Immune Response & Inflammation (Part 2)-Exam 3 Flashcards
1
Q
What type of a response is inflammation?
A
Non-specific; response to a cute is the same as a burn/radiation/infection, etc.
2
Q
What are some causes of tissue damage?
A
Pathogens, abrasions, chemical irritations, distortion/cell disturbance, extreme temps
3
Q
How does the body response to tissue damage?
A
Inflammation
4
Q
What are 4 signs of inflammation?
A
Redness
Pain
Heat
Swelling
5
Q
What is the goal of inflammation?
A
To dispose of microbes/ toxins/ foreign materials; prevents the spread, prepares for repair (restores homeostasis)
6
Q
Where does inflammation occur?
A
At the sight of injury
7
Q
What are the 3 stages of inflammation?
A
- Vasodilation: Increases permeability of blood vessels
- Emigration: Movement of phagocytes from blood to interstitial fluid
- Tissue repair
8
Q
What is the purpose of increased permeability?
A
Allows antibodies and clotting factors to leave the blood
9
Q
What is the purpose of vasodilation?
A
Allows more blood into an area
Helps remove microbial toxins and dead cells
10
Q
What are some factors that cause vasodilation and increased permeability?
A
Histamine, Kinins, prostaglandins, leukotriens, complement
11
Q
What cells release histamine?
A
Mast cells
12
Q
What simulate the release of histamine in the blood?
A
Basophils and platelets
13
Q
What does histamine cause?
A
Dilation and increased permeability
14
Q
What are kinins? What do they do?
A
Polypeptides; induce vasodilation and increase permeability; act as chemotaxic agent phagocytes
15
Q
What’s an example of a kinin?
A
Bradykinin
16
Q
What are prostaglandins? What releases them? What do they stimulate?
A
Lipids, released by damaged cells, stimulate emigration of phagocytes
17
Q
What are leukotrienes? What do they do?
A
Basophils and mast cells produce; increase permeability
18
Q
What does complement do?
A
Stimulate histamine release, attract neutrophils, promote phagocytosis
19
Q
What do clotting factors moving into the tissues initiate?
A
Clotting Cascade; fibrinogen converted to fibrin and forms fibrin mesh
20
Q
What is the function of the fibrin mesh?
A
Localizes and traps invading organisms; blocks the spread of organism
21
Q
How long after the start of the inflammatory process of phagocytes start to appear?
A
Phagocytes appear
22
Q
What do neutrophils do during inflammation?
A
Stick to the blood vessel wall with increased blood flow; squeeze through blood vessel wall to tissues “emigration”
Depends on chemotaxis
23
Q
Neutrophils attempt to destroy via what process?
A
Phagocytosis
24
Q
What cells follow neutrophils? What do they transform into?
A
Monocytes; transform into macrophages
25
Which is a more potent phagocyte: neutrophils or macrophages?
Macrophages are more potent phagocytes than neutrophils; macrophages eventually die
26
What is left behind when macrophages die?
Dead cells and fluid (pus)
27
What are 4 signs of inflammation due to vasodilation and increased permeability?
Heat, redness, swelling, pain
28
Why is there redness in inflammation?
Large amount of blood in damaged area
Local temperatures increase
Metabolic reactions speed up
More heat is released
29
What is associated with swelling?
Increased permeability, more fluid in the area
30
Why is there pain during inflammation?
Neuron injury or increased pressure (edema)
31
What causes fever?
Bacteria toxin increases body temperature; trigger release of interleukin-1
32
What does fever help do?
Inhibit the growth of some microbes, helps to speed up body reactions, aids in repair
33
What are the two major components of the complex reaction to injurious agents associated with inflammation?
Vascular reaction
| Cellular reaction
34
Acute response
Rapid onset; short duration, emigration of neutrophils
35
Chronic response
Long duration, lymphocyte involvement, proliferation of blood vessels, tissue necrosis
36
What cells are involved in inflammation?
