Module 4 - Chapter 6 - Innate Immunity Second Line Inflammation Flashcards
1
Q
How does inflammation differ from the physical and biochemical barriers of the innate immune system?
A
While the physical and biochemical barriers of the innate immune system are relatively static, inflammation is a dynamic process that responds to cellular or tissue damage, whether the damaged tissue is septic or sterile.
2
Q
What is the primary purpose of the inflammatory response in the immune system?
A
The primary purpose of the inflammatory response is to limit the extent of tissue damage, destroy infectious microorganisms, initiate the adaptive immune response, and promote the healing process.
3
Q
What are the four main characteristics of the inflammatory response?
A
The inflammatory response has four primary characteristics: (1) it occurs in tissues with a blood supply; (2) it is activated rapidly (within seconds) after damage occurs; (3) it depends on the activity of both cellular and chemical components; and (4) it is nonspecific, meaning it occurs in approximately the same way regardless of the type of stimulus or prior exposure to the same stimulus.
4
Q
Can you explain what is meant by the term “vascularized” in the context of inflammation?
A
“Vascularized” means that inflammation occurs in tissues that have a blood supply, which allows for the rapid mobilization of immune cells and molecules to the site of tissue damage.
5
Q
Why is the rapid activation of the inflammatory response crucial?
A
Rapid activation of the inflammatory response is crucial because it allows for an immediate response to cellular or tissue damage, helping to limit the damage and initiate the immune and healing processes quickly.
6
Q
What types of injuries or conditions can activate the inflammatory response in vascularized tissues?
A
Virtually any injury to vascularized tissues can activate the inflammatory response. This includes infections, tissue necrosis, ischemia, trauma, physical or chemical injury, foreign bodies, and immune reactions.
7
Q
What are the classic or cardinal signs of acute inflammation, as described by Celsus in the first century?
A
The classic signs of acute inflammation, as described by Celsus, include rubor (redness), calor (heat), tumour (swelling), dolor (pain), and functio laesa (loss of function).
8
Q
Why is the loss of function (functio laesa) considered one of the cardinal signs of acute inflammation?
A
Functio laesa, or loss of function, is considered a cardinal sign of acute inflammation because it reflects the impairment of normal tissue function at the site of injury or inflammation due to the ongoing inflammatory processes.
9
Q
What is the first microscopic inflammatory change that occurs near the site of injury, and what is its effect on blood vessels?
A
The first change is vasodilation, which leads to an increased size of blood vessels. This causes slower blood velocity and increases blood flow to the injured site.
10
Q
What happens to blood vessels during increased vascular permeability, and what is the consequence of this change?
A
During increased vascular permeability, blood vessels become porous due to the contraction of endothelial cells. This leads to the leakage of fluid out of the vessel, resulting in swelling (edema) at the site of injury.
11
Q
How does exudation, the leakage of fluid from blood vessels, contribute to the local changes observed during inflammation?
A
Exudation leads to the movement of plasma outward from blood vessels, making blood in the microcirculation more viscous and causing it to flow more slowly. This increased blood flow, along with a higher concentration of red blood cells at the site of inflammation, results in locally increased redness (erythema) and warmth.
12
Q
What is the process by which white blood cells participate in the inflammatory response, and where do they migrate during this process?
A
White blood cells adhere to the inner walls of vessels and migrate through enlarged junctions between endothelial cells lining the vessels into the surrounding tissue as part of the inflammatory response.
13
Q
What is the purpose of vasodilation in the context of inflammation?
A
Vasodilation serves to increase the size of blood vessels, which in turn slows down blood velocity and enhances blood flow to the injured site, facilitating the inflammatory response.
14
Q
How does increased vascular permeability contribute to the visible signs of inflammation?
A
Increased vascular permeability, by making blood vessels porous, causes the leakage of fluid (exudation) out of the vessels, leading to swelling (edema) at the injury site. This process also results in increased redness (erythema) and warmth due to higher blood flow and concentration of red blood cells.
15
Q
What role do white blood cells play in the inflammatory response, and where do they migrate during inflammation?
A
White blood cells adhere to the inner walls of blood vessels and migrate through enlarged junctions between the endothelial cells lining the vessels into the surrounding tissue. Their role is to combat infection and participate in the inflammatory process.
16
Q
How do these microscopic changes collectively contribute to the body’s response to tissue injury or inflammation?
A
These microscopic changes, including vasodilation, increased vascular permeability, and white blood cell migration, collectively enhance blood flow to the site of injury, increase the delivery of immune cells to the affected area, and promote the removal of pathogens and damaged tissue, facilitating the healing process.
17
Q
What are the primary outcomes of the characteristic changes associated with inflammation, and what triggers these changes?
A
The characteristic changes associated with inflammation result from the activation and interactions of various chemicals and cellular components in the blood and tissues. These changes deliver leukocytes, plasma proteins, and biochemical mediators to the site of injury, where they act together.
