Antimicrobials: Agents, Resistance and Design Flashcards
1
Q
Define
Acquired resistance
A
occurs when a particular microorganism obtains the ability to resist the activity of an antimicrobial agent to which it was previously susceptible
2
Q
Define
Aminoglycosides
A
any of a group of antibiotics (as streptomycin and neomycin) that inhibit bacterial protein synthesis and are active especially against gram-negative bacteria
3
Q
Define
Antimicrobial agents
A
A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes
4
Q
Define
Bactericidal
A
an agent that kills bacteria
5
Q
Define
Bacteriostatic
A
an agent that prevents the growth of bacteria
6
Q
Define
β-lactamases
A
enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem),
7
Q
Define
β-lactams
A
a class of antibiotic consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, carbapenems and carbacephems
8
Q
Define
Cephalosporins
A
a large group of antibiotics derived from the mold Acremonium. They are bactericidal (kill bacteria) and work in a similar way to penicillins
9
Q
Define
Colistin
A
an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. It is effective against most Gram-negative bacilli
10
Q
Define
Fidaxomicin
A
an oral macrolide antibiotic labeled for the treatment of Clostridium difficile–associated diarrhea in adults
11
Q
Define
Fluoroquinolones
A
any of a group of fluorinated derivatives (such as ciprofloxacin and levofloxacin) of quinolone that are used as antibacterial drugs
12
Q
Define
Horizontal Gene Transfer (HGT)
A
the movement of genetic material between unicellular and/or multicellular organisms other than by the (“vertical”) transmission of DNA from parent to offspring (reproduction)
13
Q
Define
Intrinsic resistance
A
a natural insensitivity in bacteria that have never been susceptible to a particular antibiotic
14
Q
Define
Klebsiella pneumoniae carbapenemase (KPC)
A
a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality
15
Q
Define
Macrolides
A
a class of antibiotic that includes erythromycin, roxithromycin, azithromycin and clarithromycin. They are useful in treating respiratory, skin, soft tissue, sexually transmitted, H. pylori and atypical mycobacterial infections
16
Q
Define
Mobilised colistin resistance (MCR)
A
a gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating Gram-negative infections
17
Q
Define
Nosocomial infections
A
infections that have been caught in a hospital and are potentially caused by organisms that are resistant to antibiotics
18
Q
Define
Oxazolidinones
A
a novel class of synthetic antimicrobial agents unrelated to any other antibacterial drug class. They were originally developed as monoamine oxidase inhibitors for treatment of depression, with subsequent recognition of their antimicrobial properties
19
Q
Define
Penicillin
A
an antibiotic or group of antibiotics produced naturally by certain blue molds, and now usually prepared synthetically
20
Q
Define
Porin protein
A
beta barrel proteins that cross a cellular membrane and act as a pore, through which molecules can diffuse
21
Q
Define
Quinolones
A
a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the compound 4-quinolone
22
Q
Define
Resistome
A
a proposed expression by Gerard D. Wright for the collection of all the antibiotic resistance genes and their precursors in both pathogenic and non-pathogenic bacteria
23
Q
Define
Rifamycins
A
a natural antibiotic produced by Streptomyces mediterranei, it is a commonly used antimycobacterial drug that inhibits prokaryotic DNA-dependent RNA synthesis and protein synthesis; it blocks RNA-polymerase transcription initiation
24
Q
Define
Selective toxicity
A
refers to the ability of the drug to targets sites that are relative specific to the microorganism responsible for infection
25
# Define
Sulphonamides
a group of man-made (synthetic) medicines that contain the sulfonamide chemical group. They may also be called sulfa drugs
26
# Define
Tetracyclines
a class of antibiotics that may be used to treat infections caused by susceptible microorganisms such as gram positive and gram negative bacteria, chlamydiae, mycoplasmata, protozoans, or rickettsiae
27
# Define
Thienamycin
one of the most potent naturally produced antibiotics known thus far, was discovered in Streptomyces cattleya in 1976. It has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes
28
# Define
Transglycosylation
A mechanism for glycosidic (see GLYCOSIDE) bond formation, particularly during polysaccharide synthesis. Nucleoside phosphate derivatives act as activated donor compounds in which the energies of their glycosidic bonds are partially conserved in the reaction products
29
# Define
Transpeptidation
a chemical reaction (as the reversible conversion of one peptide to another by a protease) in which an amino acid residue or a peptide residue is transferred from one amino compound to another
30
# Define
Trimethoprim
an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea
31
# Define
Vancomycin
