Module 9: 1.Patho: Define the factors influencing infection. COPY Flashcards
1
Q
What are some factors that can cause damage to the human body?
A
Factors include sunlight, pollutants, physical trauma, infectious agents like viruses and bacteria, and internal factors like cancer.
2
Q
How can damage impact the body?
A
Damage can range from affecting a single cell to multiple cells, tissues, or organs, potentially leading to disease and, in severe cases, death.
3
Q
Why does the body need defense mechanisms?
A
The body requires defense mechanisms to protect against the various factors that can cause damage, ensuring its survival and well-being.
4
Q
What is innate immunity?
A
Innate immunity, also called natural immunity, comprises physical and biochemical barriers and inflammation, which protect the body from injury and infection.
5
Q
What is the role of physical and biochemical barriers in innate immunity?
A
These barriers are the first line of defense, present from birth, to prevent damage and thwart infections by harmful microorganisms. They can also host helpful microorganisms known as the “normal flora.”
6
Q
What happens if an injurious agent breaches the surface barriers?
A
If an injurious agent penetrates the surface barriers, the second line of defense, the inflammatory response, is activated to protect the body from further injury, prevent infection, and promote healing.
7
Q
Describe the nature of the inflammatory response.
A
The inflammatory response is a rapid and relatively nonspecific reaction to different types of tissue damage, initiated regardless of the specific cause. It aims to protect the body.
8
Q
What is the third line of defense in the body’s immune system?
A
The third line of defense is adaptive (acquired) immunity, also known as specific immunity.
9
Q
How does adaptive immunity differ from innate immunity in terms of speed and specificity?
A
Adaptive immunity is slower and more specific, targeting particular invading microorganisms.
10
Q
What is the role of “memory” in adaptive immunity?
A
Memory in adaptive immunity results in a faster response upon re-exposure to the same microorganism.
11
Q
What are the three levels of human defenses?
A
The three levels of human defenses are Barriers, Innate Immunity, and Adaptive (Acquired) Immunity.
12
Q
What is the primary role of Barriers in the defense system?
A
Barriers serve as the first line of defense, providing physical and biochemical protections, including skin, mucous membranes, and secretory molecules.
13
Q
What characterizes the second line of defense, Innate Immunity?
A
Innate Immunity represents the second line of defense and involves immediate responses like inflammation, along with cells such as mast cells, neutrophils, and macrophages.
14
Q
How is Adaptive (Acquired) Immunity different from the other defense levels in terms of specificity?
A
While Barriers and Innate Immunity have broad specificity, Adaptive (Acquired) Immunity is highly specific, targeting specific antigens.
15
Q
What is the role of memory in the immune system?
A
While Barriers and Innate Immunity have broad specificity, Adaptive (Acquired) Immunity is highly specific, targeting specific antigens.
16
Q
What is the role of memory in the immune system?
A
Adaptive immunity involves specific immunological memory, allowing for a faster and more efficient response upon re-exposure to the same antigen.
17
Q
Which cells are involved in the third line of defense, Adaptive Immunity?
A
T cells, B cells, macrophages, and dendritic cells are among the cells involved in Adaptive (Acquired) Immunity.
18
Q
What are some active molecules used in human defenses?
A
Active molecules include defensins, complement, antibodies, and various cytokines.
19
Q
How does each level of defense provide protection?
A
Barriers offer protection through physical and biochemical mechanisms, Innate Immunity uses inflammation and immune cells, while Adaptive (Acquired) Immunity employs activated T and B cells, antibodies, and cytokines for protection.
20
Q
What are the external physical barriers in the body?
A
The external physical barriers consist of tightly associated epithelial cells in the skin and linings of the gastrointestinal, genitourinary, and respiratory tracts.
21
Q
How does the body remove pathogens attempting to breach these barriers?
A
Mechanical processes like coughing, sneezing, vomiting, flushing by urine, and the continual replacement of dead epithelial cells remove pathogens.
22
Q
What is the role of mucus and cilia in the upper respiratory tract?
A
Epithelial cells in the upper respiratory tract produce mucus and have hair-like cilia that trap and move pathogens upward, leading to their expulsion through coughing and sneezing.
23
Q
How do low temperatures and low pH levels contribute to defense against microorganisms?
A
Low temperatures and low pH levels on the skin and in the stomach generally inhibit the growth of microorganisms, as most microorganisms require higher temperatures and near-neutral pH for efficient growth.
24
Q
What protective substances are secreted by epithelial cells to guard against infection?
A
Epithelial cells secrete mucus, perspiration, saliva, tears, and earwax.
25
How do perspiration, tears, and saliva combat Gram-positive bacteria?
Perspiration, tears, and saliva contain lysozyme, an enzyme that attacks the cell walls of Gram-positive bacteria.
26
What substances are secreted by sebaceous glands in the skin, and what do they do?
Sebaceous glands secrete fatty acids and lactic acid, which have bactericidal properties against bacteria and fungi.
27
How does the pH environment created by glandular secretions affect bacteria?
Glandular secretions create an acidic and inhospitable environment with a pH range of 3 to 5, which is hostile to most bacteria.
28
What are antimicrobial peptides, and where are they found?
Antimicrobial peptides are small molecules that kill or inhibit the growth of disease-causing bacteria, fungi, and viruses. They are found in epithelial cell secretions.
29
How do cathelicidins work against bacteria, and where are they produced?
Cathelicidins disrupt bacteria by inserting into their cholesterol-free cell membranes. They are produced in epithelial cells of the skin, gut, urinary tract, and respiratory tract.
30
When is cathelicidin released, and by which cells?
Neutrophils, mast cells, and monocytes store cathelicidin and release it during inflammation.
31
What are the two subtypes of human defensins, and how do they differ in activation?
Human defensins come in two subtypes: α-defensins and β-defensins. α-defensins require activation by proteolytic enzymes, while β-defensins do not.
32
How do α-defensins work to combat bacteria, and where are they found?
α-defensins work with neutrophils to kill bacteria. They are also present in Paneth cells in the small intestine, protecting against disease-causing microorganisms.
33
Where are β-defensins primarily located, and what infections can they potentially guard against?
β-defensins are abundant in epithelial cells lining the respiratory, urinary, and intestinal tracts, as well as in the skin. They may help protect against infections like adenovirus (common cold) and human immunodeficiency virus (HIV).
34
What is the role of antimicrobial peptides in activating the body's defense systems?
Both α-defensins and β-defensins can activate cells involved in subsequent levels of defense, including innate and acquired immunity.
35
What are collectins, and what do they do in the body?
Collectins are glycoproteins produced by the lung, including surfactant proteins A-D and mannose-binding lectin. They interact with carbohydrates on the surfaces of pathogenic microorganisms and aid macrophages in recognizing and eliminating these microorganisms.
36
How does mannose-binding lectin (MBL) contribute to immune defense?
MBL is adept at recognizing a common sugar on microorganism surfaces. It activates the complement plasma protein system, resulting in damage to bacteria or increased recognition by macrophages.
37
What is the normal microbiome, and where is it found in the body?
The normal microbiome consists of various microorganisms and is located on the body's surfaces, including the skin, mucous membranes, GI tracts, respiratory tract, urethra, and vagina.
38
Do the microorganisms in the microbiome typically cause diseases?
No, the microorganisms in the microbiome do not typically cause diseases.
39
How would you describe the relationship between the microbiome and humans?
The relationship between the microbiome and humans can be commensal, where one benefits without affecting the other, or mutualistic, benefiting both.
40
What happens in the lower gut shortly after birth?
The lower gut is initially sterile at birth, but it quickly begins to get colonized by bacteria. The number, diversity, and concentration of these microorganisms increase progressively during the first year of life.
41
What are some of the benefits provided by the normal microbiome in the GI tract?
The benefits include the production of digestive enzymes, generation of essential metabolites like vitamins, and the release of antibacterial factors to prevent colonization by harmful microorganisms.
42
How do some members of the normal microbiome in the colon inhibit the growth of pathogenic microorganisms?
They produce toxic chemicals and proteins, compete for nutrients with pathogens, and block their attachment to the epithelium, a crucial step in the infection process.
43
How does the normal microbiome in the gut influence the adaptive immune system?
It promotes the growth of gut-associated lymphoid tissue, where most adaptive immune cells reside, and contributes to the development of both local and systemic adaptive immunity.
44
What is the role of GI bacteria in the brain-gut axis, and how does it impact various aspects of human health?
