Lecture 3 - Inflammation Flashcards
1
Q
State the main WBC in blood, and there % prevalence?
A
“Never let monkeys eat bananas”
Neutrophils - 60% Lymphocytes - 30% Monocytes - 6% Eosinophils - 3% Basophils - 1%
2
Q
haematoxylin:
a. ) Acidic or basic?
b. ) What stained?
c. ) basophillic or eosinophilic?
A
a. ) basic
b. ) nucleus (DNA)
c. ) basophilic
3
Q
eosin:
a. ) Acidic or basic?
b. ) What stained?
c. ) basophillic or eosinophilic?
A
a. ) acidic
b. ) cytoplasm, muscle, collagen etc
c. ) eosinophilic
4
Q
Which WBC are granulocytes?
A
- eosinophils
- basophils
- neutrophils
5
Q
A macrophage in the bloodstream is known as?
A
a monocyte
6
Q
what shape is a monocyte/ macrophage nucleus?
A
kidney shape
7
Q
t/f: a monocyte has a small perimeter of cytoplasm
A
false - these cells are phagocytic so need large amount of area for this
8
Q
Monocytes/ macrophages often have special names in resident tissues - provide 2 examples?
A
kuppfer cells - liver
histiocytes - sinus
9
Q
Complete the statement:
___phils are prevalent in large numbers because they are required to act at short notice, participating in ___ _____
A
neutrophils; acute inflammation
10
Q
In a patient with acute appendicitis, the tissue is infiltrtated by large amounts of a certain type of cell initially. Which cell is this likely to be?
A
neutrophil
11
Q
When inflammation is severe pus may form - what is this?
A
a collection of neutrophils and necrotic cells
12
Q
which WBC is the ‘principle cell involved in acute inflammation’?
A
neutrophil
13
Q
define abscess
A
a walled off collection of pus
14
Q
Acute inflammation following tissue damage may go down one of two routes - explain these?
A
- If cells can regenerate, within days this is done and normal structure and function is regained (less likely)
- If cells cannot regrow as such healing occurs by repair mechanisms, this involves scar formation (‘fibrous repair’) leading to loss of specialized function. This is the more likely outcome.
15
Q
describe the difference between regeneration and healing
A
healing - involves scar formation (more likely)
regeneration - no scar formation (less likely)
16
Q
State some vascular events of the inflammatory process?
A
“KFCC makes the cytokine storm”
- Coagulation cascade
- Fibrinolytic cascade
- Kinin cascade
- Complement cascade
Overall leads involves many chemical mediators being released, known as ‘cytokine storm’
17
Q
State the general purpose of inflammation
A
Inflammation is a protective response to:
- eliminate initial cause of cell injury
- eliminate necrotic tissue which resulted from insult
18
Q
Contrast acute and chronic inflammation in terms of:
onset
A
acute - rapid
chronic - delayed
19
Q
Contrast acute and chronic inflammation in terms of:
duration
A
acute - days
chronic - weeks to years
20
Q
Contrast acute and chronic inflammation in terms of:
cardinal signs
A
acute - pain, heat, swelling, itchiness, loss function
chronic - loss function
21
Q
Contrast acute and chronic inflammation in terms of:
specificity of response
A
acute - non-specific
chronic - specific to causative agent (thus adaptive immunity involved)
22
Q
Contrast acute and chronic inflammation in terms of:
causative agent
A
acute - pathogens, injury (physical/ chemical), tissue necrosis, immune response
chronic - persistent infection, continued presence of foreign body, autoimmunity
23
Q
Contrast acute and chronic inflammation in terms of:
fundamental cells involved
A
acute - neutrophils, subsequently macrophages
chronic - macrophages, lymphocytes, plasma cells
24
Q
define acute inflammation
A
a rapid, non-specific response to injury/ microorganisms/ foreign substances which is designed to deliver WBC’s and plasma proteins to sites of injury
25
t/f: the white blood cells and chemical mediators of acute inflammation
normally circulate in the blood
true
26
Why do the white blood cells and chemical mediators of acute inflammation
circulate in the blood?
This enables rapid delivery of these things to site of infection - rapid response
27
Heat, redness and swelling are often observed during acute inflammation. Explain this physiologically?
Due to increased permeability of blood vessels & increased blood supply to area of infection
28
Why does pain occur during acute inflammation?
Due to release of certain chemical mediators
29
Acute inflammation is (specific/ non-specific). What does this infer about the response brought about?
Acute inflammation is non-specific to causative agent, meaning regardless of causative agent the response (the inflammation) will be the same
30
State the main types of inciting agents for acute inflammation?
1. Endogenous - tissue necrosis, immune Rn
| 2. Exogenous - infection, trauma, physical and chemical damage, foreign body's
31
What is necessary for acute inflammation to begin? What cells are involved with this?
