immunity to infectious agents md class, 18-aban-93 presented by: farshid noorbakhsh md phd in the...
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![Page 1: Immunity to infectious agents MD Class, 18-Aban-93 Presented by: Farshid Noorbakhsh MD PhD In the Name of God](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d0c5503460f949e052c/html5/thumbnails/1.jpg)
Immunity to infectious agents
MD Class, 18-Aban-93
Presented by: Farshid Noorbakhsh MD PhD
In the Name of God
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Dr F Noorbakhsh, Dept Immunol, TUMS
Type of the microbe
Target organ
Localization(extra- or intracellular)
Type of Immune response
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Dr F Noorbakhsh, Dept Immunol, TUMS
Protozoa (uni-cellular)
Metazoa (multi-cellular)
Type of the microbe
Bacteria
Viruses
Fungi
Parasites
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Dr F Noorbakhsh, Dept Immunol, TUMS
Bacteria
Viruses
Fungi
Parasites
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Bacteria
Viruses
Fungi
Parasites
Extracellular Intracellular
Dr F Noorbakhsh, Dept Immunol, TUMS
E. Coli, Pneumococci, Salmonella
Mycobacteria
None All
Candida Histoplasma
Helminths Plasmodium
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Phagocytosed microbes Infected cell
Intra-vesicular Intra-cytosolic
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Bacteria
Viruses
Fungi
ParasitesDr F Noorbakhsh, Dept Immunol, TUMS
E. Coli, Pneumococci, Salmonella
Mycobacteria
None All
Candida Histoplasma
Helminths Plasmodium
Extracellular Intracellular
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Bacteria
Viruses
Fungi
Parasites
Extracellular Intracellular
I-Vesicular I-Cytosolic
All
Mycobacteria
PneumocystisHistoplasma
Plasmodium
Rickettsia,Chlamydia
Leishmania
Interstitial, blood, lymphepithelial
E.coli, Staph, Neisseria?
Candida
Helminths filaria
Staph, Strep, bacilli
Dr F Noorbakhsh, Dept Immunol, TUMS
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Extracellular Intracellular
I-Vesicular I-CytosolicInterstitial,
blood, lymphepithelial
Dr F Noorbakhsh, Dept Immunol, TUMS
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Dr F Noorbakhsh, Dept Immunol, TUMS
Phagocytosed microbes
1- Intravesicular microbes; intracellular killing
Cathionic proteins (cathepsins) damages bacterial cell wall
Lysozyme peptidoglaycal hydrolysis
Lactoferrin deprives bacteria of iron
Proteases digest microbial proteins
Oxygen-independent killing
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Dr F Noorbakhsh, Dept Immunol, TUMS
Activated macrophage
2- Activated phagocytes produce cytokines
TNF-α
Fever,
Anorexia,
Sickness behavior
Acute phase proteins (eg: CRP)
Neutrophil chemoattraction
Enhanced phagocytosis
Cytokine (IL1) production
Tumor cell lysis
TNF-α
TNF-α
TNF-α
TNF-α
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Dr F Noorbakhsh, Dept Immunol, TUMS
Phagocytosed microbes
CD4+ T cells
MHC Class2
3- Intravesicular microbes’ antigens are presented
CD8+ T cells
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Enhanced microbicidal activity
4- Intravesicular microbes, T cell activationIL-12
IFN-γ
NK cell
IL-12
IFN-γ CD40LCD40
Th1
CD28B7
IL-2
Enhanced protease activity, lower intravesicular pH ….
Th1
Th1
Th1
Th1
Th1
Production of ROS: O2-, OH-, H2O2, HClO-Oxygen-dependent killing
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Defense against intravesicular microbesIL-12
IFN-γ
NK cell
IL-12
IFN-γ CD40LCD40
Th1
CD28B7
IL-2
2NK-mediated macrophage
activation
3Th1-mediated macrophage
activation
1Initial
intravesicular killing
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Defense against intravesicular microbesIL-12
IFN-γ
NK cell
IL-12
IFN-γ CD40LCD40
TH1
CD28B7
IL-2
What happens if mechanism “1” works?