an antibiotic that when taken by mouth fights bacteria in the intestines. It is used to treat an infection of the intestines caused by Clostridium difficile, which can cause watery or bloody diarrhea
32
# Definition
occurs when a particular microorganism obtains the ability to resist the activity of an antimicrobial agent to which it was previously susceptible
Acquired resistance
33
# Definition
any of a group of antibiotics (as streptomycin and neomycin) that inhibit bacterial protein synthesis and are active especially against gram-negative bacteria
Aminoglycosides
34
# Definition
A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes
Antimicrobial agents
35
# Definition
an agent that kills bacteria
Bactericidal
36
# Definition
an agent that prevents the growth of bacteria
Bacteriostatic
37
# Definition
enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem),
β-lactamases
38
# Definition
a class of antibiotic consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, carbapenems and carbacephems
β-lactams
39
# Definition
a large group of antibiotics derived from the mold Acremonium. They are bactericidal (kill bacteria) and work in a similar way to penicillins
Cephalosporins
40
# Definition
an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. It is effective against most Gram-negative bacilli
Colistin
41
# Definition
an oral macrolide antibiotic labeled for the treatment of Clostridium difficile–associated diarrhea in adults
Fidaxomicin
42
# Definition
any of a group of fluorinated derivatives (such as ciprofloxacin and levofloxacin) of quinolone that are used as antibacterial drugs
Fluoroquinolones
43
# Definition
the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction)
Horizontal Gene Transfer (HGT)
44
# Definition
a natural insensitivity in bacteria that have never been susceptible to a particular antibiotic
Intrinsic resistance
45
# Definition
a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality
Klebsiella pneumoniae carbapenemase (KPC)
46
# Definition
a class of antibiotic that includes erythromycin, roxithromycin, azithromycin and clarithromycin. They are useful in treating respiratory, skin, soft tissue, sexually transmitted, H. pylori and atypical mycobacterial infections
Macrolides
47
# Definition
a gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating Gram-negative infections
Mobilised colistin resistance (MCR)
48
# Definition
infections that have been caught in a hospital and are potentially caused by organisms that are resistant to antibiotics
Nosocomial infections
49
# Definition
a novel class of synthetic antimicrobial agents unrelated to any other antibacterial drug class. They were originally developed as monoamine oxidase inhibitors for treatment of depression, with subsequent recognition of their antimicrobial properties
Oxazolidinones
50
# Definition
an antibiotic or group of antibiotics produced naturally by certain blue molds, and now usually prepared synthetically
Penicillin
51
# Definition
a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the compound 4-quinolone
Quinolones
52
# Definition
a natural antibiotic produced by Streptomyces mediterranei, it is a commonly used antimycobacterial drug that inhibits prokaryotic DNA-dependent RNA synthesis and protein synthesis; it blocks RNA-polymerase transcription initiation
Rifamycins
53
# Definition
refers to the ability of the drug to targets sites that are relative specific to the microorganism responsible for infection
Selective toxicity
54
# Definition
a group of man-made (synthetic) medicines that contain the sulfonamide chemical group. They may also be called sulfa drugs
Sulphonamides
55
# Definition
a class of antibiotics that may be used to treat infections caused by susceptible microorganisms such as gram positive and gram negative bacteria, chlamydiae, mycoplasmata, protozoans, or rickettsiae
Tetracyclines
56
# Definition
one of the most potent naturally produced antibiotics known thus far, was discovered in Streptomyces cattleya in 1976. It has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes
Thienamycin
57
# Definition
A mechanism for glycosidic (see GLYCOSIDE) bond formation, particularly during polysaccharide synthesis. Nucleoside phosphate derivatives act as activated donor compounds in which the energies of their glycosidic bonds are partially conserved in the reaction products
Transglycosylation
58
# Definition
a chemical reaction (as the reversible conversion of one peptide to another by a protease) in which an amino acid residue or a peptide residue is transferred from one amino compound to another
Transpeptidation
59
# Definition
an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea
Trimethoprim
60
# Definition
an antibiotic that when taken by mouth fights bacteria in the intestines. It is used to treat an infection of the intestines caused by Clostridium difficile, which can cause watery or bloody diarrhea
Vancomycin
61
What are some examples of natural antimicrobial agents?
Penicillin
Aminoglycosides
Polyenes
62
What are some examples of semisynthetic antimicrobial agents?
