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MICB 3301 Lecture > Exam 4 > Flashcards

Exam 4 Flashcards

1
Q

Adaptive immunity has two branches: ____ and ____-____ immunity

A

humoral, cell-mediated

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2
Q

Humoral Immunity

A
  • Involves antibodies made by B cells
  • Defends against extracellular pathogens
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3
Q

Cell-Mediated Immunity

A
  • Involves T cells and MHC’s
  • Largely defends against intracellular pathogens
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4
Q

Antibodies (Immunoglobulin)

A
  • Proteins made by B cells
  • Found in blood, mucosal surfaces, and tissues
  • Bind antigens (neutralizes toxins, or opsonizes cells for identification)
  • 5 antibody classes (isotypes)
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5
Q

Antibodies bind antigens to ____ or ____ them

A

neutralize or opsonize

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6
Q

Antibody classes include:

A
  • IgG
  • IgA
  • IgM
  • IgE
  • IgD
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7
Q

IgM

A

First responder Ig after antigen exposure
* Pentamer
* Plasma cells that produce them can switch and produce another Ig class

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8
Q

IgG

A

Major Ig in blood
* Monomer
* Can cross placenta and activate complement

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9
Q

IgA

A

Major Ig in secretions (ex. saliva, breast milk, tears)
* Dimer
* Defends mucosal surfaces

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10
Q

IgE

A

Ig in allergic reactions and autoimmune disease
* Monomer

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11
Q

IgD

A

Ig found on B cell surfaces, play a role in signaling
* Monomer

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12
Q

The half life of Abs is a matter of ____ to protect the ____ ____ ____, IgG is the most stable, with a half life of ____

A

days, adaptive immune response, 20 days

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13
Q

Antibody classes have unique superstructures but the same basic structure consisting of:

A

4 polypeptide chains:
* 2 identical heavy chains
* 2 identical light chains

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14
Q

VDJ Recombination

A

Rearrangement of antibody gene segments to generate antibody diversity

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15
Q

Clonal Selection

A
  • Random rearrangement of Abs gene segments occurs as B cells develop in bone marrow, generates a vast array of B cells designed for specific antigens
  • Upon infection, antigen “selects” B cell with matching Abs
  • B cell proliferates, forming a clone of identical cells, each with antibody for the antigen
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16
Q

Tolerance

A

Removal of self-reactive B cells

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17
Q

Central tolerance involves removing B cells recognizing ____ ____ largely in bone marrow (the breakdown of which is one basis of autoimmunity)

A

self antigen

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18
Q

Adaptive immunity has ____ and ____

A

specificity and memory

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19
Q

T Cells

A
  • Originate in the bone marrow, mature in thymus
  • Activate when their receptors bind antigens presented by Professional Antigen Presenting Cells (ex. DCs, B cells, Macrophages)
  • Consist of helper T cells and cytotoxic T cells
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20
Q

Helper T Cells

A

Part of adaptive immune response

  • CD4 coreceptor
  • Make cytokines, activate B cells, macrophages, or other T cells (indirectly kills antigens)
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21
Q

Cytotoxic T Cells (characteristics and how it kills cells)

A

Part of adaptive immune response, targets intracellular pathogens

  • CD8 coreceptor

Kill own cells expressing foreign antigens using
* perforins - form pores
* granzymes - induce apoptosis

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22
Q

In addition to specific receptors, immune cells have other membrane proteins called ____ ____ (CD) molecules that can function as co-receptors, used to determine the cells identity

A

Cluster of Differentiation
* CD4 molecules - Helper T cells
* CD8 molecules - Cytotoxic T cells

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23
Q

T-Cell Receptors

A
  • Bind antigens presented to them by other cells when presented by a Major Histocompatibility Complex (MHC) molecule
  • Expressed from gene segments rearranged in thymus
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24
Q

The MHC is a ____ encoding cell surface proteins for ____ recognition (Human Leukocyte Antigen complex)

A

collection of genes, self/nonself

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25
Q

Human Leukocyte Antigen (HLA) Complex

A
  • Human MHC, involves one set from each parent (both expressed)
  • The closer 2 people are related, the more similar their HLAs (important in donor selection for tissue, bone marrow, and organ transplant via HLA Typing)
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26
Q

Cell surface proteins encoded by MHC are designated as ____ and ____

A
  • Class I MHC (on all nucleated cells - not erythrocytes
  • Class II MHC (only on antigen-presentic cells - dendritic cells, macrophages, B cells)
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27
Q

MHC I and II inform the immune system of the ____ by binding and presenting foreign peptides

A

presence of nonself

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28
Q

Class I MHC

A
  • On all nucleated cells
  • Present peptides that originate in cytoplasm from intracellular pathogens
  • Present peptides to CD8+ (cytotoxic T cells)
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29
Q