Circulating White Cells ( and plts)
Connective tissue cells
extracellular matrix
37
What are some examples of connective tissue cells?
Mast cells (surround blood vessels)
Fibroblasts
Macrophages
Lymphocytes
38
What is in the extracellular matrix?
Structural fibrous protein (collagen, elastin)
Adhesive glycoproteins
Proteoglycans
Basement membrane of capillary
39
What chemical factors mediate inflammation?
Derived from plasma proteins and/or cells
| Produced in response to or activated by inflammation
40
Where does the acute inflammation response deliver mediators? What mediators?
Delivers mediators of host defense to site of injury (leukocytes/plasma proteins)
41
What are the components of acute inflammation?
Dilation of capillaries and vessels- increase BF
Structural changes in capillaries- allow plasma proteins and leukocytes to enter interstitial space
Emigration of leukocytes from capillaries where they accumulate in focus of injury- activation to eliminate offending agent
42
What are the stimuli for acute inflammation?
```
Infections and microbial toxins
Trauma
Physical and chemical agents
Tissue necrosis
Foreign bodies
Immune reactions
```
43
What are some examples of microbial toxins?
Bacterial, viral, parasitic
44
What are some physical and chemical agents that stimulate acute inflammation?
Thermal injury (burns, frostbite)
Irradiation
Environmental chemicals
45
What are some foreign bodies that are stimuli for acute inflammation?
Splinters
Dirt
Sutures
46
What is the purpose of vascular changes?
Maximize movement of plasma proteins and appropriate circulating cells into the site of injury or infection
47
How does the body create vascular changes?
Vasodilation
| Increased capillary permeability
48
What is the early manifestation of vascular changes?
Vasodilation
49
What vasodilates first? Followed by what?
Arterioles involved first, followed by opening of new capillary beds
50
What induces vasodilation?
Variety of mediators (histamine/ nitric oxide)
51
What is the result of vasodilation?
Increased BF which increased redness and warmth of tissue
52
What does increased capillary permeability result in on the capillary level?
Movement of protein rich fluid into extravascular tissue and concentration of RBCs (viscosity change)
Physical changes in endothelial structure of capillaries
53
What is the result of capillary permeability (big picture)?
Osmotic and hemodynamic change force fluid into interstitial space (results stasis)
neutrophils begin adhering to endothelium and moving into interstitial space
Physical openings in endothelium allow more fluid/protein/cells to migrate
54
What is extravasation?
Movement of leukocytes from vessel lumen to interstitial space
55
Margination
movement of leukocytes toward the wall of the capillary
56
Rolling
leukocytes tumble slowly along endothelium, adhere transiently, then are finally attached, endothelium completely lines with white cells
57
Transmigration (diapedesis)
insert pseudopods into junctions between endothelial cells; move through the junction
58
Chemotaxis
migrate through interstitial fluid to source of problem; locomotion along chemical gradient
59
What are the most common exogenous agents of chemotaxis?
Bacterial products
60
What are the most common endogenous agents?
Components of complement (C5a)
Products of lipoxygenase pathway (leukotriene B4)
cytokines
61
What is leukocyte activation induced by?
Microbes, products necrotic cells, antigen-antibody complexes, cytokines
62
What are the results of leukocyte activation?
Production of arachidonic acid metabolites
Degrannulation and secretion of lysosomal enzymes
Secretion of cytokines
Modulation of surface receptors
Phagocytosis
63
What do chemical mediators originate from?
Plasma or cells
- Plasma derived must be activated
- Cell-derived usually stored in intracellular granules
64
What is the production of active mediators triggered by?
Microbial products or host proteins (complement, etc.)
65
Where do chemical mediators usually bind?
Specific receptors on target cells
66
What could one mediator stimulate?
The release of other mediators; mediators can also act on more than one target
67
Once a chemical mediator is activated and released, how long do most live?
Most are short-lived; most have the potential to do great harm
68
What are mediators/sources of preformed mediators in secretory granules?
