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Cellular Components of the Immune Response: Stem Cells and Stem Cell Transplantation. Folder Title: Cells Without Turning Point Slides. Updated: October 21, 2013. Filename: CellsNoTP.ppt. Immune System Make-up. From 447Intro, Slides 54 and 55. - PowerPoint PPT Presentation
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Cellular Componentsof the
Immune Response:Stem Cells and Stem Cell
Transplantation
Folder Title: CellsNoTPUpdated: October 28, 2015
This is a Turning Point Slide to Open the System to Accept Your Transmitted
Questions. No need to answer.
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Questions About Cellular Components of the Immune Response
How many different cell types are there?What are the numbers of the various cell types?What do these different cell lineages do?Where do they come from?How Long do they last?What becomes of them at the end of their functional life span?What controls their replacement? (How does the hematopoietic system know what needs to be replaced?)What happens if they aren’t replaced correctly?
If they are deficient in number?If they are produced in excess to what is needed?If they are not structurally or functionally normal?
How We Learn Things:
Memorization vs Gradual Familiarity
Immune System Make-up
From 447Intro, Slides 54 and 55
Morphology & Staining of Blood Cells
Kuby, 3rd Ed. Figure 3-1
About 6 u diameter
About 20 u diameter
700 RBC to one leucocyte
Replacing Cells at the Correct Time with the Correct Cell Type
Hematopoiesis
Where Do the Blood Cells Come From?Stem Cells and Partially Differentiated Progenitor Cells
How Can We get Our Hands on Stem Cells for Treatments?
Stem Cell Therapy in Medicine
See Figure 2-1p. 28, 7th Editon
Hematopoiesis (formation
of blood cells)Fig 2-1,
Kuby 4th Ed. p. 28
Right to Left View
Hematopoiesis
Where Hematopoietic Cells Come From
Antibodies to differentiated end-product blood cells
Removesprogenitor (P) Cells
Isolation of CD34+ Pluripotent Stem Cells from Mixed Bone Marrow Mononuclear Cells Using Monoclonal Antibody to CD34 Marker on Stem Cells
Antibody conjugated to Biotin.Avidin coats insoluble beadsBiotin Sticks Strongly to Avidin
Biotin attached
To AntibodyFc Region
200,000 peripheral blood cells restore viability
1,000 mixed stem cells and progenitor cells restore viability
Pure Stem Cells
See Figure 2-5Kuby, 6th Ed.
30 to 100 Stem cells restore viability
To Here ThursdayOctober 23rd, 2014
Pluripotent Stem Cell and Lymphoid and Myeloid Lineages (Fig 2-1, Kuby 4th Ed. p. 28
Myeloid Stem CellStemCell
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Differentiation and Function Among “Granulocytes”,
Polymorpho-nuclear Leucocytes (PMN’s) :
Myeloid Lineage
Neutrophils, Eosinophils, Basophils/Mast Cells
Cells of Myeloid Lineage
Polymorphonuclear leukocytes: (Granulocytes)Neutrophils, Eosinophils, Basophils, Mast CellsAntimicrobial, allergic reactions, ADCC
Monocyte Macrophages: Mononuclear phagocytesAntimicrobial, attack virally infected cells,Phagocytosis, Endocytosis, & PinocytosisDegrade and present processed antigens
Denedritic CellsSimilar functions as for macrophages
See Slides 46, 47, 48, 49
Erythrocytes: Red Blood Cells, carrying oxygen
Megacaryocytes: Produce platelets for blood clotting
Myeloid LineageMyeloidLineage(Kuby, Fig 2-1,4th Ed., p. 28.See Figure 2-2 Hematopoiesis6th Editionp. 25)
BloodCells1
BloodCells2
Histiocyte (Connective Tissue)
Osteoclast (Bone)
Mesangial Cell(Kidney)
To HereOct. 28, 2014
Myeloid to Monocyte
Differentiation in the Myeloid Series to Monocyte
Macrophage Lineage
Tissue Macrophages
Differentiation and Function in Monocyte/Macrophage Dendritic
Cell Lineage
Differentiation and Function in the Granulocyte Lineage
Neutrophils: Eosinophils:
Basophils and Mast Cells
Differentiation and Function in the Granulocyte Lineage
Neutrophils: Multi-lobed Nucleus (PMN) Polymorphonuclear Leucocyte50% of circulating leukocytes.Short-lived (Hours or Days).PhagocyticCirculates, extravasates out of vasculature into tissue.Responds to chemotactic factors released by infection and inflammation (e.g. from complement or blood-clotting reactions or cytokines released by T-cells or macrophages).Granules release peroxidase, lysozyme, hydrolases, proteases, collagenase.Antimicrobial agents released.Part of innate natural immune response.
