Kindt • Goldsby • Osborne - York College of...
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Kuby IMMUNOLOGYSixth Edition
Kindt • Goldsby • Osborne
Chapter 2:Cells and Organs
of the Immune System
Copyright © 2007 by W. H. Freeman and Company
Review questions
• Compare and contrast lymphocytes and macrophages, discussing both morphological and functional aspects of their role in immunityimmunity.
• Compare the structure and function of the thymus and lymph node, IN DETAIL!! In addition, label the structures, describe the cells present and their activities.
questions
• Compare the primary and secondary immune response to the primary and secondary lymphoid organs.
• Is it possible for a clinical test to have high• Is it possible for a clinical test to have high sensitivity but low specificity? Explain.
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CELLS AND ORGANS OF THE IMMUNE SYSTEM
Leukocytes
Immune organs
• Primary organs: development and maturation• Thymus• Bone marrow• Secondary organs: Ag trapping and• Secondary organs: Ag trapping and presentation
• Lymph nodes• Spleen
Primary vs. secondary
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LeukocytesLeukocytes
• Adaptive: lymphocytes
• Others: accessories– Activation
C ki– Cytokines
Hematopoiesis
• Formation and development of red and white blood cells
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HematopoiesisHow to study hematopoiesis?
• HIM environment: hematopoietic‐inducing microenvironment
• Is a matrix of stromal cellsF t ll– Fat cells
– Endothelial cells
– Fibroblasts
– Macrophages
In vitro: Cell Culture SEM of cultured cells
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Hematopoietic Cytokines
• Detected by cell culture
• Survival, proliferation, differentiation, maturation
S ifi d l ll• Specific receptors develop on target cells
• CSF and EPO
Transcription factors
How to study genetic factors?
• Knock‐out mice
• Specific gene inactivated
• Determine how it affects immune response
Maintaining steady state:hematopoietic homeostasis
• Cell life ranges from days to years• Control cytokine production by bone marrow stromal cells
• Control cytokine production by activated T’sControl cytokine production by activated T s and macrophages
• Regulate expression of receptors for cytokines in stem cells and progenitor cells
• Removal by programmed cell death
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Apoptosis
Normal/Apoptosis
Genes
B cell regulation by apoptosis
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Stem cellenrichment
Results measured
reconstitutionStem cell uses
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Transplants
• Autologous
• Syngeneic
• Allogeneic
• Graft vs. Host Disease (GVHD)
Blood cell counts
Cells of the immune system Activation: Cell cycle
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Lymphocyte types
B‐lymphocytes
• Review
• APC class II MHC
• C’receptor (CD 35 & 21)
• IgG receptor (CD32)
• Recognize Th (CD40)
• B7 attach to TH
T‐lymphocytes
• Review
• TCR
• CD4
• CD8
• CD28 (receptor for B7 on APC)
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T‐helper cells
• Th‐1 response
• Inflammation: activates T cells and macs
• Th‐2 response
• Activates B cells and immune responses dependent on Abs
Cytotoxic T cells
• CD8
• Types of cells attacked
• MHC class I restricted
Natural Killer Cells
• Large granular lymphocytes
• Cytotoxic
• 5‐10% of human lymphocytes
• ADCC (antibody‐dependent cell‐mediated cytotoxicity) through CD16 attachment to Fc region of Ab
Monocyte
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Macrophage SEM macrophage
Types of macrophages
• P. 36
• Alveolar (lung)
• Histiocytes (connective tissue)
• Kupffer cells (liver)
• Mesangial (kidney)
• Microglial (brain)
• Osteoclasts (bone)
Functions
• Sustained, repeated phagocytosis
• Process and present Ag (form and dosage)
• Amplify response by releasing mediators
• Control inflammation
• Repair tissue by removing dead and dying tissue
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MAC Activation
• Causes– Phagocytosis
– Cytokines: gamma interferon from Tcell
– endotoxins
• ResultsResults– Better APC activity
– More phagocytosis.
– Greater killing
– More inflammation
Exogenous processing
antimicrobialsCh 3
Oxygen‐dependent
• Respiratory burst
• Catalase: O2 O`2 (superoxide anion)
• Nitric oxide synthase (NOS)
ch3
• Arginine + O2 + NADPH = NO (nitric oxide)
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Oxygen‐independent
• Lysozyme
• Defensins (cell‐membrane disruption)
• TNF‐alpha (tumor necrosis factor)
Factors
ch3
PMN Eosinophil
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BasophilDendritic lineage
Follicular dendritic cell: NOT APCHuman Lymphoid System
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Immune organs
• Primary: development and maturation
• Thymus
• Bone marrow
• Secondary: Ag trapping and presentation
• Lymph nodes
• Spleen
ORGANS
• Primary
• Secondary
• Tertiary: cutaneous ‐associated
• Immunocompetence
Thymusbilobed
Thymus
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T cells
• Self‐MHC restricted: keep T cells that only respond to MHC’s that match self
• Self‐tolerant: destroy T‐cells that match both self MHC and self antigensself MHC and self antigens
Age changes
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Lymphatic system
• Definition (know these)– Plasma
– Interstitial fluid
– Lymphatic vessels
– Thoracic duct
Secondary lymph organs contain:
• Primary follicle
• Secondary follicle– Germinal center
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Secondary lymphoid follicleLymph node diagram
Human Lymphoid System
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details
Spleen overview Spleen detail
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tonsils adenoids
Peyer’s patch M cells
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Antigen transportevolution