Inflammation I Flashcards
What is inflammation?
Local reaction of vascularized tissue to injury
What is the timeline for acute inflammation?
0-2 days in duration
What is the timeline for subacute inflammation?
2-14 days in duration
What is the timeline for chronic inflammation?
> 14 days
What are the primary cells seen in acute inflammation?
PMNs
What are the primary cells seen in subacute inflammation?
PMNs, monocytes, lymphocytes, plasma cells, fibroblastic elements, angioblastic elements
What are the cells seen in chronic inflammation?
Monocytes/Macrophages
Lymphocytes
Plasma cells
Granuloma cells
What are monocytes? Macrophages?
Same cell, but monocytes in blood, macrophages in tissue
What are granuloma cells?
Epitheliod cells and giant cells
What are the histological characteristics of acute inflammation?
Large eosinophilic areas, with neutrophils (poly nuclear eosinophilic)
What are the histological characteristics of subacute inflammation?
Changed to monocytes/macrophages
What are eosinophils found in?
Predominant inflammatory cells in allergic reactions and parasitic infections
How do eosinophils appear histologically?
Cells with pink granules
What is the range of eosinophils? What are the two disease processes you should suspect if it is above this value?
0.5-5%
Allergies or parasitic infection
What are the plasma derived molecular systems?
- Immune system
- Kinin system
- Clotting system
- Fibrinolytic system
- Acute phase proteins
What are the tissue derived molecular system
- Vasoactive amines
- Acidic lipids
- Cytokines
- Others
What are the uses of inflammation? (2)
- To rid the body of initial cell injury (microbe)
2. To rid the body of tissue injury
How is inflammation harmful?
- Autoimmune
- hypersensitivity rxns
- Produce scarring
What are the six cardinal signs of inflammation?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
- Systemic changes
What causes the heat and redness of inflammation? Cytokines?
Increased blood flow to site from–histamine, PGs, bradykinin
What causes the swelling of inflammation? Cytokines?
Increased postcapillary venule permeability–Histamine, C5a, C3a, Leukotrienes C4 D4 E4
What causes the pain of inflammation?
PGE2, Bradykinin sensitize neurons
What causes fever? How?
Il-1, TNFalpha increase PGE2 synthesis in the hypothalamus via COX pathway
What are the two major cytokines involved in inflammation?
IL-1, TNF-alpha
What is serous inflammation?
Outpouring of watery, relatively protein-poor fluid (effusion) derived from either serum or mesothelial cell secretions
What is fibrinous inflammation?
Seen in more severe injury; increased vascular permeability allows leakage of larger molecules (fibrinogen)
What happens if fibrin is not completely removed during fibrinous inflammation?
ingrowth of fibroblasts and blood vessels
What is suppurative inflammation?
(purulent inflammation) manifested by large amounts of pus
What is pus?
dead PMNs, necrotic tissue
What is an abscess?
Focal collections of pus; central necrotic region surrounded by layer of preserved PMNs
What happens to abscesses in chronic inflammation?
Walling of via fibroblasts
What is ulceration?
Local defect, excavation produced by sloughing of inflammatory necrotic tissue; can only occur on or near a surface
What are in the margins of the skin that sloughs off in ulceration?
PMNs, and vascular dilation
What are the four outcomes of acute inflammation?
- Resolution (complete restoration)
- Healing by scarring
- Abscess
- Chronic infx
When does healing by scarring occur? (2)
- After substantial damage
2. In tissues that cannot regenerate
What happens to blood flow in inflammation? How?
Increases, via alterations in vascular caliber
What enables plasma proteins and leukocytes to leave the circulation?
Structural changes in the microvasculature
What are the two possible hemodynamic changes in vasculature in inflammation? When does each occur?
Vasoconstriction (first)
Vasodilation (after)
What allows capillaries to enlarge in inflammation?
Relaxation of precapillary sphincters
What is transudation? Is there protein leakage?
Increased hydrostatic pressure, and lower colloid osmotic pressure in capillaries leading to fluid leakage. THERE IS NO PROTEIN LEAKING OUT
What is exudation? Is there protein leakage? Why?
Vasodilation leading to fluid AND proteins d/t loss of junction b/t endothelial cells
What is the difference between transudation vs exudation?
Exudation is the result of endothelial cells separating, whereas transudation is d/t changes in osmotic/oncotic pressure in capillaries
What are the four mechanisms that lead to vascular leakage?