Macrophage and PMN Killing Agents
MPhKill
Kuby, 4th Edition, p. 43
Differentiation and Function in the Granulocyte Lineage
Eosinophils: Acidic GranulesAnti-parasitic immunity1% of circulating leukocytesPhagocytic
Basophils: Less than 1% of circulating leukocytesNon-phagocyticDegranulate to release substances supporting allergic attack
Mast Cells:Similar to Basophils, but in tissue sitesSecrete histamine in allergic attacks
Monocyte to Macrophage
Monocyte
Macrophage (MPH or MO)
Monocyte to MacrophageKuby, Immunology. 6th EditionFigure 2-7
MC&MPH
Macrophage Ingesting and Degrading Bacterial TargetsKuby, Immunology, 6th Edition, Figure 2-8
MPHIngest
bacteria
Macrophage
Antigen presentation
Macrophage Factors
MPhMake
Kuby, 4th Edition, p. 44
Types of Antigen-PresentingDendritic Cells.
(Shown in Lymphoid Series in Slide 53)
Dendritic Cells from Sci Am
Dendritic and T-Cell
Dendritic Cell micrograph
Natural Killer Cells• Large Granular Lymphoctyes• Part of innate natural immune response• Usually without T-Cell Receptor or Membrane Antibody• Recognize patterns of surface molecules or unusual
expression of self-molecules (Class I MHC)• Have anti-tumor and anti-viral activity• CD16 Membrane Receptor for specific antibody regions
gives Antibody-dependent cell-mediated cytotoxic activity• NKT Cells have TCR,
– Bind to MHC-like molecules CD1– Secrete cytokines
Megakaryocyte – Platelet Lineage:
Blood-Clotting Function
Differentiation and Function in the Lymphocyte Series
Cells of Lymphocyte Lineage
B-Lymphocytes: Antibody receptors and antibody production
T-Lymphocytes (Thymus-derived lymphocytes):T-Cell ReceptorsHelper T-Cells “CD4 positive”Cytotoxic T-Cells “CD8 Positive”
Natural Killer Cells (“Non-B-Cell, Non-T-Cell Lymphocytes)Recognize virally infected or transformed cellsBind to antibody labelled cells as part of antibody-
dependent, cell mediated cytotoxicity (ADCC)
Lymphoid LineageFig 2-1 Kuby 4th Edp. 28
TH1 and TH2
Antigen-activated B- Cells
Differentiation Antigen Markers (CD Antigens) on Lymphocytes
Used to identify sub-populations of lymphocytes and to isolate them
p. 34
Unique T-Cell Marker
Unique T-Cell Marker
Unique T-Cell Marker
Unique B-Cell Markers
Unique NK-Cell Marker
Unique NK-Cell Marker
Unique B-Cell Marker
Distinguishes Tc from TH
Edition 6 (2007) :Appendix 1: Pages A1 to A26339 CD Antigens on Leucocytes
Edition 7 (2013): Apendix 1: Pages A1 to A29350 CD Antigens on Leucocytes
What cells types express them
What they do
e.g. CD4 is a co-receptor on helper T-cells.Confirms binding of T-Cell with its T-Cell Receptor
to an antigen-presenting cell.
Blood Cell Replacement Problems
At the correct time: When cells are damaged, aged, or no longer functional or necessary.
Replace with the correct cell type.
