Lecture 4 Vaccines Classification Metabolism (E1) Flashcards

Ch 11, 12, 13

1
Q

Passive Immunization

A

Transfer of Immune serum or cells- Not permanent, no memory
Typically a transfer of functional antibody
May constitute a transfer of immune cells
Raise immunity to protective levels in very short time
Does not confer memory on the new host
Immunity will wane at the normal rat based on the half-life of the immune component
Ex: Rabies Ig after animal bite(at site)
Mother to child (placenta)

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2
Q

Active Immunization

A

Memory
Introduction of Live, Attenuated, or killed pathogen into host
Induces Host Innate and Adaptive immunity
Specific Host memory is induced (may last years)
ex: Inactivated, live, DNA, or Conjugated Vaccines)

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3
Q

Capsular Polysaccharide Conjugate Vaccines

A

Want to raise anti-body count
Capsular Polysaccharides are T-independet Ag
-B-cell response(IgM, but no memory), no T-cell help
-Conjugated to protein can drive reaction to T-dependent (Want IgG)
*add Diptheria toxoid to polysaccharide to cause an immune response
-Causes BCR to internalize entire conjugate (induces IgM to present to T-cell via MHC-II)
Induced Class switch to IgG

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4
Q

Ideal Vaccine

A

-Microbe/pathogen cause significant disease
-one or few serotypes
-antibody is protective
-Vaccine is stale (Killed vs Live)
-Cost efficient
-Herd Immunity

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5
Q

Vaccine issues

A

Live vaccines occasionally revert to pathogenic
Immunocompromised individuals at risk
Allergies to Vaccine
Expensive
Misinformation

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6
Q

Bacillus Calmette-Guerin (BCG) Vaccine

A

Camille Guerin and Albert Calmette respectively, were the developers of the BCG (nonvirulent) Vaccine, an attenuated strain of Mycobacterium bovis
-Die less from other infectious disease
-One of the oldest
-Suggested cascade of immune responses in bladder mucosa induced by intravesical BCG instillation(bladder cancer)

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7
Q

BCG Vaccine

A
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8
Q

Attenuated Vaccine

A
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9
Q

Killed Vaccine

A
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10
Q

Sub-unit Vaccine

A
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11
Q

Cell-mediated Immunity

A

the adaptive immune response that is independent of antibodies but involves immune cells that specifically recognize, target, and clear infected host cells

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12
Q

Toxoid

A

a chemically modified toxin that is no longer toxic but can still trigger the body’s immune response to produce antibodies. Toxoids are used in vaccines to protect against diseases like tetanus and diphtheria

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13
Q

Bacteriophage

A

A bacteriophage also known informally as a phage is a virus that infects and replicates within bacteria and archaea

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14
Q

Bacteriophage -Resistance

A

Difficult to occur

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15
Q

Bacteriophage- Self-Titrating Dose

A

Removes itself

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16
Q

Bacteriophage downside

A

Is a virus so you will develop your own immunity
Sepsis- Rapid lysis of bacteria (release LPS, type 4) may release toxic amounts
Gene Transfer- Some phages can transfer genetic material
Hypersensitivity- Immune reaction to high doses of phage

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17
Q

Bacteriophage- Toxicity

A

Does not infect host cells

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18
Q

Bacteriophage- Biofilms

A

Able to penetrate

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19
Q

Bacterial Structures

A

Glycocalyx
Ribosome
Cell wall
Plasma membrane
Cytoplasma
Bacterial Chromosome
Plasmid
Pilus
Actin cytoskeleton
Flagellum
Fimbriae
Inclusion/Granule
Outer Membrane

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20
Q

Bacterial Cell wall structures

A

The cell wall consists mainly of peptidoglycan (PG), a mesh of polysaccharide strands (composed of a poly-[N-acetylglucosamine (GlcNAc)-N-acetylmuramic acid (MurNAc)] backbone) cross-linked via short peptide bridges attached to the MurNAc residues

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21
Q

Peptidoglycan

A

Peptidoglycan is a large macromolecule that makes up the main part of bacterial cell walls. It’s a mesh-like polymer of sugars and amino acids that protects bacterial cells from environmental stress and helps maintain their shape and division

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22
Q

Lipopolysaccharide (Gram Negative)

A

(Endotoxin) important outer membrane components of gram-negative bacteria. They are large amphipathic glycoconjugates that typically consist of a lipid domain (hydrophobic) attached to a core oligosaccharide and a distal polysaccharide.
establishes a permeability barrier that protects the cell from the entry of toxic molecules such as antibiotics and bile salts
They are composed of: Lipid A: the hydrophobic domain, which is an endotoxin and the main virulence factor
O-antigen, the repeating hydrophilic distal oligosaccharide
The hydrophilic core polysaccharide

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23
Q

Teichoic acid (Gram positive)

A

anionic polymers found in Gram-positive bacteria CW and are made of polyglycerol phosphate units (approximately 20–30 repeats). They are involved, among others, in the regulation of cell morphology as well as in cell division. They can represent up to 50% of the dry-weight of the Cell wall.

