IMMUNOLOGY BASICS Lactation Biology Animal Science 337 Leo Timms Iowa State University

IMMUNOLOGY BASICSLactation Biology

Animal Science 337

Leo Timms

Iowa State University

MEANS OF AQUIRING IMMUNITY

1. ACTIVE: make own antibody

chance encounter w/Ag

a) natural

pregnancy

vaccination

b) artificial

introduce Ag via trt.

MEANS OF AQUIRING IMMUNITY

2. PASSIVE: transfer preformed antibody

a) natural : mother to fetus (6 mo protection) placental vs. colostral

b) artificial: immune therapy

Type of immune response

• Innate• defense we are

born with– phagocytic

cells– complement

proteins– anatomical *– physiological *

• Adaptive/acquired• defense that

develops with exposure/time – serum

antibodies– T cells (CMI)

* 1st line of defense!!!

Mechanisms of immunity:

• Cellular

– cells responsible for protection

– lymphocytes

– phagocytes

• Humoral

– antibodies (in serum) are responsible for protection

Two Arms of The Immune System

Neutrophils Macrophages B lymphocytesT lymphocytes

Innate Immunity Adaptive Immunity

Phagocytes Lymphocytes

Antigenpresentation

TH1 or TH2 CytokinesTH1 Cytokines

chemokines

Antigenpresentation

TH1 Cytokines

Antibodies

pathogens pathogens

Cytotoxicity

© Jeanne L. Burton, Michigan State University

Cells of the Immune System

Helper T cell (TH)

TH

Tissue macrophage

MPMN

Circulating neutrophil

Myeloid-lineage cells of the innate immune system

Lymphoid-lineage cells of the adaptive immune system

B cell

B

Cytotoxic T cell (TC )

TC

© Jeanne L. Burton, Michigan State University

• large cell (10-25 um dia)• main purpose: phagocytosis / kill• act non specifically• “chemotactic” capability• potent phagocytosis when activated by T lymphocytes (lymphokines)• Express Ag on surface to T / B cells

• multilobulated nucleus• lysosomal granules

• phagocytosis and kill• 1st white blood cell to infection site

• die and release contents• irritate surrounding tissue / recruit cells

• Phago. improved by opsonization with Ig

Circulating neutrophil

Inflammatory neutrophil

Extracellular bacteria

M

PMN

PMN

Tissue macrophage

IL-1, IL-6, IL-8,TNF-

IFN-TNF-

Infected Gland

Blood

Macrophages and neutrophils are needed to kill extracellular bacteria,such as those the infect the mammary glands of dairy cows

No memory M or

PMN cells develop

© Jeanne L. Burton, Michigan State University

Inflammation: part of innate immunity

• poor at phagocytosis• granules contain histamine / serotonin

• vasodilators / permeability factors• requires binding of 2 IgE for release

lymphocytes

• small (5 – 15 um)• No lysosomes : all “brain” until activated

• distinguish self from non self• specific : recognize specific antigens

• MEMORY**• need presentation of Ag by macrophage

cytokines• interactions - antigen - macrophage - T cell (Th) - B cell - cytokines

• interactions - antigen

- macrophage - T cell (Th) - cytokines

T helper (Th)T suppressor

T killerothers

Bob LuebkeITB/ETD/NHEERL

US EPA

Role of the Immune Systemin Homeostasis

• Bidirectional interaction with other systems– Reproduction

• “Self control” to prevent rejection of the fetus• Stimulation of placental growth• Linked to breeding success (rodents!)