GI bacteria play a role in modulating cognitive function, behavior, pain, and stress responses through their influence on the brain-gut axis.
45
What can prolonged use of broad-spectrum antibiotics do to the normal microbiome?
Prolonged antibiotic use can disrupt the normal microbiome, reducing its protective activity and promoting overgrowth of harmful microorganisms.
46
What are some of the potential consequences of microbiome disruption in the intestine?
Disruption of the microbiome can lead to the overgrowth of Candida albicans and Clostridium difficile, potentially causing conditions like pseudomembranous colitis.
47
What is the role of Lactobacillus in the normal GI and vaginal microbiome of healthy women?
Lactobacillus produces protective chemicals like hydrogen peroxide, lactic acid, and bacteriocins, which help prevent infections in the vagina and urinary tract by other microorganisms.
48
How does prolonged antibiotic treatment affect Lactobacillus colonization and what are the associated risks?
Extended antibiotic use can reduce the presence of Lactobacillus, increasing the risk of urological or vaginal infections, such as vaginosis.
49
What types of microorganisms are predominantly found on the skin, and what variations exist?
Predominantly, the skin hosts Gram-positive cocci and rods. Specific areas may have variations, and some individuals may also carry yeasts like Candida and Pityrosporum.
50
What is the typical composition of microorganisms in the nose?
The nose primarily contains Gram-positive cocci and rods. Some individuals may carry pathogenic bacteria like S. aureus and β-hemolytic streptococci.
51
Describe the complex mix of bacteria found in the mouth.
The mouth hosts a complex mix of bacteria, including several species of streptococci, Actinomyces, lactobacilli, and Haemophilus. Anaerobic bacteria and spirochetes colonize gingival crevices.
52
What microorganisms are typically present in the colon?
The colon contains a diverse range of microorganisms, including Bacteroides, lactobacilli, clostridia, Salmonella, Shigella, Klebsiella, Proteus, Pseudomonas, enterococci, and other streptococci, bacilli, and Escherichia coli.
53
Which bacteria are typically found in the distal urethra, and what other microorganisms might be present?
The distal urethra typically contains bacteria found on the skin, such as S. epidermidis and diphtheroids. It may also have lactobacilli and nonpathogenic streptococci.
54
How does the composition of the vaginal microbiome change with age?
The vaginal microbiome varies with age. In newborns, it's similar to adults. From 1 month to puberty, S. epidermidis, diphtheroids, E. coli, and streptococci are common. During puberty to menopause, Lactobacillus acidophilus becomes dominant. Postmenopause, it becomes similar to the prepubescent microbiome.
55
What is the primary purpose of the inflammatory response?
The inflammatory response is designed to limit tissue damage, eliminate infectious microorganisms, initiate adaptive immunity, and promote healing.
56
What are the four key characteristics of the inflammatory response?
The four key characteristics are: (1) it occurs in tissues with a blood supply, (2) it is activated rapidly (within seconds) after damage occurs, (3) it depends on both cellular and chemical components, and (4) it is nonspecific, responding similarly to various stimuli.
57
Why does inflammation occur in tissues with a blood supply?
Inflammation occurs in vascularized tissues because they have a blood supply, allowing for a rapid and efficient response to damage or infection.
58
How quickly does the inflammatory response become activated after tissue damage?
The inflammatory response is activated very rapidly, often within seconds after tissue damage occurs.
59
What is meant by the nonspecific nature of inflammation?
The nonspecific nature of inflammation means that it responds in a similar way regardless of the type of stimulus or whether exposure to the same stimulus has occurred in the past.
60
What can activate the inflammatory response in vascularized tissues?
Virtually any injury, including infection, tissue necrosis (e.g., ischemia, trauma, chemical injury), foreign bodies, and immune reactions, can activate the inflammatory response.
61
What are the cardinal signs of acute inflammation described by Celsus?
The cardinal signs are rubor (redness), calor (heat), tumour (swelling), dolor (pain), and functio laesa (loss of function).
62
What happens at the microscopic level near the site of injury during inflammation?
Microscopic changes include vasodilation (increased blood vessel size), increased vascular permeability with fluid leakage (edema), and white blood cell adherence and migration through vessel walls.
63
How does vasodilation contribute to inflammation?
Vasodilation leads to slower blood velocity and increased blood flow at the injury site, contributing to redness and warmth.
64
What causes the swelling (edema) associated with inflammation?
Increased vascular permeability and fluid leakage out of the vessels cause swelling (edema) at the site of injury.
65
What are the key components involved in inflammation at the site of injury?
Inflammation involves leukocytes (especially neutrophils), plasma proteins, and various biochemical mediators in the blood and tissues.
66
How do vascular changes contribute to inflammation?
Vascular changes allow the delivery of leukocytes, plasma proteins, and mediators to the injury site, promoting the inflammatory response.
67
What role do some chemical mediators play in inflammation?
Some chemical mediators activate pain fibers, contributing to the sensation of pain during inflammation.
68
How does tissue injury, pain, and swelling collectively affect the body?
Tissue injury, pain, and swelling can lead to a loss of function at the site of inflammation.
69
What happens to lymphatic vessels during inflammation, and what are the consequences for lymph nodes?
Lymphatic vessels drain extravascular fluid to lymph nodes. Inflammation can lead to lymphangitis in the lymph vessels and lymphadenitis in the nodes, which become hyperplastic, enlarged, and painful.
70
What are the benefits of inflammation in preventing infection and further damage?
Inflammation prevents infection by invading microorganisms, dilutes bacterial toxins, and activates plasma protein systems to contain and destroy bacteria. Phagocytes (neutrophils, macrophages) eliminate cellular debris and microorganisms.
71
72
How does inflammation limit and control the inflammatory process?
Inflammation prevents the spread of the inflammatory response to areas of healthy tissue through the influx of plasma protein systems, plasma enzymes, and cells (e.g., eosinophils).
73
How does inflammation interact with the adaptive immune system?
Inflammation brings macrophages and lymphocytes to the site, which destroy pathogens, eliciting a more specific immune response.
74
What is the role of inflammation in preparing the area of injury for healing and repair?
Inflammation removes bacterial products, dead cells, and other inflammatory substances, creating a favorable environment for healing and repair.
75
How does the drainage of fluid and debris at an inflamed site contribute to the development of acquired immunity?
Fluid and debris are drained by lymphatic vessels, allowing microbial antigens in lymphatic fluid to encounter lymphocytes in the lymph nodes, contributing to acquired immunity.
76
What are the three key plasma protein systems essential to an effective inflammatory response?
The three key plasma protein systems are the complement system, clotting system, and kinin system.
77
What is a common characteristic of these plasma protein systems in their inactive forms?
In their inactive forms, these systems comprise multiple proteins, with some being enzymes circulating as proenzymes.
78
How are the components within these systems activated during inflammation?
Activation of the initial components triggers sequential activation of other components, creating cascades, referred to as the complement cascade, clotting cascade, or kinin cascade.
79
What may be required for the activation of a specific protein in these systems?
In some cases, activation of a particular protein may require enzymatic cleavage into two differently sized fragments.
80
What are the three plasma protein systems involved in inflammation?
The three plasma protein systems are the Complement, Clotting, and Kinin systems.
81
How is the complement system activated, and what are the major components produced during its activation?
The complement system can be activated by three mechanisms, leading to the proteolytic activation of C3. The major components produced are C3a and C3b.
82
What are the functions of C3a and C3b in the complement system?
C3a acts as a potent anaphylatoxin that triggers mast cell degranulation, while C3b can bind to cell surfaces (e.g., bacteria) for phagocytosis and activate the next complement component, C5.
83
How is the clotting system initiated, and what is the role of thrombin in this system?
The clotting system can be initiated by the tissue factor (extrinsic) or contact activation (intrinsic) pathways, leading to the activation of factor X and thrombin. Thrombin proteolytically activates fibrinogen to form fibrin, which promotes clot formation and increases vascular permeability.
84
How is the kinin system linked to the clotting system, and what role does bradykinin play in inflammation?
XIIa produced by the clotting system can be activated by kallikrein from the kinin system. Kallikrein converts prekallikrein to kininogen, which activates bradykinin. Bradykinin increases vascular permeability, acts similarly to histamine, and stimulates pain through nerve endings.
85
What percentage of the total circulating serum protein do the proteins of the complement system constitute?
The proteins of the complement system make up approximately 10% of the total circulating serum protein.
86
What is the primary outcome of complement system activation in terms of immune defense?
Activation of the complement system results in the production of factors that can directly destroy pathogens or boost the activity of various components in the immune response.
