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Cellular Components of the Immune Response: Stem Cells and Stem Cell Transplantation

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Title: Cellular Components of the Immune Response: Stem Cells and Stem Cell Transplantation


1
Cellular Componentsof theImmune ResponseStem
Cells and Stem Cell Transplantation
  • Folder Title Cells
  • Without Turning Point Slides

Updated October 21, 2013
Filename CellsNoTP.ppt
2
Immune System Make-up
From 447Intro, Slides 54 and 55
3
Morphology Staining of Blood Cells
Kuby, 3rd Ed. Figure 3-1
ImmCells
4
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 arent replaced correctly? If they are
deficient in number? If they are produced in
excess to what is needed? If they are not
structurally normal?
5
Blood Counts
5x109/ml blood
RBC
7.3x106/ml blood
WBC
Ratio RBC to WBC 6851
WBC White Blood Cells (Leucocytes)
See Table 2-4, p. 30, Kuby 6th Edition
6
Mouse Whole Blood with Human Leukemia Cells
Added at 0.5 Diluted 1500 for Counting
7
Blood Cell Survival Times and Turn-Over Erythroc
ytes (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)
8
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.
9
Replacing Cells at the Correct time Getting Rid
of Aged or Damaged Cells Without generating
inflammation Genetically Programmed Cells Death
(Apoptosis)vs Inflammatory Lysis and Necrosis
10
Genetically Programmed Cell Death Apoptosis
11
Bcl-2 gene B-cell Leukemia associated gene
12
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)
13
Replacing Cells at the Correct Time with the
Correct Cell Type Where Do the Blood Cells Come
From? Stem Cells and Partially Differentiated
Progenitor Cells Stem Cell Therapy in Medicine
14
200,000 peripheral blood cells restore viability
1,000 mixed stem cells and progenitor cells
restore viability
15
Pure Stem Cells
30 to 100 Stem cells restore viability
See Figure 2-5 Kuby, 6th Ed.
16
Please put away all notes and any devices except
for your Turning Point NXT Transmitter. No
papers or computers on your desk please. No
communication between or among students.
17
It takes 200,000 cells to restore viability in
the lethally irradiated mouse at the top, but
only 1,000 cells are required for the mouse at
the bottom? Why is that?









18
CD34 Purification of Stem Cells
Isolation of CD34 Pluripotent Stem Cells from
Mixed Bone Marrow Mononuclear Cells Using
Monoclonal Antibody to CD34 Marker on Stem Cells
See Figure 3-9 Kuby, 3rd Ed.
Antibody conjugated to Biotin. Avidin coats
insoluble beads Biotin Sticks Strongly to Avidin
19
Stem Cell Transplantation in Medicine In
Immune deficiency diseases In immuno-suppressed
states Autologous Transplants Syngeneic
Donors Allogeneic Donors
20
Autologous Transplant
See p.38 Kuby, 4th Ed.
21
(No Transcript)
22
Pluripotent Stem Cell and Lymphoid and
Myeloid Lineages (Fig 2-1, Kuby 4th Ed. p. 28
StemCell
Myeloid Stem Cell
23
Hematopoiesis (formation of blood cells)Fig
2-1, Kuby 4th Ed. p. 28
HematoAll
24
Lymphoid Lineage Fig 2-1 Kuby 4th Ed p. 28
Lymphoid
25
Cells of Lymphocyte Lineage B-Lymphocytes
Antibody receptors and antibody
production T-Lymphocytes (Thymus-derived
lymphocytes) T-Cell Receptors Helper T-Cells
CD4 positive Cytotoxic T-Cells CD8
Positive Natural Killer Cells (Non-B-Cell,
Non-T-Cell Lymphocytes) Recognize virally
infected or transformed cells Bind to antibody
labelled cells as part of antibody-dependent,
cell mediated cytotoxicity (ADCC)
26
(No Transcript)
27
Differentiation Antigen Markers (CD Antigens) on
Lymphocytes
p. 34
Used to identify sub-populations of lymphocytes
and to isolate them
28
Appendix 1 Pages A1 to A26 339 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.
29
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