18
Q
Which types of leukocytes are particularly important in the context of inflammation, and what role do they play?
A
Neutrophils are especially crucial leukocytes in inflammation. They migrate to the site of injury and participate in the immune response to combat infection and promote tissue healing.
19
Q
How do some chemical mediators in the inflammatory process contribute to pain perception?
A
Some chemical mediators activate pain fibers, contributing to the perception of pain during inflammation.
20
Q
What role do lymphatic vessels play in the process of acute inflammation, and what secondary effects can occur in these vessels and lymph nodes?
A
Lymphatic vessels drain extravascular fluid to the lymph nodes and may become secondarily inflamed. This can result in lymphangitis (inflammation of lymph vessels) and lymphadenitis (enlargement and inflammation of lymph nodes), which can be painful and hyperplastic.
21
Q
How does inflammation prevent infection and further damage by invading microorganisms?
A
Inflammation prevents infection and further damage by diluting toxins produced by bacteria and released from dying cells. It activates plasma protein systems like complement and clotting systems, which help contain and destroy bacteria. Phagocytes like neutrophils and macrophages are recruited to destroy cellular debris and microorganisms.
22
Q
What role does inflammation play in limiting and controlling the inflammatory process itself?
A
Inflammation limits and controls itself through the influx of plasma protein systems (e.g., clotting system), plasma enzymes, and cells like eosinophils. These components prevent the spread of the inflammatory response to healthy tissue.
23
Q
How does inflammation interact with components of the adaptive immune system?
A
Inflammation interacts with the adaptive immune system by facilitating the influx of macrophages and lymphocytes, which destroy pathogens. This interaction leads to a more specific immune response against contaminating pathogens.
24
Q
What role does inflammation play in preparing the area of injury for healing and repair?
A
Inflammation prepares the area of injury for healing and repair by removing bacterial products, dead cells, and other inflammatory products. This can occur through channels in the epithelium or drainage via lymphatic vessels.
25
How are fluid and debris that accumulate at an inflamed site removed, and what additional benefit does this process provide?
Fluid and debris at an inflamed site are drained by lymphatic vessels. This process not only removes the accumulated material but also facilitates the development of acquired immunity because microbial antigens in lymphatic fluid pass through lymph nodes, where they encounter lymphocytes.
26
Three key plasma protein systems are essential to an effective inflammatory response:
System 1: The complement system.
System 2: The clotting system.
System 3: The kinin system.
27
What do the complement system, clotting system, and kinin system have in common in terms of their protein components?
They each consist of multiple proteins found in the blood, usually in inactive forms, including enzymes that circulate as proenzymes.
28
What happens when the first components of these plasma protein systems are activated during inflammation?
Activation of the first components leads to sequential activation of other components in a cascade, resulting in a biological function that helps protect the individual.
29
What are the three cascades formed due to the sequential activation of plasma protein systems during inflammation?
The three cascades are the complement cascade, the clotting cascade, and the kinin cascade.
30
31
What percentage of the total circulating serum protein does the complement system constitute?
The complement system constitutes about 10% of the total circulating serum protein.
32
What is the primary function of the complement cascade within the immune response?
The primary function of the complement cascade is to activate C3 and C5, leading to the production of molecules with various functions in defending against pathogens.
33
What are the three main functions of the molecules produced during complement system activation?
The molecules produced during complement system activation can serve as (1) opsonins, (2) chemotactic factors, or (3) anaphylatoxins.
34
What is the role of opsonins in the immune response?
Opsonins coat the surface of bacteria, making them more susceptible to phagocytosis by inflammatory cells like neutrophils and macrophages.
35
How do anaphylatoxins contribute to the inflammatory response?
Anaphylatoxins, such as C3a and C5a, induce rapid degranulation of mast cells, leading to histamine release, vasodilation, and increased capillary permeability, which are significant components of inflammation.
36
What happens when terminal complement components C5b through C9 are activated?
Activation of C5b through C9 results in the formation of a complex known as the membrane attack complex (MAC), which creates pores in the outer membranes of cells or bacteria, leading to cell death.
37
How many major pathways control the activation of complement, and what are they?
There are three major pathways controlling complement activation: the classical pathway, the alternative pathway, and the lectin pathway.
38
What primarily activates the classical pathway of complement activation?
The classical pathway is primarily activated by antibodies, which bind to antigens on target cells or pathogens.
39
What activates the alternative pathway of complement activation?
The alternative pathway is activated by certain substances found on the surface of infectious organisms, such as bacteria and yeast.
40
How does the lectin pathway of complement activation differ from the classical pathway?
The lectin pathway is similar to the classical pathway but does not depend on antibodies. It is activated by specific plasma proteins that recognize carbohydrate patterns on the surfaces of various pathogenic microorganisms.
41
What are the four main functions of the products of the complement cascade?