87
Which type of infection are the factors produced during complement system activation particularly effective against?
The factors produced during complement system activation are highly effective defenders against bacterial infections.
88
What is the primary function of opsonins in the complement cascade?
Opsonins coat the surface of bacteria, increasing their susceptibility to being phagocytized and killed by inflammatory cells.
89
What do chemotactic factors do in the context of inflammation?
Chemotactic factors diffuse from an inflammation site and attract phagocytic cells to that location.
90
How do anaphylatoxins, such as C3a and C5a, contribute to inflammation?
Anaphylatoxins induce rapid degranulation of mast cells, leading to histamine release, vasodilation, and increased capillary permeability, which are essential components of inflammation.
91
Which complement products are considered the most potent, and what are their roles?
The most potent complement products are C3b (opsonin), C3a (anaphylatoxin), and C5a (anaphylatoxin and chemotactic factor).
92
What is the result of activating terminal complement components C5b through C9?
Activation of these components leads to the formation of a membrane attack complex (MAC), which creates pores in the outer membranes of cells or bacteria, causing cell death.
93
What is the primary activator of the classical complement pathway?
Antibodies, which are components of the acquired immune system, serve as the primary activators of the classical pathway.
94
What must happen before the classical complement pathway can be activated?
Antibodies need to bind to their targets, known as antigens, typically found on bacteria or other infectious agents.
95
How does the classical pathway initiate complement activation?
Activation of the classical pathway begins with the first complement component, C1, and leads to the subsequent activation of complement components like C3 and C5.
96
Which immune system component can use the classical pathway to combat bacteria and trigger inflammation?
Antibodies from the acquired immune response can use the classical pathway.
97
How does the alternative complement pathway differ from the classical pathway in terms of activation?
The alternative pathway is activated by specific substances on the surface of infectious organisms directly, without the need for antibodies.
98
How does the lectin pathway differ from the classical pathway in terms of activation?
The lectin pathway does not rely on antibodies for activation, while the classical pathway is antibody-dependent.
99
What initiates the lectin pathway of complement activation?
he lectin pathway is initiated by several plasma proteins that recognize specific carbohydrate patterns on the surfaces of pathogenic microorganisms.
100
What types of infectious agents can be targeted by the lectin pathway?
The lectin pathway can target a wide range of pathogenic microorganisms, including bacteria, viruses, protozoa, and fungi, based on the specific carbohydrate patterns they exhibit.
101
Why is the lectin pathway important for complement activation?
The lectin pathway provides an additional means of complement activation, ensuring that even infectious agents unable to activate the complement system directly through the alternative pathway can still be targeted by complement.
102
What are the four primary functions of complement cascade products?
The four functions of complement cascade products are opsonization (C3b), anaphylatoxic activity resulting in mast cell degranulation (C3a, C5a), leukocyte chemotaxis (C5a), and cell lysis (C5b–C9, also known as the membrane attack complex or MAC).
103
What is the primary role of the clotting (coagulation) system?
The clotting system is responsible for forming blood clots in response to injuries to blood vessels.
104
What does a blood clot consist of?
A blood clot is composed of a meshwork of protein strands, primarily fibrin. It also contains platelets and can trap other cells like erythrocytes, phagocytes, and microorganisms.
105
What are the three primary functions of blood clots?
Blood clots serve three main functions: plugging damaged blood vessels to stop bleeding, trapping microorganisms to prevent their spread to nearby tissues, and providing a framework for future tissue repair and healing.
106
What can activate the clotting system?
The clotting system can be activated by various substances released during tissue injury and infection, including collagen, proteinases, kallikrein, plasmin, and bacterial products such as endotoxins.
107
How does the clotting system resemble the complement system?
imilar to the complement cascade, the clotting system can be activated by multiple pathways, ultimately leading to the formation of a blood clot.
108
What is tissue factor (TF) and its role in the clotting system?
Tissue factor (TF), also known as tissue thromboplastin, is released by damaged endothelial cells in blood vessels. It activates the extrinsic pathway of the clotting system.
109
How is the intrinsic pathway of the clotting system activated?
Damage to the vessel wall initiates the intrinsic (or contact activation) pathway, which involves contact between Hageman factor (factor XII) in plasma and negatively charged subendothelial substances.
110
What is the common pathway activated by both the intrinsic and extrinsic pathways of the clotting system?
The common pathway leads to the activation of factor X, which, in turn, initiates the formation of fibrin to create a fibrin clot.
111
How does activation of the clotting system contribute to the inflammatory response?
Activation of the clotting system produces protein fragments called fibrinopeptides (FPs) A and B, which have chemotactic effects on neutrophils and increase vascular permeability, enhancing the inflammatory response. Fibrinopeptide B works in synergy with bradykinin from the kinin system.
112
What is the relationship between the kinin system and the coagulation system?
The kinin system interacts closely with the coagulation system, and the activation of Hageman factor (factor XII) to factor XIIa can initiate both systems.
113
What is another name for factor XIIa, and what role does it play in the kinin system?
Factor XIIa is also known as prekallikrein, and it enzymatically activates the first component of the kinin system.
114
What is the final product of the kinin system, and where does it come from?
The final product of the kinin system is bradykinin, which is derived from a larger precursor molecule called kininogen.
115
What are the effects of bradykinin on the body?
Bradykinin causes the dilation of blood vessels, acts in conjunction with prostaglandins to induce pain, triggers the contraction of smooth muscle cells, and increases vascular permeability.
116
Why is tight regulation of the interactions between the three plasma protein systems essential?
Tight regulation is crucial because these systems are highly interactive, and their activation can result in the production of potent biologically active substances. Regulation is necessary to ensure the efficient activation of the inflammatory process and to prevent potentially harmful effects on the individual.
117
What are the two main reasons for the strict regulation of these plasma protein systems?
The first reason is that the inflammatory process is critical for an individual's survival, and efficient activation must be guaranteed, regardless of the cause of tissue injury. The second reason is that the biochemical mediators generated during these processes are potent and potentially detrimental to the individual, and their action should be limited to only injured or infected tissues.
118
What are some mechanisms to regulate plasma protein systems during inflammation?
Enzymes found in the plasma that enters tissues during inflammation, like carboxypeptidase, kininases, and histaminase, can inactivate mediators of inflammation.
119
How is clot formation related to the regulation of these systems?
The formation of clots triggers the fibrinolytic system, which limits clot size and removes clots after bleeding stops. This helps regulate the plasma protein systems involved in inflammation.
120
How does plasmin, formed during clot dissolution, interact with other cascades?
Plasmin can activate both the complement cascade (components C1, C3, and C5) and the kinin cascade by activating factor XII and producing prekallikrein activator.
121
What is the role of C1 esterase inhibitor (C1 INH) in regulating inflammation?
C1 INH inhibits complement activation, helping to regulate the inflammatory response.
122
What condition results from a genetic defect in C1 INH?
Hereditary angioedema, characterized by self-limiting edema of cutaneous and mucosal layers.
123
How do some cells protect themselves from complement damage?
They have factors on their cell membrane surfaces that prevent the activation of C3 and inhibit the membrane attack complex (MAC) to protect against complement damage.
124
What is inflammation, and where does it occur in the body?
Inflammation is a process that happens in both blood vessels and the surrounding tissues.
125
What is the role of endothelial cells in blood vessels during inflammation?
Endothelial cells in blood vessels help regulate blood flow and also coordinate blood clotting and the movement of cells and fluid during inflammation.
126
Name two types of cells found in tissues near blood vessels that are involved in the inflammatory response.
The two types of cells are mast cells, which activate inflammation, and dendritic cells, which connect the innate and acquired immune responses.
127
What are the three main types of cells found in the blood?
The three main types of cells in the blood are erythrocytes (red blood cells), platelets, and leukocytes (white blood cells).
128
What is the main function of erythrocytes in the blood?
Erythrocytes carry oxygen to the body's tissues.
129
How do platelets contribute to the blood's function?
Platelets are involved in blood clotting, helping to stop bleeding.
130
What are leukocytes, and how are they classified?
Leukocytes are white blood cells. They are classified into granulocytes, monocytes, and lymphocytes.
131
What distinguishes granulocytes from each other, and what are the three main types of granulocytes?
Granulocytes differ based on the staining of their granules. The three main types of granulocytes are basophils, eosinophils, and neutrophils.
132
What do monocytes eventually become, and where are they found in the body?
Monocytes mature into macrophages and are found in various tissues.