– Endocrine• Immune (autoimmune) diseases

– CNS• Repair• Neurogenesis• Neurotransmitter/cytokine production and utilization

Bob LuebkeITB/ETD/NHEERL

US EPA

Basics of ImmunologyThe Immune ResponseThe Immune Response

Innate ImmunityInnate Immunity Adaptive (Acquired) ImmunityAdaptive (Acquired) Immunity-Phylogenetically ancient-Phylogenetically ancient-Limited recognition-Limited recognition-Rapid (minutes – hours)-Rapid (minutes – hours)-- No cell proliferation requiredNo cell proliferation required-Limited memory (? mammals) -Limited memory (? mammals)

-First appeared in jawed fishes-First appeared in jawed fishes- Infinite array of specificities- Infinite array of specificities- Slow (days)- Slow (days)-Requires proliferation and differentiation-Requires proliferation and differentiation-Long-lasting memory-Long-lasting memory

Bob LuebkeITB/ETD/NHEERL

US EPA

Basics of Immunology

• The adaptive immune response to antigen– Recognition as foreign

• First encounter: usually initiated by innate immune system cells

• Receptor-mediated

– Antigen processing and presentation• B cells, macrophages, dendritic cells

– Gene transcription, mediator release, cellular proliferation and differentiation, effector protein synthesis

– All steps must work properly or function will suffer

Bob LuebkeITB/ETD/NHEERL

US EPA

Organs of the Immune System

Bone Marrow: source of immune system cells

Bob LuebkeITB/ETD/NHEERL

US EPA

Immune System Anatomy

Bob LuebkeITB/ETD/NHEERL

US EPA

Organs of the Immune SystemThymus: source of naive T cellsThymus: source of naive T cells

Bob LuebkeITB/ETD/NHEERL

US EPA

Fate of T Cells in the Thymus

Positive selection: optimal binding to self Ag prevents apoptosisPositive selection: optimal binding to self Ag prevents apoptosis

Negative selection: superoptimal binding to self Ag induces apoptosisNegative selection: superoptimal binding to self Ag induces apoptosis

Bob LuebkeITB/ETD/NHEERL

US EPA

B cells: Tolerance to “Self”

Anergy: low expression ofAnergy: low expression ofIgM on surface; can’t bind AgIgM on surface; can’t bind Ag

Clonal ignorance: too fewClonal ignorance: too fewcopies of Ag in the periphery copies of Ag in the periphery

Bob LuebkeITB/ETD/NHEERL

US EPA

Thymus size and architecture: Thymus size and architecture: May be very sensitive to xenobioticsMay be very sensitive to xenobioticsAlso sensitive to acute toxicityAlso sensitive to acute toxicity

Figure from IPCS: ENVIRONMENTAL HEALTH CRITERIA 180 Principles and Methods for Assessing Direct Immunotoxicity Associated with Exposure to Chemicals

Bob LuebkeITB/ETD/NHEERL

US EPA

Organs of the Immune SystemSpleen: Antigen trapping and presentation,Spleen: Antigen trapping and presentation,

clonal expansion, cellular exportclonal expansion, cellular export

Bob LuebkeITB/ETD/NHEERL

US EPA

Organs of the Immune SystemLymph nodes: Antigen trapping and presentation,Lymph nodes: Antigen trapping and presentation,

clonal expansion, cellular exportclonal expansion, cellular export

Bob LuebkeITB/ETD/NHEERL

US EPA

Cells of the Immune SystemInnate Immune System: GranulocytesInnate Immune System: Granulocytes

Neutrophil (“PMN”)Neutrophil (“PMN”)First respondersFirst respondersPhagocytosis and killing Phagocytosis and killing of bacteriaof bacteriaInflammationInflammation

EosinophilEosinophilAllergyAllergyKilling parasite larvae Killing parasite larvae

BasophilBasophilCirculating mast cells Circulating mast cells Allergy/anaphylaxisAllergy/anaphylaxis

Bob LuebkeITB/ETD/NHEERL

US EPA

Cells of the Immune SystemInnate Immune System: GranulocytesInnate Immune System: Granulocytes

Neutrophil (“PMN”)Neutrophil (“PMN”)First respondersFirst respondersPhagocytosis and killing Phagocytosis and killing of bacteriaof bacteriaInflammationInflammation

Bob LuebkeITB/ETD/NHEERL

US EPA

Cells of the Immune SystemInnate Immune System: MonocytesInnate Immune System: Monocytes

Monocyte/macrophageMonocyte/macrophage

Macrophage with ingested Macrophage with ingested asbestos fiber asbestos fiber (encarta.msn.com)(encarta.msn.com)

Phagocytosis and killing of bacteriaPhagocytosis and killing of bacteriaAntigen processing Antigen processing InflammationInflammation

©Dennis Kunkel Microscopy, Inc.