β-lactams
Cephalosporins
63
What are some examples of synthetic antimicrobial agents?
Oxazolidinones
Quinolones
64
What is the mode of action of antibiotics?
Disruption of cell membrane funciton
Inhibition of cell wall synthesis
Inhibition of RNA and DNA synthesis
Inhibition of folic acid metabolism
Inhibition of protein sythesis
65
What is the basic monomer of peptidoglycan
A peptapeptide with D-ala D-ala at the end of the stem
66
What do Penicillin-Binding proteins (PBPs) do?
PBPs play multiple roles in cell wall synthesis and maintenance of peptidoglycan:
* transglycosylation (wall synthesis for growth and septation)
* transpeptidation (crosslinking and remodelling)
* peptide cleavage (D-Ala carboxypeptidases, endopeptidases)
* control of crosslinking, insertion of new strands
67
What is a critical part in the action of PBPs? What happens when you interupt it?
A critical part of these processes is the recognition of the D-Ala-D-Ala sequence of the MurNac-GlcNac pentapeptide. Interfering with this recognition disrupts the cell wall synthesis
68
How do β-lactams act as antibiotics (general idea)?
The β-lactam ring mimics the structure of the D-Ala-D-Ala link and bind to the same place in the PBPs (the active site), disrupting the crosslinking process.
β-lactams inactivate PBPs.
69
β-lactams are *bacteriocidal/bacteriostatic*
β-lactams are **bacteriocidal**
70
How does resistance to β-lactams occur?
Resistance occurs through production of β-lactamases or PBP and porin mutations
71
How do glycopeptide antibiotics, like Vancomycin, work?
Bind to the terminal D-Ala-D-Ala dipeptide inhibiting transglycosylation and transpeptidation of peptidoglycan.
72
Which antibiotics interfere with cell wall biosynthesis?
β-lactams
Vancomycin
73
What antibiotics inhibit protein synthesis?
Tetracyclines
Aminoglycosides
Macrolides
Oxazolidinones
74
Why can molecules that target bacterial ribosomes be used as antibiotics?
Selective toxicity due to differences in bacterial/eukaryotic ribosomes
75
What are examples of antibiotics that target the 30S subunit?
Aminoglycosides
Tetracyclines
76
What are examples of antibiotics that target the 50S subunit?
Macrolides
Oxazolidinones
77
How do tetracyclines function?
Bind to the 30S ribosomal subunit preventing entry of amino acyl-tRNA into the A-site
78
How does resistance to tetracyclines occur?
Resistance through efflux or ribosomal protection proteins
79
How do aminoglycosides funtion?
Interfere with proof-reading process for incoming aa-tRNA • Results in premature termination or proteins with amino acid substitutions
80
How does resistance to aminoglycosides occur?
Resistance through target mutations and modifying enzymes
81
How do macrolides function?
Bind reversibly to 23S rRNA in 50S subunit (peptidyl transferase domain)
Disrupt movement of tRNA from A site to P site thereby inhibiting peptide chain elongation.
82
How does resistance to macrolides occur?
Multiple resistance mechanisms
* Target modification (e.g., RNA methylation)
* Efflux
* Enzymatic modification
83
How do Oxazolidinones function?
Bind to rRNA on the A side of the peptidyltransferase center (PTC) of the ribosome
84
How does resistance to Oxazolidinones occur?
Resistance mediated through rRNA mutations
85
Which antibiotics act as inibitors of nucleic acid synthesis?
Fluoroquinolones
Rifamycins
Fidaxomicin
86
How do Fluoroquinolones function?
Bind to DNA gyrase and topoisomerases blocking formation of complex with nicked DNA
Blockage of DNA replication and DNA repair
87
How does resistance to Fluoroquinolones develop
Resistance through gyrA and gyrB mutations and through expression of gyrase-binding proteins
88
How do Rifamycins and Fidaxomicin function?
Bind to DNA-dependent RNA polymerase and block synthesis of mRNA
89
What are metabolic antagonists?
Antimicrobials that inhibit or block metabolic pathways
90
What are examples of metabolic antagonists?
Sulphonamides
Trimethoprim
91
Why are metabolic antagonists that target folic acid selective for bacteria and not human cells?
Selective because humans obtain folic acid from diet and human dihydrofolate reductase is relatively resistant to trimethoprim.
92
How do bacteria become resistant to antimicrobials?