133
What are the roles of lymphocytes in the immune system, and which lymphocytes are involved in the innate and acquired immune responses?
Lymphocytes have various immune system roles. Natural killer (NK) cells participate in the innate immune response, while B and T cells are involved in the acquired immune response.
134
What is the role of immune system cells in response to molecules at the site of cellular damage?
Immune system cells respond to these molecules to enhance protective responses.
135
Where do the molecules that trigger immune cell responses come from?
These molecules can originate from damaged cells, invading microbes, activation of plasma proteins, or secretions from other immune system cells.
136
How do immune cells recognize these molecules, and what happens when they do?
Immune cells have specific surface receptors that bind to these molecules, leading to intracellular signaling and cell activation.
137
What can happen when immune cells are activated in response to these molecules?
Immune cell activation can result in gaining functions important for the inflammatory response, releasing more substances that increase inflammation, or both.
138
What are the primary goals of inflammatory cells and proteins at the site of tissue injury?
Inflammatory cells and proteins work to limit damage, combat microorganisms, clear cellular debris, and promote healing, tissue regeneration, or repair at the injury site.
139
What are the surface receptors used by B and T lymphocytes in the adaptive immune system?
B and T lymphocytes use surface receptors known as BCR and TCR, respectively, to bind to a wide range of antigens.
140
What type of receptors do cells in the innate immune system have, and what do these receptors recognize?
Cells in the innate immune system have pattern recognition receptors (PRRs) that recognize specific molecules or ligands.
141
What are the two types of molecular patterns that PRRs can identify?
PRRs recognize pathogen-associated molecular patterns (PAMPs) found on infectious agents and damage-associated molecular patterns (DAMPs) from cellular damage.
142
How does the recognition of PAMPs and DAMPs benefit the innate immune system?
Recognizing both PAMPs and DAMPs allows the innate immune system to respond to both sterile (DAMPs) and septic (PAMPs and DAMPs) tissue damage.
143
Approximately how many different PRRs are there, and how many molecules can they recognize?
There are at least 100 different PRRs, each capable of recognizing over 1,000 different molecules.
144
Where are PRRs generally found in the body, and what is their role?
PRRs are mainly present in surface tissues like the skin, respiratory tract, GI tract, and genitourinary tract. They monitor the environment for signs of cellular damage and potential infectious microorganisms.
145
How do different classes of cellular PRRs differ from one another?
Different classes of cellular PRRs differ in the types of ligands they can bind.
146
What are the different locations where PRRs can be found within the cell?
PRRs can exist on the cell surface, in endosomes (vesicles inside the cell), in the cytosol (inside the cell), or they can be secreted into the extracellular environment.
147
Can you provide an example of a secreted PRR, and what pathway is it associated with?
Mannose-Binding Lectin (MBL) is an example of a secreted PRR, and it is associated with the lectin pathway of complement activation.
148
What do Toll-like receptors (TLRs) primarily recognize?
TLRs primarily recognize pathogen-associated molecular patterns (PAMPs) on microorganisms.
149
Where can PAMPs be located on microorganisms, and what are some examples of PAMPs?
PAMPs can be found on the cell wall, surface structures, and nucleic acids of microorganisms. Examples include bacterial lipopolysaccharide (LPS), peptidoglycans, bacterial flagellin, and viral double-stranded RNA.
150
How many TLRs are known in humans?
There are 11 known TLRs in humans.
151
Where are TLRs found on the surface of cells, and what types of cells have them?
TLRs are found on the surface of cells that have early contact with potential pathogens, including mucosal epithelial cells, mast cells, neutrophils, macrophages, dendritic cells, and some lymphocyte subpopulations.
152
What pathways are activated by TLRs, and what do these pathways lead to?
TLRs activate pathways leading to the production of cytokines through NF-κB and antiviral type I interferons through interferon regulatory factors (IRFs).
153
What types of cells have complement receptors, and what do these receptors recognize?
Complement receptors are found on various immune cells and some epithelial cells. They recognize specific fragments produced during complement system activation, such as C3a, C5a, and C3b.
154
What is the primary role of scavenger receptors, and on which cells are they primarily found?
Scavenger receptors primarily facilitate the recognition and phagocytosis of bacterial pathogens, damaged cells, and altered lipoproteins associated with vascular damage. They are primarily found on macrophages.
155
Can scavenger receptors recognize specific components of the cell membrane, and if so, what component?
Yes, some scavenger receptors, like SR-PSOX, can recognize the cell membrane component phosphatidylserine (PS). This is externalized during erythrocyte senescence and cellular apoptosis.
156
Why is it important that scavenger receptors can recognize externalized phosphatidylserine?
Scavenger receptors recognizing phosphatidylserine help macrophages identify and remove old red blood cells and cells undergoing apoptosis.
157
What are NOD-like receptors (NLRs), and where are they located?
NLRs are receptors found inside cells that can recognize substances from microbes and damaged cells.
158
How many different NLRs are there in humans?
Humans have at least 22 different NLRs.
159
What do NOD-1 and NOD-2 NLRs recognize, and what is their role?
NOD-1 and NOD-2 NLRs detect fragments of peptidoglycans from intracellular bacteria. They trigger the production of proinflammatory molecules like tumor necrosis factor (TNF) and interleukin-6 (IL-6).
160
What are inflammasomes, and what do they primarily bind to?
Inflammasomes are complexes formed by some NLRs inside cells. They primarily bind to cellular stress-related molecules, a type of damage-associated molecular pattern (DAMP).
161
What is the main role of inflammasomes in the cell?
Inflammasomes control the production of inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18, in response to cellular stress-related molecules.
162
What is the role of cytokines in the immune response?
Cytokines are small signaling molecules that play a crucial role in regulating both innate and adaptive immunity by facilitating intercellular communication.
163
How do cytokines affect the inflammatory response, and what are the two categories of cytokines?
Cytokines can either promote (proinflammatory) or inhibit (anti-inflammatory) the inflammatory response.
164
Do cytokines mainly act over short or long distances in the body?
Cytokines typically act over short distances, but some can have systemic effects, like causing fever.
165
What happens when cytokines bind to target cells?
Binding of cytokines to target cells often triggers the synthesis and release of additional cellular products. For example, when tumor necrosis factor-alpha (TNF-α) binds to a cell, it may result in the synthesis and release of interleukin-1.
166
What is a cytokine storm, and what can trigger it?
A cytokine storm is an excessive and uncontrolled immune response that generates a large number of proinflammatory cytokines. It can be triggered by infections, malignancies, and other disorders.
167
How does a cytokine storm affect the body, and what can it lead to?
A cytokine storm can damage epithelial and endothelial cells, cause vascular leakage, lead to acute respiratory distress syndrome, and affect multiple organ systems.
168
What is the significance of elevated cytokine levels in COVID-19 infection?
Elevated cytokine levels in COVID-19 often indicate a poor prognosis and a severe immune response.
169
How does COVID-19 specifically impact the immune response, and what treatment approach involves targeting a specific cytokine?
COVID-19 selectively stimulates IL-6 and can lead to lymphocyte exhaustion. One treatment approach is using monoclonal antibodies against IL-6, such as tocilizumab.
170
What are lymphokines and monokines, and what types of cells produce them?
Lymphokines are cytokines secreted by lymphocytes, and monokines come from monocytes. However, cytokines are produced by various cell types.
171
What is the role of chemokines, and what type of cells do they primarily attract?
Chemokines are a special family of cytokines that primarily attract white blood cells (leukocytes) to sites of inflammation.
172
Which cells produce chemokines, and what triggers their production?
Various cells like macrophages, fibroblasts, and endothelial cells produce chemokines. They are produced in response to proinflammatory cytokines like TNF-α.
173
Can you provide examples of chemokines and the types of immune cells they primarily attract?
Examples of chemokines include monocyte/macrophage chemotactic proteins (MCP-1, MCP-2, and MCP-3) that attract macrophages, and interleukin-8 (IL-8) that primarily attracts neutrophils.
174
Which cells, when stimulated, primarily produce interleukins (ILs)?
Macrophages and lymphocytes are key producers of interleukins in response to stimulation.
175
How many different interleukins (ILs) are there, and what are some of their effects?
There are more than 30 different ILs, and they can alter adhesion molecule expression on cells, attract leukocytes to sites of inflammation, promote leukocyte growth in the bone marrow, modulate inflammation, and contribute to the development of the acquired immune response.
176
What is the role of ILs in attracting leukocytes to sites of inflammation?