2NK-mediated macrophage
activation
3Th1-mediated macrophage
activation
1Initial
intravesicular killing
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Defense against intravesicular microbesIL-12
IFN-γ
NK cell
IL-12
IFN-γ CD40LCD40
TH1
CD28B7
IL-2
What happens if mechanism “1” works?
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Bacteria
Viruses
Fungi
Parasites
Extracellular Intracellular
I-Vesicular I-Cytosolic
All
Mycobacteria
PneumocystisHistoplasma
Plasmodium
Rickettsia,Chlamydia
Leishmania
Interstitial, blood, lymphepithelial
E.coli, Staph, Neisseria?
Candida
Helminths filaria
Staph, Strep, bacilli
Dr F Noorbakhsh, Dept Immunol, TUMS
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Dr F Noorbakhsh, Dept Immunol, TUMS
Interferon response against virusesIntracellular microbes (intra-cytosolic)
Antiviral state Antiviral stateAntiviral state
IFNα/β IFNα/βIFNα/β
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Dr F Noorbakhsh, Dept Immunol, TUMS
MHCI
Cytolysis by CD8+ lymphocytes
Intracellular microbes (intra-cytosolic)
CD8+ T cell
FAS FASL
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Dr F Noorbakhsh, Dept Immunol, TUMS
CD8+ T cell
MHCI
Cytolysis by NK cells
Intracellular microbes (intra-cytosolic)
Some viruses block MHCI expression
NK cell
Killer inhibitory receptor
MHCI
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Dr F Noorbakhsh, Dept Immunol, TUMS
MHCI
Cytokine production by CD8+ or NK cells
Intracellular microbes (intra-cytosolic)
MHCI
IFN-γIFN-γ
CD8+ T cell
NK cell
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Dr F Noorbakhsh, Dept Immunol, TUMS
MHCI
Intracellular microbes (intra-cytosolic)
MHCI
IFN-γIFN-γ
CD8+ T cell
CD8 T cell-mediated cell lysis
NK cell
NK-mediated cell lysis
IFNα/β
IFNα/β
Interferon response
IFNα/β
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IL-12
CD4+
CD8+CTL
MHC Class 2MHC Class 1
IFN-g
IFN-g
Pre-CTL
Escaping vesicle
Cross-presentation of Ag
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Bacteria
Viruses
Fungi
Parasites
Extracellular Intracellular
I-Vesicular I-CytosolicInterstitial,
blood, lymphepithelial
Dr F Noorbakhsh, Dept Immunol, TUMSDr F Noorbakhsh, Dept Immunol, TUMS
CD4- m
ediated Mφ
activation
NK- m
ediated Mφ
activation
Initial intravesicular killing
CD8- m
ediated cell lysis
NK- m
ediated cell lysis
Interferon response
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Dr F Noorbakhsh, Dept Immunol, TUMS
Now let’s look at immune defense against extracellular microbes!