The products of the complement cascade have four main functions: opsonization (C3b), anaphylatoxic activity resulting in mast cell degranulation (C3a, C5a), leukocyte chemotaxis (C5a), and cell lysis (C5b–C9 [MAC]).
42
What is the clotting (coagulation) system, and what does it create when activated?
The clotting system is a group of plasma proteins that, when activated sequentially, forms a blood clot, which is a meshwork of protein (fibrin) strands.
43
What are the three primary functions of blood clots in the body?
Blood clots plug damaged vessels to stop bleeding, trap microorganisms to prevent their spread, and provide a framework for future repair and healing.
44
What substances can activate the clotting system during tissue injury and infection?
The clotting system can be activated by substances like collagen, proteinases, kallikrein, plasmin, and bacterial products such as endotoxins.
45
How are the clotting pathways similar to the complement cascade in terms of activation?
Just like the complement cascade, different pathways that converge can activate the coagulation cascade, resulting in blood clot formation.
46
Just like the complement cascade, different pathways that converge can activate the coagulation cascade, resulting in blood clot formation.
Just like the complement cascade, different pathways that converge can activate the coagulation cascade, resulting in blood clot formation.
47
How do the intrinsic and extrinsic pathways of the clotting system converge, and what do they lead to?
How do the intrinsic and extrinsic pathways of the clotting system converge, and what do they lead to?
48
What are fibrinopeptides (FPs) A and B, and how do they influence the inflammatory response?
Fibrinopeptides (FPs) A and B are protein fragments produced when fibrin is created. They enhance the inflammatory response by being chemotactic for neutrophils and increasing vascular permeability, similar to how bradykinin (from the kinin system) affects endothelial cells.
49
What is the kinin system?
The kinin system is one of the plasma protein systems involved in inflammation.
50
How does the kinin system interact with the coagulation system?
The activation of Hageman factor (factor XII) to factor XIIa can initiate both the clotting and kinin systems.
51
What is another name for factor XIIa, and what does it do in the kinin system?
Factor XIIa is also known as prekallikrein, and it enzymatically activates the first component of the kinin system.
52
Factor XIIa is also known as prekallikrein, and it enzymatically activates the first component of the kinin system.
The final product of the kinin system is a small-molecular-weight molecule called bradykinin.
53
Where does bradykinin come from, and what are its effects in inflammation?
Bradykinin is derived from a larger precursor molecule called kininogen. It has several effects in inflammation, including causing blood vessel dilation, working with prostaglandins to induce pain, promoting contraction of smooth muscle cells, and increasing vascular permeability.
54
Why is tight regulation of plasma protein systems essential?
Tight regulation is essential because these systems are critical for survival and can produce potent substances that may be harmful if not controlled.
55
What happens when one plasma protein system is activated?
Activation of one system can lead to the production of biologically active substances that further activate other plasma protein systems.
56
What are some mechanisms to regulate plasma protein systems during inflammation?
Mechanisms include enzymes that destroy inflammation mediators, such as carboxypeptidase, kininases, and histaminase.
57
How does blood clot formation relate to other plasma protein systems?
Blood clot formation activates a system that limits clot size and removes it. This system can also activate the complement and kinin cascades.
57
What is the role of bradykinin in the kinin system?
Bradykinin, produced in the kinin system, causes blood vessel dilation, works with prostaglandins to induce pain, contracts smooth muscle cells, and increases vascular permeability.
58
What is inflammation, and where does it occur?
Inflammation is a process in vascular tissue. It occurs in both blood and tissue surrounding blood vessels.
59
What are endothelial cells, and what is their role during inflammation?
Endothelial cells line blood vessels and help maintain normal blood flow. During inflammation, they coordinate blood clotting and the movement of cells and fluids into tissues.
60
What are mast cells, and what role do they play in inflammation?
Mast cells are key activators of inflammation. They are found in tissues near blood vessels and release substances that initiate the inflammatory process.
61
What are dendritic cells, and how do they connect to the immune response during inflammation?
Dendritic cells are cells that bridge the innate and acquired immune responses. They are present in tissues near blood vessels and help coordinate immune system actions during inflammation.
62
What types of cells are present in the bloodstream, and what are their functions?
Blood cells include erythrocytes (red blood cells, for oxygen transport), platelets (involved in clotting), and leukocytes (white blood cells, part of the immune system).
63
What are granulocytes, and how do they differ from each other?
Granulocytes are a type of leukocyte with enzyme-filled granules. They include basophils, eosinophils, and neutrophils and differ based on granule staining. They play roles in immune responses.
64
What are monocytes, and where are they found?
Monocytes are precursors to macrophages and are found in tissues. They contribute to the body's immune defense by transforming into macrophages.
65
What are lymphocytes, and what forms do they come in?
Lymphocytes are white blood cells with various forms, including natural killer (NK) cells and B and T cells. They have roles in both the innate and acquired immune responses.
66
What attracts immune cells to the site of cellular damage?
Molecules produced at the site of damage attract immune cells to enhance the protective response.