Chromosomally-mediated resistance
Plasmid-mediated resistance
Plasmid-mediated resistance on a transposon
93
What does chromosomally-mediated resistance produce?
Chromosomal mutation can produce a drug-resistant target, which confers resistance on the bacterial cell and allows it to multiply in the presence of antibiotic.
94
How does plasmid-mediated resistance work?
Resistance genes carried on plasmids can spread from one cell to another more rapidly than cells themselves divide and spread
95
How does plasmid-mediated resistance on a transposon work?
Resistance genes on transposable genetic elements move between plasmids and the chromosome and from one plasmid to another, thereby allowing greater dissemination of the resistance gene.
96
What are the features of acquired resistance by mutation?
* Usually result in resistance to a single class of antibiotics
* Generally alters the antimicrobial target site, a modifying enzyme or an efflux system
* Cross-resistance to structurally related compounds only
97
In what ways do bacteria modify the antibiotic molecule?
1. Inactivate the drug by chemically cleaving it
2. Inactivate the drug by adding chemical moieties.
98
How do β-lactamases confer resistance?
Inactivate the drug by chemically cleaving it
99
How do aminoglycoside modifying enzymes confer resistance?
Inactivate the drug by adding chemical moieties.
100
In what ways can modified antibiotic transport confer resistance?
Decreased cell wall pemeability
Increased efflux from the cell
101
How does decreased cell wall permeability prevent the action of some antibiotics?
Altered porin or Omp proteins lead to decreased uptake of βlactam antibiotics in Klebsiella pneumoniae and Pseudomonas aeruginosa.
102
How does modification of the target site confer resistance?
Alteration of the target site to reduce susceptibility to antibiotic
Acquisition of genes encoding enzymes that alter target
103
What does Vancomycin resistance involve?
Vancomycin resistance involves acquisition of genes encoding enzymes that alter the D-Ala-D-Ala to D-Ala-D-Lac, reducing the binding of the vancomycin drug.
104
How do we treat patients with resistant Gram-negative infections?
The β-lactams were the ‘golden bullet’ for a long time for infections with Gram-negative pathogens
Other current options for treatment include
* Tigecycline (tetracycline derivative)
* Colistin (also known as polymyxin E)
Not well suited to serious infections (poor pharmacokinetic profiles)
* Polymixins have side effects including kidney and neurotoxicity
* Tetracyclines have gastrointestinal side effect
105
Efflux pump mechanism
106
Aminoglycoside-modifying enzymes act to change the chemical structure of the aminoglycoside, preventing it from binding to its target.
Select one:
True
False
Aminoglycoside-modifying enzymes act to change the chemical structure of the aminoglycoside, preventing it from binding to its target.
Select one:
**True**
False
107
The major role of penicillin-binding proteins in bacterial cells is to
Select one:
a. bind penicillin and thereby confer penicillin resistance.
b. crosslink peptidoglycan strands by catalyzing transpeptidation.
c. bind penicillin and thereby block protein biosynthesis.
d. act as an essential co-factor in protein biosynthesis.
The major role of penicillin-binding proteins in bacterial cells is to
Select one:
a. bind penicillin and thereby confer penicillin resistance.
**b. crosslink peptidoglycan strands by catalyzing transpeptidation.**
c. bind penicillin and thereby block protein biosynthesis.
d. act as an essential co-factor in protein biosynthesis.
108
The structure below is a cell wall from which microorganism?
Fungus
109
Beta-lactamases are a diverse set of enzymes that can inactivate many different types of beta-lactam antibiotics.
Select one:
True
False
Beta-lactamases are a diverse set of enzymes that can inactivate many different types of beta-lactam antibiotics.
Select one:
**True**
False
110
Which of the following is the major reason why it has been difficult to treat viral infections with chemotherapeutic agents?
Select one:
a. Viral metabolism resembles that of their hosts so there is no selective point of attack.
b. Viruses use the metabolic machinery of their hosts, which limits many of the potential points of attack.
c. Viruses have no metabolism and therefore offer no selective point of attack.
d. Actually, viruses are not difficult to treat with chemotherapeutic agents.
Which of the following is the major reason why it has been difficult to treat viral infections with chemotherapeutic agents?
Select one:
a. Viral metabolism resembles that of their hosts so there is no selective point of attack.
**b. Viruses use the metabolic machinery of their hosts, which limits many of the potential points of attack.**
c. Viruses have no metabolism and therefore offer no selective point of attack.
d. Actually, viruses are not difficult to treat with chemotherapeutic agents.
