Exam 3 Flashcards
(98 cards)
1
Q
what are chemotherapeutic agents?
A
chemical agents used to treat disease
destroy pathogenic microbes or inhibit their growth within host.
most are antibiotics
2
Q
what are antibiotics?
A
microbial products or their derivatives that kill susceptible microbes or inhibit their growth.
3
Q
how was penicillin discovered?
A
accidentally by Alexander Fleming in 1928
He observed penicillin activity on a contaminated plate
4
Q
penicillin’s effectiveness demonstrated by
A
Florey, Chain, and Heatley in 1939
they received the nobel prize in 1945 for the discovery and production
5
Q
selective toxicity
A
the ability of a drug to kill or inhibit pathogen while damaging host as little as possible.
6
Q
theraputic dose
A
drug level required for clinical treatment
7
Q
toxic dose
A
drug level at which the drug becomes too toxic for the patient
8
Q
therapeutic index
A
ratio of toxic dose to therapeutic dose
9
Q
narrow spectrum drugs
A
attack only a few different pathogens
10
Q
broad spectrum drugs
A
attack many different kinds of bacteria
11
Q
cidal agent
A
kills the target pathogen
12
Q
static agent
A
reversibly inhibits growth of microbes
13
Q
how is antimicrobial drug effectiveness expressed?
A
- minimal inhibitory concentration (MIC) - lowest concentration of drug that prevents growth of the pathogen
- minimal lethal concentration (MLC) - lowest concentration of drug that kills pathogen
14
Q
main modes of action of antimicrobial drugs
A
- inhibit cell wall synthesis
- inhibit protein synthesis
- inhibit nucleic acid synthesis
- metabolic antagonists
15
Q
cytokinesis
A
septation - formation of cross wall between two daughter cells
16
Q
cell wall synthesis
A
- bactoprenol flips NAM and NAG across plasma membrane
- glycosyltransferase attach sugars
- transpeptidase join amino acids (form bridge of layers)
17
Q
what is the most crutial feature of penicillins?
A
beta-lactam ring
it is essential for bioactivity
blocks transpeptidase
18
Q
what can we include in penicillins to increase efficiency?
A
beta lactamase inhibitors with the antibiotic
19
Q
cephalosporins
A
similar to penicillins
broad spectrum antibiotics that can be used by most patients that are allergic to penicillin
four categories based on their spectrum of activity
20
Q
vancomycin
A
antibiotic
inhibit cell wall synthesis
21
Q
many antibiotics bind specifically to the
A
bacterial ribosome
22
Q
aminoglycosides
A
bind to 30S ribosomal subunit, interfere with protein synthesis by directly inhibiting the process and by causing misreading of the messenger RNA
23
Q
tetracyclines
A
target the 30S subunit of the ribosome inhibiting protein synthesis
24
Q
Macrolides
A
binds to 50S ribosomal subunit to inhibit bacterial protein elongation
25
what are metabolic antagonists?
- they act as antimetabolites - block functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes
- are structural analogs - structurally similar to and compete with naturally occurring metabolic intermediates to block normal cellular metabolism.
26
sulfa drugs
competitive inhibition of folic acid synthesis enzymes
27
trimethoprim
synthetic antibiotic that also interferes with folic acid production
28
nucleic acid synthesis inhibition drugs are not as selectively toxic as other antibiotics because
bacteria and eukaryotes do not differ greatly in the way they synthesize nucleic acids
29
fluoroquinolones
inhibit bacterial DNA gyrase and topoisomerase II
30
main mode of action for antibiotics used in lab
bacitracin - inhibit dephosphoylation
penicillin
furazolidone - block DNA transcription
optochin - interfere with metabolic processes
31
HANDOUT - who is associated with the disease and what are the characteristics and which medicine to use
32
antiviral drugs
limit the duration of the illness or its severity
33
antiviral drug for influenza is _____. what does it do?
