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Inflammation and Repair AHD presentation November 2015 Mahra Nourbakhsh

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Page 1: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Inflammation and Repair

AHD presentationNovember 2015

Mahra Nourbakhsh

Page 2: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Definition• A response of vascularized tissues to infections

and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents.

• The Purpose:o To get rid of initial cause of injuryo To get rid of consequences of such injury

Page 3: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Historical Aspects• Celsus a Roman writer:

1. Rubor: Redness2. Tumor: Swelling3. Color: Heat4. Dolor: Pain

• Virchow:5. Functio Laesa: Loss of function

Page 4: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Inflammation: Useful VS. Harmful

• Protective but may be the cause of diseases:1. Misdirected reaction:• Autoimmune

2. Inadequate reaction:• Hypersensitivity reactions type I to IV

3. Chronic reaction• Fibrosis: pulmonary, cirrhosis, constrictive

pericarditis.

Page 5: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Injurious Agents (Causes of Inflammation)

• Infection: Viral, bacterial, fungal, parasites or toxins• Tissue Necrosis: Ischemia, trauma, physical and

chemical injuries.• Foreign Bodies: Urate crystals, cholesterol crystals,

lipids.• Immune Reactions: Hypersensitivity syndromes.

Page 6: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Sequential Steps of Typical inflammatory reaction

• Recognition of offending agents.• Recruitment of leukocytes and plasma protein to

the site of injury.• Elimination of the offending agents by activated

leukocytes and proteins.• Control and termination of the inflammatory

reaction.• Damages tissue is repaired.

Page 7: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Inflammation: Acute VS. Chronic

Feature Acute Chronic

Onset Fast: minutes or hours Slow: days

Cellular infiltrate Mainly neutrophils

Monocytes/macrophages and lymphocytes

Tissue injury, fibrosis

Usually mild and self-limited

Often severe and progressive

Local and systemic signs Prominent Less

Innate Adaptive?

Page 8: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

How a pathogen is recognized by innate immune system? Is there a specific structure or pattern?

If yes bring two examples

Page 9: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Recognition of offending agents

• Specific molecular pattern on offending agents help to recognize the pathogens; Pathogen Associated Molecular Pattern (PAMP):

1. Lipopolysacharides (LPS) on gram negatives2. Lipoteicoic acids on gram positives3. Flagellin on bacteria4. Unmethylated CpG5. Ds RNA in viruses.

Page 10: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Recognition of offending agents • Sensing the presence of foreign invaders:

Pattern Recognition Receptors (PRRs) 1. Membrane bounds (plasma membrane and endosomes) receptors: Toll-Like

Receptors (TLRs), C-Type Lectin Receptors (CLRs)2. Cytosolic Receptors: NOD-Like Receptors (NLRs)

• Sensing the cell damage: activation of inflammasomes and production of IL-1

1. Mitochondria damage: ATP2. Break down of DNA : Uric acids3. Damage to Na+/ K+ pump: Increased intracellular K+

4. DNA fragments: DNA damage response, Ataxia Telangiectasia Mutated (ATM) and ATM RAD3-Related (ATR) kinases

• Leukocytes Receptors for FC tail of antibodies and C3b of complement system: Opsonization

• Circulating proteins: Complement system, Mannose-binding lectins and collectins

Page 11: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Which cells from innate immune system are able to recognize the foreign invaders?

How do they activate the remainder of the innate system?

Page 12: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Recognition of offending agents (Cells and Chemicals)

• Cells:1. Tissue Macrophages2. Mast Cells

• Chemicals for example:1. Tumor necrosis factor (TNF)2. Interleukin-1 (IL-1)3. Chemokines4. Histamine5. Kinin and bradykinin6. Thrombin

• Leading to initiation of acute inflammatory response

Page 13: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation

Page 14: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

What is the major cell of acute inflammation in the first 24h?What is the major cell of acute inflammation after the first 24h?

Page 15: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute InflammationCells

Cells:

6-24h: Neutrophils24-48h: MonocytesException: Pseudomonas infection, viral infection, allergic reaction

Page 16: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute InflammationSteps

1. Vascular reaction and changes.2. Recruitment of Neutrophils to the site of

inflammation.3. Phagocytosis and clearance of offending agents

Page 17: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

What are the two common vascular changes that are seen in acute inflammation?

What is the difference between exudate and transudate?

