Acute Inflammation Flashcards
1
Q
What is inflammation?
A
A well ordered vascular and cellular response of tissues to aggression.
• It is a defense mechanism to eliminate initial cause of injury and the consequences of that injury (i.e necrotic cells) and initiate repair
2
Q
What are the two components of acute inflammation?
A
Vascular: Vascular component characterized by hyperemia, vasodilation and vascular leakage. This is to “dilute” the cause of injury.
Cellular: Cellular component is to heal/ repair the injury
3
Q
What is a consequence of inflammation?
A
• Potential for substantial tissue damage. Sometimes the inflammation will cause a worse injury.
4
Q
What is the purpose of inflammation?
A
- contain injury
- destroy/ dilute or wall off offending agents
- remove damaged or necrotic tissue (macrophages)
- prepare tissue for repair / healing
5
Q
What are the beneficial aspects of inflammation? The harmful aspects of inflammation?
A
- Good: Diluting and/or inactivating biological
and chemical toxins. Killing or sequestering microbes,
foreign material, necrotic tissue, and neoplastic cells. Providing wound healing factors. Restricting movement for healing and repair
• Bad: Prolonged release of inflammatory mediators, excessive fibrosis, hypersensitivity and autoimmunity, chronic inflammation can lead to neoplastic transformation,
6
Q
What are the 5 cardinal signs of inflammation?
A
◦ Heat and redness (Hyperemia and vasodilation)
◦ Swelling ( edema and emigration of leukocytes)
◦ Pain (chemical mediators)
◦ Loss of function ( can preserve tissue and allow for healing)
7
Q
What are the vascular changes associated with acute inflammation?
A
- Vascular: Hyperemia, Vasodilation, Increased vascular permeability (edema)
- Cellular: - Emigration of leukocytes (predominantly neutrophils) and delivery at the site of injury, to kill and/or neutralize the inciting stimulus
8
Q
What orchestrates cellular and vascular changes of acute inflammation?
A
• Cellular and vascular changes are orchestrated by chemical mediators (many of them)
9
Q
What is the clinical definitions of inflammation? Pathologic definitions? What is seen in subacute inflammation?
A
Clinical definition
• Acute: Hours to days
• Chronic: weeks to months to years
Pathologic definition
• Acute: edema, fibrin, neutrophils
• Chronic: macrophages, lymphocytes, plasma
cells, few neutrophils, fibrosis
Subacute: Lymphocytes and Plasma cells.
10
Q
What is the general process of acute inflammation?
A
- Bacteria and other pathogens enter wound
- Macrophages “senses” bacteria through their receptors and phagocytize
- Chemical mediators secretion by activated
macrophages and mast cells 4. Hyperemia, vasodilation and increase vascular permeability - Leakage of fluid (edema) and neutrophils
- Neutrophils phagocyte and/or secrete
granules that kill and degrade pathogens - Macrophages secrete cytokines that attract leukocytes to the site and activate cells involved in tissue repair
- Inflammatory response continues until the foreign material is eliminated and the
wound is repaired
11
Q
What are the causes of acute inflammation?
A
• Infections (bacteria, viruses, parasites)
• Trauma
• Physical agents (heat, cold)
• Toxins
• Tissue necrosis (of any origin; products of degenerate or
neoplastic processes)
• Foreign bodies (grass awn, sutures)
• Immunological reactions
12
Q
What are the primary vascular and cellular responses during acute inflammation?
A
- Mast cell will sense injury and will secrete cytokines that will increase vascular permeability, endothelial cell contraction, chemotaxis of neutrophils.
- Diapedesis of erythrocytes can also occur - mild hemorrhage.
13
Q
What occurs during the fluidic phase of acute inflammation? What is the purpose?
