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Understanding the Immune System
• Defends the host against infectious organisms• Triggered into action with any injury, in anticipation that microbes either
caused the injury or will become involved• Self vs. non-self• Foreign substances: microbes, proteins polysaccharides, synthetic
materials
1
Monday, March 3, 14
Understanding the Immune System
• Defends the host against infectious organisms• Triggered into action with any injury, in anticipation that microbes either
caused the injury or will become involved• Self vs. non-self• Foreign substances: microbes, proteins polysaccharides, synthetic
materials
1
Immune system can be divided up into innate and adaptive, which function coordinatively
Monday, March 3, 14
The Immune System
SARS virus
Parasite in red blood cell
Fungus
Bacteria
2Monday, March 3, 14
Markers of Non-Self
Non-self leukocyte
Antibody
Epitope Class I MHC protein
Epitope
Antibody
Antigen
Antigen
Bacteria
Non-self nerve cell
SARS virus
3Monday, March 3, 14
Recognition and effector pathwaysComponents of the innate system recognize structures that are characteristic of microbial
pathogens and are not present on mammalian tissues. Includes: - ! Double stranded RNA found in cells containing replicating viruses; induces cytokines
production by infected cells leading to destruction of the virus.- Unmethylated CpG DNA sequences characteristic of bacterial infections; induces
autocrine macrophage activation and more effective intracellular killing of phagocytosed organisms.
- N-formylmethionine peptides from bacterial protein synthesis. Binding to receptors on neutrophils and macrophages causes chemotaxis and activation. Can also be engendered by protein fragments released during complement activation, lipid mediators of inflammation and chemokine proteins released by stressed cells.
- Mannose rich oligosaccharides from bacterial or fungal cell walls. Engagement of receptors on macrophages will induce phagocytosis; soluble mannose-binding protein in the plasma opsonizes or enhances phagocytosis of microbes bearing mannose.
- Bacterial or fungal wall oligosaccharides directly activate complement and induce either direct microbial lysis or microbial coating with complement that enhances phagocytosis
- Phosphorylcholine in bacterial cell walls binds to circulating CRP, induces opsonization and also activates complement
- Lipopolysaccharide from certain (gram negative) bacteria binds to circulating LPS-binding protein which binds to CD14 surface molecules on macrophages. Cytokine response includes tumor necrosis factor and interleukin-12. Septic shock
- Teichoic acid from gram positive bacteria elicits responses comparable to LPS
Monday, March 3, 14
Markers of Self
Muscle cell
Nervecell
Epithelialcell
Leukocyte
Class I MHC self-marker protein
5Monday, March 3, 14
Markers of Self
Muscle cell
Nervecell
Epithelialcell
Leukocyte
Class I MHC self-marker protein
5
MHC = HLA in humans
Monday, March 3, 14
Markers of Self:Major Histocompatibility Complex
Antigenic peptide
Antigen-presenting cell uses MHC Class I or II
Cell membrane
MHC Class II
Antigenic peptide
Viral infection
Infected cell
MHC Class I
Antigenic peptide
MHC Class I
6Monday, March 3, 14
Markers of Self:Major Histocompatibility Complex
Antigenic peptide
Antigen-presenting cell uses MHC Class I or II
Cell membrane
MHC Class II
Antigenic peptide
Viral infection
Infected cell
MHC Class I
Antigenic peptide
MHC Class I
6
MHC I distinguishes self from non-self and presents fragments of intracellular proteins
Monday, March 3, 14
Markers of Self:Major Histocompatibility Complex
Antigenic peptide
Antigen-presenting cell uses MHC Class I or II
Cell membrane
MHC Class II