111
A single mutation to a gene can be enough to induce resistance.
Select one:
True
False
A single mutation to a gene can be enough to induce resistance.
Select one:
**True**
False
112
Peptidoglycan synthesis inhibitors often induce bacterial lysis, while protein synthesis inhibitors do not. Beta-lactam antibiotics (e.g. penicillin, cefoxitin) cause bacterial lysis because:
Select one:
a. They block the ribosomal exit tunnel
b. They disrupt cell wall biosynthesis
c. They induce DNA breaks
d. They induce the synthesis of aberrant proteins
Peptidoglycan synthesis inhibitors often induce bacterial lysis, while protein synthesis inhibitors do not. Beta-lactam antibiotics (e.g. penicillin, cefoxitin) cause bacterial lysis because:
Select one:
a. They block the ribosomal exit tunnel
**b. They disrupt cell wall biosynthesis**
c. They induce DNA breaks
d. They induce the synthesis of aberrant proteins
113
The mechanisms that resistant bacteria can use to generate a resistant phenotype include
Select one:
a. Modification of the drug target, drug transport or drug itself
b. The acquisition of resistance genes
c. Horizontal gene transfer of plasmids containing transposons.
d. Spontaneous mutation of the chromosome
The mechanisms that resistant bacteria can use to generate a resistant phenotype include
Select one:
**a. Modification of the drug target, drug transport or drug itself**
b. The acquisition of resistance genes
c. Horizontal gene transfer of plasmids containing transposons.
d. Spontaneous mutation of the chromosome
114
HOW DO I MEDIATE RESISTANCE? I alter the sequence of the D-Ala-D-Ala sequence of the MurNac-GlcNac pentapeptide to D-Ala-D-Lac?
Alteration of the antibiotic target. Vancomycin resistance is mediated by the acquisition of genes that encode enzymes that change the target of vancomycin (D-Ala-D-Ala of the starting pentapeptide of peptidoglycan). This reduces the ability of vancomycin to bind and act.
115
Which of the following is a desirable general characteristic of antimicrobial drugs?
Select one:
a. Selective toxicity
b. Broad-spectrum of activity
c. Bactericidal rather than bacteriostatic
d. All of the choices are correct.
Which of the following is a desirable general characteristic of antimicrobial drugs?
Select one:
a. Selective toxicity
b. Broad-spectrum of activity
c. Bactericidal rather than bacteriostatic
**d. All of the choices are correct.**
116
The blaKPC gene encodes resistance to carbapenems.
Select one:
True
False
The blaKPC gene encodes resistance to carbapenems.
Select one:
**True**
False
117
MCR-1 refers to the protein the encodes resistance to the polymyxins.
Select one:
True
False
MCR-1 refers to the protein the encodes resistance to the polymyxins.
Select one:
**True**
False
118
As long as the antibiotic can get inside the bacteria (through the cell wall and membrane), it will be active.
Select one:
True
False
As long as the antibiotic can get inside the bacteria (through the cell wall and membrane), it will be active.
Select one:
True
**False**
119
Which of the following is likely to have the most toxic side effects to humans?
Select one:
a. Inhibitors of cell wall synthesis
b. Inhibitors of protein synthesis
c. Disrupters of cell membrane structure
d. Inhibitors of DNA synthesis
Which of the following is likely to have the most toxic side effects to humans?
Select one:
a. Inhibitors of cell wall synthesis
b. Inhibitors of protein synthesis
**c. Disrupters of cell membrane structure**
d. Inhibitors of DNA synthesis
120
If you come into contact with a multi-drug resistant bacteria, you will probably die.
Select one:
True
False
If you come into contact with a multi-drug resistant bacteria, you will probably die.
Select one:
True
**False**
121
Transposable genetic elements can move between plasmids and chromosomes and from one plasmid to another, thereby allowing greater dissemination of the resistance gene?
Select one:
True
False
Transposable genetic elements can move between plasmids and chromosomes and from one plasmid to another, thereby allowing greater dissemination of the resistance gene?