tamiflu
neuraminidase inhibitor - facilitates the release of virus
- shorten the course of illness
34
anti HIV drugs
- nucleoside reverse transcriptase inhibitors (NRTI's) - target and interfere with the critical steps in viral replication process
- nonnucleoside reverse transciptase inhibitors (NNRTI's) - prevent HIV DNA synthesis by selectively binding to and inhibiting the viral reverse transcriptase enzyme
- protease inhibitors (PI's) - block activity of HIV protease
- integrase inhibitors - prevent incorporation of HIV genome into hosts chromosomes
- fusion inhibitors - prevent HIV entry into cells
35
what are the most successful at anti HIV?
drug cocktails to curtail resistance
36
treating superficial mycoses
topical and oral
disrupt membrane permeability and inhibit sterol synthesis
disrupts mitotic spindle - may inhibit protein and DNA synthesis.
37
treating systemic mycoses (in the bloodstream)
difficult to control and treatments can be fatal
38
antiprotozoan drug mechanism is
not precisely known.
39
types of drug resistance
- intrinsic - part of structural/born with it. mycoplasma resistance to beta lactam antibiotics and other cell wall inhibitors and other cell wall inhibitors simply because they lack a cell wall
- acquired - occurs when there is a change in the genome of a bacterium that converts it from one that is sensitive to an antibiotic to one that is resistant.
40
drug tolerant bacteria (persisters) lack the mechanisms for _____ ______ and ignore the presence of antibiotics.
antibiotic resistance
41
mechanisms of drug resistance
- modify the target of the antibiotic - change the plasma membrane and alter enzymes so it can be targeted
- drug inactivation - enzyme from plasmid break up antibiotics
- minimize the concentration of antibiotic in the cell - antiporter kicks out antibiotic
- bypass the biochemical reaction inhibited by the agent or increase the production of the target metabolite. - bacteria make their own or they are producing enough of their own that they have enough to function.
42
overcoming drug resistance
- give drug in appropriate concentrations to destroy susceptible microbes and most spontaneous mutants
- give 2 or more drugs at same time - maybe it didn't change target for one of the drugs so it might work
- use drugs only when necessary and take the full dosage so there arent any that create resistance
43
possible future solutions to overcoming drug resistance
use of bacteriophages to treat bacterial disease
44
immune system
composed of widely distributed cells, tissues, and organs
recognizes foreign substances or microbes and acts to neutralize or destroy them
45
nonspecific immune response (innate)
first line of defense
offers resistance to any microbe or foreign material
lacks immunological memory
46
specific immune response (adaptive)
resistance to a particular foreign agent
has "memory"
effectiveness increases on repeated exposure to agent
47
physical barriers of nonspecific (innate) resistance (direct and indirect factors)
direct factors - nutrition, physiology, fever, age, genetics
indirect factors - personal hygiene, socioeconomic status, living conditions
48
along with host's secretions (flushing), barriers are the __ __ _ _ against microbes.
first line of defense
49
skin - innate characteristics
- strong mechanical barrier to microbial invasion
- inhospitable environment for microbes
- shedding of outer skin cells, slightly acidic, high NaCl conc., subject to periodic drying
50
mucous membranes
- resists penetration and traps many microbes
- antimicrobial secretions
- lysozyme - hydrolyzes bond connecting sugars in peptidoglycan
- lactoferrin - secreted by certain immune cells and sequesters iron from plasma
- lactoperoxidase - produces superoxide radicals
51
respiratory system
- mucociliary blanket traps microbes and once they are trapped they are transported away from the lungs by coughing or sneezing or salvation washing the microbes to the stomach
52
GI tract
stomach - gastric acid
small intestine - pancreatic enzymes, bile, intestinal enzymes, peristalsis
large intestine - shedding of columnar epithelial cells, secretory IgA, normal microbiota
53
Genitourinary tract
unfavorable environment - low pH, lactobacilli, urea and other toxic metabolic end products in urine
- flushing urine and mucus
- distance barrier of male urethra
54
what is the secretion of the eye and what is in the secretions?