Bob LuebkeITB/ETD/NHEERL

US EPA

Cells of the Immune SystemAdaptive Immune System: LymphocytesAdaptive Immune System: Lymphocytes

Activated B cellActivated B cellPeripheral bloodPeripheral blood Activated T cell (SEM)Activated T cell (SEM)

B cells: Mature into plasma cells, secrete antibody (IgM, IgG, IgA, IgE, IgD)B cells: Mature into plasma cells, secrete antibody (IgM, IgG, IgA, IgE, IgD)T cells: T helper - produce stimulatory and regulatory cytokinesT cells: T helper - produce stimulatory and regulatory cytokinesT cells: T cytotoxic/suppressor – contact-dependent cytotoxicity, T cells: T cytotoxic/suppressor – contact-dependent cytotoxicity, regulation of immune responseregulation of immune responseNK cells: direct killing of cells (innate arm of IS)NK cells: direct killing of cells (innate arm of IS)

Cell Mediated Immunity

T Lymphocytes

• Recognize Ag only with MHC proteinsRecognize Ag only with MHC proteins

• Produce Lymphokines (not antibodies)Produce Lymphokines (not antibodies)

• Cell Mediated ImmunityCell Mediated Immunity

T-Cell Subpopulation

CD-4CD-4 CD-8CD-8

Help B-Cells produce AntibodyHelp B-Cells produce Antibody Cytotoxicity ReactionsCytotoxicity Reactions

T-CellT-Cell

Cell-mediated immunity

• T cells can only recognize and respond to processed fragments of protein.

• T cells are suited for cell to cell interaction and target body cells infected by virus, bacteria and abnormal or cancerous body cells or cells that are transplanted or infused.

Cytotoxic T cells

Cell-mediated immunity: T-cells

• Activation of T cells—T cell receptors bind to antigen presented by the antigen-MHC complex.

• CD4 and CD8 proteins interact with antigen and help maintain MHC-antigen coupling.

• Types of T-cells– Helper T cells (CD4)– Cytotoxic T cells (CD8)– Memory T-cells

05 Dec. 200705 Dec. 2007 Immunity.ppt 3737

Antigen-presenting cells

Antigen-presenting cells

T-Cell Activation

“ “ Activation and clonal expansion of CD4 and CD8 Cells”Activation and clonal expansion of CD4 and CD8 Cells”

Goal: Goal:

T cell activation T cells must accomplish a double recognition.

• They must recognize nonself (antigen) and self (MHC protein of a body cell) (Antigen recognition) .

• Co-stimulation by binding to other proteins on APC

• Cytokines (IL 1 and 2) are released by APC or T cell following co-stimulation

Antigen recognition and co-stimulation lead to activation.

Antigen binding without co-stimulation leads to anergy in T and B cells.

Class II MHC

Peptide

TCR

CD4

Specific Antigen RecognitionSpecific Antigen Recognition

APCAPCAPCAPC

B7B7B7B7MHC IIMHC II

CD24CD24

CD28CD28CD28CD28TCRTCRTCRTCR TCRTCRTCRTCR

T-CellT-CellT-CellT-Cell

Activated T cell

• Activation leads to enlargement, differentiation and proliferation of T cells.

• T cells that are reproduced are clones of originally activated T cell.

• Activation, differentiation and proliferation occurs in secondary lymph organs and tissue.

• Activation leads to release of inflammatory cytokines.