Select one:
**True**
False
122
Protein synthesis inhibitors generally do not result in bacterial lysis, while peptidoglycan synthesis inhibitors do. Aminoglycoside antibiotics (e.g. Streptomycin, Kanamycin) cause bacterial death because:
Select one:
a. They block the ribosomal exit tunnel
b. They disrupt cell wall biosynthesis
c. The induce DNA breaks
d. The induce the synthesis of aberrant proteins
Protein synthesis inhibitors generally do not result in bacterial lysis, while peptidoglycan synthesis inhibitors do. Aminoglycoside antibiotics (e.g. Streptomycin, Kanamycin) cause bacterial death because:
Select one:
a. They block the ribosomal exit tunnel
b. They disrupt cell wall biosynthesis
c. The induce DNA breaks
**d. The induce the synthesis of aberrant proteins**
123
Generally, a bacterium only has one resistance mechanism per antibiotic.
Select one:
True
False
Generally, a bacterium only has one resistance mechanism per antibiotic.
Select one:
True
**False**
124
WHO AM I? I am a major cause for concern for Gram negative pathogens. I am an enzyme and can cleave the beta-lactam ring in beta-lactam antibiotics. I have lots of friends and family spread around the world. I can be found in the chromosome, on plasmids and transposons. There are over 1000 different classes of me.
beta-lactamases
125
WHO AM I? I am a resistance-mediating enzyme. I alter the target binding site of the macrolide antibiotics by methylating a residue in the 23S RNA of the 50S ribosomal subunit. There are at least 30 different classes of me.
The erythromycin ribosomal mediating (Erm) enzyme
126
# Define
Acellular vaccines
A vaccine that may contain cellular material but does not contain complete cells
127
# Define
Acquired immunity
Immunity acquired by infection or vaccination (active immunity) or by the transfer of antibody or lymphocytes from an immune donor (passive immunity)
128
# Define
Active immunity
the immunity which results from the production of antibodies by the immune system in response to the presence of an antigen
129
# Define
Adjuvant
a substance which enhances the body's immune response to an antigen.
130
# Define
Alum
the classical adjuvant most often used in vaccines in humans, includes a range of salts of aluminum precipitated under basic conditions, usually aluminum sulfate mixed with sodium or potassium hydroxide plus a variable amount of phosphate.
131
# Define
Antigen
a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies
132
# Define
Damage associated molecular patterns (DAMPs)
molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response
133
# Define
Efficacy
the percentage reduction of disease in a vaccinated group of people compared to an unvaccinated group, using the most favorable conditions
134
# Define
Herd immunity
a form of indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune
135
# Define
Killed inactivate vaccines
a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then lose disease producing capacity
136
# Define
Live attenuated vaccines
a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live")
137
# Define
Measles
a highly contagious infectious disease caused by the measles virus
138
# Define
Nanopatches
a needle-free vaccine delivery device
139
# Define
Opsonise
make (a foreign cell) more susceptible to phagocytosis
140
# Define
Passive immunity
the short-term immunity which results from the introduction of antibodies from another person or animal
141
# Define
Recombinant vaccines
a vaccine produced through recombinant DNA technology
142
# Define
Reservoir
is the population of organisms or the specific environment in which an infectious pathogen naturally lives and reproduces, or upon which the pathogen primarily depends for its survival
143
# Define
Subunit vaccines
a fragment of a pathogen, typically a surface protein, that is used to trigger an immune response and stimulate acquired immunity against the pathogen from which it is derived
144
# Define
Toxoid vaccines
A vaccine made from a toxin (poison) that has been made harmless but that elicits an immune response against the toxin
145
# Define
Tropism
the turning of all or part of an organism in a particular direction in response to an external stimulus
146
# Definition
A vaccine that may contain cellular material but does not contain complete cells
Acellular vaccines
147
# Definition
Immunity acquired by infection or vaccination (active immunity) or by the transfer of antibody or lymphocytes from an immune donor (passive immunity)
Acquired immunity
148
# Definition
the immunity which results from the production of antibodies by the immune system in response to the presence of an antigen
Active immunity
149
# Definition
a substance which enhances the body's immune response to an antigen.
Adjuvant
150
# Definition
the classical adjuvant most often used in vaccines in humans, includes a range of salts of aluminum precipitated under basic conditions, usually aluminum sulfate mixed with sodium or potassium hydroxide plus a variable amount of phosphate.