ILs promote chemotaxis, which is the attraction of white blood cells (leukocytes) to the sites of inflammation.
177
How do ILs contribute to the development of the acquired immune response?
ILs play a role in the development of the acquired immune response, which is the body's ability to remember and respond to specific pathogens.
178
What are the two major proinflammatory interleukins, and which cytokine do they cooperate closely with?
The two major proinflammatory interleukins are interleukin-1 (IL-1) and interleukin-6 (IL-6), which work closely with another cytokine, TNF-α.
179
Which cells are the main producers of interleukin-1 (IL-1), and how many forms of IL-1 are there?
Macrophages primarily produce IL-1, which exists in two forms: IL-1α and IL-1β.
180
What are some effects of IL-1 on various immune cells, including neutrophils?
IL-1 activates monocytes, macrophages, and lymphocytes, enhancing both innate and acquired immunity. It also acts as a growth factor for many cell types. Regarding neutrophils, IL-1 induces their proliferation, attracts them to inflammatory sites (chemotaxis), and enhances their ability to kill bacteria.
181
How does IL-1 contribute to the development of fever, and what is it called in this context?
IL-1 is an endogenous pyrogen, which means it causes fever. It does so by reacting with receptors on cells in the hypothalamus, affecting the body's thermostat and resulting in an increase in body temperature.
182
Which cells are the primary producers of interleukin-6 (IL-6)?
Macrophages, lymphocytes, and fibroblasts are the main producers of IL-6.
183
What is the role of IL-6 in inflammation and wound healing?
IL-6 directly stimulates hepatocytes (liver cells) to produce proteins needed for inflammation (acute-phase reactants) and promotes the growth and differentiation of blood cells in the bone marrow. It also contributes to the growth of fibroblasts, which are essential for wound healing.
184
What cytokine is secreted by macrophages and some other cells in response to TLR stimulation, and what are its main effects?
Macrophages and other cells secrete tumor necrosis factor-alpha (TNF-α). TNF-α has various proinflammatory effects, particularly on the vascular endothelium and macrophages.
185
What are the systemic effects of TNF-α when it is secreted in large amounts?
In cases of high secretion, TNF-α can induce fever (as an endogenous pyrogen), increase the synthesis of inflammation-related proteins by the liver, and lead to muscle wasting (cachexia) and intravascular thrombosis in severe infections and cancer.
186
What can very high levels of TNF-α, a proinflammatory cytokine, potentially lead to?
Very high levels of TNF-α can be lethal and are associated with fatalities from shock caused by Gram-negative bacterial infections.
187
What are anti-inflammatory cytokines, and which two are considered the most important?
Anti-inflammatory cytokines reduce the inflammatory response. The most important ones are interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β).
188
Which cells primarily produce interleukin-10 (IL-10), and what does it do to the immune response?
Lymphocytes are the main producers of IL-10. IL-10 suppresses the growth of other lymphocytes and the production of proinflammatory cytokines by macrophages. This downregulates both the inflammatory and acquired immune responses.
189
What is the role of transforming growth factors like TGF-β, and what do they induce in response to inflammation?
In response to inflammation, various cells produce transforming growth factors like TGF-β. These growth factors stimulate cell division and the differentiation of different cell types, including immature blood cells.
190
What is the role of cytokines in the immune response?
Cytokines are small signaling molecules that play a crucial role in regulating both innate and adaptive immunity by facilitating intercellular communication.
191
How do cytokines affect the inflammatory response, and what are the two categories of cytokines?
Cytokines can either promote (proinflammatory) or inhibit (anti-inflammatory) the inflammatory response.
192
Do cytokines mainly act over short or long distances in the body?
Cytokines typically act over short distances, but some can have systemic effects, like causing fever.
193
What happens when cytokines bind to target cells?
Binding of cytokines to target cells often triggers the synthesis and release of additional cellular products. For example, when tumor necrosis factor-alpha (TNF-α) binds to a cell, it may result in the synthesis and release of interleukin-1.
194
What is the role of interferons (IFNs) in the body?
Interferons are a family of cytokines that protect against viral infections and help regulate the inflammatory response.
195
How do virally infected cells respond to viral components, and what type of interferons do they produce?
Virally infected cells produce type I interferons, primarily IFN-α and IFN-β, in response to viral double-stranded RNA and other viral components (PAMPs).
196
What is the primary function of type I interferons like IFN-α and IFN-β?
Type I interferons don't directly kill viruses. Instead, they induce the production of antiviral proteins and protect neighboring healthy cells.
197
Which type of interferon is mainly produced by lymphocytes, and what does it do in the body?
Lymphocytes primarily produce type II interferon, IFN-γ. IFN-γ activates macrophages, enhancing the body's ability to combat infectious agents, including viruses and bacteria. It also supports the development of acquired immune responses against viruses.
198
What is the role of mast cells in the inflammatory response?
Mast cells are essential activators of the inflammatory response in the body.
199
Where are mast cells primarily located in the body, and what are their counterparts found in the blood?
Mast cells are primarily located in loose connective tissues near blood vessels, especially in the skin, GI tract, and respiratory tract. Basophils found in the blood likely function similarly to tissue mast cells.
200
How do mast cells release potent inducers of inflammation, and what are the two main mechanisms involved?
Mast cells release inducers of inflammation through two main mechanisms: degranulation (release of granule contents) and synthesis (new production and release of mediators in response to a stimulus).
201
What do mast cells release in response to a stimulus, and what are some examples of these mediators?
In response to a stimulus, mast cells release biochemical mediators, including histamine, chemotactic factors, and cytokines like TNF-α and IL-4.
202
What are vasoactive amines, and how do they affect blood circulation?
Vasoactive amines like histamine and serotonin influence blood circulation by causing rapid constriction of smooth muscle and dilation of postcapillary venules, resulting in increased blood flow into the microcirculation.
203
How does histamine increase vascular permeability, and what are its effects on cells?
Histamine increases vascular permeability by causing retraction of endothelial cells lining the capillaries and enhanced adherence of leukocytes to the endothelium. It affects cells by binding to histamine H1 and H2 receptors on the target cell surface.
204
What is the purpose of antihistamines, and how do they work?
Antihistamines are medications that block the binding of histamine to its receptors, leading to decreased inflammation and alleviation of histamine-induced effects.
205
What are the two types of histamine receptors, and how do they affect inflammation?
Histamine can bind to H1 and H2 receptors. H1 receptor binding promotes inflammation, while H2 receptor binding is generally anti-inflammatory, suppressing leukocyte function.
206
Where is the H1 receptor mainly found, and what effect does its stimulation have?
The H1 receptor is present on smooth muscle cells, especially bronchial smooth muscle. Stimulation of H1 receptors causes bronchoconstriction (bronchoconstriction).
207
Do H1 and H2 receptors exist on the same cells, and how do they sometimes interact?
H1 and H2 receptors can be found on the same cells and may act antagonistically. For instance, H1 receptor stimulation on neutrophils enhances chemotaxis, while H2 receptor stimulation inhibits it.
208
What is the primary role of the H2 receptor, and where is it most abundant?
The H2 receptor is especially abundant on parietal cells of the stomach mucosa and stimulates the secretion of gastric acid as part of the normal physiology of the stomach.
209
What are some chemotactic factors found in mast cell granules, and what is the purpose of chemotaxis in inflammation?
Mast cell granules contain chemotactic factors like neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor of anaphylaxis (ECF-A). Chemotaxis is the directional movement of cells along a chemical gradient created by chemotactic factors and is involved in guiding cells to the site of inflammation.
210
What are the roles of neutrophils and eosinophils in inflammation, and when are they predominant?
Neutrophils are predominant during the early stages of inflammation and are primarily involved in killing bacteria. Eosinophils help regulate the inflammatory response.
211
What do activated mast cells initiate the synthesis of in the context of inflammation, and what are these mediators produced from?
Activated mast cells initiate the synthesis of other mediators of inflammation, including leukotrienes, prostaglandins, and platelet-activating factor. These mediators are produced from lipids, specifically arachidonic acid, in the plasma membrane.
212
What are leukotrienes, and how are they produced?
Leukotrienes, also known as slow-reacting substances of anaphylaxis (SRS-A), are sulfur-containing lipids produced by lipoxygenase.
213
What effects do leukotrienes induce, and how do they compare to histamine?
Leukotrienes induce histamine-like effects, such as smooth muscle contraction and increased vascular permeability. They are known to stimulate slower and more prolonged inflammatory responses compared to histamine.