A
1) Increase blood flow (hyperemia) and vasodilation (mediated by Histamine, NO, PGD2, Bradykinin, LTB4) 2)↑Vascular permeability (mediated by Histamine, Bradykinin, C5a, C3a, PGE2, Leukotrienes, PAF, IL-1, TNF)
- Leads to leakage of fluid, plasma proteins and leukocytes (neutrophils) to the tissue
- Exudate
- Purpose: Dilute, isolate (surround), and trap (contain) the injurious agent and damag
14
Q
What is transudate? What is exudate?
A
• Transudate - accumulation of fluid- clear, watery, translucent, low protein/ plasma cells.
◦ Think of mechanism of edema, increased hydrostatic (CHF), decreased osmotic (parasitism, PLN, PLE, Liver failure), lymphatic obstruction (tumors)
• Exudate: inflammation, accumulation of opaque, thick fluid. A lot of plasma proteins, neutrophils, macrophages, inflammatory cells, ect. Mechanism is increased vascular permeability.
◦ Fibrin also present due to decreased vascular permeability
15
Q
What mediates increased vascular permeability?
A
• Mediated by vasoactive amines (histamine, bradykinin), C5a and C3a, prostaglandins, leukotrienes, PAF, IL-1 and TNF
16
Q
What are the mechanisms of increased vascular permeability?
A
1) Retraction of endothelial cells
2) Direct endothelial cell injury 3) Leukocyte-mediated vascular injury
4) Increased transcytosis
17
Q
What occurs during retraction of endothelial cells?
A
• Mediated by vasoactive amines
• most common
• Gap formed between endothelial cells to allow fluid and plasma cells to leak out.
- Mediated by vasoactive amines
(histamine, bradykinin, serotonin), NO,
IL-1 and TNF
18
Q
What occurs during direct endothelial cell injury?
A
• can cause necrosis, and detachment of cell from underlying basement membrane
• activation of platelets, clotting and complement cascades
• Thermal injury, chemotherapeutic drugs, radiation, bacterial cytotoxins, viral and protozoal infections
◦ Protozoa can cause vasculitis, ect
19
Q
What occurs during leukocyte mediated vascular injury?
A
- can cause necrosis, and detachment of cell from underlying basement membrane
- Neutrophils/ other leukocytes attach to endothelial cells and release ROS and proteolytic enzymes ( from lysosomes)
• usually associated with bacteria, or viruses that affect neutrophils.
- Ricckketsia is one example. RMSF
20
Q
What is the end result of increased vascular permeability? What is fibrin?
A
- end results are fibrin, strands of fibrin.
- Fibrinous pleuritis.
- Fibrin is chemoattractant to neutrophils
- If inflammation does not resolve or if it is exacerbated by chemical mediators (pro- inflammatory cytokines), there will be accumulation of neutrophils
21
Q
What is seen in this image?
A
Fibrin : Fibrinous pleuritis
22
Q
What is seen in this image?
A
Fibrinosuppurative pleuritis
**Fluidic and cellular phase occur together
23
Q
What is the purpose of cellular phase of acute inflammation? What is the result?
A
• Purpose of cellular phase: Deliver leukocytes into the exudate so they can kill and/or inactivate the stimulus
Results in:
- Exudation
- Cellular activation
• Microbial killing ( by phagocytosis, or release of proteolytic degradative enzymes)
• Extent/ intensity of this process causes varying degrees of injury to adjoining normal tissue.
- Clear necrotic cells and debris
24
Q
What are the steps of the leukocyte adhesion cascade? What is it mediated by?
A
1) Margination
2) Rolling
3) Activation and Stable Adhesion
4) Transendothelial cell migration
Mediated by adhesion molecules and cytokines/chemokines (histamine, TNF, IL-1):
- Selectins (Rolling)
- Integrins + VCAM and ICAM (Activation and Stable Adhesion)
- PECAM and JAM (Transendothelial cell migration)
25
What drive migration of leukocytes to the site of inflammation?