Class II MHC

A
  • Only found on antigen-presenting cells
  • Present peptides from extracellular pathogens taken up by phagocytosis
  • Present peptides to CD4+ (helper T cells)
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30
Q

Pathogen

A

Organism that produces disease

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31
Q

Opportunistic Pathogen

A

Infects host with compromised immune system (ex. Pseudomonas aeruginosa)

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32
Q

Carrier

A

Infected individual with no observable symptoms, potential source of infection

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33
Q

Zoonoses

A

Diseases transmitted to humans from animals

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34
Q

Vectors

A

Organisms (usually insects) that transmit disease to humans (ex. mosquitoes, ticks, fleas)

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35
Q

Pathogenicity

A

Ability to produce disease

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36
Q

Virulence

A

Degree of pathogenicity

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37
Q

Genetic, biochemical, structural features that contribute to virulence (ex. capsule, pigment, toxin)

A

Virulence Factors (determinants)

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38
Q

Latency

A

Pathogen stops reproducing (dormant), can become active again (ex. varicella-zoster virus, causative agent of chicken pox and shingles)

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39
Q

Infectious Dose 50 (ID50)

A

Number of pathogens required to cause clinical disease in hosts
(increased virulence indicates lower ID50)

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40
Q

Pathogens, virulence, and pathogenicity are tested by:

A
  • Model systems - animal models, cell culture
  • Epidemiology - examine incidence, distribution, and control of disease
  • Human studies - clinical trials, case studies
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41
Q

Pathogen ____ and ____ properties initiate disease

A

adherence and invasion
(allow for evasion of immune response)

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42
Q

____ and ____ spike proteins mediate viral attachment

A

Capsid and envelope
(ex. Hemagglutinin spike of inflenza which binds sialic acid, GP120 spike of HIV binds CD4 receptor and CCR5 coreceptor on helper T cell, S spike of SARS-CoV-2 binds ACE2 receptor)

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43
Q

Viruses can spread via ____, ____, or ____ systems

A

blood, neuronal, or lymphatic

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44
Q

Syncytia

A

Virus-induced cell fusion, forming multinucleated cells and providing virus with resources and allows them to evade detection by extracellular defenses (ex. Respiratory Syncytial Virus (RSV))

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45
Q

Viruses can evade both innate and adaptive immune responses by

A

Innate - block complement and interferon (cytokine) production

Adaptive - block antigen processing and presentation, evade Abs through antigenic variation

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46
Q

Antigenic Variation

A

Amino acid changes in virion spikes, common in RNA viruses (ex. SARS-CoV-2 Omicron subvariants BA.2,3,4,5)

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47
Q

Bacterial attachment occurs via:

A
  • Pili
  • Capsules (ex. S. pneumoniae, H. influenzae, N. meningitidis, and sometimes P. aeruginosa)
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48
Q

Mucoid Strains

A

Strains of Pseudomonas aeruginosa that make capsules, are opportunistic pathogens in burn victims and cystic fibrosis patients

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49
Q

Bacterial virulence determinants:

A
  • Coagulase
  • Streptokinase
  • IgA Proteases
  • Hemolysins
  • Siderophores
  • DNase

All can lead to spread of bacteria to bloodstream (bacteremia)

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50
Q

Coagulase

A

Clots fibrinogen in plasma, clot protects pathogens

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51
Q

Streptokinase

A

Activates plasmin, digests fibrin clots, pathogen moves from clotted area (used in medical procedures to remove blood clots therapeutically)

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52
Q

IgA Proteases

A

Destroy antibody

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53
Q

Hemolysins

A

Digest erythrocytes, releases iron

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54
Q

Siderophores

A

Released by microbes, bind available iron needed by the host

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55
Q

DNase

A

Degrades extracellular DNA used in Neutrophil Extracellular Traps (NETs), lowers viscosity of secretions, leading to spread of bacteria

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56
Q

Neutrophil Extracellular Traps (NETs)

A

Comprised of DNA and antimicrobial proteins and enzymes
* Traps pathogens
* DNase enzyme (virulence factor) contributes to bacteria escaping NET

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57
Q

Bacteria can evade both innate and adaptive immune responses

A

Innate - capsules block complement opsonization and membrane attack complex formation, proteases degrade complement C3b or C5a

Adaptive - capsules can also prevent Abs binding, some pathogens make proteases that degrade IgA

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58
Q

Bacterial intracellular pathogens include:

A
  • Chlamydia
  • Rickettsia
  • Mycobacterium tuberculosis
  • Salmonella
  • Listeria
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59
Q

Listeria monocytogenes

A
  • Gram +, food-borne pathogen found in produce, raw (unpasteurized) milk, cheese, deli meat
  • Psychrophile
  • Can cross placenta
  • Movement via actin tail
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60
Q