Recognition of the injurious agent is necessary
macrophages and mast cells resident in tissues responsible for this
32
Describe the two main components of acute inflammation?
1. Cellular changes - leucocyte activation/ recruitment, phagocytosis
2. Vascular changes - permeability, vasodilation
33
Detail vascular changes which occur in acute inflammation?
1. Vasodilatation:
- caused by chemical mediators (Histamine from mast cell)
- leading to increased blood flow
- leads to redness and heat
2. Increased permeability:
- allowing plasma proteins and cells to leave circulation (enter extravascular space)
- leads to swelling
34
Detail cellular changes which occur in acute inflammation?
1. Leucocyte activation
2. Leucocyte recruitment - via chemotaxis (?)
3. Phagocytosis & degradation
35
what's the consequence of vasodilation in acute inflammation (clinically)?
heat and redness
36
what's the consequence of increased permeability in acute inflammation (clinically)?
swelling
37
physiologically how does the BV become more permeable?
by retraction of endothelial cells, which is controlled by chemical mediators (histamine, bradykinin, leukotrienes)
38
for the following mediator, state the source (cells) and action:
histamine
mast cells, platelets, basophils
vasodilate, increase permeability
39
for the following mediator, state the source (cells) and action:
serotonin
platelets
vasodilate, increase permeability
40
for the following mediator, state the source (cells) and action:
prostoglandins
mast cells, leucocytes
increase permeability
41
for the following mediator, state the source (cells) and action:
leukotrienes
Leucocytes, mast cells
Increase permeability
42
for the following mediator, state the source (cells) and action:
Platelet-activating factor
leucocytes (Inc. eosinophils), mast cells
vasodilate, increase permeability, activate platelets
43
for the following mediator, state the source (cells) and action:
kinins
plasma (prod. in liver)
vasodilate, increase permeability
44
explain how leucocyte recruitment occurs?
1. cytokines & chemokines released from macrophages in damaged tissue. These cause expression of selectins (endothelial cells) and integrins (leucocytes), allowing adhesion of WBC to vascular walls
2. leucocytes move from vascular lumen to extravascular space toward site
45
define chemotaxis
movt. organism in response to chemical stimulus: WBC's move along a chemical gradient to site
46
define chemokine
chemotactic cytokine = chemokine, binds to cell surface receptor on leucocytes
47
What are integrins/ selectins? Contrast their purpose?
Selectins - on endothelial cells, allow loose adhesion
integrins - on WBC, allow stable adhesion
allow leucocyte adhesion to vascular wall
48
what produces chemokines?
- microorgansism themselves
- macrophages
- WBC
49
how do WBC move?
contractile filaments used to extend pseudopods
50
state some of the main functions of WBC once activated at the site of insult?
- phagocytosis
- lysis/ killing engulfed pahogens
- production mediators which amplify inflammation
51
what activates WBC?
- bacteria/ viral products
| - inflammatory mediators secreted by mast cells and macrophages
52
explain steps involved in phagocytosis?
1. Recognition, attachment by receptors on WBC surface
2. Engulfment, formation of phagsosome
3. Killing and degradation - fusion of phagsosome with lysosome to form phagolysosome, degradation with enzymes and lisosomal acid hydrolases
53
name a enzyme involved in phagocytosis?
myeloperoxidase
54
for the following chemical mediator, state the source and action:
cytokines
macrophages, endothelial cells and mast cells
endothelial activation (expression of selectins)
55
for the following chemical mediator, state the source and action:
chemokines
leucocytes, macrophages
chemotaxis, leucocyte activation (expression of integrins)
56
for the following chemical mediator, state the source and action:
prostoglandins
mast cells, leucocytes
leucocyte adhesion, chemotaxis, degranulation
57
for the following chemical mediator, state the source and action:
leukotrienes
mast cells, leucocytes
WBC adhesion and activation, chemotaxis
58
for the following chemical mediator, state the source and action:
nitric oxide
endothelium, macrophages
killing microbes
59
for the following chemical mediator, state the source and action:
Reactive oxygen species
WBC
killing microbes
60
for the following chemical mediator, state the source and action:
Proteases
Plasma (made in liver)
leucocyte chemotaxis & activation
61
for the following chemical mediator, state the source and action:
complement
plasma (made in liver)
endothelial activation, WBC recruitment
62
3 possible outcomes of acute inflammation?
1. Resolution - restoration to completely normal extent, only possible if noxious stimuli removed, cell death and tissue damage must be minimal
2. Healing with scarring - injurious stimuli removed but damage is too severe to allow complete restoration
3. Progression to chronic inflammation - when injurious stimuli persists
63
what's meant by chronic inflammation
inflammation persisting for weeks to years
64
cause of chronic inflammation (basic)?
ongoing active inflammation; tissue injury and healing occur simultaneously
65
what is chronic inflammation characterized by?
mononuclear cell infiltrate
66
causes of chronic inflammation (reasons why inflammation would continue)?