* migration driven by chemokines
* chemokines: bacterial products, IL-8, complement components (C5a and C3a) and arachadonic acid metabolites ( LTR4) (act as GPS for neutrophils)
* Produced at sites of inflammation and diffuse out into surrounding tissues.
* Activates leukocytes.
26
What occurs once neutrophils enter the site of inflammation?
Kill pathogens and degrade foreign material by two mechanisms:
– Phagocytosis (ROS)
– Secretion of granule contents into the exudate (can contribute to tissue injury)
- Enzymes (proteases) - Myeloperoxidases (MPO) - Matrix metalloproteinases - Lactoferrin lysozyme
27
What are the effector cells of acute inflammation?
* Endothelial cells
* Mast cells and basophils
* Neutrophils
* Eosinophils
* NK cells Macrophage
* Monocytes and Macrophages
28
What are the cell derived mediators of inflammation? Plasma protein derived mediators?
– Preformed (in granules)
• Histamine
– Synthesized
* Prostaglandins
* Leukotrienes
* Cytokines and Chemokines
* Platelet-activating factor (PAF)
* Reactive oxygen species
* Nitric oxide
29
What are archidonic acid metabolites (lipid mediators)? What are the sources? What pathwayas are they formed in?
Arachidonic Acid Metabolites (Lipid Mediators): Prostaglandins, Thromboxanes, Leukotrienes and Lipoxins
Sources: Resident cells, leukocytes, mast cells, eosinophils
Cell injury → Increase intracytoplasmic Ca++ concentration → activation of phospholipase A2
• Cyclooxygenase pathway → Prostaglandins and Thromboxanes
* 3 COX isoenzymes (COX1= constitutively expressed; COX2= induced by inflammatory stimuli; COX3= splice variant of COX1, can cross BBB)
* Lipoxygenase pathway → Leukotrienes and lipoxins
30
What will inhibit phospholipase? What are Cox-1 and Cox 2 inhibitors? what does PGI2, TXA2, PGD2, PGE2, 5-lipoxygenase, and lipoxin A4 and B4 do?
Steroids will inhibit phospholipase
COX -1 and COX 2 inhibitors: aspirin, indomethacin, inhibit)
Immunosuppressive and anti inflammatory drugs will inhibit.
COX-2 to prostaglandins.
PGI2 -\> Causes vasodilation, inhibits platelet aggregation.
TXA2 -\> causes vasoconstriction, promotes platelet aggregation.
PGD2, PGE2 -\> causes vasodilation, increased vascular permeability.
5-Lipoxygenase -\> leukotrienes ( C4, D4, E4 - in cases of asthma (bronchospasm , increased vascular permeability.
lipoxin A4, and B4 ( inhibition inflammation , during healing)
31
What is the roles of cytokines TNF, IL-1, IL-6?
• Sources: Resident cells, leukocytes, mast cells, eosinophils
• Most important roles:
– Endothelial activation: Both cause increased expression of endothelial adhesion molecules (selectins and ligands for WBC integrins)
– Activation of WBCs and other cells:
• TNF augments response of neutrophils and stimulates microbicidal activity of
macrophages
– Systemic acute-phase response: TNF & IL-1 (along with IL-6) induce systemic acute- phase response associated with infection or injury
- Increased production: C-reactive protein, Fibrinogen, Hepcidin, others - Stimulate innate immune system against infection
Decreased abumin production
32
What can TNF, IL-1 cause?
Insulin resistance
33
What is the most important part of the reparative phase? What categories of tissue repair are possible?
• Macrophage movement into areas of entrapped
stimulus/inciting agent to further process and remove cellular debris
• Macrophage release molecules initiating tissue repair
Macrophages most important
- Tissue repair may be (1) regenerative or by (2) scarring (fibrosis)
1 - Mild tissue injury with preservation of supporting stroma
and basement membrane: Regeneration
2 - Tissue injury with destruction of supporting stroma and
basement membrane: Scarring (fibrosis)
34
What cells are considered labile? Stable? Permenant?