67
Where do chemotactic molecules that recruit immune cells come from?
Chemotactic molecules can originate from damaged cells, microbes, activation of plasma protein systems, or secretions by other immune cells.
68
What happens when immune cell surface receptors bind to these molecules?
Binding of these molecules to immune cell surface receptors leads to intracellular signaling and cell activation.
69
What can occur when immune cells are activated?
Activation of immune cells can result in gaining functions crucial to inflammation or the release of additional substances that promote inflammation.
70
What are the primary goals of inflammatory cells, protein systems, and their products at the site of tissue injury?
Their goals include containing damage, eliminating microorganisms, clearing cellular debris, and activating processes for healing, tissue regeneration, or repair.
71
What are the surface receptors of B and T lymphocytes in the adaptive immune system called?
They are called T-cell antigen receptors (TCR) and B-cell antigen receptors (BCR).
72
What type of receptors do cells in the innate immune system have?
Cells in the innate immune system have pattern recognition receptors (PRRs).
73
What do PRRs recognize?
PRRs recognize two types of molecular patterns: PAMPs (molecules expressed by infectious agents) and DAMPs (products of cellular damage).
74
Why do PRRs allow innate immune cells to respond to both sterile and septic tissue damage?
PRRs recognize DAMPs (sterile tissue damage) and PAMPs and DAMPs (septic tissue damage).
75
How many different PRRs are there, and what do they recognize?
There are over 100 different PRRs that recognize more than 1,000 different molecules.
76
Where are PRRs typically found in the body?
PRRs are typically found on cells near the body's surface, including the skin, respiratory tract, GI tract, and genitourinary tract.
77
What is the role of Toll-like receptors (TLRs) in the immune system?
TLRs recognize various PAMPs and are present on cells with early contact with potential pathogens.
78
What types of molecules do TLRs recognize?
TLRs recognize molecules like bacterial LPS, viral RNA, and flagellin.
79
Where are complement receptors found, and what do they recognize?
Complement receptors are found on various immune cells and recognize fragments produced during complement system activation.
80
What is the function of scavenger receptors, and where are they mainly found?
Scavenger receptors facilitate recognition and phagocytosis of pathogens and damaged cells, mainly on macrophages.
81
What do NOD-like receptors (NLRs) recognize, and where are they located?
NLRs recognize products of microbes and damaged cells and are cytoplasmic receptors.
82
What are cytokines?
Cytokines are small-molecular-weight soluble signaling molecules that regulate innate or adaptive immunity.
83
What is a cytokine storm, and when can it occur?
A cytokine storm is an unregulated immune response involving excessive cytokine production. It can occur in response to infections, malignancy, and other disorders.
84
What is the role of chemokines in inflammation?
Chemokines attract leukocytes to sites of inflammation.
85
How many different human chemokines are there?
There are over 50 different human chemokines.
86
What is the primary role of interleukins (ILs) in the immune system?
Interleukins have various effects, including altering adhesion molecule expression, attracting leukocytes, enhancing or suppressing inflammation, and developing the acquired immune response.
87
What are two major proinflammatory interleukins, and what are their roles?
Interleukin-1 (IL-1) activates immune cells and acts as an endogenous pyrogen. Interleukin-6 (IL-6) induces hepatocytes to produce acute-phase reactants and stimulates blood cell growth and fibroblast growth.
88
Name two anti-inflammatory cytokines.
Two anti-inflammatory cytokines are interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β).
89
What is the role of tumor necrosis factor-alpha (TNF-α) in the immune system?
TNF-α has various proinflammatory effects, including inducing fever, increasing inflammation-related serum proteins, and causing muscle wasting in severe infections and cancer.
90
What is the role of interferons (IFNs) in the immune system?
Interferons protect against viral infections and modulate inflammation. Type I IFNs induce antiviral proteins, while type II IFN (IFN-γ) activates macrophages.
91
Which cells are considered key activators of the inflammatory response?
Mast cells and basophils are key activators of the inflammatory response.
92
How can mast cells and basophils release potent mediators during inflammation?
They can release mediators through degranulation (release of granule contents) or synthesis (new production in response to a stimulus).
93
What is the role of mast cells in the inflammatory response?
Mast cells are essential cellular activators of the inflammatory response.
94
Where are mast cells primarily located in the body?
Mast cells are located in loose connective tissues near blood vessels, especially in the skin and lining of the gastrointestinal (GI) and respiratory tracts.
95
What are basophils, and where are they found?
Basophils are a type of white blood cell found in the bloodstream. They likely function similarly to tissue mast cells.
96
How do mast cells release potent inducers of inflammation?
Mast cells release these inducers through two mechanisms:
Degranulation: This involves the release of the contents stored in mast cell granules.
Synthesis: They can also produce and release mediators in response to a stimulus.
97
What is the significance of these released inducers?
These inducers play a crucial role in initiating and propagating the inflammatory response when the body encounters various stimuli or triggers.