214
What are the roles of prostaglandins in inflammation?
Prostaglandins contribute to inflammation by causing increased vascular permeability, promoting neutrophil chemotaxis, and directly affecting nerves to generate the sensation of pain.
215
How are prostaglandins produced, and what is the enzyme involved in their synthesis?
Prostaglandins are long-chain, unsaturated fatty acids produced by the action of the enzyme cyclo-oxygenase (COX) on arachidonic acid.
216
What are the different types of prostaglandins, and how are they designated?
Prostaglandins have different structures, such as E, D, A, F, and B, with numeral subscripts indicating the number of double bonds.
217
Can you provide an example of the effects of specific prostaglandins?
For example, prostaglandins E1 and E2 cause increased vascular permeability and smooth muscle contraction.
218
What are the two forms of COX, and where are they typically found in the body?
COX exists in two forms: COX-1 is found in most tissues and has a general protective function, while COX-2 is associated with inflammation.
219
How do nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin affect COX, and what potential issue arises with COX-1 inhibition?
NSAIDs inhibit both COX-1 and COX-2. Inhibition of COX-1 can lead to gastrointestinal (GI) toxicity.
220
Question: Are there options to selectively target COX-2 for inflammation without as many GI side effects?
Answer: Yes, selective COX-2 inhibitors like Celebrex (celecoxib) are available to target inflammation while minimizing GI side effects.
221
Question: How is platelet-activating factor (PAF) produced, and what enzyme is involved in its generation?
Answer: PAF is produced when a fatty acid is removed from plasma membrane phospholipids by an enzyme called phospholipase A2.
222
Question: Which cells are major sources of PAF, and what are some other cells that can produce PAF?
Answer: Mast cells are a major source of PAF, but neutrophils, monocytes, endothelial cells, and platelets can also produce PAF.
223
Question: What are the biological effects of PAF, and how do they compare to leukotrienes?
Answer: PAF's biological effects are similar to leukotrienes, including causing endothelial cell retraction to increase vascular permeability, promoting leukocyte adhesion to endothelial cells, and activating platelets.
224
Flashcard 1:
Question: What comprises the lining of blood vessels, and what proteins are present in the underlying connective tissue matrix?
Answer: The lining of blood vessels consists of endothelial cells adhering to an underlying connective tissue matrix containing proteins like collagen, fibronectin, and laminins.
225
Question: What is the role of endothelial cells in blood vessels?
Answer: Endothelial cells regulate the inflammatory system and maintain normal blood flow by preventing spontaneous activation of platelets and clotting system components.
226
Question: What is the function of nitric oxide (NO) in blood vessels, and how is it derived?
Answer: NO acts as a signaling molecule, relaxing vascular smooth muscle to induce vasodilation and suppressing the effects of low levels of cytokines. It is derived from its immediate precursor, arginine (an amino acid).
227
Question: How does prostacyclin (PGI2) contribute to blood vessel function, and where does it come from?
Answer: PGI2 maintains blood flow and pressure while inhibiting platelet activation. It originates from arachidonic acid.
228
Question: How do PGI2 and NO work together in regulating blood flow?
Answer: PGI2 and NO are synergistic, causing more significant vasodilation when they work together than either can achieve on its own. PGI2 production increases when there is a need for additional blood flow regulation.
229
Question: What happens when the endothelial cell lining of blood vessels is damaged?
Answer: Damage to the endothelial cell lining exposes the subendothelial connective tissue matrix, which triggers platelet activation and clot formation via the intrinsic clotting pathway.
230
Question: How do proinflammatory mediators like histamine and prostacyclin affect the endothelium?
Answer: Proinflammatory mediators influence the endothelium, leading to the adherence of leukocytes to the vessel surface, the migration of leukocytes into the tissue, and the movement of plasma from the vessel into the surrounding tissue.
231
Question: What are platelets, and how are they formed?
Answer: Platelets are anucleate cytoplasmic fragments formed from megakaryocytes.
232
Question: What activates platelets, and what functions do they perform when activated?
Answer: Platelets become activated in response to triggers like collagen, thrombin, and platelet-activating factor (PAF). When activated, they participate in blood clot formation, release mediators like serotonin, and synthesize vasoconstrictor and platelet aggregation-inducing thromboxane A2 (TXA2).
233
Question: How does prolonged use of low-dose aspirin affect platelet function?
Answer: Prolonged use of low-dose aspirin selectively suppresses the production of TXA2 by platelets without interfering with the production of the anti-inflammatory prostacyclin (PGI2) by the endothelium.
234
Question: What additional role do platelets play in the body?
Answer: Platelets also release growth factors that promote wound healing.
235
Question: What is the primary function of granulocytes and monocytes/macrophages?
Answer: Granulocytes (neutrophils, eosinophils, basophils) and monocytes/macrophages primarily perform phagocytosis, which involves ingesting and disposing of damaged cells and foreign material, including microorganisms.
236
What are neutrophils, and what is characteristic about their nuclei and granules?
Neutrophils, also known as polymorphonuclear neutrophils (PMNs), are a type of white blood cell with multilobed nuclei and specific granule staining patterns.
237
What is the primary role of neutrophils in the early stages of inflammation?
Neutrophils are the predominant phagocytes that arrive at the early inflammatory site within 6 to 12 hours after an initial injury.
238
What attracts and activates neutrophils in the inflammatory process?
Various inflammatory mediators, such as bacterial proteins, complement fragments C3a and C5a, and mast cell NCF, specifically and rapidly attract and activate neutrophils from the circulation.
239
What happens to neutrophils at the inflammatory site, and how are they eventually removed from the body?
Neutrophils are short-lived at the inflammatory site and become part of purulent exudate (pus). They are eventually removed from the body through the epithelium or drained via the lymphatic system.
240
What are the primary roles of neutrophils in the body's immune response?
Neutrophils play essential roles in removing debris and dead cells in sterile lesions like burns and in destroying bacteria in nonsterile lesions.
241
What are eosinophils, and what are their primary functions?
Eosinophils are a type of granulocyte with mild phagocytic abilities. Their primary functions are defending against parasites and regulating vascular mediators released from mast cells.
242
How do eosinophils collaborate with the acquired immune system in parasite defense?
Eosinophils collaborate with specific antibodies produced by the acquired immune system in defending against parasites.
243
Why is it important to regulate mast cell-derived inflammatory mediators?
It's crucial to control inflammation in a circumscribed area and for a limited time, so regulatory mechanisms are needed to prevent excessive inflammation.
244
What attracts eosinophils to the site of inflammation?
Mast cell eosinophil chemotactic factor of anaphylaxis (ECF-A) attracts eosinophils to the site of inflammation.
245
How do eosinophils help control inflammation at the site of an injury?
Eosinophil lysosomal granules contain enzymes that degrade vasoactive molecules, such as histamine and leukotrienes, which helps control the vascular effects of inflammation.
246
What is the prevalence of basophils in the blood?
Basophils are the least prevalent type of granulocyte in the blood.
247
How do the granules in basophils compare to those in mast cells?
Basophils have granules similar to those found in mast cells.
248
What is the primary role of basophils in the immune system?
Basophils serve as a source of the cytokine IL-4, which plays a key role in regulating the adaptive immune response.
249
What are basophils often associated with in the context of health conditions?
Basophils are often associated with allergies and asthma.
250
Is the primary role of basophils fully understood?
No, the primary role of basophils is not fully understood despite their association with allergies and asthma.
251
What are monocytes, and where are they produced?
Monocytes are the largest normal blood cells, typically measuring 14 to 20 µm in diameter. They are produced in the bone marrow.
252
What is the fate of monocytes once they enter the bloodstream?
Monocytes enter the bloodstream and migrate to inflammatory sites, where they develop into macrophages.
253
Where can tissue macrophages be found, and what are some examples?
Tissue macrophages are found in various tissues, including Kupffer cells in the liver, alveolar macrophages in the lungs, and microglia in the brain.
254
How do macrophages differ from monocytes in terms of size and phagocytic activity?
Macrophages are generally larger (20 to 40 µm) and more active as phagocytes compared to monocytes.
255
What role do tissue-resident macrophages typically play in the inflammatory response?
Tissue-resident macrophages are often important cellular initiators of the inflammatory response, serving as key players in the immune system.
256
What is the main difference in the arrival time between neutrophils and macrophages at the inflammatory site?
Neutrophils arrive at the injury site first, while macrophages move more slowly and typically appear 3 to 7 days later.
257
How do the active lifespans of neutrophils and macrophages differ in the inflammatory site?
