acute inflammation Flashcards
Types of inflammation:
Serous inflammation
Effusion of thin watery exudate that can be found in the peritoneal, pleural, or pericardial cavities, or be seen as blisters on the skin
No bacteria, it comes from vascular permeability or tissue damage
Types of inflammation:
Fibrinous inflammation
Accumulation of fibrin-rich exudate in meninges, pericardium, or pleura. This can either be resolved or lead to scarring.
Ex. Fibrinous pericarditis ass with MI or Rheumatic fever
Types of inflammation:
Purulent (Suppurative) inflammation
Production of pus, neutrophils, necrotic tissue, and edema
Ex. Acute pancreatitis
Types of inflammation:
Ulcers
Local defect/excavation in the surface of an organ due to necrotic tissue shedding off
common areas are mouth, duodenum, and skin
Types of infection:
Pseudomembranous inflammation
Bacterial toxin-induced damage of mucosal linings (causes a shaggy membrane)
Ex clostridium difficile (pseudomembranous colitis) & corynebacterium diphtheriae
Mediators of acute-phase response of inflammation are?
TNF
IL-1,6
INFs
Mechanisms of fever are mediated by which pyrogenic cytokines?
IL1, 6
TNF
INFs
Liver-made plasma proteins that mediate acute inflammation include:
C-reactive protein
Fibrinogen
Hepcidin
Serum amyloid A protein
IL-6 stimulates ______&_____
C-reactive protein
&
Fibrinogen
Erythrocyte sedimentation rate is due to which acute-phase protein?
Fibrinogen
It binds to RBCs and causes them to form stacks (rouleaux)
Leukocytosis is described as a ______ reaction with leukocyte levels avg ____ -_____
Leukemoid reactions showing levels 40,000 to 100,000 leukocyte counts
Neutrophilia
increase in neutrophil count usually due to bacterial infections
Lymphocytosis
Increase in number of lymphocytes in viral infections
Eosinophilia
Allergies & parasitic infections which increase the number of eosinophils
What are the 3 outcomes of acute inflammation?
Resolution
Scarring/fibrosis
Chronic inflammation
Myeloperoxidase deficiency
Auto REC condition, no HOCL production leads to recurrent fungal infections (candida)
The acquired form of MPO usually happens due to
Myelomonocytic leukemia & acute myeloid leukemia
Chediak Higashi Syndrome
An AUTO REC
Defect in protein trafficking due to mutated CHS1 gene for Lysosomal transport protein
*Albinism
*Leukocytes with GIANT granules
*Hemostasis
*Impaired phagolysosome (recurrent infections)
*Peripheral neuropathy
Chronic Granulomatous disease
Deficient NADPH oxidase
(due to mutated CYBB) absent respiratory burst. It causes deep tissue bacterial and fungal abscesses in macrophage-rich organs (lymph nodes, liver, lungs etc)
Most common are catalase + (S. aureus, Nocardia, Aspergillus, & Candida)
What test is used for CGD and what results indicate what?
Nitroublue Tetrazolium dye test
Blue = NADPH okay
Colorless = NADPH is fucked
LAD (Leukocyte Adhesion Deficiency)
AUTO REC condition
Caused by deficient B2 integrin
-Delayed umbilical separation
- Hyperleukocytosis (>30,000)
- Poor wound healing
- Severe gingivitis
- Ulcers in genital area
LAD 2
AUTO REC
messed up selectin-leukocyte rolling
defective Sialyl-Lewis X glycoproteins
LAD 3
AUTO REC
Defective kindlin (which helps activate the ligands affinity of B2 integrins)
Phagocytic receptors:
Mannose receptor
A lectin that binds the terminal mannose and fucose residues of glycoproteins and glycolipids on microbial cell walls
Phagocytosis process (3 steps)
- Recognition/attachment of particle
- Engulfment + formation of phagocytic vacuole
- Killing/degradation
Chemotactic factors of leukocytes include:
IL-8
C5a
LTB4
Leukocyte Recruitment to inflammation steps (5)
- Margination
- Rolling
- Adhesion
- Transmigration/diapedesis
- Migration in interstitial tissue to injury
Steps of leukocyte recruitment:
Margination
Fibrinogens cause circulating leukocytes aggregate into rouleaux in the venules aka now marginating leukocytes.
Steps of leukocyte recruitment:
Rolling of neutrophils
Happens in the venules where selectins on neutrophils and endothelial cells bind to each other “speed bumps.”
L-selectin is on neutrophils (bind GlyCam-1 endo)
P&E-selectin are on endothelium (bind Sialyl-Lewis x-mod glycoprotein neutrophil)
IL-1 & TNF stimulate the expression of selectins
Where is P-selectin formed?
Wiebel Palade bodies in vascular endothelial cells
Steps of leukocyte recruitment:
Adhesion of neutrophils
Integrins bind and firmly adhere the neutrophil to the endothelium:
VCAM & ICAM (Vascular endothelium)
MAC-1, LFA-1, & VLA-4 (Neutrophil)
Steps of leukocyte recruitment:
Transmigration/Diapedesis
Mostly in the post-capillary venules, chemokines help leukocytes move through interendothelial spaces to reach sites of inflammation
PECAM-1 (intercellular junctions)
C5A
LTB4
Leukocytes use __________ to breach the basement membrane and enter interstitial tissues
collagenases
Chronic Granulomatous disease
Pseudomembranous inflammation
CGD
Ulcerative inflammation
Purulent/suppurative inflammation
Fibrous inflammation
Chediak Higashi syndrome
Selectins:
Selectins are induced by _______ & ________?