98
What is degranulation?
Degranulation is a process in which mast cells release biochemical mediators stored in their granules in response to a stimulus.
99
What substances are released during degranulation?
During degranulation, mast cells release substances such as histamine, chemotactic factors, and cytokines.
100
What is the immediate effect of histamine release?
Histamine, a vasoactive amine, causes temporary constriction of smooth muscle and dilation of postcapillary venules, leading to increased blood flow into the microcirculation.
101
How does histamine affect vascular permeability?
Histamine causes increased vascular permeability by retracting endothelial cells lining capillaries and increasing the adherence of leukocytes to the endothelium.
102
What receptors does histamine bind to on target cells?
Histamine binds to histamine H1 and H2 receptors on the surface of target cells.
103
What is the role of antihistamines?
Antihistamines block the binding of histamine to its receptors, resulting in decreased inflammation.
104
What is the proinflammatory effect of H1 receptor binding?
Binding of histamine to the H1 receptor is proinflammatory and can promote inflammation.
105
What is the anti-inflammatory effect of H2 receptor binding?
Binding to the H2 receptor is generally anti-inflammatory, leading to the suppression of leukocyte function.
106
Where are H1 receptors abundant, and what effect does their stimulation have?
H1 receptors are abundant on bronchial smooth muscle cells and cause bronchoconstriction when stimulated.
107
What are chemotactic factors, and how do they affect cells?
Chemotactic factors are substances that induce directional movement of cells along a chemical gradient. They include neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor of anaphylaxis (ECF-A).
108
What is the role of neutrophils and eosinophils in inflammation?
Neutrophils are predominant during the early stages of inflammation and play a crucial role in killing bacteria. Eosinophils help regulate the inflammatory response.
109
What happens when mast cells are activated?
When mast cells are activated, they start producing substances that contribute to inflammation.
110
What are the key mediators produced during inflammation?
The key mediators produced are leukotrienes, prostaglandins, and platelet-activating factor (PAF).
111
How are leukotrienes produced?
Leukotrienes are produced from lipids, specifically arachidonic acid, which is found in the cell's membrane.
112
What is the role of lipoxygenase in leukotriene production?
Lipoxygenase is an enzyme responsible for producing leukotrienes from arachidonic acid.
113
What effects do leukotrienes have on the body?
Leukotrienes cause effects similar to histamine, including smooth muscle contraction and increased vascular permeability.
114
When are leukotrienes particularly important in the inflammatory response?
Leukotrienes are particularly important in the later stages of inflammation, leading to slower and more prolonged responses compared to histamine.
115
What are prostaglandins, and how are they produced?
Prostaglandins are long-chain, unsaturated fatty acids produced when the enzyme cyclo-oxygenase (COX) acts on arachidonic acid.
116
What are the different types of prostaglandins?
Prostaglandins come in various types, such as E1, E2, D, A, F, and B, with numeral subscripts indicating the number of double bonds.
117
What role do prostaglandins play in inflammation?
Prostaglandins contribute to inflammation by increasing vascular permeability, guiding neutrophils to the site of injury (neutrophil chemotaxis), and causing pain by directly affecting nerves.
118
What are the two forms of COX, and where are they found?
COX-1 is found in most tissues with a general protective function, while COX-2 is associated with inflammation.
119
What is the impact of inhibiting both COX-1 and COX-2?
Inhibiting both COX-1 and COX-2, as done by medications like Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), can lead to complications like gastrointestinal (GI) toxicity.
120
Are there selective COX-2 inhibitors available?
Yes, selective COX-2 inhibitors like Celebrex (celecoxib) are available, targeting COX-2 without affecting COX-1.
121
How is platelet-activating factor (PAF) produced?
PAF is produced by removing a fatty acid from the cell's membrane phospholipids using an enzyme called phospholipase A2.
122
Besides mast cells, what other cells can produce PAF?
Neutrophils, monocytes, endothelial cells, and platelets can also produce PAF.
123
What are the biological effects of PAF?
PAF has similar effects to leukotrienes, including causing endothelial cell retraction (increasing vascular permeability), promoting leukocyte adhesion to endothelial cells, and activating platelets.
124
How do corticosteroids work in inflammation?
Corticosteroids work by inhibiting phospholipases.
125
What are phospholipases, and why are they important in inflammation?
Phospholipases are enzymes that play a role in the production of inflammatory mediators. Inhibition of phospholipases reduces the synthesis of these mediators.
126
What is the mechanism of action for nonsteroidal anti-inflammatory drugs (NSAIDs) in inflammation?
NSAIDs inhibit cyclo-oxygenase (COX) from producing prostaglandins.
127
What are prostaglandins, and why are they significant in inflammation?
Prostaglandins are lipid compounds that contribute to inflammation by increasing vascular permeability, promoting cell migration, and causing pain. NSAIDs block their production.
128
How does acetaminophen work in relation to inflammation?