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24
Q

Cell Wall synthesis

A

Lipid II, the monomer for bacterial cell wall, is synthesized inside the cytoplasm and then flipped outward by the transporter MurJ. It is then polymerized by glycosyltransferases (GTs) and crosslinked by transpeptidases (TPs) to make the protective mesh that is cell wall.

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25
Q

Sporulation

A

or endospore formation, is a process that bacteria use to create protective structures called spores that help them survive harsh conditions

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26
Q

Bacterial Charaterization (Metabolic)

A

What food sources (sugar, fats, proteins) are utilized
How are the food sources utilized (aerobic, anaerobic respiration)
Metabolic end products (acids, alcohols)
Presence or absence of enzymes (catalase, lipase, urease etc)

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27
Q

Bacterial Characterization (Serologic)

A

Antigenic- surface makers (proteins, polysaccharides)
Rapid identification for dangerous or difficult to grow organisms
Monoclonal or polyclonal antibody detection/producation

28
Q

Bacterial Characterization (Nucleic acid)

A

Genetic- rRNA or DNA(genome) sequencing
PCR, Southern blots, Lab on a chip
Detection of virulence factor genes
Mass Spectroscopy

29
Q

Eukaryote

A

Algae, Fungi, protozoa, plants, animals
Size- >5um
Nucleus-classic membrane
Chromosomes- strands of DNA diploid genome
Cytoplasmic structures
Mitochondria (respiration)
Golgi bodies
Endoplasmic reticulum
Ribosomes 80S (60S + 40S)
Cytoplasmic membrane contains sterols
Cell wall- present for fungi; otherwise absent
Reproduction- Sexual and asexual
Movement- complex flagellum if present

30
Q

Prokaryote

A

Bacteria
Size- 0.5-3.0um
No nuclear membrane
Chromosomes- Single, circular DNA haploid genome
Ribosomes- 70S (50S + 30S)
Cytoplasmic membrane Does not contain sterols (except mycoplasma)
Cell wall- Complex structure containing protein, lipids, and peptioglycan
Reproduction- Asexual (Binary fission)
Movement- Simple flagellum if present
Respiration- via cytoplasmic membrane

31
Q

Peptidogylcan (Structure, synthesis, antibiotics)

A

Basically a chain link fence around cell
Mesh around cell
Polysaccharide polymer linked via peptide bonds
Peptides cross-linked via D-Ala - Lys linkage
This is what antibiotics target
Penicillian activity- Binds and blocks carboxy-peptidases transpeptidases

Staphyloccus auresus has Gly5 linker- different bacteria have variations in peptidoglycan
Site of vancomycin activity- Binds to terminal D-Ala- Block cross linkage

32
Q

Beta-lactam(ases)

A

Beta-lactam antibiotics work by inactivating enzymes that are involved in the synthesis of bacterial cell walls. They are effective against many gram-positive, gram-negative, and anaerobic organisms
Penicillian is one of these!
beta-lactam ring in their chemical structure
NH2 for cross linkage
Inhibit formation of peptide bonds

33
Q

Gram Stain

A

Iodine fixes crystal violet to cell wall; but does not penetrate outer membane
Alcohol dissolves OM: solubilizes Iodine from Gram(-) cell wall
Safranin stains gram(-) cell wall red
So gram (+) peptidoglycan absorbes Crystal violet and it is trapped, alcohol does not remove it and the safranin doesnt change the purple color

34
Q

Techoic acid/ Lipotechoic acid

A

Gram Posistive
Polymer of modified ribose or glycerol linked by phosphates
Antigenic specificity
Lipid anchor in membrane
Synthesized in a similar manner to peptidoglycan
Ribitol teichoic acid is ring
Glycerol Teichoic acid is NH3 linked in a line ish

35
Q

Mycobacteria

A

ex: Tuberculosis
Peptidoglycan interwoven with mycolic acid(s)-hard to stain, density of car wax
they stain gram (-)
Typically use Acid-fast staining to identify
immobile, slow-growing rod-shaped, gram-positive bacteria with high genomic G+C content (61-71%). Due to their special staining characteristics under the microscope, which is mediated by mycolic acid in the cell wall, they are called acid-fast. This is also the reason for the hardiness of mycobacteria

36
Q

Lipopolysaccharide (LPS)

A

Lipid (A) endotoxin-Gram Negative (causes problem when split open)
Core polysaccharide-Branched, 9,12 sugars
O antigen- Long linear polysaccharide, up to 40 units (4-7 carbon sugars) repeat unit

37
Q

Mycoplasma

A

No peptidoglycan, Gram (-) Incorporate sterols from host into cell membrane (unusual)
Naturally resistant to penicillian type antibiotics
M. pneumonia-walking
smallest free living organism
Pleomorphic- from cocci to long filaments
Difficult to culture directly (however, bane of eukaryotic tissue culture)
Stain with nuclear (DNA) stains