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Bacteria
Viruses
Fungi
Parasites
Extracellular Intracellular
I-Vesicular I-Cytosolic
All
Mycobacteria
PneumocystisHistoplasma
Plasmodium
Rickettsia,Chlamydia
Leishmania
Interstitial, blood, lymphepithelial
E.coli, Staph, Neisseria
Candida
Helminths Filaria
Staph, Strep, bacilli
Dr F Noorbakhsh, Dept Immunol, TUMS
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Functions of different classes of antibodies
B CellsYYYYYYYYYY
YYY
Neutralization (mucosal)
YYYYYYYYY
F Noorbakhsh, Dept Immunology, TUMS
Neutralization(serum)
Opsonization & phagocytosis
Complement activation
Eos & mast cell degranulation
IgA IgG IgM IgE
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Dr F Noorbakhsh, Dept Immunol, TUMSYY B
cell
YYYY YY YY Y YYYYY
NK/ PMNs
Antibody-dependent cell cytotoxicity(ADCC)
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Dr F Noorbakhsh, Dept Immunol, TUMS
YY
B cell
YYYY YY YY Y Y
YYYY
Antibody-dependent cell cytotoxicity(ADCC)
NK/ PMNs
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Effector mechanisms of humoral immunity
B CellsYYYYYYYYYY
YYY
Neutralization (mucosal)
YYYYYYYYY
F Noorbakhsh, Dept Immunology, TUMS
Neutralization(serum)
Opsonization & phagocytosis
Complement activation
Eos & mast cell degranulation ADCC
IgA IgG IgM IgE
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IL-12
IFN-γ
IL-4
B Cells
YYYYYYYYYYYYY YYY YYY
IgG1IgG3IgG2
IL-4
IgE
TGF-β
IgA
TH1TH2
TH3
IL-10
Neutralization
Opsonization
Complement activationMucosal defense
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IL-4
TH2
B Cells
YYYYYYYYYYYYY YYY YYY
IL-4
IgE
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Dr F Noorbakhsh, Dept Immunol, TUMS
Mast cell Eosinophil
Defense against helminthsIL-4
TH2
B Cells
YYYYYYYYYYYYY YYY YYY
IL-4
IgE
IL-5
YY
YYY
YYYY YYY Y Y
Y YYY IgG4
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IL-12
IFN-γ
IL-4
B Cells
YYYYYYYYYYYYY YYY YYY
IgG1IgG3IgG2
IL-4
IgEIgG4
TGF-β
IgA
TH1TH2
TH3
IL-10
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IL-12
IFN-γ
IL-4
IL-4TGF-β
TH1TH2
TH3
TH17
IL-21,IL-23
TGF-β,IL-6
NeutrophilIL-17IL-22Antimicrobial peptides (AMPs) at epithelial
surfaces
IL-10
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Bacteria
Viruses
Fungi
Parasites
Extracellular Intracellular
I-Vesicular I-CytosolicInterstitial,
blood, lymphepithelial
Dr F Noorbakhsh, Dept Immunol, TUMSDr F Noorbakhsh, Dept Immunol, TUMS
Th17 IL22 epithelium AM
Ps
Th17 IL17 neutrophils
Th3 TGFβ B cell IgA
Th1 IFNγ B cell IgG
Th2 IL4 B cell IgE
CD4- m
ediated Mφ
activation
NK- m
ediated Mφ
activation
Initial intravesicular killing
CD8- m
ediated cell lysis
NK- m
ediated cell lysis
Interferon response
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B CellYY
Y
Y Y Y
Y
B Cell
CD4 T cell
B CellY
Y
Y
Y Y Y YY
Help from T cells (cytokines)
CD4 T cell
Help from T cells (cytokines)
Weak help
Strong help
Happens during primary response
Happens during secondary response
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Dr F Noorbakhsh, Dept Immunol, TUMS
Microbial evasion of immune response
Change in the immune
system
Change in the microbe
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Dr F Noorbakhsh, Dept Immunol, TUMS
Inhibition of phagolysosome formation: M Tuberculosis, L Pneumophila
Inactivation of ROS: M Leprae (phenolic glycolipid)
Disruption of phagolysosome: Listeria (hemolysin)
Immune evasion in intracellular/intravesicular pathogens
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Dr F Noorbakhsh, Dept Immunol, TUMS
MHCI
Immune evasion in Intracytosolic microbes
MHCI
IFN-γIFN-γ
CD8+ T cell
NK cell
IFNα/β IFNα/βIFNα/β
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Dr F Noorbakhsh, Dept Immunol, TUMS
CD8+ T cell
Adenoviruses block MHCI expressionAdenovirus
Adenovirus blocks MHCI expression!!