Acetaminophen blocks a variant of cyclo-oxygenase (COX), but it does not have anti-inflammatory effects.
129
What is the difference between acetaminophen and NSAIDs regarding their anti-inflammatory effects?
NSAIDs have anti-inflammatory effects by inhibiting COX, while acetaminophen lacks significant anti-inflammatory properties.
130
What is IL (Interleukin) in the context of inflammation?
IL stands for Interleukin, which is a group of cytokines involved in various immune responses, including inflammation.
131
What is the role of TNF-α (tumor necrosis factor-alpha) in inflammation?
TNF-α is a cytokine that plays a key role in inflammation and immune responses. It can promote inflammation and cell death.
132
What is the endothelium?
The endothelium is the inner lining of blood vessels.
133
What does the endothelium adhere to?
The endothelium adheres to an underlying matrix of connective tissue that contains proteins like collagen, fibronectin, and laminins.
134
The endothelium adheres to an underlying matrix of connective tissue that contains proteins like collagen, fibronectin, and laminins.
Endothelial cells help maintain normal blood flow by preventing spontaneous activation of platelets and members of the clotting system.
135
What is nitric oxide (NO), and how is it produced in the endothelium?
Nitric oxide (NO) is a signaling molecule produced from its precursor, arginine (an amino acid), in endothelial cells. It can relax vascular smooth muscle, resulting in vasodilation.
136
What is prostacyclin (PGI2), and where does it come from?
Prostacyclin (PGI2) is a molecule derived from arachidonic acid. It is produced by endothelial cells and helps maintain blood flow and pressure while inhibiting platelet activation.
137
How do NO and PGI2 work together in regulating blood flow?
NO and PGI2 have synergistic effects and work together to cause more effective vasodilation when regulating blood flow.
138
What happens when the endothelial cell lining is damaged?
Damage to the endothelial cell lining exposes the subendothelial connective tissue matrix, which can initiate platelet activation and the formation of blood clots.
139
What is the contact activation (intrinsic) clotting pathway?
The contact activation clotting pathway is initiated when the subendothelial connective tissue matrix is exposed due to endothelial cell damage.
140
How do proinflammatory mediators affect the endothelium?
Proinflammatory mediators like histamine and prostacyclin can lead to leukocyte adherence to the vessel's inner surface, invasion of leukocytes into the surrounding tissue, and plasma leakage into the interstitium.
141
What role does PGI2 production play in blood flow regulation?
PGI2 production can vary, and it increases when additional regulation of blood flow is needed.
142
What are platelets?
Platelets are tiny cell fragments formed from megakaryocytes. They lack a nucleus and are involved in blood clotting.
143
Where do platelets circulate?
Platelets circulate in the bloodstream and are always ready to act when there's blood vessel damage.
144
What activates platelets?
Platelets are activated by various substances produced during tissue damage and inflammation, such as collagen, thrombin, and PAF (platelet-activating factor).
145
What are the functions of activated platelets?
Activated platelets have several functions:
They interact with the coagulation cascade to help form blood clots.
They release biochemical mediators, including serotonin, which affects blood vessels similarly to histamine.
They synthesize thromboxane A2 (TXA2), a potent vasoconstrictor that encourages platelet clumping.
146
How does low-dose Aspirin affect platelet function?
Low-dose Aspirin selectively suppresses the production of TXA2 by platelets without interfering with the production of anti-inflammatory prostacyclin (PGI2) by the endothelium. This helps reduce the risk of clot formation in blood vessels.
147
Besides blood clotting, what else do platelets do?
Platelets release growth factors that promote wound healing.
148
What is the primary role of granulocytes?
The primary role of granulocytes, including neutrophils, eosinophils, and basophils, is phagocytosis. They ingest and dispose of damaged cells and foreign material, including microorganisms.
149
What is phagocytosis?
Phagocytosis is the process by which cells, such as granulocytes and macrophages, engulf and digest foreign particles, pathogens, and cellular debris to remove them from the body.
150
What are eosinophils?
Eosinophils are another type of granulocyte that plays a role in the immune response, particularly in dealing with parasitic infections and allergic reactions.
151
What is the role of monocytes and macrophages in phagocytosis?
Monocytes are white blood cells that can mature into macrophages, which are specialized immune cells. Both monocytes and macrophages are important phagocytes that ingest and remove foreign material, microorganisms, and cellular debris from the body.
152
What are basophils?
Basophils are a less common type of granulocyte involved in allergic and inflammatory responses. They release substances like histamine.
153
How do these immune cells contribute to immune defense?
By performing phagocytosis, these immune cells help protect the body from infections and maintain tissue homeostasis by cleaning up damaged cells and debris.
154
What are neutrophils?
Neutrophils are a type of white blood cell, also known as polymorphonuclear neutrophils (PMNs).
155
What distinguishes neutrophils from other white blood cells?
Neutrophils are characterized by their staining pattern of granules and their multilobed nucleus.