• Labile: Bone marrow stem cells, GI epithelium, keratinocytes
- Always Regenerating
• Stable: Hepatocytes, renal tubular epithelium
- Sometimes regenerating
• Permanent: Neurons, skeletal and cardiac muscle
- Never regenerating
35
What are the potential outcomes of acute inflammation?
* outcome depends on damage severity and location
* mild -\> Resolution
* moderate: Healing by repair
* Severe : Chronic inflammation
36
What occurs in resolution? What are characteristics of resolution?
• Short-term damage
• Little tissue destruction with regeneration
- Tissue stroma and basement membrane are intact
• Removal of cellular debris by macrophages
37
What causes healing by fibrosis?
• Substantial tissue destruction, without regeneration capacity, or abundant exudation of fibrin.
38
What is occuring in this image?
Fibrosis
39
What is occuring in this image?
Healing by fibrosis
40
What is abcess formation?
Marked neutrophilic response with tissue destruction
41
What is occuring in this image?
Abcess formation
42
What occurs if offending agent is not removed?
Inflammation progresses to chronic inflammation
43
What is the type of lesions in this image?
Offending agents have not been removed ( tuberculosis) so their ar multiple granulomas seen in this section of tissue.
44
What are the morphological classifications of exudates in acute inflammatory lesions?
Assists to understand the pathogenesis
* Serous
* Catarrhal
* Fibrinous
* Suppurative (purulent)
* Hemorrhagic
* Necrotizing
* Combination (mucopurulent, fibrinonecrotic, necrohemorrhagic, etc)
45
What is serous exudate? What are some causes?
• Leakage or accumulation of fluid with a low concentration of plasma
proteins and no to low numbers of leukocytes
• Burns • Acute allergic response • Vesicular stomatitis (Foot and Mouth Disease)
46
What kind of exudate is seen in this image?
Serous
47
What catarrhal exudate?
• ↑ Mucus (thick, gelatinous fluid)
• Seen in Tissues with abundant goblet cells or mucous glands (respiratory and
gastrointestinal tracts)
48
What is seen in these images?
Mucoid or Catarrhal exudate
49
What is fibrinoud exudate? What does it indicate? What is found within the exudate?
Endothelial cell damage, ↑ vascular permeability • Fluid with a high concentration of plasma proteins • Bacteria (bacterial toxins, bloodstream dissemination), virus, etc..
50
What is seen in this image?
Fibrinous exudate
51
What is suppurative exudate?
Exudate with a large number of neutrophils
52
What is pus? What kind of exudate is it seen in? What is a collection of pus with a surrounding capsule called?
Pus = collection of viable and dead neutrophils Collection of pus surrounded by a capsule = Abscess
53
What kind of exudate is seen in this image?
Suppurative (purulent discharge) Abcess
54
What is mucopurulent sinusitis?
Mucus + neutrophils
55
What is occuring in this image?
Mucupurulent exudate
56
What is hemmorhagic exudate?
Most of the exudate is composed of blood
Hook worms infection in dogs can cause hemorrhagic exudate.
57
What is occuring in this image of tissue?
Hemorrhagic exudate
58
What is necrotizing exudate?
- An acute inflammatory reaction in which the predominant change is necrosis
* tissue response of necrosis -\> this picture is herpes virus
* All white dots are areas of necrosis with areas of inflammatory cells.
59
What is fibronecrotic exudate? What is another name for it?
The necrotic mucosa is covered by a layer of fibrin and cellular debris
(pseudomembrane)
60
What is occuring in this image?
Fibrinonecrotic (pseudomembranous)
61
What is necrohemorrhagic exudate?
Necrohemorrhagic = Necrotizing + hemorrhagic
62
How would you categorize the tissue in this image?
Necrohemorrhagi
63
What changes can you see in a fibrinonecrotic section of intestine?