flushing action of tears
lysozyme, lacterferrin, secretory IgA in tears
55
chemical mediators in nonspecific (innate) resistance
- gastric juices, lysosome, urea
- variety of defensive chemicals such as defensins and other polypeptides are also found in blood, lymph, and other body fluids
- defensive proteins found in the blood
56
complement system 3 major activities
- stimulating an inflammatory response by helping to recruit white blood cells
- lysing microbial cells
- promoting phagocytosis (opsonization)
57
opsonization
- microbes are coated by serum components (opsonins) in preparation for recognition/ingestion by phagocytic cells
- bind to microbial cells, coating them for phagocyte recognition - can be antibody, complement, or antibody and complement
58
Functions of complement proteins
- function as chemotactic signals that recruit phagocytes to their activation site
- puncture cell membranes causes lysis
- many complement activities unite the innate and adaptive arms of the immune system to destroy and remove invading pathogens
59
complement activation
- activated following enzymatic cleavage
- must be activate in cascade fashion
- 3 pathways of activation - alternative, lectin, classical
60
alternative complement pathway
- dependent on interaction of complement with repetitive structures on pathogens
- begins with activation of C3
- results in formation of membrane attack complex
61
lectin complement pathway
- also called the mannose binding lectin pathway - mannose is a part of a lot of pathogens
- activation of C3 and lectin binding
- dependent on interaction of host mannose-binding protein (MBP) with pathogen surfaces - enhances phagocytosis
62
classical complement pathway
- dependent on antigen-antibody interactions
- acquired immunity and not as fast as other pathways
- produces cleavage products that participate in opsonization, chemotaxis, and the membrane attack complex.
63
cytokines are soluble __or _____ that are released by one cell population that act as _______ ______ or _______ ______
proteins or glycoproteins
intracellular mediators or signaling molecules
64
3 simplified categories of cytokines
- regulators of innate immunity
- regulators of adaptive immunity
- stimulators of hematopoiesis
65
cytokines are divided into 4 functional groups. what are they?
- chemokines - stimulate cell migration
- interleukins - released from one leukocyte and act on another leukocyte
- interferons - regulatory cytokines produced in response to infection
- colony stimulating factors (CSF's) - stimulate growth and differentiation of immature leukocytes in bone marrow
additional class - tumor necrosis factors - - (TNF) - stimulates an inflammatory response
66
mast cells
- bone marrow derived cells
- differentiate in blood and connective tissue
- contain granules containing vasoactive mediators
- play important role in development of allergies and hypersensitivities
67
granulocytes
- irregularly shaped nuclei with two to five lobes
- cytoplasm has granules with reactive substances - kill microbes enhance inflammation
- three types - basophils, eosinophils, neutrophils
68
neutrophils (type of granulocyte)
- highly phagocytic
- circulate in blood then migrate to sites of tissue damage
- kill ingested microbes with lytic enzymes and reactive oxygen metabolites contained in primary and secondary granules
69
monocytes and macrophages
- highly phagocytic cells
- monocytes - produced in bone marrow and released into blood circulation - after circulating for 8 hours they turn into macrophages
- macrophages - larger than monocytes, reside in specific tissues, highly phagocytic. release chemokines to recruit neutrophils
70
dendritic cells
- many long cellular projections
- present in blood, skin, and mucous membranes of the nose, lungs, and intestines
- contact, phagocytose, and process antigens - display foreign antigens on their surfaces (antigen presentation)
- capable of eliciting immune response from T-cells activating adaptive immune system
71
lymphocytes
major cells of the adaptive immune system
major populations include T cells, B cells, and NK cells
72
innate lymphoid cells
NK cells - do not have memory
stimulated same methods as neutrophils, macrophages, and DCs
73
phagocytosis
process by which phagocytic cells (monocytes, tissue macrophages, dendritic cells, and neutrophils) recognize, ingest and kill extracellular microbes
74
2 mechanisms for recognition of microbe and phagocyte
- opsonin-independent (nonspecific) recognition