156
When do neutrophils typically arrive at the site of inflammation?
Neutrophils are early responders and usually arrive at the inflammatory site within 6 to 12 hours after an injury or infection.
157
What attracts and activates neutrophils during inflammation?
Inflammatory mediators like certain bacterial proteins, complement fragments C3a and C5a, and mast cell NCF (neutrophil chemotactic factor) specifically and rapidly attract and activate neutrophils from the bloodstream.
158
How long do neutrophils typically live at the site of inflammation?
Neutrophils have a short lifespan at the site of inflammation because they cannot divide and are sensitive to acidic environments.
159
What happens to neutrophils after their mission at the site of inflammation?
Neutrophils become part of pus, a thick, yellowish fluid containing dead cells and debris. Pus is eventually removed from the body through the epithelium or drained via the lymphatic system.
160
What are the primary roles of neutrophils?
Neutrophils have two primary roles:
In sterile lesions, such as burns, they help remove debris and dead cells.
In nonsterile lesions, they are responsible for destroying harmful bacteria.
161
What type of white blood cell are basophils?
Basophils are a type of white blood cell known as granulocytes.
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How prevalent are basophils in the blood?
Basophils are the least common type of granulocyte in the blood.
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What is the similarity between basophils and mast cells?
Basophils and mast cells have similar granule contents.
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What cytokine do basophils produce?
Basophils are a source of the cytokine IL-4.
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What is the role of IL-4 in the immune system?
IL-4 is a key regulator of the adaptive immune response, helping coordinate immune defenses.
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What is the primary role of basophils?
The primary role of basophils is not fully understood, although they are often associated with allergies and asthma.
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What type of white blood cell are eosinophils?
Eosinophils are a type of white blood cell known as granulocytes.
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What are the two specific functions of eosinophils?
Eosinophils serve as the body's primary defense against parasites and help regulate vascular mediators released from mast cells.
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How do eosinophils collaborate with the acquired immune system in resisting parasites?
Eosinophils collaborate with specific antibodies produced by the acquired immune system in fighting against parasites.
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Why is the regulation of mast cell-derived inflammatory mediators important?
Regulation is crucial to control inflammation and ensure it occurs only in specific areas and for a limited time.
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What chemical attracts eosinophils to the site of inflammation?
Mast cell eosinophil chemotactic factor of anaphylaxis (ECF-A) attracts eosinophils to the site of inflammation.
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How do eosinophil lysosomal granules contribute to inflammation control?
Eosinophil lysosomal granules contain enzymes that degrade vasoactive molecules, controlling the vascular effects of inflammation. For instance, histaminase degrades histamine, and arylsulfatase B degrades leukotrienes.
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What are monocytes, and where are they produced?
Monocytes are large blood cells (14 to 20 µm in diameter) produced in the bone marrow.
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What happens to monocytes after they are produced?
Monocytes enter the circulation and migrate to inflammatory sites, where they develop into macrophages.
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What are tissue macrophages, and where are they found?
Tissue macrophages are derived from monocytes and are found in various tissues, including the liver (Kupffer cells), lungs (alveolar macrophages), and brain (microglia).
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How do macrophages compare to monocytes in terms of size and phagocytic activity?
Macrophages are generally larger (20 to 40 µm) and more active as phagocytes than their monocyte precursors.
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What is the typical arrival time of monocyte-derived macrophages at an inflammatory site?
Monocyte-derived macrophages may appear at the inflammatory site as soon as 24 hours after neutrophil infiltration, but they usually arrive 3 to 7 days later.
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How do neutrophils and macrophages differ in terms of speed at the injury site?
Neutrophils arrive faster at the injury site, while macrophages move more sluggishly.
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What allows macrophages to survive and divide in an inflammatory site, unlike neutrophils?
Macrophages can survive and divide in the acidic environment of an inflammatory site.
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What are the key differences between neutrophils and macrophages in terms of chemotactic factors and enzymatic content of their lysosomes?
Neutrophils and macrophages are attracted by different factors, and neutrophils have more active NADPH oxidase, producing more hydrogen peroxide, while macrophage lysosomes are more acidic, favoring the activity of acidic proteases and enzymes.
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What role do macrophages play in the immune response that neutrophils do not?
Macrophages are involved in activating the adaptive immune system, which neutrophils do not participate in.
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How do macrophages contribute to wound repair?
Macrophages are primary cells in tissue wounds, removing debris, promoting blood vessel growth (angiogenesis), and producing cytokines and growth factors that suppress inflammation and initiate healing processes.
183
What two subpopulations of macrophages result from activation, and what are their roles?
Macrophage activation leads to M1 macrophages with greater bacterial-killing capacity and M2 macrophages with more healing and repair functions.
184
Which cells or cytokines can enhance the bactericidal activity of macrophages?
Inflammatory cytokines from the acquired immune system (T lymphocytes) and cells activated through TLRs can increase the bactericidal activity of macrophages.