• loss of villi, loss of epithelial cells , layer of fibrin covering it
64
What can you see in necrosis of muscle fibers?
Necrosis of muscle fibers + emphysema
65
What is occuring in this histology section of tissues?
Hemorrhage
66
What are the chemical mediators of inflammation?
• Vasodilation: Prostaglandins, Histamine, NO
• Vascular permeability: Histamine, C3a, C5a, Bradykinin, Leukotrienes
• Chemotaxis: IL-8, C5a, LTB 4
, Microbial products, fibrin
• Fever: IL-1, TNF, PGE2
• Pain: Bradykinin, PGE2
67
What are chemokines? What is their role?
Chemoattractants for leukocytes, recruiting monocytes, neutrophils and other effector cells
from the blood to sites of infection or tissue damage
• Activate cells to initiate an immune response or promote wound healing
68
What chemokines activate which cells?
* IL-8 → Neutrophils
* Eotaxin→ Eosinophils
* Monocytes chemoattractant protein 1 (MCP-1) → Macrophages
* RANTES → T lymphocytes and eosinophils
69
What are cytokines?
• Proteins produced by many cell types, principally activated lymphocytes, macrophages, and dendritic cells
– Also endothelial, epithelial, connective tissue cells
• Modulate functions of other cell types in both acute & chronic inflammation; other roles:
– Adaptive immunity (i.e., lymphocyte proliferation via IL-2; activation of TH1 or TH2 responses)
70
What are the functions of the arachidonic acid metabolites?
* Prostaglandins: Vasodilation and increased vascular permeability
* Thromboxane and Leukotrienes: Vasoconstriction
* Leukotrienes: Increased vascular permeability
* Leukotriene B 4 : Chemotaxis
* Lipoxins: Inhibition of inflammation
71
What is occuring in this image? What step is it in the leukocyte adhesion cascade?
Margination
• With vasodilation and reduced blood flow, leukocytes exit the central region of the vascular lumen and
move to the periphery near the endothelial cell surface
72
What occurs during the rolling stage of leukocyte adhesion?
• Initial contact between leukocytes and endothelial cells
• Transient, weak binding interactions between Selectins (adhesion molecules) and their
receptors
• Under the influence of cytokines (histamine, TNF, IL-1), endothelium express P-selectin and E-
selectin
• Reduces the velocity of the travelling leukocyte, creating the microenvironment for activation
and “stable adhesion” (the next step)
73
What occurs during the activation and stable adhesison step of leukocyte adhesion? What needs to be activated for it to occur?
* For stable adhesion to occur, neutrophils and endothelial cells need to become activated
* Activation is mediated by cytokines (IL-1, TNF) and chemokines (IL-8)
• Activation is characterized by expression of INTEGRINS on leukocytes and vascular cell adhesion
molecule (VCAM) and intercellular adhesion molecule (ICAM) on endothelial cells.
• Stable adhesion: Binding of INTEGRINS on leukocytes to VCAM and ICAM on endothelial cells
74
What occurs during the transendothelial cell migration (emigration) step of the leukocyte adhesion cascade?
• Firmly adhered leukocytes emigrate across the endothelial layer by passing between endothelial cells
• Mediated by expression and binding of Platelet endothelial cell adhesion molecule 1 (PECAM-1) and
junctional adhesion molecules (JAM) on both leukocytes and endothelial cells
75
What is leukocyte adhesion deficiency? What animals can it be seen in? What are the clinical signs?
• Holstein Cattle, dogs (Irish setters), and human
beings with LAD lack functional expression of
the β2 integrins
• High numbers of neutrophils, exceeding 125,000/μL
in the blood
• Oral ulcers, gingivitis, tooth loss, enteric ulcers,
cutaneous ulcers, abscesses that lack pus formation,
and pneumonia
76
Where do leukocytes migrate too during inflammation? What are the main chemoattractants?