- opsonin-dependent (opsonic) recognition
75
phagocytosis can be greatly increased by
opsonization
76
opsonin dependent pathogen recognition
recognize serum components attached to pathogens
77
opsonin independent pathogen recognition
common pathogen components are nonspecifically recognized to activate phagocytes - signaling mechanism involved
- involves nonspecific/specific receptors on phagocytes
78
intracellular digestion
once bound, microbes can be internalized and delivered to a lysosome to become a phagolysosome
- respiratory burst reactions occur once phagolysosome forms
- toxic oxygen products are produced which can kill invading microbes
79
innate immune system host response is
inflammation - nonspecific response to tissue injury can be caused by pathogen or physical trauma
80
acute inflammatory response
- release of inflammatory mediators from injured tissue cells initiates a cascade of events which result in the signs of inflammation
- involves chemical mediators
81
chemical mediators involved in acute inflammatory response
- selectins - cell adhesion molecules on activated capillary endothelial cells
- integrins - adhesion receptors on neutrophils
- chemotaxins - chemotactic factors released by injured cells
82
what happens during an acute inflammatory response
- margination
- diapedesis/extravasion - diapedesis - cell squish through capillary call into tissue - extravasion - get rid of bacteria
- capillary widening
- increased permeability
- attraction of leukocytes
- systemic response
83
macrophages release chemotaxins that
stimulate permeability of cell wall and recruit other cells that perform phagocytosis
84
what processes and or signals initiated immediately after the stick broke through the barriers?
- macrophages on skin and in tissue
- chemotaxins and mast cells are released - increase membrane permeability and dialate them (increase blood flow)
- neutrophils stick to selectins and integrins that recruit them to that area. now they can move through the membrane and destory pathogen and recruit others
85
describe the innate immune defenses occurring two days after the skin being punctured by the stick
- cells and signals increase blood flow
- neutrophils consume bacteria so much to the point that they kill themself (pus)
86
innate immune defenses once the wound has been cleaned
- macrophages and dendritic cells becoming antigen presenting cells
- what type of antimicrobial drug is prescribed? broad spectrum
87
binary fission process
- a cell prepared for division by enlarging the cell wall, plasma membrane, and overall volume.
- dna replication starts
- the septum begins to grow inward as the chromosomes move towards opposite sides of the cell. other cytoplasmic components are distributed to the two developing cells
- the septum is synthesized completely through the cell center creating 2 separate cell chambers
- the daughter cells are divided.
88
cytokinesis (septation) steps
- selection of site for septum formation
- assembly of Z ring (composed of protein FtsZ
- assembly of cell wall synthesizing machinery
- constriction of cell and septum formation
89
what are the different things that protein synthesis inhibitors target?
- aminoacyl-tRNA binding
- peptide bond formation
- mRNA reading
- translocation
90
antibacterial drugs that inhibit nucleic acid synthesis functioning by inhibiting
DNA polymerase and topoisomerases (fluoroquinolones)
RNA polymerase (rifamycins)
91
antiviral drug development is slower because....
it is hard to specifically target viral replication
92
why are there fewer antifungal agents than antibacterial agents?
the similarity of eukaryotic fungal cells and human cells.
many have low therapeutic index and are toxic
93
what is phagocytosis?
the process by which phagocytic cells (monocytes, tissue macrophages, dendritic cells, and neutrophils) recognize, ingest, and kill extracellular microbes.
94
____ _____ is the immediate response of body to injury or cell death
acute inflammation
95
cardinal signs of inflammation
-redness
-swelling
-warmth
-pain
-altered function
96
penicillin mode of action
blocks the enzyme that catalyzes transpeptidation and prevents the synthesis of complete cell walls leading to lysis of the cell.
acts only on growing bacteria that are synthesizing new peptidoglycan.
97
how are drug tolerant bacteria drug tolerant?
embedded in biofilms or are growing too slowly to be inhibited.
98
alveolar macrophages are
phagocytic cells in alveoli of lungs