T-Cell Activation

Lymphocyte activationLymphocyte activation

(periarteriolar sheats)(periarteriolar sheats) paracortical areaparacortical area

T Cell-mediated Immunity

Principal function-Response to intracellular pathogens and cells

expressing foreign antigens

Recirculation-Naïve T cells circulate between the blood stream and the

lymphatic system

Antigen presentation-Naïve T cell cells only respond to APCs

Priming of T Cells

• Three types of effector T cells– CD8 (TC)

– CD4 (TH1)

– CD4 (TH2)

• Each type– Responds to different types of Ags– Activated by different Ag presentation– Has different effector function

T Cell Effector Types• CD8

– Viruses and intracellular bacteria– MHC I– Cytotoxic effector cells

• CD4 TH1

– Bacteria and parasites in APCs– MHC II– Effectors activate macrophages, CTLs and induce B cells to

produce opsonins

• CD4 TH2

– Extracellular bacteria and toxin producers– MHC II– Activate B cells to produce multiple antibody classes

T- Helper Subsets Different types of T- Helper Different types of T- Helper subsetssubsetsTh-1Th-1• Hypersensityvity ReactionsHypersensityvity Reactions• Produce IL2 and Gamma IFNProduce IL2 and Gamma IFN• Cell mediated cytotoxicity (virucidal activity)Cell mediated cytotoxicity (virucidal activity)

Th-2Th-2• Principal role in B-cell activationPrincipal role in B-cell activation• Produce IL-4 and IL-5 (no IL-2 or Gamma Produce IL-4 and IL-5 (no IL-2 or Gamma IFN)IFN)• Antibody mediated activity (bactericidal Antibody mediated activity (bactericidal activity)activity)

APCs

• Dendritic cells

• Macrophages

• B cells

كمن ” القيه فهو حسنا وعدا وعدناه أفمنثم الدنيا الحياة متاع متعناه

المحضرين “القصص 61 من القيامة يوم هو

Dendritic Cells

• Antigen presentation is sole function

• Antigenic uptake is followed by migration to lymph nodes

• Expression of MHC I, MHC II and B7• Loses phagocytic property• Secretes chemokines

Macrophages

• Involved in both innate and adaptive immunity

• May destroy pathogens or present Ag to T cells

• Expression of MHC I, MHC II and B7

• Scavenges dead cells

B Cells

• Binds soluble antigens

• Constitutively expresses MHC II

• Induced to express B7

NK Cells

• 5% of lymphocytes

• Nonspecific cytotoxicity

• No TCR/CD3

• Not MHC restricted

• No memory

Immunity.ppt 6161

Cell-mediated immunity• T cells can only recognize and respond to

processed fragments of protein.

• T cells are suited for cell to cell interaction and target body cells infected by virus, bacteria and abnormal or cancerous body cells or cells that are transplanted or infused.

• Antibodies can only inactivate an antigen and NOT destroy it.

• Antibodies prepare an organism for destruction by innate defenses.

T-Cell Activation• Lymphokines produced by lymphocytes

• Cytokines produced by other cells

Autocrine Stimulation

Paracrine Stimulation

HUMORAL IMMUNITY (Ab or AMI)

• Antigen + Macrophage + T cell + B cell

• Antibodies or Immunoglobulins

• SPECIFICITY!• MEMORY

• (immunity: short, long, or no term)

cytokines

Antibodies are produced by antigen-activated B lymphocytes and, in cattle, come in six isotypes

Fab = antigen binding = Fab

Fc = biological function

IgM ()IgG1 (1)IgG2 (2)IgG3 (3)IgA (IgE ()

variable region

constant region

H H

LL

(Fc-

© Jeanne L. Burton, Michigan State UniversityL = light chainH + heavy chain

Antibodies

Functions• Variable region (Fab) bind specifically-neutralize, ppt

or agglutinate

**** antigen binding region

• Constant region (Fc) –

- activate effector cells or

complement - opsonin end

Immunoglobulin classes

• IgD is attached to B-cell plasma membrane

• IgM is released during primary response

• IgG functions in late primary and secondary response

• IgA found in body secretions

• IgE causes release of histamine

Antibody Isotypes-5

Antibody defense: PLANe

• Precipitation

• Lysis: Complement fixation and activation

• Agglutination

• Neutralization

• Enhancing phagocytosis

Opsonization

• Free IgG binds Fc receptors with low affinity

• IgG bound to Ag, binds to Fc receptors with high affinity

• Cross-linking receptors sends signal

IgG:

IgG1 IgG2

• Principle Ab in serum• 14 – 18 mg / ml• IgG1: 11 mg/ml• IgG2: 7 mg/ml

• fixes complement• late response to Ag

IgG1 IgG2 • selective transfer (colostrum) 10 opsonin• fetal / neonatal defense for• toxin inactivation phagocytosis• principal milk / colostrum Ig (farm species)

IgM

IgE

• largest Ig• pentamer

• serum (1-3 mg/ml)• fixes complement• 1st Ig produced to Ag challenge!

• Binds to mast cells basophils

• ACTIVATION• RELEASE OF

- histamine - serotonin

The various Fc portions of antibody molecules have very different biological functions, including pathogen blocking, complement fixation, toxin neutralization, and opsonization of bacteria for

enhanced phagocytosis by neutrophils and macrophages

IgG1 = endotoxin neutralization &

complement fixation

IgG2 = opsonization & neutrophil phagocytosis

IgM = blocking & complement

fixation

serum complement

© Jeanne L. Burton, Michigan State University

IgA

• 3 different forms in serum• different form in secretion ( secretory piece)

• serum: 1-3 mg/ ml• activates complement: serum (yes) milk (no)

Secretory piece

• local immunity and secretions• prevents bacterial adherence• maternal milk: very important• primary Ig in colostrum (humans)!

Type Number of ag binding sites

Site of action Functions

IgG 2 •Blood

•Tissue fluid

•CAN CROSS PLACENTA

•Increase macrophage activity

•Antitoxins

•Agglutination

IgM 10 •Blood

•Tissue fluid

Agglutination

IgA 2 or 4 •Secretions (saliva, tears, small intestine, vaginal, prostate, nasal, breast milk)

•Stop bacteria adhering to host cells

•Prevents bacteria forming colonies on mucous membranes

IgE 2 Tissues •Activate mast cells

HISTAMINE

•Worm response

CYTOKINES / LYMPHOKINES• Small polypeptide messengers

• very powerful in low doses• multiple uses

• hormones1. Interleukins2. Interferon: viral3. Colony Stimulating factors: GCFS4. Tumor Necrosis Factor (TNF) inflammation / cell movement / traffic

OTHER IMMUNE FACTORS

• Complement: 9 specific serum proteins

- interaction of components provide

numerous biological events

• Lactoferrin: Iron binding protein

*** competes with bacteria for iron

• Lactoperoxidase ( LP/ SCN- / H2o2 syst.)

** antioxidant / oxygen radicals

Cell Adhesion Molecules

• Selectins

• Mucins

• Integrins

• Immunoglobulin superfamily

Torloni MD

VCA

MVC

AM

VCA

MVC

AM

ICAM-1ICAM-1ICAM-1ICAM-1 P-

sele

ctin

P-se

lect

in

P-se

lect

in

P-se

lect

in

Adhesion MoleculesAdhesion Molecules

LFA1LFA1

LFA3LFA3

APCAPCT-CellT-Cell

CD2CD2

Endothelial CellEndothelial Cell

B7B7

CD28CD28

CD4CD4TCRTCR

IL1IL1

T-CellT-Cell

IL2IL2IL2IL2

Clonal ExpansionClonal Expansion

IL2IL2IL2IL2

MacrophageMacrophageCD4 CellCD4 Cell

IL1IL1CD4CD4

CD4CD4

MHC IIMHC II

IL2IL2receptorsreceptors

IL2IL2

IL2IL2

B-CellB-Cell

IL2IL2IL4IL4

IL5IL5

IL6IL6 ProlifereationProlifereation

Plasma CellPlasma Cell Memory B CellMemory B Cell

1- CD4 Cells are stimulated by contact with 1- CD4 Cells are stimulated by contact with antigenantigen