1. Persistent infection - by microbes difficult to kill
2. Hypersensitivity - ie. rheumatoid arthritis
3. prolonged exposure toxic agent - ie. silicosis
67
Main cells of chronic inflammation?
MONONUCLEAR CELLS:
- macrophages
- lymphocytes
- plasma cells
(eosinophils, neutrophils, mast cells somewhat involved)
68
name the archetypal cell of chronic inflammation?
macrophage
69
what're macrophages derived from?
monocytes in blood
70
what activates macrophages?
mainly cytokines, chemical mediators
71
what're activated macrophages called?
histiocytes
72
how are lymphocytes involved in chronic inflammation?
B and T cells attracted to site by chemokines (chemotaxis), then T cells secrete more cytokines helping to activate macrophages
73
how are plasma cells involved in chronic inflammation?
they prod. antibodies
74
what's meant by granulomatous inflammation? Explain the process of formation
1. T cells release cytokines in response to persistent inflammation
2. collection epithelioid histiocytes which fuse to form giant cell
75
why do granulomas form?
1. organisms which are resistant to phagolysosomal degradation cause them to form
2. foreign bodies which immune system cannot remove (ie. splinter), this called a foreign body granuloma
76
In which disease do granulomas most commonly form?
TB
77
why do fevers occur?
in response to pyrogens, which may be:
1. Exogenous (bacterial lipopolysachharide)
2. Endogenous (cytokines, prostoglandins)
78
how do prostoglandins exert there effect to cause fever?
resetting of the hypothalamic thermostat
79
define sepsis
massive immune response leading to excess inflammation, potentially fatal
80
what can cause sepsis
in severe infections, sepsis can be caused by:
1. Exogenous (bacterial lipopolysachharide)
2. Endogenous (cytokines, prostoglandins)
81
what is sepsis characterized by?
hypotensive shock, disseminated intravascular coagulation
82
define leucocytosis
elevated number WBC
83
list the systemic effects of inflammation (4)
1. elevated plasma levels of acute-phase proteins (can cause chronic disease)
2. Fever
3. sepsis
4. Leucocytosis
84
define repair
restoration of tissue architecture and function after injury
85
ways in which repair can occur?
1. regeneration (no scarring) - when damage less severe so damaged components can return to normal state
2. healing (scarring) - when damage severe to a point where CT (scar tissue) must be laid down
86
examples of 'permanent tissues'?
cardiac, neurons
87
t/f: permanent tissues can only heal, not regenerate
true
88
how often does regeneration occur in labile tissues (ie. epithelium?
continuously
89
t/f: organs with stable populations (ie. liver) cannot regenerate, only heal
false - they can regenerate
90
explain the process of healing with scarring
1. angiogenesis (formation new BV)
2. migration and proliferation of fibroblasts
3. deposition of extracellular matrix
4. maturation and organisation of fibrous tissue (remodelling)
1+2= granulation tissue
91
healing with scarring is the likely outcome for what circumstances (~5)
1. acute inflammation (if severe)
2. chronic inflammation
3. ischaemic necrosis
4. wounds in skin
5. bone fractures
92
repair is under control of growth factors - which ones specifically?
* Transforming growth factor beta (TGF-B)
* Vascular endothelial growth factor (VEGF)
* Platelet derived growth factor (PDGF)
* Epidermal growth factor (EGF)
* Fibroblast growth factor (FGF)
"epidermal fibroblasts are transforming into vascular platelets"
(add growth factor on end - done!)
93
which cells produce growth factors for repair?
macrophages and platelets at site of injury
94
explain some of the actions of growth factors (not specific ones, just general)?
1. chemotaxis (attracts more macrophages in chronic and late acute inflammation)
2. fibroblast migration and proliferation
3. angiogenesis
4. increase synthesis extra-cellular matrix collagen
5. stimulate epithelial proliferation (ie. skin)
95
what is granulation tissue?
the new CT and microscopic BV's which first forms in the process of scar formation (healing with scarring).
Specifically it is the new BV's + fibroblasts and their depositions.
96
acute inflammation is characterised by? (cellular level - not clincially)
rapid influx of neutrophils into injured tissue
97
chronic inflammation is characterized by?
activated macrophages and lymphocytes
98
Three growth factors controlling tissue repair after inflammation are?
any 3 of the following...
("epidermal fibroblasts transform into vascular platelets")
```
TGF-B = transforming type B
EGF = epidermal
FGF = fibroblast
PDGF = platelet derived
VEGF = vascular endothelial
```