30
Hematopoiesis
31
Hematopoiesis (formation of blood cells)Fig
2-1, Kuby 4th Ed. p. 28
HematoAll
32
Cells of Myeloid Lineage Polymorphonuclear
leukocytes (Granulocytes) Neutrophils,
Eosinophils, Basophils, Mast Cells Antimicrobial,
allergic reactions, ADCC Monocyte Macrophages
Mononuclear phagocytes Antimicrobial, attack
virally infected cells, Phagocytosis,
Endocytosis, Pinocytosis Degrade and present
processed antigens Denedritic Cells Similar
functions as for macrophages (Note Follicular
Dendritic Cells, p. 40) Different from
bone-marrow derived dendritic cells Erythrocytes
Red Blood Cells, carrying oxygen Megacaryocytes
Produce platelets for blood clotting
33
Myeloid Lineage
Myeloid Lineage (Kuby, Fig 2-1, 4th Ed., p.
28. See Figure 2-2 Hematopoiesis 6th Edition p.
25)
34
Myeloid to Monocyte
Differentiation in the Monocyte Macrophage Lineage
35
Tissue Macrophages
36
BloodCells1
37
BloodCells2
Histiocyte (Connective Tissue)
Mesangial Cell (Kidney)
Osteoclast (Bone)
38
Monocyte to Macrophage
Macrophage (MPH or MO)
Monocyte
Monocyte to Macrophage Kuby, Immunology. 6th
Edition Figure 2-7
MCMPH
39
Macrophage Ingesting and Degrading Bacterial
TargetsKuby, Immunology, 6th Edition, Figure 2-8
Macrophage
bacteria
Antigen presentation
MPHIngest
40
Macrophage Factors
Kuby, 4th Edition, p. 44
MPhMake
41
Dendritic Cells from Sci Am
42
Dendritic and T-Cell
43
Dendritic Cell micrograph
44
Types of Antigen-Presenting Dendritic Cells.
45
Differentiation and Function in the Granulocyte
Lineage Neutrophils Eosinophils Basophils
and Mast Cells
46
(No Transcript)
47
(No Transcript)
48
BloodCells2
Histiocyte (Connective Tissue)
Mesangial Cell (Kidney)
Osteoclast (Bone)
49
Differentiation and Function in the Granulocyte
Lineage Neutrophils Multi-lobed Nucleus (PMN)
Polymorphonuclear Leucocyte 50 of circulating
leukocytes. Short-lived (Hours or
Days). Phagocytic Circulates, 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.
50
Macrophage and PMN Killing Agents
Kuby, 4th Edition, p. 43
MPhKill
51
Differentiation and Function in the Granulocyte
Lineage Eosinophils Acidic Granules Anti-parasit
ic immunity 1 of circulating leukocytes Phagocyti
c Basophils Less than 1 of circulating
leukocytes Non-phagocytic Degranulate to release
substances supporting allergic attack Mast
Cells Similar to Basophils, but in tissue
sites Secrete histamine in allergic attacks
52
Cytokine Signaling and Cytokine Receptors in
Normal Hematopoiesis and in Leukemia
53
Myeloid Leukemia
See Figure 3-6 Kuby, 3rd Ed.
54
Macrophage Factors
Kuby, 4th Edition, p. 44
MPhMake
55
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 - EPO
GrowFact
56
Cytokine Table
See Table 3-1 Kuby 3rd Ed.
57
TH1 and TH2
58
Appendix II, Pages A27 to A31 52 Cytokines from
Interleukin 1 to Tumor Necrosis Factor Beta
(TNF-B)
59
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. Im totally lost.
  2. Im having hard time, but I follow some of it.
  3. Im OK. I can figure most of it out later.
  4. Im following very well. There is no problem with
    the level of the course.
  5. This isnt pitched at a level appropriate for an
    upper division undergraduate course. Please move
    to a higher level of challenge.

Response Counter
60
An Exercise in the Unification of the Human
Family in the Digital Age. Search Maria
Sophia and Violanda
61
To Get to Molecular Visualizations Produced for
Kuby Immunology http//bcs.whfreeman.com/immunolo
gy6e/ Or search Kuby Immunology, Click on
Kuby Immunology 6e , go to Student Resources
62
I am here!
  1. Yes
  2. No

Also try message to leader
The next slide is a time to respond slide. This
is designed in response to complaints about
students consulting their notes or each other.
Well try it out to see how it works, but I
think this puts students for whom English is not
their primary language at a disadvantage.
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63
An Exercise In Cytokine Signaling and Cytokine
Receptors
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