2- T-Cell finds B-Cell with that specific 2- T-Cell finds B-Cell with that specific AntigenAntigen

2- T-Cell causes that specific B-Cell to 2- T-Cell causes that specific B-Cell to expandexpand

Triggering of IL1

B7B7

CD28CD28

CD4CD4TCRTCR

IL1IL1

IL2IL2IL2IL2

Stimulation of B-Cells

B-CellB-Cell

T-CellT-Cell

ICAM-1

ICAM-1

ICAM-1

ICAM-1

LFA1LFA1

LFA3LFA3CD2CD2

No antigen specificityNo antigen specificity

1- Binding1- Binding

2- Release2- Release

T-CellT-Cell

ICAM-1

ICAM-1

ICAM-1

ICAM-1

LFA1LFA1

LFA3LFA3CD2CD2

1- Binding1- Binding1- Binding1- Binding

B-CellB-Cell

2- Antigen specificity2- Antigen specificity2- Antigen specificity2- Antigen specificity

B-CellB-Cell

ProlifereationProlifereationPlasma CellPlasma Cell

Memory CellMemory Cell

3- B-Cell Proliferation3- B-Cell Proliferation3- B-Cell Proliferation3- B-Cell Proliferation

First exposure Re-exposure

Time

Activation of Cytotoxic T-Cells

• Recognize Ag in conjunction with MHC-1Recognize Ag in conjunction with MHC-1• All host cells express class I antigensAll host cells express class I antigens• Serve as 1st line of defense against changed “self” antigens Serve as 1st line of defense against changed “self” antigens

- - Virus infected cells Virus infected cells - Tumor cells- Tumor cells

TNF-TNF-

T-Cells with same specificityT-Cells with same specificity

B Cell (plasma cell)

B Cell (plasma cell)

IgG, IgM, IgA, IgE, IgDIgG, IgM, IgA, IgE, IgD

Mac

roph

age

B Cell

T Cell TdTH

NK Cell

Mast Cell

T8 (cytotoxic)

T8 (suppressor)

MIF ,MAF

CF

IL-1

IL-1

BCDF,

BCGF

IL-1

IL-1

IL-2, IFN

IL-2IL-2

Cytokines

Effect

1) TNF-1) TNF- produced produced

2) TNF-2) TNF- binds to binds to receptorreceptor

3) Recptor and TNF- 3) Recptor and TNF- are internalizedare internalized

4) TNF- 4) TNF- + receptor + receptor are degradedare degraded

5) Endonuclease is activated5) Endonuclease is activated

outside celloutside cell

cytoplasmcytoplasm

6)Endonuclease cuts DNA6)Endonuclease cuts DNA

7) Fragmented DNA appears in cytoplasm7) Fragmented DNA appears in cytoplasm

8) Cell function is disrupted8) Cell function is disrupted

Activation of lysosymes &Activation of lysosymes &

production of free radicalsproduction of free radicals

also occurs.also occurs.

Role of Cytokines : Interleukin-1

MacrophageMacrophage

MonocyteMonocyte

LPSLPS

ToxinsToxins

Foreign materialForeign material

IL-2 productionIL-2 production

IL2 receptor productionIL2 receptor production

B-Cell ProliferationB-Cell Proliferation

NK Cell ActivityNK Cell Activity

Acute phase reactantsAcute phase reactants

FeverFever

PMN demarginationPMN demargination

PMN degranulationPMN degranulation

Prostaglandin release (fibroblasts & monocytes)Prostaglandin release (fibroblasts & monocytes)

Muscle wastingMuscle wasting

DepressionDepression

Sleep disturbanceSleep disturbance

Loss of appetiteLoss of appetite

Chronic Effects:Chronic Effects:

Acute Effects:Acute Effects:

Role of Cytokines : Interleukin-2

• Detected 2 - 6 hrs after after antigen stimulationDetected 2 - 6 hrs after after antigen stimulation

• Short half lifeShort half life

• Amplifies Cellular Immune response locallyAmplifies Cellular Immune response locally

• Stimulates B-Cell proliferationStimulates B-Cell proliferation

• Induces IgGInduces IgG22 production production

• activity of NK cellsactivity of NK cells

• Induces LAK cell activity*Induces LAK cell activity*

*Kills cells resistant to NK cell - independent of MHC *Kills cells resistant to NK cell - independent of MHC

Role of Cytokines : Interleukin-3

• “ “ Hemopoiteic growth factor”Hemopoiteic growth factor”

- Myeloids- Myeloids- Megakariocytic - Megakariocytic - Erythrocytic- Erythrocytic- T- Cell- T- Cell- B- Cell- B- Cell

Stimulates Proliferation of Hematopoietic Precursors: Stimulates Proliferation of Hematopoietic Precursors:

Half Life = Less than 30 minutesHalf Life = Less than 30 minutes

permeabilitypermeability

phagocytosisphagocytosis

SEM Picture of a Mast CellSEM Picture of a Mast Cell

TEM of a Mast CellTEM of a Mast Cell

YYYYYY

YYYY

YY

AAAntigens from plasmaAntigens from plasmabind to pre-formed IgEbind to pre-formed IgEattached to mast cellsattached to mast cells

YY

YYYYYY

YY

YYBB

Antigen binding causesAntigen binding causesactivation of histamineactivation of histaminerelease mechanism fromrelease mechanism frommast cells.mast cells.

YY

YYYYYY

YY

YY

CC

Histamine is releasedHistamine is releasedfrom mast cells and from mast cells and causes increase in causes increase in vascular permeabilityvascular permeability

Pluripotential Stem Cell

Committed Stem Cells

CFU-MegCFU-Meg

Meg

akar

yocy

te

Meg

akar

yocy

te

Gra

nulo

cyte

Gra

nulo

cyte

Mon

ocyt

e

Mon

ocyt

e

Basop

hil

Basop

hil

Eosin

ophi

l

Eosin

ophi

l

RBCRBC

LymphocytesLymphocytes

BB TT

CFU-BaCFU-Ba CFU-EoCFU-Eo CFU-ECFU-E CFU-BCFU-B CFU-TCFU-T

BFU-EBFU-E

CFU-MsCFU-Ms

Mas

tM

ast

CFU-GMCFU-GMCFU-GMCFU-GM

CFU-GCFU-GCFU-GCFU-G CFU-MCFU-M

IL3 IL3 IL3 IL3

Role of Cytokines : Interleukin-4

• Produced by T-Helper cells Produced by T-Helper cells • Activation / Proliferation of B cells previously stimulated by antigenActivation / Proliferation of B cells previously stimulated by antigen• Enhances expression of MHC II moleculesEnhances expression of MHC II molecules• Induces production of CD-23 on B Cells surfaceInduces production of CD-23 on B Cells surface• Induces IgG 1 synthesisInduces IgG 1 synthesis• Essential in IgE formation Essential in IgE formation • Role in converting other cytokinesRole in converting other cytokines• Similar to IL-13Similar to IL-13

“ “ promotes resting B-Cell expansion”promotes resting B-Cell expansion”

IL-4IL-4

B-CellB-Cell

ProlifereationProlifereation

Plasma CellPlasma CellMemory CellMemory Cell

IL-5IL-5TThh-Cell-Cell

Role of Cytokines : Interleukin- 5Role of Cytokines : Interleukin- 5

IL-5IL-5

IL5 induces production of IGM and class IL5 induces production of IGM and class switching to IGAswitching to IGA

Eosinophil productionEosinophil production

IL-6IL-6 IgAIgA

IgMIgM IgGIgG