Macrophages have a longer active lifespan and can survive and divide in the acidic inflammatory site, whereas neutrophils cannot.
258
What factors attract neutrophils and macrophages to the injury site, and how do they differ?
Neutrophils and macrophages are attracted by different chemotactic factors. Neutrophils release macrophage chemotactic factor, which attracts them.
259
How do the enzymatic contents of neutrophil lysosomes and macrophage phagolysosomes differ?
Neutrophils have a more active NADPH oxidase and produce more hydrogen peroxide. Macrophage phagolysosomes are more acidic, favoring acidic protease and enzyme activity.
260
Which immune cells are involved in the activation of the adaptive immune system, neutrophils or macrophages?
Macrophages play a role in the activation of the adaptive immune system, while neutrophils do not.
261
What is the primary role of macrophages in wound repair and tissue healing?
Macrophages are the primary cells involved in wound repair, promoting angiogenesis, removing debris, and initiating healing by promoting epithelial cell division, activating fibroblasts, and synthesizing extracellular matrix and collagen.
262
What are the two subpopulations of activated macrophages, and how are they activated?
Macrophages can be activated as M1 macrophages through Toll-like receptors (TLRs) or as M2 macrophages by cytokines produced by lymphocytes.
263
What is the main function of M1 macrophages activated through TLRs?
M1 macrophages have greater bacterial-killing capacity and are primarily involved in inflammatory responses.
264
What is the primary function of M2 macrophages activated by lymphocyte-produced cytokines?
M2 macrophages have a healing and repair function, promoting tissue repair and recovery.
265
Which type of bacteria can survive inside macrophages and remain dormant?
Several bacteria, including Mycobacterium tuberculosis, Mycobacterium leprae, Salmonella typhi, Brucella abortus, and Listeria monocytogenes, can survive inside the phagolysosomes of macrophages.
266
What is an example of a disease caused by bacteria that can survive inside macrophages?
Mycobacterium tuberculosis causes tuberculosis and can remain dormant or multiply inside macrophages.
267
What is the primary function of dendritic cells in the immune system?
Dendritic cells are the primary phagocytic cells in peripheral organs and the skin, responsible for recognizing molecules from infectious agents and initiating immune responses.
268
How do dendritic cells recognize infectious agents?
Dendritic cells recognize infectious agents through pattern recognition receptors (PRRs), which enable them to identify and phagocytose these agents.
269
What is the next step after dendritic cells phagocytose infectious agents?
After phagocytosing infectious agents, dendritic cells migrate to lymphoid tissues, such as lymph nodes, through the lymphatic vessels.
270
What role do dendritic cells play in lymphoid tissues?
In lymphoid tissues, dendritic cells interact with T lymphocytes (T cells) to initiate an acquired immune response.
271
How do dendritic cells guide the development of immune responses?
Dendritic cells produce cytokines that guide the development of T-helper cells, which coordinate the development of functional B and T cells in the immune response.
272
What are the two main types of phagocytic cells in the immune system?
Neutrophils and macrophages are the two key phagocytic cells.
273
Where are neutrophils and macrophages located before they can initiate phagocytosis?
Neutrophils and macrophages circulate in the blood before they need to migrate to sites of inflammation to initiate phagocytosis.
274
How do inflammation products affect cell-to-cell adherence during phagocytosis?
Inflammation products cause both leukocytes and endothelial cells to increase their stickiness by expressing selectins and integrins.
275
What is the process called when leukocytes adhere more firmly to endothelial cells in capillaries and venules?
This process is known as margination or pavementing.
276
How do leukocytes move from the bloodstream to the site of inflammation?
Leukocyte-endothelial interactions lead to diapedesis, allowing the cells to pass through loosened junctions between endothelial cells, facilitated by inflammatory mediators.
277
What are some of the primary chemotactic factors that attract leukocytes to the inflammatory site?
Chemotactic factors include bacterial products, NCF (neutrophil chemotactic factor) from mast cells, the chemokine IL-8, complement fragments C3a and C5a, and products of the clotting and kinin systems.
278
What is the process by which leukocytes move toward the site of inflammation in a directed manner?
This process is called chemotaxis.
278
As part of their normal lifespan, what happens to aging red blood cells in the body?
Aging red blood cells are phagocytosed by macrophages.
279
What is the first step of phagocytosis at the inflammatory site?
The first step is the recognition and adherence of the phagocyte to its target.
280
What happens in the second step of phagocytosis?
The phagocyte engulfs the target through a process called endocytosis.
281
What is a phagosome?
A phagosome is a membrane-bound vesicle that forms within the phagocyte and contains the target.
282
What occurs in the fourth step of phagocytosis?
The phagosome fuses with lysosomal granules inside the phagocyte, creating a phagolysosome.
283
What is the final step in the process of phagocytosis at the inflammatory site?
The target is digested and destroyed within the phagolysosome by enzymes, while the phagocyte remains protected from the harmful effects of the target and its own enzymes
284
How do phagocytes trap and engulf bacteria?
Phagocytes can trap and engulf bacteria using pattern recognition receptors (PRRs).
285
What is the role of opsonization in phagocytosis?
Opsonization enhances adherence by acting as a glue between the phagocyte and the target cell.
286
How are highly specific antibodies produced for a particular microorganism?
Specific antigens on the bacteria's surface trigger the production of antibodies that are highly specific to that microorganism.
287
How can bacterial and fungal polysaccharide coatings enhance phagocytosis?
Some bacterial and fungal polysaccharide coatings activate the alternative and lectin pathways of complement activation, leading to the deposition of C3b on the bacterial surface and increasing phagocytosis.
288
What are efficient opsonins that enhance phagocytosis?
Efficient opsonins include antibodies and C3b from the complement system.
289
What specific receptors on phagocytes strongly bind to opsonins?
Phagocyte surfaces contain specific receptors, including complement receptors for C3b and Fc receptors for antibody molecules, that strongly bind to opsonins.
290
What is the pH of the phagolysosome, and how does it contribute to microbial killing?
The phagolysosome has an acidic pH (3.5 to 4.0), which contributes to microbial killing.
291
How do cationic proteins contribute to microbial killing?
Cationic proteins bind to and damage the membranes of target cells.
292
Which enzymes are involved in the enzymatic attack of microorganisms?
Enzymes like lysozyme and others attack the cell wall of microorganisms.
293
How does lactoferrin inhibit bacterial growth?
Lactoferrin inhibits bacterial growth by binding to iron.
294
What happens when a phagocyte dies at an inflammatory site?
When a phagocyte dies at an inflammatory site, it may lyse and release its cytoplasmic contents into the tissue.
295
How do the contents of neutrophil granules contribute to tissue destruction?
Neutrophil granules contain enzymes that can digest the connective tissue matrix, contributing to tissue destruction.
296
What are the natural inhibitors in the blood that minimize the destructive effects of enzymes and reactive oxygen molecules released by dying phagocytes?
Natural inhibitors in the blood, such as superoxide dismutase, catalase, α1-antitrypsin, and α2-macroglobulin, help minimize these effects.
297
What is the consequence of an inherited deficiency of α1-antitrypsin?
An inherited deficiency of α1-antitrypsin can lead to chronic lung damage and emphysema as a result of inflammation.
298
What is the main function of natural killer (NK) cells?
The main function of NK cells is to recognize and eliminate cells infected with viruses and abnormal cells, including cancer cells.
299
In which location are NK cells more efficient at eliminating infected or abnormal cells?
NK cells are more efficient at eliminating these cells when encountered in the circulatory system.
300
How do NK cells differentiate between infected or tumor cells and normal cells?
NK cells possess inhibitory and activating receptors that allow them to differentiate between infected or tumor cells and normal cells.
301
What happens when NK cells bind to a target cell through activating receptors?
When NK cells bind to a target cell through activating receptors, they produce cytokines and toxic molecules to kill the target.
302
What are the two main categories of inflammation?
Inflammation can be categorized as acute or chronic.
303
What happens if acute inflammation is inadequate?
Inadequate acute inflammation can progress to chronic inflammation, which may persist for weeks or months.
304
How long does acute inflammation typically last, and when does it end?
Acute inflammation usually lasts for 8 to 10 days and ends when the threat to the host is eliminated.
305
What is a granulomatous response in inflammation?
A granulomatous response is designed to contain tissue damage and infection, often forming granulomas to wall off the cause of damage.
306
Give an example of a disease where a granulomatous response occurs.
Tuberculosis (TB) is an example of a disease with a granulomatous response.