In the correct number.
Do not propagate errors arising during cell division.
Blood Cell Survival Times and Turn-Over
Erythrocytes (Red Blood Cells) ~ 4 Months
Neutrophils 1 Day
Lymphocytes Years
White Blood Cell Generation 3.7 x 1011/day(50 x World Human Population per Day)
Replacing Cells at the Correct time
Getting Rid of Aged or Damaged CellsWithout generating inflammation:
Genetically Programmed Cells Death (Apoptosis)vs Inflammatory Lysis and Necrosis
Genetically ProgrammedCell Death: Apoptosis
Bcl-2 gene: B-cell Leukemia associated gene
Cysteine – aspartate protease
Hematopoeisis and Leukemogenesis (Leukemia)
What happens if damaged cells are not destroyed?What happens if Apoptosis is not invoked?
Bcl-2 gene up-regulation in leucocytes leads to leukemia.(Strong inhibition of Apoptosis)
FAS Gene or Caspase Genes down-regulated or lost in cells leads to leukemia and other cancer.(Failure to initiate or promote Apoptosis)“Caspase” = cysteine-aspartate proteaase
Bcl-2 gene: B-cell Leukemia associated gene
Cysteine – aspartate protease
Shutting these down leads to failure of cell death and to leukemia
Increasing this leads to failure of cell death as to leukemia
Mouse Whole Blood with Human Leukemia Cells Added at ~0.5%Diluted 1:500 for Counting
Leukemia CellAbout 20 u
Cytokines, Cytokine Receptors, and Normal and Pathological
Cell Signaling
How do the multiplicity of hematopoietic cells at distant sites in the host “talk” to one another?
How do the cells “know” where to go and what to do?
Cytokine Signaling and Cytokine Receptorsin
Normal Hematopoiesis and in Leukemia
An ExerciseIn Cytokine Signaling and Cytokine
Receptors
Need persons who speak:SpanishChineseTibetan
Key Hematopoietic Growth Factors and Their Targets
Relatively Multi-Specific: Granulocyte-Macrophage Colony-Stimulating Factor GMCSF Interleukin III - IL3
Relatively Mono-Specific:
Granulocyte Colony Stimulating Factor - GCSF
Macrophage Colony Stimulating Factor - MCSF
Erythropoietin - EPOGrowFact
Cytokine Table
See Table 3-1Kuby3rd Ed.
See Figure 3-6Kuby, 3rd Ed.
Autocrine stimulation (Self-Signaling) and the
Generation of Leukemias and other Cancers
Appendix II, Pages A27 to A3152 Cytokines from Interleukin 1
to Tumor Necrosis Factor Beta (TNF-B)
Autologous Cells in Transplantation Medicine
Stem Cell Therapy in Medicine
Autologous Transplant
Step 1
Step 2
Step 3
Stem Cell Transplantation in Medicine:(See pages 42-43, 7th Edition)
Treatments with Stem CellsIn Immune deficiency diseases
In immuno-suppressed states
Autologous Transplants
Non-Self DonorsSyngeneic DonorsAllogeneic Donors
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In the picture below: What cell is labelled Cell 1?
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To Get to Animations & Molecular VisualizationsProduced for Kuby Immunology
http://bcs.whfreeman.com/immunology6e/
(Or search “Kuby Immunology”, Click on “Kuby Immunology 6e” , go to Student Resources)
AnimationsChapter 2: Cells; Cell DeathChapter 10: Cell DeathChapter 11: Signal TransductonChapter 13: Leucocyte Extravasation
Molecular Visualization Chapter 2: Cells and Organs Chose Other Chapters for Other Molecular Visualization
How Well Are You Following What is Being Presented so Far in theCourse?
(This will be set to anonymous so you will not be identified and your response will not be graded)
1. I’m totally lost.2. I’m having hard time, but I follow some of it.3. I’m OK. I can figure most of it out later.4. I’m following very well. There is no problem with
the level of the course.5. This isn’t pitched at a level appropriate for an upper
division undergraduate course. Please move to a higher level of challenge.
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