IL-1 & TNF
Selectins:
Describe what L-selectins are?
Expressed on neutrophils and bind to endothelial mucin-like molecules like GlyCam-1
Selectins:
Describe what E & P Selectins are?
These are expressed on endothelial cells and bind to oligosaccharides like Sialyl-Lewis X on leukocytes.
Selectins:
Where are P selectins stored?
They’re stored in endothelial Weibel-Palade bodies and platelet alpha granules & released y histamine & thrombin
Immunoglobin-family adhesion proteins:
Describe where ICAM-1 & VCAM receptors are and what they bind to?
They are expressed on endothelial cells and bind to integrins on leukocytes
Immunoglobin-family adhesion proteins:
Describe where integrins are and what they bind to?
LFA-1, MAC-1, & VLA-4 are all expressed on leukocytes & all bind to the endothelial Ig-family adhesion proteins
Acute inflammation:
Describe the vasoactive changes that happen in acute inflammation.
- First vasoconstriction
- Then vasodilation of arterioles, capillaries, & post capillary venules
Acute inflammation:
Describe the changes to vascular permeability following the vasoactive changes of acute inflammation
After the initial vasoconstriction then dilation causes transudate to leak out of capillaries into the interstitial space (edema)
Acute inflammation, cellular response of leukocytes (Margination –> Transmigration)
- Margination (leukocytes move to the outer margin of blood flow to the vascular endothelium)
- Rolling (Selectins L (leukocytes) & P/E (endothelium) loosely bind GlyCam-1 & Sialyl-Lewis X glycoprotein respectively to slow the leukocyte down)
- Adhesion (Integrins (leukocyte) bind ICAM & VCAM (endothelium) to firmly adhere the leukocyte to endothelium)
- Transmigration (PCAM-1/CD31 mediated the movement of leukocytes across the endothelium membrane)
Acute inflammation, Chemotaxis:
What are the chemotactic factors for neutrophils
- Products from bacteria
- Complement proteins C5a
- LTB4 (Lipoxygenase), Kallikrein, & HETE (hydroxyeicosatetranoic acid)
direct the leukocyte to the site of injury/infection
Chemotactic factors:
Neutrophils
C5a
HETE
LTB4
Fibrinogen
PDGF
Chemotactic factors:
Eosinophils
PAF
Fibronectin
Chemotactic factors:
Macrophages
PDGF
TGF-B
Most important opsonins for phagocytosis are ____ & ____
IgG & C3b
Vasoconstriction is mediated by
TxA2 (platelets)
LTC4, LTD4, LTE4 (Leukotrienes)
PAF (Platelet aggregation factor)
Vasodilation is mediated by
PGI2, PGE2, PGF2a (Prostaglandins)
Bradykinin
PAF
Nitric oxide
Increased vascular permeability is mediated by
Histamine
Serotonin
PGE2, PGD2, PGF2 (Prostaglandins)
LTC4, LTD4, LTE4 (Leukotrienes)
Bradykinin
PAF
Endogenous mediators, vasoactive amines:
Describe the vasoactive features of histamine
It mediates an increase in capillary permeability causing contraction of endothelial cells in postcapillary venules (during mild injuries)
It comes from basophils, mast cells, & platelets
Endogenous mediators, vasoactive amines:
Describe the process of how histamine is released from basophils & mast cells ?
Histamine is released via degranulation when triggered by:
- Ag binding IgE to a basophil & mast cell
- C3a & C5a bind to receptors on basophils & mast cells
- heat/cold
- IL-1
- Factors from neutrophils, monocytes, & platelets
Serotonin (5-hydroxytryptamine) acts similarly to ___________ & it’s derived from ____________
similar to histamine & it’s derived from platelets
Arachidonic acid metabolites:
What stimulates the release of arachidonic acid from cell membranes?
Phospholipase A2
Arachidonic acid metabolites:
The cyclooxygenase pathway is catalyzed by two enzymic isoforms _____ & _____, what is the pathway inhibited by?
COX-1 & COX-2
&
The pathway is inhibited by aspirin (any anti-inflammatory drugs)
The cyclooxygenase pathway yields which two factors?
Platelet TxA2 (a powerful vasoconstrictor & platelet aggregate)
&
Endothelial PGI2 (a powerful vasodilator & inhibitor of platelet aggregation)
The lipoxygenase pathway yields _____________ & its derivatives ______ in platelets & _____/____ in leukocytes
HPETE (Hydroperoxyeicosatetraenoic acid)
12-HPETE
5-HPETE/15-HPETE
Describe the properties of 5-HPETE
- It gives rise to HETE a chemotactic for neutrophils & Leukotrienes LTB4 (chemotactic for neutrophils), LTC4, D4, E4 (Vasoconstrictors, bronchoconstrictors, & increase vascular permeability)
interferon-γ are made from ____/___ & activate ______
made from t-cells and NK cells and activates monocytes into macrophages
Cytokines IL-1 & TNF are secreted by ________
monocytes-macrophages
IL-1 & TNF induce acute phase systemic effects