185
Which microorganisms are known to be resistant to killing by granulocytes and can survive inside macrophages?
Microorganisms like Mycobacterium tuberculosis, Mycobacterium leprae, Salmonella typhi, Brucella abortus, and Listeria monocytogenes can resist killing by granulocytes and survive inside macrophages.
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What is the role of dendritic cells in the immune response?
Dendritic cells serve as a major link between the innate and acquired immune responses.
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Where are dendritic cells primarily located in the body?
Dendritic cells are primarily found in peripheral organs and the skin.
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How do dendritic cells encounter molecules released from infectious agents?
Dendritic cells encounter infectious agent molecules through phagocytosis, facilitated by the recognition of Pattern Recognition Receptors (PRRs).
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What is the next step after dendritic cells phagocytose infectious agents?
After phagocytosis, dendritic cells migrate through the lymphatic vessels to lymphoid tissues, such as lymph nodes.
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What is the key interaction that dendritic cells have in lymphoid tissues?
In lymphoid tissues, dendritic cells interact with T lymphocytes (T cells).
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What is the outcome of the interaction between dendritic cells and T cells?
Dendritic cells and T cells interact to generate an acquired immune response.
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What role do dendritic cells play in guiding the development of T-helper cells?
Dendritic cells produce a family of cytokines that guide the development of T-helper cells, which, in turn, coordinate the development of functional B and T cells.
191
What are the two most important types of phagocytes?
Neutrophils and macrophages are the two most important types of phagocytes.
192
How do neutrophils and macrophages initiate phagocytosis?
Neutrophils and macrophages first leave the circulation and migrate to the site of inflammation before initiating phagocytosis.
193
What is the role of selectins and integrins during inflammation?
Selectins and integrins are molecules that increase cell-to-cell adherence, promoting leukocytes to adhere more firmly to the endothelial cells in capillaries and venules, a process called margination or pavementing.
194
Describe diapedesis.
Diapedesis is the emigration of leukocytes through loosened junctions between endothelial cells in response to inflammatory mediators once they are inside the tissue.
195
What is chemotaxis, and what are some primary chemotactic factors?
Chemotaxis is the directed migration of leukocytes to the inflammatory site. Primary chemotactic factors include bacterial products, NCF, IL-8, complement fragments C3a and C5a, and products of the clotting and kinin systems.
196
What is opsonization, and how does it enhance phagocytosis?
Opsonization enhances phagocytosis by acting as a glue to strengthen the bond between phagocytes and target cells. Antibodies and C3b from the complement system are efficient opsonins.
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How do phagocytes engulf microorganisms during phagocytosis?
Small pseudopods extend from the plasma membrane, surrounding the adherent microorganism, and forming an intracellular phagocytic vacuole or phagosome.
198
What happens after the formation of the phagosome?
Lysosomes converge, fuse with the phagosome, and discharge their contents, creating a phagolysosome where the microorganism is destroyed through both oxygen-dependent and oxygen-independent mechanisms.
199
Explain the respiratory burst and its role in phagocytosis.
The respiratory burst is a process accompanying phagocytosis where a burst of oxygen uptake occurs. NADPH oxidase uses NADPH to generate toxic oxygen species, such as superoxide and hydrogen peroxide, which can damage bacteria.
200
What are some oxygen-independent mechanisms of microbial killing?
Oxygen-independent mechanisms include the acidic pH of the phagolysosome, cationic proteins damaging target cell membranes, enzymatic attack of the microorganism's cell wall, and lactoferrin inhibiting bacterial growth by binding iron.
201
What happens when a phagocyte dies at an inflammatory site?
When a phagocyte dies, it often lyses and releases its cytoplasmic contents into the tissue, including enzymes and reactive oxygen molecules that can contribute to tissue destruction.
202
How are the destructive effects of enzymes and reactive oxygen molecules released by dying phagocytes minimized?
Natural inhibitors in the blood, such as superoxide dismutase, catalase, α1-antitrypsin, and α2-macroglobulin, help minimize the destructive effects of these molecules.
203
What can an inherited deficiency of α1-antitrypsin lead to?
An inherited deficiency of α1-antitrypsin can lead to chronic lung damage and emphysema due to inflammation.
204
What is the primary function of natural killer (NK) cells?
The primary function of NK cells is to recognize and eliminate cells infected with viruses, and they can also target abnormal cells like cancer cells.
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Where are NK cells more efficient in eliminating infected cells?
NK cells are more efficient at eliminating infected cells when encountered in the circulatory system rather than within tissues.
206
How do NK cells differentiate between infected or tumor cells and normal cells?
NK cells possess both inhibitory and activating receptors that help them distinguish between infected or tumor cells and normal cells.
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What happens when an NK cell binds to a target cell through activating receptors?
When an NK cell binds to a target cell through activating receptors, it releases several cytokines and toxic molecules that can kill the target cell.