Page 18: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation (Step 1: Vascular Reaction)

• Vasodilation of arterioles by mediators such as histamine: 1. Increased capillary bed and blood flow (Rubor and Color), brings more

neutrophils2. Increases the hydrostatic pressure, helps filtration of fluid to

extravascular spaces.3. Slower blood flow helps the margination and attachment of

neutrophils to endothelial cells (see the following)• Increased Permeability (vascular leakage):

1. Immediate transient response (15-30 mins): contraction of endothelial cells

2. Endothelial Injury (several hours):injury by toxins, direct chemical or physical injuries, is healed by thrombosis and repair.

3. Transcytosis: Transport of protein and fluids through endothelial cells, activated by VEGF.

• Transudate VS. Exudate: Exudate means vascular damage

Page 19: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Can you recall three steps of leukocyte recruitment??

Page 20: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation Step 2: Leukocyte recruitment

• Margination: vasodilation results in slower blood flow, therefore reduced wall shearing force and accumulation of cells in periphery rather than central column of blood.

• Rolling: Leukocytes sequentially binds and detaches to the receptors with low affinity on the surface of endothelial cells. This results in rolling of leukocytes on the surface of endothelial cells.

• Attachment: Leukocytes binds to the receptors with high affinity on the surface of endothelial cells

Page 21: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation Step 2: Leukocyte recruitment

• Rolling: Is mediated by family of cell surface receptors found on endothelial and leukocyte surface called Selectin (CD62)

• Leukocytes: L-selectin• Endothelial cells : E-selectin• Platelets and Endothelial cells: P-selectin

Page 22: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation Leukocyte recruitment1. Increase TNF, IL-1 and chemokine

o Endothelial cells: increase E-selectin and ligands for L-selectin.o Neutrophils: increase L-selectin and ligands for E-selectin.

2. Increase histamin and thrombin

o Endothelial cells: redistribution of P-selectin from Wiebel Palade bodies.

o Neutrophils: Increase ligands for P-selectin.

Page 23: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Can you recall the family of receptors for the attachment of Leukocytes ??

Page 24: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation Leukocyte recruitment (Attachment)

Molecules Distribution Ligands

LFA-1(CD11aCD18)

Neutrophils, monocytes, T cells (naïve, effector,memory)

ICAM-1 (CD54), ICAM-2 (CD102);expressed on endothelium(upregulated on activatedendothelium)

MAC-1(CD11bCD18)

Monocytes, DCs ICAM-1 (CD54), ICAM-2 (CD102);expressed on endothelium(upregulated on activatedendothelium)

VLA-4(CD49aCD29)

MonocytesT cells (naïve, effector,memory)

VCAM-1 (CD106); expressed onendothelium (upregulated on activatedendothelium)

α4β7(CD49DCD29)

Monocytes, T cells (gut homing naïve effector, memory)

VCAM-1 (CD106), MAdCAM-1;expressed on endothelium in gut andgut-associated lymphoid tissues

Page 25: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation

Step 3: Phagocytosis and clearance of the offending

agentsRecognition and attachment of the particle to be ingested by leukocytes:

1. Mannose and Fucose terminal residue of glycoprotein and glycolipids on microbial walls (human does not contain these residues)

2. Scaveneger recptors on phagocytes: Integrin CD11b/CD8

3. Engulfment with clathrin based coated pit4. Formation of phagosome5. Merging with lysosomes and formation of

phagolysosomes.

Page 26: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Can you name three methods for destruction of offenders in lysosomes?

Page 27: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Phagocytosis and clearance of the offending agents

Intracellular destruction:

1. ROS: Respiratory burst, NADPH oxidase produce O2

Which later changes to H2O2 and reacts with CL- to form OCl2- (mediated by myeloperoxidase).

2. RNS: NO is formed by inducible NO synthase (iNOS) and reacts with O2

- to form ONOO-.3. Lysosomal Enzyme and Proteins:

o Specific Granules: Lysosyme, collagenase, lactoferin, plasminogen, alkaline phosphatase.

o Azurophilic gransules: Myeloperoxidase, bactericidal factors (defensin), acid hydrolase, neutral protease.

Page 28: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Can you recall some of the antioxidant mechanisms?

Page 29: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Antioxidant and antiproteases

Anti oxidants:• Superoxide Dismutase• Catalase• Glutathione peroxidase• Ceruloplasmine• Iron free transferrin

Anti Proteases:• α1- Antitrypsin• α2-macroglubin

Page 30: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Two Vasoactive amines and roles in inflammation??

