 Vasodilatation  Prostaglandins

 Nitric Oxide
 Histamine
 Histamine and serotonin
 Increased vascular permeability  C3a and C5a (by liberating vasoactive amines from
mast cells, other cells)
 Bradykinin
 Leuktrienees C4, D4, E4
 PAF
 Substance P
 TNF, IL-1
 Chemokines
 Leukocyte recruitment and activation  C3a, C5a
 Lukotriene B4
 (Bacterial products, e.g., N-formyl methyl peptides)
 IL-1, TNF
 Fever
 Prostaglandins
 Prostaglandins
 Bradykinin
 Pain  Neuropathies
 Lysosonal enzymes of leukocytes
 Tissue damage
 Reactive oxygen species
 Nitric oxide
INFLAMMATORY EVENT CHEMICAL MEDIATOR
Vasodilation PGs; NO

 vascular permeability Vasoactive amines; C3a & C5a; Bradykinin;

LTC4 , D4, & E4; PAF

Chemotaxis, C5a; LTB 4; bacterial products;

leukocyte adhesion cytokines (IL-8)

Fever IL-1; IL-6; TNF; PGs

Pain PGs; Bradykinin

Tissue damage Lysosomal enzymes;

Oxygen metabolites; NO
NM Almasri JUST
 Vision:

The vision of Faculty of Medicine at Jordan

University of Science & Technology is to lead
medical education using creativity and innovation, to
advance health with quality and compassion, to search
and discover with imagination and innovation; and to
achieve and maintain human health and well-being to
the maximum attainable levels.
 Mission:

Faculty of Medicine at Jordan University of

Science & Technology is a community of
scholars who stimulate & inspire medical
students to be leaders in advancing medicine at
different levels of health care and who
participate in advancing medical science and
research .
 Restoration of tissue architecture and function
after an injury.
 Regeneration
• Replacement of damaged cells by similar
parenchymal cells, e.g. liver regeneration
• Requires intact connective tissue scaffold
• Returns to normal state

 Healing & Fibrosis (scar formation )

• ECM framework is severely damaged
• Replacement by connective tissue
• Organization : in tissue spaces occupied by an
inflammatory exudates (organizing pneumonia)
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 Remnants of the injured tissue (attempting to
restore normal structure )
 Vascular endothelial cells
( create new blood vessels )
 Fibroblasts ( source of fibrous tissue )
 Proliferations of these cells is driven by
proteins that are called GROWTH FACTORS

10
11
 Labile cells (continuously dividing & continuously dying)
• Stem cells divide: self renewal and differentiation
• Examples:
 Skin epidermis,oral cavity,vagina,cervix,ducts draining exocrine organs.
 GIT epithelium, uterus, fallopian tubes, bladder urothelium.
 Bone marrow cells
 Stable cells (quiescent)
• Examples:
 Liver and pancreas
 Kidney
 Smooth muscle, endothelial cells, fibroblasts
 Permanent (nondividing),
• Examples:
 Cardiac muscle
 Neurons
12
 S
G1

G0
G0 (Labile cells)

(Stable G2
cells)

(Permanent
cells) M
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15
 Self renewal capacity
 Asymmetric replication (after each cell division,
some progeny enter a differentiation pathway, while others
remains undifferentiated )
 Capacity to develop into multiple lineages
 Extensive proliferative potential

Embryonic stem cells: Pluripotent cells that

can give rise to all tissues of the body

Adult stem cells: Restricted differentiation capacity

(lineage specific), except BM and some other adult
tissues… 16
 Study of specific cell signaling and
differentiation steps
 Production of knockout mice
 Potentially, generation of specific cell types to
regenerate damaged tissue (therapeutic
cloning)
 Differentiation plasticity and transdifferentiation
has led to the Regenerative Medicine

17
18
19
20
 Bone marrow Hemetopoietic stem cells
 Liver Hering canal
 Skeletal muscle Satellite cells
 Intestine Base of crypts
 Skin Hair follicle bulge

21
 Family of proteins that control entry of the cells at
specific stages of cell cycle
 Level of a specific cyclin increases at a specific stage,
then decreases rapidly after the cell departs that stage
 In order to accomplish their function, they have to bind
to cyclin-dependent kinases (CDKs)
 Different combinations are associated with each phase
of the cell cycle
 They exert their function by phosphorylating certain
proteins (kinase phosphorylate proteins)
 Examples:
• Cyclin B-CDK1 activate G2 to M transition
• Cyclin D-CDK4,6 activate G1 to S phase
22
23
 Hypophosphorylated RB, forms a complex with E2F
transcription factor and DP1, blocking the effect of
E2F.
 Blocking is mediated by histone deacetylase causing
chromatin compaction.
 CyclinD/CDK4, and cyclinE/CDK2 phosphorylate RB.
 Phosphorylated RB dissociated from the complex,
leading to activation of E2F.
 Target genes for E2F include: cyclin E, DNA
polymerase, thymidine kinase, dihydrofolate
reductase, and others.

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26
 Regulate cell cycle checkpoints (G1-S,
& G2-M)
 Cip/Kip family: p21, p27 and p57
 INK4/ARF family: p16INK4A, p14ARF

27