Antigenic peptide
Viral infection
Infected cell
MHC Class I
Antigenic peptide
MHC Class I
6
MHC I distinguishes self from non-self and presents fragments of intracellular proteins
Monday, March 3, 14
Markers of Self:Major Histocompatibility Complex
Antigenic peptide
Antigen-presenting cell uses MHC Class I or II
Cell membrane
MHC Class II
Antigenic peptide
Viral infection
Infected cell
MHC Class I
Antigenic peptide
MHC Class I
6
MHC I distinguishes self from non-self and presents fragments of intracellular proteins
MHC II are found on APCs, and presents fragments of extracellular proteins
Monday, March 3, 14
Cells of the Immune System Bone graft
Multipotentialstem cell
Hematopoieticstem cell
Platelets
Macrophage
ErythrocytesEosinophil
Neutrophil
Megakaryocyte
Mast cell
Basophil
T lymphocyte
Natural killer cell
Dendritic cell
B lymphocyte
Lymphoid progenitor cell
Myeloid progenitor
cell
Monocyte
Marrow
Bone
7Monday, March 3, 14
Cells of the Immune System Bone graft
Multipotentialstem cell
Hematopoieticstem cell
Platelets
Macrophage
ErythrocytesEosinophil
Neutrophil
Megakaryocyte
Mast cell
Basophil
T lymphocyte
Natural killer cell
Dendritic cell
B lymphocyte
Lymphoid progenitor cell
Myeloid progenitor
cell
Monocyte
Marrow
Bone
7produce ABs
Monday, March 3, 14
Cells of the Immune System Bone graft
Multipotentialstem cell
Hematopoieticstem cell
Platelets
Macrophage
ErythrocytesEosinophil
Neutrophil
Megakaryocyte
Mast cell
Basophil
T lymphocyte
Natural killer cell
Dendritic cell
B lymphocyte
Lymphoid progenitor cell
Myeloid progenitor
cell
Monocyte
Marrow
Bone
7produce ABs
some T cells kill cells with non-self markers
Monday, March 3, 14
Cells of the Immune System Bone graft
Multipotentialstem cell
Hematopoieticstem cell
Platelets
Macrophage
ErythrocytesEosinophil
Neutrophil
Megakaryocyte
Mast cell
Basophil
T lymphocyte
Natural killer cell
Dendritic cell
B lymphocyte
Lymphoid progenitor cell
Myeloid progenitor
cell
Monocyte
Marrow
Bone
7produce ABs
kill cells with no markers of self
some T cells kill cells with non-self markers
Monday, March 3, 14
Phagocytes in the Body
Brain: microglial cells
Joint:synovial A cells
Precursors in bone marrow
Lymph node: resident and recirculating
macrophages
Blood: monocytes
Kidney:mesangial phagocytes
Spleen: macrophages
Liver: Kupffer cells
Lung:alveolar
macrophages
8Monday, March 3, 14
Innate Immunity Complement System
• Will bind to biomaterial surfaces• Group of proteins in blood that must be activated by pathogens or certain
materials to exert their effect• Pathways of complement activation
– classical pathway– alternate pathway
• Mechanisms of action– enhanced inflammation(stimulates release of inflammatory chemicals)– opsonization (promotes phagocytosis)– cytolysis (membrane attack complex)
Monday, March 3, 14
Complement
C9Enzyme
C2
C5C3b
C3aC3
C4Antigen
IgG
C1 C8
C7
C6C5b
C5b
C5a
10Monday, March 3, 14
Immunity and Cancer
Antibody
Helper T cell
Natural killer cell
Cancer cell
Macrophage
Cytotoxic T cell
11
Monday, March 3, 14
Immunotherapy
Antibody
Breast cancer cell
Growth factor Herceptin blocks receptor
Growth slows
Radioisotope
Antigen
Lymphoma cell Lymphoma cell
destroyed
Herceptin
12
Monday, March 3, 14
Seven Major Classes of Cell-Surface Receptors
Receptors linked to trimeric G-proteinsReceptors with intrinsic or associated enzymatic activity
Pathways involving Proteolysis
changes in activity of existing proteins (sometimes changes in gene expression)
modulate gene expression
13
Monday, March 3, 14
Peptide Epitopes from Biomacromolecules
FibronectinRGDSLDV
REDVPHSRN
EDGIHELLIGRKK
FibrinogenRGDSRGDF
KQAGDV
Collagen IRGDTDGEA
VitronectinRGDV
LamininYIGSRPDGSRLRGDNIKVAVLREIKLLI
ElastinVGVAPG
OsteopontinSVVYGLR
Monday, March 3, 14
Monday, March 3, 14