Page 31: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Mediators of InfllamationVasoactive Amines

• Histamine:1. Richest source: Mast cells but also in basophils and platelets2. Released By: attachment of Ab to mast cells, anaphylatoxines (C3a

and C5a) and by direct injury (cold, warm), substance p and IL-1 and IL-8.

3. Function: vasodilation on arterioles through H1 receptors

• Serotonin:1. Richest source: Platelets and NEC2. Function: vasoconstrictor, function in inflammation unknown.

Page 32: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Name two pathways for formation of Arachidonic Acid derivatives that are involved in inflmmation?? Name the

products.

Page 33: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

AA derivative (Eicosanoids)

Page 34: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Cyclooxygenase Pathway and Prostaglandins (PG)

COX-1 and COX-2, COX-2 is activated specifically for inflammation.• TXA2: Secreted by platelets, platelets aggregators and also a

potent vasoconstrictor.• PGI2 (prostacyclin): Secreted by endothelial cells, potent

inhibitor of platelet aggregation, vasodilators.• PGD2: Secreted by mast cells, chemoattractant for neutrophils,

vasodilator, increase permeability of post-capillary veins.• PGE2: similar to PGD2 but secreted by almost any cell.• PGF2α: smooth muscle contraction (uterine, bronchial walls,

small arterioles).• PGE2: Hyperalgesia, is involved in cytokine induced fever.

Inhibitors: NSAID, Aspirin for both COX-1 and 2 and Coxib for COX-2

Page 35: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Lipooxygenase Pathway and Leukotrienes (LT)

5-Lipooxygnease is one of the most important lipooxygenases.• 5-hydroxyeicosatetranoic acid: an intermediate product, a

potent chmeoattractant for neutrophils• LTB4: potent chmeoattractant for neutrophils• LTC4, LTD4 and LTE4: Vasoconstriction, bronchospasm,

increases vascular permeability• Lipoxin: inhibits recruitment of leukocytes therefore is an anti

inflammatory. Requires two steps for production; 1) intermediate lipoxin released by neutrophils then converted to lipoxin by platelets.

Inhibitors:1) lipooxygnease inhibitors: Zileuten, 2)leukotrienes receptor antagonists (Monteleukast).

Page 36: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Cytokines and ChemokinesTNF and IL-1

• Secreted by dendritic cells and macrophages• Stimulated by immune complex, foreign bodies,

microbial products, physical injury.• Role: 1. Formation of other cytokines, chemokines,

growth factors, eicosanoids.2. Activation of leukocytes, production of NO.3. Systemic acute phase reactant: Fever, SIRS,

decrease appetite, regulates energy balance. TNF causes Cachexia

Page 37: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Chemokines • Proteins 8-10 KDa, classified based on the

position of terminal Cysteines (C).1. C-X-C: like IL-8 secreted by macrophages and

endothelial cells chmotactic agent for neutrophils.

2. C-C: Like Monocytes chemoattractant protein 1 (MCP-1)

3. C: like Lymphotactin, chemoattractant for lymphocytes.

4. C-X3-C: Fractalkine, chemoattractant factor for monocytes

Page 38: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Name three pathways lead to activation of complement system.

Page 39: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Complement System

Three activation pathways

Page 40: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Complement System• All three pathways lead to activation of an enzyme called

C3 convertase which cleaves C3 to C3a and C3b.• C3b accumulates and activates more formation of C3b,

then activates C5 convertase which cleaves C5 to C5a and C5b

• C5b activates late complement protein (C6-C9) to form membrane attack complex (MAC).

• C5b and C3b are important for opsonization.• Released C3a and C5a: activates anaphylaxis by release

of histamines, chemotactic agents, activation of AA pathways.

• MAC is important for lysis of microbes such as N.Gonnorhea, deficiency causes predisposition

Page 41: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Complement SystemInhibitors and disease• C1 inhibitor (C1-INH):inhibits C1 activity Deficiency of C1-INH causes hereditary angioedema

• Decay Accelerating Factor (DAF): prevents formation of C3 convertase

• CD59: Prevents formation of MAC

CD59 and DAF are attached to Glycophosphatidyl inositol (GPI) anchor. Deficiency of formation of GPI, prevents the action of CD59 and DAF on RBCs can causes paroxysmal nocturnal hemoglobinuria (PNH)

Page 42: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Morphologic Pattern of Acute Inflammation• Serous inflammation: Low vascular permeability, Exudation

of cell-poor fluid. Examples Blister, Parapneumonic effusion.• Fibrinous Inflammation: Higher vascular permeability,

Fibrinous exudate, mostly seen in the lining of body cavity, such as pericardium or meninges, can dissolve completely or changes to scar tissue (organization).

