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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