* Migration to extracellular matrix ( to site of inflammation)
* Migration via chemoattractant substances (chemotaxis)
• Main chemoattractant substances: bacterial products, chemokines (IL-8), complement components
(C5a), arachadonic acid metabolites (LTB4)
* They are produced at sites of inflammation and diffuse out into the surrounding tissues
* Also activate leukocytes and get them ready for battle
77
What is the speed of emigration ( listed in order of fastest to slowest of edema, neutrophils, or macrophages/ monocytes?
1. ) Edema ( within 1.5 days)
2. ) Neutrophils ( Within 2.5 days)
3. ) macrophages/ monocytes ( \> 3 days)
78
What are the 3 steps of phagocytosis?
• 1. Recognition and attachment - Facilitated by opsonins (C3b and IgG)
• 2. Engulfment - Form a phagosome and fuse with lysosome = phagolysosome
• 3. Killing/degradation
- Lysosomal enzymes (acid hydrolases, proteases)
- Oxidative (Respiratory) burst: formation of ROS
- Formation of NO
- Release of granule contents: myeloperoxidase (absent in avian and reptiles), elastase, collagenase, lysozyme, defensins, etc…)
- Releasing of these granules into the extracellular space leads to tissue damage
79
What occurs to endothelial cells during the fluidic phase? The Cellular phase?
• Fluidic phase
- Endothelial cells are activated and contract → fluid leakage
- Vascular tone controlled by vasoconstrictive & vasodilatory substances produced by endothelial cells:
• Vasoconstriction: Endothelin, angiotensin II
• Vasodilation: NO, prostacyclin (PGI2)
• Cellular phase
– Activated endothelial cells express adhesion molecules/receptors:
• Selectins, PECAM-1, JAM, and ICAM-1 (integrin ligand)
• Inflammation is associated with an increase of endothelial cell pro-coagulative properties:
– Release of tissue factor and other pro-coagulative substances
80
What is the role of mast cells and basophils in acute inflammation?
• Located around small blood and lymphatic vessels of skin and mucous membranes
• Both MCs and basophils play a role in IgE-mediated hypersensitivity reactions
•Degranulation → Mucus secretion, bronchoconstriction, vasodilation, fluid accumulation in airways
•Granules → Preformed/Synthesized Mediators: Histamine, Chymase and Tryptase (degradation of ECM),
cytokines, growth factors, PAF, LTC4, PGD2…
81
What stimulates the release of histamine from mast cells?
* IgE
* C3a, C5a
* Heat
* Cold
* Trauma
82
83
What is the role of neutrophils in acute inflammation?
• First leukocytes to enter the exudate:
– Kill microbes (bacteria, fungi, protozoa, viruses)
– Kill tumor cells
– Eliminate foreign materials • Kill pathogens and degrade foreign material by two mechanisms:
–Phagocytosis → fusion with lysosome
– Secretion of granule contents into exudate (can contribute to tissue injury) • Activated leukocytes (including neutrophils) also produce cytokines
84
What are the chemokines for neutrophils? What happens to neutrophils during apoptosis?
* Chemokines for neutrophils: IL-8, C3a, C5a, LTB4, bacterial products
* Phagocytosis and microbial killing (ROS and NO)
• AI resolves → cytokines withdrawal → neutrophil apoptosis
– During apoptosis, neutrophils lose capacity to activate/degranulate → prevents release of lysosomal enzymes and allows for phagocytosis by macrophages
85
What is the roll of eosinophils in acute inflammation? What are the chemoattractants for eosinophils ?
• Recruited in response to allergic or parasitic disease; often come in transition from acute→chronic
inflammation
– Worms, wheezes & weird diseases
• When activated, eosinophils can also elaborate:
– CKs, Chemokines, proteases, oxidative radicals • Eosinophil chemoattractants (released from epithelial cells, eosinophils, mast cells, and helminths):
– Histamine – C5a – Eotaxin – Cytokines (IL-4, Il-5, IL-13)
86
What is the role of natural killer cells?