• Purulent inflammation (Abscess): necrotic tissue in the middle, neutrophiles around the central core and fibroblasts, vascular tissue at the outside of this lesion. Example: appendicitis.

• Ulcer: a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue, Example: Gastric ulcer.

Page 43: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Outcomes of Acute Inflammation

• Complete resolution with no or minimal scar tissue.

• Healing by connective tissue repair, scar formation and fibrosis.

• Progression to chronic infection, due to persistence of the injurious agent or difficulties in repair processing.

Page 44: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Chronic Inflammation

Page 45: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Chronic InflammationCauses

• Persistent infection: o Infection is not cleared by innate inflammation,o Examples: MTB, Some viral infection, parasites, fungal infection

• Hypersensitivity and autoimmune Diseases:o Hypersensitivity type I-IVo Autoimmune disease such as SLE, RA

• Prolong exposure to toxic agents:o Talk, Slilcosis, Asbestosis

Page 46: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Name two major type of cells involved in chronic inflammation.

Page 47: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Where are the macrophages derived from?Name three tissue macrophages.

Name Two methods of activation of macrophages.

Page 48: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Chronic InflammationCells: Macrophages

• Macrophages:o Derived from bone marrow, embryonic yolk sac and fetal liver.o Circulate in blood as monocytes and transfer to tissue and resident

macrophages such as Kupfer cells, microglial cells, Langerhans cells, alveolar macrophages .

• Activation:o Classical activation: by TLR or IFN-Υand foreign substance, Classically

activated macrophages (M1) are acting as the effector cells in inflammation.o Alternative activation: By IL-4 and IL-13 of T-lymphocytes. These activated

macrophages (M2) are important in tissue repair by secreting growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis.

• Function:o Phagocytosiso Tissue repairo Secrete mediator of inflammation such as TNF and IL-1o Antigen presenting cells

Page 49: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Can you recall three major forms of CD4+ T cells and their function in inflammation?

Page 50: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Chronic InflammationCells: Lymphocytes

• Lymphocytes:o Major cells of chronic inflammation and major cells of adaptive

immunity.o Antigen stimulated lymphocytes are recruited to the site of injury

similar to neutrophils.• CD4+ T cells:

o TH-1 cells secrete IFN-Υand activates M1 macrophages .o TH-2 cells secrete IL-4, IL-5 and IL-13 and activates M2 macrophages

and also eosinophils.o TH-17 secrete IL-17 induces secretion of chemokines responsible for

neutrophil recruitment.• Function:

o TH-1 and TH-17: against bacteria and viruses.o TH-2: against helminthic parasites.o Macrophages present the antigen to T cells and also secrete IL-12 to

activate these cells.

Page 51: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Chronic InflammationCells: Others

• Eosinophils:o Major basic protein extremely toxic for parasites.

• Mast Cells:o Part of primary innate response by scereting inflammaotry mediators.o Contains Fcε RI receptor for FC protion of IgE, therefore involves in

allergic reaction• Neutrophils:

o Although involves in acute inflammation, they can be seen in burst of inflammation as acute on chronic inflammation..

Page 52: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Systemic Effects of Inflammation

• Acute phase response is mediated by TNF, IL-1 and IL-6.

1. Fever: Bacterial products such as LPS (exogenous pyrogens) stimulates leukocytes to secrete TNF and IL-1 (endogenous pyrogens), induces COX which increases PGE2, PGE2 at hypothalamic area increases neurotransmitters that set the temperature at higher points.

2. Acute Phase Proteins: Examples are SAA, CRP and fibrinogen. They are produced by liver and their levels increase 100 times following inflammation.1. Fibrinogen binds to RBC causes rouleuax formation (bases of ESR)2. Long time activation of SAA causes amyloidosis3. Hepcidin another phase reactant protein reduce availability of iron and

causes anemia of chronic disease.3. Leukocytosis4. Other manifestations: such as rigors and chills, loss of appetite, malaise.5. Septic shock: High levels of TNF and f IL-1 associated with DIC, hyperglycemia,

hypotension.