- Direct injury
- Leukocyte injury
- New blood vessel leakage
- endothelial cell contraction
What are the hemodynamic changes in vasculature? (3)
- Leakage of fluid to interstitial space
- Stasis of circulation
- Decreased absorption of fluid from interstitial space
What is margination?
leukocytes line up along EC surface
What is adhesion?
Cells sticking to EC surface
What is emigration?
Migration between EC and across BM to interstitial space
What is chemotaxis?
Directed movement along chemical gradient towards injury
What is the cellular structure that allows leukocytes to migrate?
Filopodium
What is the mechanism of leukocyte exudation?
Rolling, adhesion, transmigration
What are the two proteins that allow leukocytes to stick and integrate (respectively)
- Selectins allow for adhesion
2. Integrins allow for integration
What are the three classes of cell adhesion molecules (CAM) that allow for leukocyte attachment and participation in the inflammation response?
- Selectins
- Immunoglobulin family
- Integrins
What type of molecules are CAMs?
Glycoproteins
What are selectins? What ion are they dependent on?
Ca-dependent lectins that allow for ROLLING
Are selectins involved in firm adhesions?
No, just slow down circulating leukocytes
What are the three family membranes of selectins?
P selectin
E selectin
L selectins
What is ICAM-1? Where is it found? What does it bind to?
Intercellular adhesion molecule 1 in immunoglobin 1 family
expressed on the endothelium
binds to integrin LFA-1 and Mac-1
What is VCAM-1? Where is it found? What does it bind to?
Immunoglobin family II
Binds to integrin VLA-4 that is on molecule on lymphocytes/monocytes
What is PECAM-1? Where is it found? What does it bind to?
Immunoglobin family II (CD31)
Found on both endothelium and leukocytes.
Homophilic binding to CD-31
Plays an important role in diapedesis step of leukocytes emigration
What are beta1 integrins? What are the two molecules of this group, where are they found, and what do they bind to?
Integrin family I
VLA4 expressed on leukocytes and binds to VCAM -1 on endothelium
What is the integrin family I?
Group of adhesion molecules composed of heterodimers of alpha and beta subunits, which act in regulation of cell-matrix and cell-cell adhesion
What are the integrin family II members? What are the three molecules of this group, where are they found, and what do they bind to?
Beta-2 integrins
LFA1, CR3/CR4, which bind to ICAM1 and assist in localization of phagocytes to injury sites and extravasation
What are the five principle processes of acute inflammation?
- Increased blood flow/exudation
- Attraction of leukocytes
- Activation of chemical mediators
- Degradation of extracellular debris
- Restoration of tissue
The suffix “-itis” means what?
Inflammation
The suffix “-osis” means what?
Full of
Can normal tissues be restored after fibrinous inflammation?
Yes
Can there be inflammation if there is no vasculature to the area?
No
What is suppurative/purulent inflammation? What are the contents of pus?
Inflammation with pus, (where pus = PMNs, necrotic cells, edema)
What are ulcers?
Excavation produced by sloughing off of necrotic tissue
True or false: ulcers can present anywhere on or in the human body
False-Necrotic tissue must be near a surface
What are the two divisions of molecular systems?
- Plasma derived
2. Cell/tissue derived
Increased permeability in acute inflammation occurs at which vessel level?
Capillaries and postcapillary venules
What are the two changes in sterling’s law forces that allow for the acute inflammation?
- Increased capillary hydrostatic pressure
2. Increase extracellular osmotic pressue
What is the sequence of events of leukocyte exudation? (4)
- Margination
- Adhesion
- Emigration
- Chemotaxis
What are the major chemotactic agents?
C5a, Leukotriene B4
Where are P selectins stored? What signals their release? What does it bind to?
Stored in Weibel-Palade bodies, released in response to TNF or IL-1
Binds to P-selectin glycoprotein ligand 1
Where are E selectins stored? What signals their release? What does it bind to?
Synthesized de novo by endothelium
activated by TNF or IL-1
Binds to sialylated Lewis-X type oligosaccharides on surface proteins
What is the function of L selectins? What does it bind to?
homing receptors of Leukocytes to bind to endothelium via CD34
Which of the selectins recognize sialylated Lewis-X type oligosaccharides on surface proteins
P and E
Which of the selectins recognized CD34?
L
What is the endothelial receptor that binds to LFA-1/Mac-1 on leukocytes?
ICAM-1
What is the cell receptor that binds to integrin VLA-4?
VCAM-1
What is the cell adhesion molecule that binds to CD-31?
opposing PECAM-1
What is the cell adhesion molecule that plays an important role in the diapedesis step of leukocyte emigration?
PECAM-1