Alum
151
# Definition
a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies
Antigen
152
# Definition
molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response
Damage associated molecular patterns (DAMPs)
153
# Definition
the percentage reduction of disease in a vaccinated group of people compared to an unvaccinated group, using the most favorable conditions
Efficacy
154
# Definition
a form of indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune
Herd immunity
155
# Definition
a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then lose disease producing capacity
Killed inactivate vaccines
156
# Definition
a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live")
Live attenuated vaccines
157
# Definition
a highly contagious infectious disease caused by the measles virus
Measles
158
# Definition
a needle-free vaccine delivery device
Nanopatches
159
# Definition
make (a foreign cell) more susceptible to phagocytosis
Opsonise
160
# Definition
the short-term immunity which results from the introduction of antibodies from another person or animal
Passive immunity
161
# Definition
a vaccine produced through recombinant DNA technology
Recombinant vaccines
162
# Definition
is the population of organisms or the specific environment in which an infectious pathogen naturally lives and reproduces, or upon which the pathogen primarily depends for its survival
Reservoir
163
# Definition
a fragment of a pathogen, typically a surface protein, that is used to trigger an immune response and stimulate acquired immunity against the pathogen from which it is derived
Subunit vaccines
164
# Definition
A vaccine made from a toxin (poison) that has been made harmless but that elicits an immune response against the toxin
Toxoid vaccines
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# Definition
the turning of all or part of an organism in a particular direction in response to an external stimulus
Tropism
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# Definition
the method first used to immunize an individual against smallpox (Variola) with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result
Variolation
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What is the first main barrier to infectious agents?
Skin
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Which three main types of leukocytes are there?
Lymphocytes
APCs
Innate cells (NK, neutrophils etc.)
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What does immunological memory require?
Innate immune responses
Antigen uptake and presentation to trigger
Adaptive immune responses (B and T cells)
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What does vaccination and immunological memory do to the number of B or T cells that recognise a specific antigen?
Increases the number of B or T cells that recognise a specific antigen
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What does vaccination and immunological memory do to the amount of signal needed to activate antigen-specific memory B and T cells?
Decreases the amount of signal needed to activate antigen-specific memory B and T cells
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What are the two types of acquired immunity?
Active and Passive
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What is passive immunisation good for?
* Toxins: snake bites, tetanus, rabies, gas gangrene
* Outbreaks where antibody can provide protection to survivors but vaccines are not developed
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Passive immunisation is ideally given *before/after* infection
Passive immunisation is ideally given **before** infection
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Passive immunisation provides *delayed/immediate* onset of protection
Passive immunisation provides **immediate** onset of protection
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Passive immunisation is *long-lasting/limited*
Passive immunisation is **limited**
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Active immunisation is ideally given *before/after* infection
Active immunisation is ideally given **before** infection
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Active immunisation protection is *delayed/immediate*
Active immunisation protection is **delayed**
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What is active immunisation good for?
* Inducing widespread immunity in the community to highly transmissible diseases
* Influenza, measles, HPV
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What is the ultimate aim of vaccination? What are the secondary aims?
Eradication of disease from population
* Prevent infection
* Reduce infectious load/severity
* Reduce infection transmission
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What is the major limit of herd immunity?
Herd immunity only applies for diseases that spread from human to human
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\_\_\_\_\_\_\_\_\_\_\_: a compound that triggers innate immunity
\_\_\_\_\_\_\_\_\_\_\_: a component of the virus, bacteria or parasite that is immunogenic
**Adjuvant**: a compound that triggers innate immunity
**Antigen**: a component of the virus, bacteria or parasite that is immunogenic
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What are the criteria for selecting suitable antigens?
1. Abundantly expressed and accessible to protective immune mechanisms:
* Expressed on the pathogen surface or a secreted toxin if antibody‐mediated immunity provides protection
* Expressed on infected cells if T cell‐mediated immunity provides protection
2. Does not vary:
* Some pathogens can mutate antigens if immune responses are directed against those antigens (HIV, influenza, etc.)
* Some pathogens change antigens during their natural lifecycle (malaria, TB, etc.)
* Therefore, choose an antigen which is essential to critical life stages of the pathogen
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Why do viruses live HIV-1 ungergo extremely rapid rates of mutation?
RNA polymerase doesn't proofread
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What does a good adjuvant do?
1. Increases the magnitude of the adaptive immune response
2. Shapes the type of adaptive immune response (antibody isotype, CD4+ T cell subset, CD8+ T cells)
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How do adjuvants augment the immune response?
1. Trigger innate immunity
2. Promote uptake of antigen by DCs
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What are some examples of PRRs that recognise PAMPs and DAMPs?
TLR
RLR
CLR
NLR
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What do PRRs bind to?
PAMPs
DAMPs
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What molecules are usually used as adjuvants?
PAMPs or induced DAMPs
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What do you need to consider about adjuvant that you choose?