307
Why is TB challenging to treat, and how can its spores persist?
TB is challenging to treat because its spores can remain dormant for long periods, and they can activate when the host's immune defenses weaken.
308
How do the early (acute) and later (chronic) inflammatory responses differ?
The early inflammatory response differs from the later response in terms of the mediators and cells involved.
309
What is the potential outcome when inflammation is successfully contained?
Successful containment of tissue damage and infection can lead to healing with limited permanent tissue damage.
310
What are the local characteristics of acute inflammation?
The local characteristics of acute inflammation include swelling, pain, heat, and redness (erythema).
311
What causes these local characteristics of acute inflammation?
These characteristics result from vascular changes and the leakage of circulating components into the tissue.
312
How are the local characteristics of acute inflammation produced?
The interaction of cells and plasma protein systems in the inflammatory response produces the local characteristics of inflammation.
313
What causes the formation of exudate in inflammation?
Exudate in inflammation results from increased vascular permeability.
314
How does the composition of exudate vary in different stages of inflammation?
The composition of exudate varies based on the stage of inflammation and the nature of the injurious stimulus.
315
What is serous exudate, and when is it typically seen?
Serous exudate is watery and contains few plasma proteins or leukocytes. It's commonly seen in early or mild inflammation, like the fluid in a blister.
316
What is fibrinous exudate, and in which condition is it observed?
Fibrinous exudate is thick and clotted and is seen in severe inflammation, such as in the lungs of individuals with pneumonia.
317
What is purulent exudate, and when is it characteristic?
Purulent or suppurative exudate contains a large number of leukocytes and is characteristic of walled-off lesions like cysts or abscesses.
318
When does an exudate become hemorrhagic?
An exudate becomes hemorrhagic when bleeding occurs and is filled with red blood cells.
319
What are the three primary systemic changes associated with acute inflammation?
The three primary systemic changes are fever, leukocytosis (an increase in circulating leukocytes), and increased levels of circulating plasma proteins.
320
What happens to circulating plasma proteins during acute inflammation?
There is an increased level of circulating plasma proteins in response to acute inflammation, often involving acute-phase proteins that help modulate the inflammatory response.
321
What is leukocytosis?
Leukocytosis is a transient increase in the levels of circulating leukocytes, particularly white blood cells, during acute inflammation.
322
What are endogenous pyrogens?
Endogenous pyrogens are specific cytokines like IL-1 released from neutrophils and macrophages that induce fever.
323
Where do pyrogens act to induce fever?
Pyrogens act directly on the hypothalamus, the brain's temperature control center.
324
Why is fever often considered beneficial in the context of infections?
Fever can be beneficial because it helps combat microorganisms that are sensitive to increased body temperature.
325
What are the potential adverse effects of fever?
Fever may have adverse effects by increasing susceptibility to endotoxins associated with Gram-negative bacterial infections.
326
What is leukocytosis?
Leukocytosis is an increase in the number of circulating white blood cells in the blood.
327
What happens to the ratio of immature to mature neutrophils during leukocytosis in infections?
In infections, there is a left shift, resulting in a higher ratio of immature to mature neutrophils, including band cells, metamyelocytes, and myelocytes.
328
Where are immature leukocytes primarily produced during leukocytosis?
Immature leukocytes are primarily produced in the bone marrow, with increased proliferation and release of granulocyte and monocyte precursors.
329
What are acute-phase reactants in inflammation?
Acute-phase reactants are plasma proteins primarily produced by the liver in response to inflammation.
330
When do acute-phase reactants reach their highest levels in the circulation?
Acute-phase reactants reach their highest levels within 10 to 40 hours after the start of inflammation.
331
How is the synthesis of acute-phase reactants triggered in response to inflammation?
IL-1 indirectly triggers the synthesis of acute-phase reactants by inducing IL-6, which directly stimulates liver cells to produce these proteins.
332
Do acute-phase reactants have proinflammatory or anti-inflammatory effects?
Acute-phase reactants can have both proinflammatory and anti-inflammatory effects, depending on the specific proteins involved.
333
Which proteins show increased levels in circulation during inflammation?
Several proteins with increased levels during inflammation include fibrinogen, α1-Antitrypsin, haptoglobin, C-reactive protein (CRP), and many others.
334
Which proteins show decreased levels in circulation during inflammation?
Some proteins that have decreased levels during inflammation include Inter-α1-antitrypsin, transferrin, albumin, and prealbumin.
335
Why are these changes in protein levels important during inflammation?
Changes in protein levels, particularly acute-phase reactants, play a crucial role in the body's response to inflammation and can have both proinflammatory and anti-inflammatory effects.
336
What does the erythrocyte sedimentation rate (ESR) measure?
The ESR measures the rate at which red blood cells settle in a tube over a specified time, typically an hour.
337
What is an increased ESR associated with?
An increased ESR is associated with elevated levels of acute-phase reactants, particularly fibrinogen.
338
Is the ESR a specific indicator of inflammation?
No, the ESR is a nonspecific indicator of inflammation and can be elevated in various conditions.
339
What is C-reactive protein (CRP), and how is it used in clinical practice?
CRP is a protein produced by the liver during acute inflammation. It is a more commonly used and specific indicator of inflammation in clinical practice compared to ESR.
340
What is the primary difference between acute and chronic inflammation?
Acute inflammation is of short duration (up to 2 weeks), while chronic inflammation lasts for 2 weeks or longer.
341
Can chronic inflammation be preceded by an acute inflammatory response?
Yes, chronic inflammation can be preceded by an unsuccessful acute inflammatory response.
342
When might a prolonged acute inflammatory response occur?
A prolonged acute response may occur when bacterial contamination or foreign objects persist in a wound.
343
What are some features associated with chronic inflammation?
Chronic inflammation is associated with features like pus formation, suppuration (purulent discharge), and incomplete wound healing.
344
Can chronic inflammation occur as a distinct process without prior acute inflammation?
Yes, chronic inflammation can occur independently without preceding acute inflammation.
345
What is an example of a microorganism with a resistant cell wall that can trigger chronic inflammation?
Mycobacteria, such as those causing tuberculosis, have cell walls with high lipid and wax content that can lead to chronic inflammation.
346
How do microorganisms causing leprosy, syphilis, and brucellosis contribute to chronic inflammation?
These microorganisms can survive within macrophages and evade the acute inflammatory response, leading to chronic inflammation.
347
Why might inflammation persist even after the elimination of certain microorganisms?
Some microorganisms produce tissue-damaging toxins that can cause persistent inflammation.
348
What non-microbial factors can also lead to prolonged inflammation?
Prolonged inflammation can be triggered by exposure to chemicals, particulate matter, or physical irritants like dust, wood splinters, and suture materials.
349
What cellular infiltrate characterizes chronic inflammation?
Chronic inflammation is characterized by a dense infiltration of lymphocytes and macrophages.
350
Why does the body form granulomas in chronic inflammation?
Granulomas are formed to isolate and wall off infected areas when macrophages are unable to protect the host from tissue damage.
351
In which type of infections is granuloma formation observed?
Granuloma formation is seen in infections caused by specific bacteria, fungi, and parasites.
352
Which molecule primarily drives the formation of granulomas?
TNF-α (tumor necrosis factor-alpha) primarily drives granuloma formation.
353
What specialized cells form the center of a granuloma?
Specialized cells, including epithelioid cells and multinucleated giant cells, form the center of a granuloma.
354
What surrounds the central cells in a granuloma, and how may a granuloma change over time?
The central cells in a granuloma are surrounded by a wall of lymphocytes, and the granuloma may become encapsulated by fibrous collagen deposits, cartilaginous, or even calcified by calcium carbonate and calcium phosphate.
355
What is the composition of the classic granuloma associated with tuberculosis?
The classic tuberculosis granuloma consists of a wall of epithelioid cells surrounding a center made up of dead and decaying tissue (caseous necrosis) and mycobacteria.
356
What happens when cells within the tuberculosis granuloma decay?
The decay of cells within the granuloma results in the release of acids and lysosomal enzymes from dead phagocytes.
357
What is the outcome of cellular decay and enzymatic activity within the granuloma?
Within the granuloma, cellular debris breaks down into its basic constituents, and a clear fluid may remain (liquefactive necrosis).
358
How does the granuloma change over time in tuberculosis, and what effect does it have on the affected tissue?
Over time, the liquefied fluid diffuses out, leaving a hollow, thick-walled structure that replaces normal tissue and impairs the function of the lung.