Page 53: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Can you recall two types of reaction for tissue repair?Hint: in regards to tissue that can proliferate vs. not.

Page 54: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Repair

• Two types of reaction:1. Regeneration: by

proliferation of remained uninjured cells and/or by activation of stem cells.

2. Connective tissue deposition and scar formation: if injured tissue is incapable of proliferation or damage is so severe

Page 55: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Tissue RegenerationThree types of cells:

1. Labile/Continuously dividing cells: such as majority of surface epithelia, can regenerate as long as pool of stem cells are preserved.

2. Stable quiescent (G0 phase) cells: such as solid organs, fibroblast, endothelial and smooth muscle cells, only regenerates in response to injury and have a limited capability of regeneration.

3. Permanent tissue: Such as neuron, cardiac myocytes and skeletal muscles, except to very limited stem cell proliferation, they never regenerate

Page 56: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Tissue Regeneration Liver

• Priming phase: priming the hepatocyte by IL-6 secreted from Kupffer cells.

• Growth factor phase: From G0 to G1 and then S phase on primed hepatocytes by HGF and TGF-α.

• Termination phase: return to quiescence, by TGF-β.

Page 57: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Scar FormationSteps of scar formation:1. Angiogenesis2. Deposition of connective tissue

These two first steps forms a tissue with a loose extracellular matrix, proliferated fibroblasts and thin-walled leaky vessels with presence of macrophages. This tissue is called Granulation Tissue.

3. Remodeling of connective tissue

Page 58: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Scar FormationAngiogenesis

1. Vascular Endothelial Growth Factor (VEGF): specifically VEGF-1 stimulates capillary sprouting

2. Fibroblast Growth Factor (FGF): Specifically FGF-2 stimulates endothelial proliferation.

3. Angiopoeitin 1 and 2: stabilized newly formed vessels by the recruitment of pericytes and smooth muscle cells and by the deposition of connective tissue.

4. PDGF and TGF-β: stabilizing the tissue by enhanced production of extracellular matrix

Page 59: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Deposition of Connective Tissue

• M2 Macrophages release TGF-β, PDGF and FGF-2 which lead to migration and proliferation of fibroblast into the site of injury.

• TGF-βstimulates synthesis and deposition of ECM (collagen, fibronectin and elastin) by fibroblast and inhibits matrix metalloproteinase (MMP), therefore increases the net accumulation of collagen.

• Some of the fibroblasts also acquire features of smooth muscle cells (myofibroblast) and are important in scar contraction.

Page 60: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Remodeling of connective tissue

• Removal and remodeling of extracellular matrix by Matrix Metalloproteinase (MMP).

• MMP-1 to -3: are collagenase which cleaves fibrillar collagen.

• MMP-2 and -9 are gelatinase which cleaves fibronectin.• MMP-3, -10 and -11 are stromelysins which cleaves ECM

constituents, including proteoglycans, laminin, fibronectin,• tissue inhibitors of metalloproteinases (TIMPs),

inhibits MMP and contorls the remodeling.• ADAMs (a disintegrin and metalloproteinase) family

are attached to plasma membrane and deactivates TNF, TGF-β, and members of the EGF family.

Page 61: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

Give some examples for the factor that are able to affect tissue repair?

Page 62: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Factor influencing repair

• Infection• Diabetes• Nutritional status: protein deficiency and Vit. C

deficiency.• Steroids: preventing TGF-B production.• Mechanical factors: pressure, torsion• Poor perfusion• Foreign body• Type of tissue and extent of damage

Page 63: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Question

What is the difference between hypertrophic scar and keloids?

Page 64: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Abnormal Tissue Repair

• Fibrosis in internal organs activated by TGF-B.• Inadequate formation of granulation tissue

and scar: leads to wound dehiscence and ulceration

• Excessive formation of the components of the repair process can give rise to hypertrophic scars (raised edge) and keloids (beyond the boundaries of original wound.

• Exuberant granulation tissue, prevents reepithelialization

• contraction

Page 65: Dr. Mahra Nourbakhsh's Presentation, Inflammation and Repair

Acute Inflammation (Step 1: Vascular Reaction)

• Increased number of lymph vessels to remove the exudates:

• Inflammation of Lymph Vessels: Lymphangitis• Inflammation of draining lymph node: Reactive

Lymphadenitis