Histamine- mast cells, basophils, platelets
Serotonin- platelets
Lysosomal enzymes- neutrophils, macrophages
69
What are newly synthesized mediators and sources?
Prostaglandins (all leukocytes, plts, EC)
Leukotrienes (All leukocytes)
Plt-activating facotrs (All leukocytes, EC)
Activated oxygen species (all leukocytes)
Nitric oxide (macrophages)
Cytokines (lymphocytes, macrophages, EC)
70
What mediators are involved in vasodilation?
Prostaglandins
Nitric Oxide
Histamine
71
What mediators are involved in increased vascular permeability?
```
Vasoactive amines
C3a and C5a (through liberating amines)
Bradykinin
Leukotrienes C4, D4, E4
PAF
Substance P
```
72
What mediators are involved in chemotaxis,leukocyte recruitment and activation?
```
C5a
Leukotriene B4
Chemokines
IL-1, TNF
Bacterial products
```
73
What mediators are involved in fever?
IL-1, TNF
| Prostagladins
74
What mediators are involved in pain?
Prostaglandins
| Bradykinin
75
What mediators are involved in tissue damage?
Neutrophil and macrophage lysosomal enzymes
Oxygen metabolites
Nitric oxide
76
SIRS
systemic inflammatory response syndrome
77
What is SIRS?
Common systemic response to a wide variety of insults
78
2 or more of this list must be present for diagnosis of SIRS
1. Body temp above 38C or below 36C
2. HR > 90 BPM
3. RR >20 /min or PaCO2 < 32 mmHg
4. Leukocyte count > 12,000 cell/mm^2
(or < 4000 cells/mm^3)
(or present of < 10% immature neutrophils)
79
SIRAB
Systemic inflammatory response after bypass
80
Wide spectrum of injuries for SIRAB
Pulmonary, Renal, Gut, CNS, Myocardial Dysfunction, Coagulopathy, Hemolysis, fever, increase susceptibility to infection, Leukocytosis
81
Who gets SIRS?
Widely accepted that SIRS is induced in all patients undergoing bypass
82
What is the incidence and severity of SIRS?
Variable; most have few clinical symptoms. Minority develop severe hemodynamic changes or organ failure after bypass
83
What is the response of patients to bypass?
Degree of response is not predictable nor type of response.
84
What is a risk factor for SIRAB?
Length of CPB; frequently a risk factor but not necessarily
85
What does SIRAB set into motion?
Cytokine mediated events that activate vascular endothelium; allow further neutrophil mediated inflammatory injury
86
What is the most common culprit of SIRAB?
Contact with foreign surfaces
87
What are other factors of developing SIRAB?
```
Altered arterial blood flow patterns
Shear stress (blood pumps)
Cardiotomy suction
Tissue ischemia
Reperfusion
Hypothermia
Relative anemia
anticoagulants (low temps, blood more viscous)
```
88
What is relative anemia?
Accepting a lower HCT on bypass; better for out circuit
89
What is involved in contact activation in developing SIRAB?
ECC (coated?)
| Activation of contact proteins (XII, XI, prekallikrein, HMWK)
90
What is the end result of SIRAB?
Formation of bradykinin
Conversion of plasminogen into plasmin
Initiates fibrinolysis
Triggers classical complement cascade
91
What does exposure to ECC result in?
Multiple inflammatory mediators released
Disrupts homeostasis
Generalized whole inflammatory response
Stimulate or catalyze other reactions in cycle of SIRAB
92
What is the general whole inflammatory response mediated by?
Chemokine mediated; activates vascular endothelium, further neutrophil-mediate injury
93
What happens to patients post operatively?
Pts more susceptible to infections
Serum immunoglobulins/complement decreased
Chemotaxis ability of granulocytes decreased
Natural killer cells decreased (#/fcn)
CD3+/CD4+ cells decreased
CD8 + cells slightly increased
Leukocyte number remains low for about 1 week post bypass
