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Basic immunology
Lecture 8.
Inflammatory reaction
Timea Berki
•  Local acute inflammation
InnateandAdapEveImmunity
Fig.1-1
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RoutesofAnEgenEntry
Fig.6-3
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AcEvaEonoftheimmunesystem
Fig.2-6
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2011 byby
Saunders,
an imprint
Elsevier Inc.o
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
©©2012
Saunders,
anof imprint
Effectorphase:cellsandanEbodiesreachthe
siteofinfecEon
Fig.2-6
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2011 byby
Saunders,
an imprint
Elsevier Inc.o
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
©©2012
Saunders,
anof imprint
Acute, local inflammation:
- Infection or tissue-injury initiate the cascade of non-specific reactions
-  Immediate reaction
-  Its role is to inhibit the spreading of infection and tissue injury
Celsus: 4 signs of inflammation: - rubor (red), calor (hot), dolor (painfull),
tumor (swelling) + functio laesa (loss of function)
3 main events: - Vasodilation – minutes
- Increased capillary permeability, fluid efflux, oedema
- Phagocytes migration: - hours
Goldsby RA, Kindt TJ, Osborne BA:
Kuby Immunology 4th Edition, 2000.
Molecular mediators of inflammation
Plasma enzyme mediators:
- kinin kallikrein system
-  Fibrinolytic system
-  Complement cascade
-  Clotting cascade
Lipid mediators:
leukotrienes,
prostaglandins (PGE)
Chemoattractants:
- Chemokines: IL-8
- Complement components
-  PAF (platelet activating
factor)
Inflammatory cytokines:
IL-1, IL-6, TNFalpha
Goldsby RA, Kindt TJ, Osborne BA:
Kuby Immunology 4th Edition, 2000.
Molecular mediators of inflammation
Initation of acute inflammation
Goldsby RA, Kindt TJ, Osborne BA:
Kuby Immunology 4th Edition, 2000.
MaturaEonofMacrophagesandDCs
Fig.2-2
Copyright
2011 byby
Saunders,
an imprint
Elsevier Inc.o
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
©©2012
Saunders,
anof imprint
Role of macrophages in acute inflammation:
classical activation
Resting macrophage: à
Phagocytosis
LPS
Activated macrophage: à antigenpresentation, MHCII ↑
cytokine-production
IFNγ
Hyperactivated macrophage: à citotoxicity
(TNFα)
MHCII ↓
Abbas, Lichtman, Pillai: Cellular and
Molecular Immunology 7th Edition, 2012.
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.
Activated macrophages produce infalmmatory
cytokines
LPS originated from Gram – bacterium LPS activates the macrophages, those
produce various cytokines
Local effects
Activation of
endothel and
effector
lymphocytes
Chemotaxis of
leukocytes,
Activation of
effector cells
Activates vascular
endothelium and
increase vascular
permeability
Lymfocyteactivation,
Increased
antibody
production
Systemic effects
fever,
IL-6 production
GM-CSF
Complement
IFNα
fever,
septic shock
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.
fever,
Production of acutephase-proteins
Activates NK-cells,
Th cells induce
Th1 differentiation
•  Extravasation, homing (leukocyte
migration)
FuncEonsServedbyLeukocyte
MigraEon
Fig.3-1
All lymphocyte circulates approx. 1-2 times per day.
Copyright
2011 by
an imprint
Elsevier Inc.
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© ©2012
bySaunders,
Saunders,
anofimprint
of
LeukocyteRecruitmentIntoTissues
Fig.3-3
Copyright
2011 by
an imprint
Elsevier Inc.
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© ©2012
bySaunders,
Saunders,
anofimprint
of
Neutrophil extravasation through the inflamed
endothelium
1. Selectin-mediated
rolling
Goldsby RA, Kindt
TJ, Osborne BA:
Kuby Immunology
4th Edition, 2000.
2. Chemoattractant
mediated activation
3. Integrin-mediated 4. Transendothelial
adhesion
migration
IntegrinAcEvaEonbyChemokines
Fig.3-2
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2011 by
an imprint
Elsevier Inc.
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© ©2012
bySaunders,
Saunders,
anofimprint
of
Chemokine action
Migration of memory (effector) lymphocytes
Inflammatory tissue
Goldsby RA, Kindt TJ, Osborne BA:
Kuby Immunology 4th Edition, 2000.
Outcomes of acute inflammation
Polarization of macrophages
Abbas, Lichtman, Pillai: Cellular and
Molecular Immunology 7th Edition, 2012.
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.
•  Systemic inflammation
Local and systemic effects of TNF
TNF inhibitors,
Steroids
Abbas, Lichtman, Pillai: Cellular and
Molecular Immunology 7th Edition, 2012.
Systemic acute inflammation = acute phase reaction
Bone marrow
Goldsby RA, Kindt TJ, Osborne BA:
Kuby Immunology 4th Edition, 2000.
Acute phase proteins in serum
Nobel Laureates in 2011 for medicine and physiology
Jules A. Hoffmann
Bruce A. Beutler
Ralph M. Steinmann