• NK cells: Lysis/apoptosis of tumor & virus infected cells without previous
encounter by releasing perforin & granzymes
• MHC class I (ubiquitous expression by normal cells) is inhibitory - prevents
NK cells from killing host cells
– If MHC I is downregulated by pathogen → NK can kill the cell – Virus-infected and neoplastic cells often downregulate MHC1→ susceptible to NK mediated lysis
• All other nucleated cells express MHC I and are protected
87
What is the role of monocytes/ macrophages in acute inflammation? What are the 2 types of tissue macrophages? What is its role in inate and adaptive immunity?
• During AI, monocytes express receptors for chemical mediators → migration, chemotaxis, etc→ once in
lesion, receptors bound by inflammatory mediators → mature into macrophages
• Tissue macrophages (2 types):
– Reside within specific organs/tissues
• Histiocytes, alveolar macrophages, Kupffer cells, osteoclasts, microglial cells
– Derived from monocytes
* Inflammation: Monocyte receptors bound by CKs, antigens, etc→ maturation to macrophages
* Part of innate immunity: Phagocytosis, release CKs
* Adaptive immunity: APC, T-lymphocyte regulation
88
What are the cell derrived chemical mediators of inflamation that are preformed( in granules)? Synthesized? Ones that are Plasma protein derrived?
**_Cell-derived mediators_**
– Preformed (in granules)
• Histamine
• Serotonin
• Lysosomal enzymes
– Synthesized
* Prostaglandins
* Leukotrienes
* Cytokines and Chemokines
* Platelet-activating factor (PAF)
* Reactive oxygen species
* Nitric oxide
Plasma protein-derived mediators
Produced in liver as inactive precursors
* Complement products
* Kinins
* Proteases activated during coagulation
* Acute phase proteins
89
What are the general features of chemical mediators?
• Initiated by other mediators or initial insult
• Bind to receptors on target cells and often activate target cells or cause the target cell to secrete
additional inflammatory mediators (amplifying [pro-inflammatory] or suppressing [anti-inflammatory])
• Local or systemic effects
* Once activated and released or secreted, most inflammatory mediators:
* Have short half-lives and decay rapidly
* Are destroyed enzymatically
* Are scavenged by protective mechanisms such as antioxidants
90
What is histamine? what is its sources? What is it released in response to? What is its effects?
* Sources: Mast cells, basophils, platelets
* Released in response to: physical injury, IgE binding, C3a & C5a (anaphylatoxins), and cytokines (IL-1, IL-8)
• Effects: Increased vascular permeability, Vasodilation (H1 receptors in endothelial cells), Eosinophil chemotaxis, Pain and
itching
91
What is serotonin? what is its sources? What is it released in response to? What is its effects?
* Sources: Platelets
* Released during platelet aggregation
* Effects: Increased vascular permeability, Vasodilation
92
What are the 3 pathways of complement activation? What activates them?
• Classic pathway
- Activated by antibody complexes: IgG or IgM bound to Ag
• Lectin pathway
- Plasma mannose-binding lectin bind to carbohydrates on microbes
• Alternative pathway
- Activated by products from microbes (LPS, endotoxin, fungal cell wall polysaccharides), venom
93
What is the complement system? What is the critical step in activating complement? What do all pathways form? What does complement system generate and what is the result of this molecule?
- Part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to
clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell
membrane
• Inactive plasma proteins, made in the liver, activated after tissue injury (or clotting or immune responses) → generates pro-inflammatory, chemotactic, opsonizing, microbicidal molecules
* Critical step in activating complement is the activation of C3 via classical/lectin/alternative pathways
* All pathways form C3 convertases (classical/lectin vs. alternative forms are slightly different but do the same thing): –Generate the membrane attack complex (MAC) → perforates cell membrane of foreign invaders & naïve host cells
94
