factorsColony stimulating factors..

Functions:Functions:

Control of lymphocyte growth.Control of lymphocyte growth.

Activation of innate immunity.Activation of innate immunity.

Control of hemopoiesis.Control of hemopoiesis.4242

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Further proceed to Further proceed to understand the basis of understand the basis of

immune responseimmune response