What branch of the immune system does it fire up
Each PAMP/DAMP elicits a different set of innate cytokines, which acts on B cell and T cells to skew the immune system in distinct directions:
i.e. IL‐12 + IFN‐γ= IgG2a antibody, Th1 CD4 T cells and CD8 T cells
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Which adjuvant triggers innate immunity and promotes antigen uptake?
Alum
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True or False:
Only one adjuvant can be used per vaccine
False
There can be synergy when adjuvants are combined‐ RTS’S (Malaria) and Shingrix (Shingles)
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What are the three main considerations when designing a vaccine?
Route of delivery
Adjuvant
Antigen
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What are the four phases for the clincial testing of vaccines?
Phase I: Safety
Phase II: Immunogenicity (and Safety)
Phase III: Immunogenicity, Feasibility (and Safety)
Phase IV: Post‐approval monitoring (i.e. Safety)
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What are the potential side-effects of vaccines?
* Swelling at vaccine site, fever, muscle aches, fatigue: activation of innate immunity causes immune cell recruitment and pyrexia, etc
* Anaphylaxis: some vaccines are cultured in eggs or yeast expression systems (15 min wait after vaccination)
* Seizures in children: due to vaccine‐induced innate immunity causing fevers. Similar to infection‐induced febrile seizures.
* Guillian‐Barré syndrome: due to vaccine‐induced innate immunity triggering auto‐immunity. Can also be induced by infections.
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What are the three types of vaccines?
Live attenuated vaccines
Killed inactivated vaccines
Subunit vaccines
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What does attentuated mean?
passage through cell culture or use of genetic techniques to induce mutations that remove virulence but retain immunogenicity
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How are pathogens killed to created killed inactivated viruses
Uses chemical (formalin or phenol treatment) or heat inactivation to kill pathogen, which is then used in the vaccine, sometimes with an additional adjuvant
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What was initially used to prevent Smallpox?
Variolation (essentially infecting people with smallpox sores by scratching the material into their arm. Hope was to present some type of immunity)
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Why was Smallpox successfully eradicated?
* A stable, cheap, very efficacious (90‐97%) vaccine available
* The reservoir was limited:
* Only infects humans (no animal reservoir)
* Infected died or resolved infection (no chronic infection)
* Infection was easily recognised (isolate the infected)
* Only 2 viral variants (variola major and variola minor)
* Intensive, co‐ordinated, global surveillance‐ ring vaccination
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What are the differences between polysaccharide-only and conjugate vaccines?
* Bacterial capsules made of polysaccharide are targets for antibody
* But polysaccharide isn’t immunogenic for T cells:
* Polysaccharide‐only vaccines lack CD4 T cell help for B cell responses and immunity is weak and short‐lived
* Conjugate polysaccharide to immunogenic protein (i.e toxoid):
* In conjugate vaccines, a CD4 T cell response to the protein provides “help” for the B cell response to the polysaccharide
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What are the pros and cons of Live Attenuated vaccines?
**Pros:**
* Induces strong life-long immunity for antibody and T-cells
**Cons:**
* Can cause more severe side-effects
* Can cause disease in immunocompromised people
* Chance of reversion of virulence
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What are the Pros and Cons of Killed Inactivated vaccines?
**Pros:**
* Can induce strong, long-lasting immunity
**Cons:**
* Reliant on effective inactivation
* Can be more reactogenic
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What are the Pros and Cons of Subunit vaccines?
**Pros:**
* Very safe
* Can induce antibody immunity
**Cons:**
* Not good for T-cell imunity
* Immunity may wane or be less effective at preventing infection
* Requires multiple shots
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How are viral vector vaccines made?
Take a harmful pathogen:
* Identify gene for a target antigen
Take a minimally pathogenic virus:
* Remove genetic material associated with virulence
* Insert target antigen
Infects cells like vector virus:
* Not virulent
* Expresses target antigen
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What is the antigen for viral vector vaccines?
inserted gene that encodes the required protein
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What are the advantages of viral vector vaccines?
* Very safe
* Quick and cheap to make (pandemic situations)
* Mimics a “live” infection more closely because it combines mechanisms of adjuvancy
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What are the disadvantages of viral vector vaccines?
Pre‐existing immunity to the virus used as the vector may limit immune responses
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What does attentuation remove and what does it retain?
Remove: Virulence factors
Retain: Infectivity
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Name one eradicated pathogen
Smallpox
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Name one near-eradicated pathogen
Polio