38
Q

Glucose Metabolism

A

3 major pathways
Aerobic respiration (ATP=38) per glucose
Anaerobic respiration (ATP= 2-36)-Electron transport
Fermentation (anaerobic)- (ATP= 2)-Some bacteria only do this bc its very quick, efficient

39
Q

Fermentation

A

Anaerobic
Leads to 2ATP/Pyruvic acid
Typically acid or alcohol endproducts
Different bacteria make different stuff

40
Q

Kreb’s Cycle

A
  1. Is the most efficient way to produce ATP (up to 19x more than fermentation, 38 vs 2)
  2. Serves as final common pathway for catabolic oxidation of amino acids, lipids, and carbohydrates (it really is in the middle of things)
  3. Supplies key intermediates for anabolic metabolism (a-ketoglutarate, pyruvate, oxaloacetate)
41
Q

Amphibolic pathway

A

Goes both ways
(Catabolic and Anabolic)

42
Q

70S Ribosome

A

70S- how they sediment in centrifuge
protein translation coupled to transcription

43
Q

Operon

A

lac-Operon
P= promotor (binds RNA polymerase)
I= Repressor (repressor gene)
O= Operator (binds repressor protein)
CAP= Catabolite gene activator protein
cAMP= Cyclic AMP
A. Lactose operon (lac) transcribed as polycistronic mRNA (single strand)
B. No allolactose- Repressor binds operator sequence and stops transcription
C. Repressor + allolactose- Transcription proceeds at low level. Repressor is inactive
D. Low glucose + lactose- Inducer and CAP-cAMP turn on promotor at high level; Z, Y, and A produced at high levels (repressor blocked)
E. Low glucose/Lactose- Repressor binds operator sequence and stops transcription

44
Q

Attenuation anti-termination

A

In this mechanism, a regulatory molecule induces transcription termination. The default pathway is read through. Attenuation is characterized by the presence of a stop signal, or attenuator, that prevents the ribosomal complex from functioning properly.
Attenuation: Typically involves one transcription terminator, which is directly targeted by the control mechanism.
Antitermination: Affects a large number of terminators, and the target is RNAP

45
Q

Bacterial Growth

A

4 phases:
Lag-getting used to things (little growth, little death)
Exponential- Living is easy (growth»>death)
Stationary- settling in (growth=death)
Death- times are tough again (death»>growth)

46
Q

Infection progress

A

6 phases
Incubation period (lag phase)
Prodomal (early log phase)
Invasion (log phase to stationary phase)
Covalescence (death Phase)
Recovery
Chronic Carriers (control infection, but still infectious)

47
Q

Transition mutation

A

Purine to purine (A->G, G->A)

48
Q

Transversion mutation

A

purine to pyrimidine (A or G -> T or C)

49
Q

Silent Mutation

A

DNA base change, no change in amino acid (codon wobble-part that codes)

50
Q

Missense Mutation

A

DNA base change, change in animo acid

51
Q

Nonsense Mutation

A

DNA base change, stop codon inserted (translation)

52
Q

Conditional Mutation

A

responds to some environmental factor (temp. metabolite, etc) to alter translation- how they made attenuated vaccine in old days

53
Q

Frameshift Mutation

A

DNA base insertion/deletion resulting in shift of frame downstream

54
Q

Transposon

A

mobile genetic units (“jumping genes”), move between sites within DNA

55
Q

Transduction

A

Transfer of DNA via bacteriophage; phage infects recipient cell

56
Q

Transformation

A

Direct uptake of DNA from environment (competence)

57
Q

Conjugation

A

Direct transfer of bacterial DNA between (within/between species, via pili)

58
Q

Sex pili

A

Used in Conjugation (Type IV secretion device)

59
Q

F(+), F(-)

A

Example of conjugation
F (+)- contains F plasmid

60
Q

Point mutation

A

Discrete substitutions, deletions, or insertions in the genetic code. Often be found in the active site of the target protein, upon which the drug is designed to act. In some instances, a single point mutation can engender the resistance phenotype, for chloroquine, seven such mutations are necessary

61
Q

Gene Amplification

A

Common resistance mechanism- cancers, pesticide, antibiotics. Increase in overall copy number of the target gene. Can also increase production of detoxifying enzymes (Come in and get pumped out)

62
Q

Metabolic Degradation

A

Pests and pathogens can also evolve mechanisms to metabolize toxic compounds, as is often seen in plants

63
Q

Exclusion or sequestration

A

Organisms can pump toxins out-efflux channels
Enhanced sequestration are mechanisms of some pesticide resistances

64
Q

Stress Respones

A

Restistance can also emerge due to the effects of the drug itself if the method of action affects mutation rates. Similarly, resistance can arise through conditioning if the cellular response pathway activated by the drug triggers an up-regulation of compensatory changes

65
Q

Ecological Avoidance

A

Organisms can physically avoid the drug or pesticide. For example, viruses and bacteria can enter latent phases of their lifecycle in which they do not replicate, remain hidden to both the immune system and therapeutic approaches. Bacterial biofilms. Cancerous cells in the interior of a tumor.