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Dr F Noorbakhsh, Dept Immunol, TUMS
Poxvirus blocks MHCI loading and produces decoy receptors
CD8+ T cell
Poxvirus blocks MHCI loading!!
Poxvirus
IFN-γPox virus produces decoy IFNγ receptors
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Dr F Noorbakhsh, Dept Immunol, TUMS
NK cell
CMV generates an MHCI homologCMVCMV generates an
MHCI homolog!
CMV blocks MHCI
expression!!
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TH1TH2
TH3
TH17
IL-12IL-4
IL-10
B cell
YYYYYYYYY
YYYYEBV
IL10 homolog IL10 homolog
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Dr F Noorbakhsh, Dept Immunol, TUMS
CD4
CD4+
CD28B7
How HIV suppresses immune response?
CD4+
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CD4
CD4+
CD28B7
HIV infects macrophages
Nef blocks MHCII expression!!
HIV infects CD4 T cells
Nef Nef
Nef blocks CD4 expression!!
Nef blocks CD28 expression!!
Finally, HIV kills CD4 cells!
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Dr F Noorbakhsh, Dept Immunol, TUMS
Viruses have different ways of immune evasion!
Poxvirus
HIV
Adenovirus
EBV
CMV
Blocks MHCII, CD4, B7, kills CD4 T cells
Blocks MHCI expression
Blocks MHCI loading, produces decoy receptors
Expresses MHCI homolog (to block NK cells)
Expresses IL10 homolog
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B CellsYYYYYYYYYY
YYYNeutralization
of AntigenOpsonization &
phagocytosisYYY
Complement activationADCC
YYYYYY
Immune evasion in extracellular pathogens
Resistance to phagocytosis
(pneumococcus)Inactivation of complement
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Dr F Noorbakhsh, Dept Immunol, TUMS
Microbial evasion of immune response
Change in the immune
system
Change in the microbe
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Dr F Noorbakhsh, Dept Immunol, TUMS
Genetic recombination
Change in microbial antigens
Antigenic drift/shift
Multiple antigenic variants
Antigenic variation during
life cycle
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Dr F Noorbakhsh, Dept Immunol, TUMS
Immune evasion via multiple antigenic variants of microbes (serotypes).
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Dr F Noorbakhsh, Dept Immunol, TUMS
Immune evasion via multiple antigenic variants of microbes (serotypes).
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Dr F Noorbakhsh, Dept Immunol, TUMS
Immune Evasion via antigenic drift/shift.
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Dr F Noorbakhsh, Dept Immunol, TUMS
Immune Evasion via antigenic drift/shift
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Dr F Noorbakhsh, Dept Immunol, TUMS
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Trypanosomes have a special way of escaping from immune response!
Sleeping sickness, caused by Trypanosoma brucei, Chagas disease, caused by Trypanosoma cruzi.
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Achilles heel! What if he had multiple copies of the heel?!
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Immune evasion via sequential DNA rearrangements of trypanosomal antigens
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Plasmodium’s antigenic variation during life cycle
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النجوم بمواقع اقسم ... فال
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Dr F Noorbakhsh, Dept Immunol, TUMS
QUIZتولید- 1 به منجر روند زیر های مسیر از لمفوسیت IgGکدامیک بوسیله
دهد؟ Bهای می نشان درستی به را.aAPC IL2 Th1 IL4 B cell IgG.b APC IL12 Th1 IL4 B cell IgG.cAPC IL2 Th1 IFNγ B cell IgG.dAPC IL12 Th1 IFNγ B cell IgG
در- 2 واقع ویروسهای مورد در معموال زیر دفاعی های روند از کدامیک
نمیدهد؟ رخ سیتوزول فضای.e Interferon response.fNK-mediated cell lysis.gCD8-mediated cell lysis.hmacrophage activation by NK cells