Actin Tail

A

L. monocytogenes polymerizes actin component of human cells at a pole, pushing the cell outwards (Listeria Actin Rockets)

  • Endocytosed by other cells to hide from extracellular Abs response
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61
Q

Encapsulated, causative agent of Otitis Media (infection of middle ear) and bacterial meningitis

A

Streptococcus pneumoniae

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62
Q

Staphylococcus and Enterococcus are both causative agents of ____ infections (endocarditis)

A

heart valve

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63
Q

Streptococcus mutans (et. al)

A

Dental plaque biofilms

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64
Q

Bacteria can evade innate and adaptive immunity by forming biofilms, rendering antibiotics ineffective and leading to ____ ____

A

“frustrated phagocyte”

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65
Q

Toxins

A

Substances that damage the host
* Exotoxins - proteins made and released outside of cell (ex. AB toxins)
* Endotoxins - components of bacteria that are toxic (ex. Lipid A on LPS of Gram - species)

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66
Q

Exotoxin Types

A
  • Superantigens
  • AB (A = toxin, B = cell targeting)
  • Membrane-disrupting
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67
Q

Membrane-disrupting exotoxins (such as ____ and ____) function by ____

A

forming pores, causing swelling/lysis
(ex. leukocidins, hemolysins)

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68
Q

Superantigens

A
  • Exotoxin
  • Cause T cells (>30%) to overexpress cytokines (pro-inflammatory effect, unregulated overstimulation of helpter T cells)
  • Resulting in failure of multiple host organs
  • Ex. Toxic Shock Syndrome caused by S. aureus strain producing superantigen
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69
Q

AB Exotoxins

A
  • Contains two subunits (dimeric): A - toxic effect, B - binds target cell receptor
  • Many are ADP-ribosyl transferases (remove ADP-ribose group from NAD and attach it to a host cell protein, resulting in inactivation or abnormal ribosomal function)
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70
Q

Diphtheria toxin (Corynebacterium diphtheriae)

A
  • AB toxin that binds to growth factor receptor, enters by endocytosis
  • ADP-ribosyl transferase
  • Attaches ADP ribose from NAD onto elongation factor (EF-2, plays important role in protein synthesis, inhibited by toxin)
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71
Q

Many AB toxins are also ____ ____ specific (ex. cholera toxin, botulinum toxin, tetanospasmin)

A

host site

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72
Q

Cholera toxin

A
  • Produced by Vibrio cholerae
  • Enterotoxin (intestinal tract)
  • ADP-ribosyl transferase
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73
Q

Botulinum Toxin

A
  • Produced by Clostridium botulinum
  • Neurotoxin (brain/CNS)
  • Blocks release of acetylcholine at neuromuscular junctions, resulting in flaccid paralysis (ex. Botox)
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74
Q

Exotoxins are ____ proteins

A

antigenic

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75
Q

Antibodies can ____ toxicity of the toxin (antitoxin)

A

neutralize

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76
Q

Exotoxins are generally unstable, can lose ____ but remain ____

A

toxicity, antigenic
(ex. toxoid)

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77
Q

Toxoid

A

Inactivated toxin that can still illicit an immune response (bases of toxoid vaccines, ex. DTaP)

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78
Q

Endotoxin component of Gram - Lipopolysaccharide (LPS) and 2 things about it

A

Lipid A
*heat stable
*toxic in nanogram amounts but weakly immunogenic

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79
Q

During infection, bacterial LPS binds TLR4, activates NF(Kappa)B to transcribe genes for cytokine, leading to:

A

fever, inflammation, and blood vessel leakage (hypotension), Septic Shock

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80
Q

Sepsis

A

Systemic response to microbial infection, elevated temperature, heart, and respiratory rate, leukocyte count

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81
Q

Shock

A

Sepsis with hypotension (low bp)

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82
Q

Septic shock causes ____ (red blotches on skin caused by hypotension), and in severe cases ____ (shut off blood to extremities)

A

petechiae, gangrene

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83
Q

Cidal

A

Kills microbes

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84
Q

Static

A

Inhibits microbial growth

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85
Q

Sterilization

A

Processes by which all living cells, spores, and viruses are destroyed or removed

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86
Q

Disinfection

A

Reduction of microbial population, destruction of pathogens

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87
Q

Sanitization

A

Reduction of microbial contamination to levels safe by public health standards

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88
Q

Antiseptic

A

Chemical agent applied to tissue to prevent infection by inhibition or killing

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89
Q

Microbial control methods include:

A

mechanical removal (ex. filtration), chemical reagents (ex. gases), and physical agents (ex. radiation and heat)

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90
Q

Radiation microbe control

A
  • UV - can sterilize, but poorly penetrates, mostly used to disinfect
  • Ionizing (X, gamma ray) - penetrates, sterilizes
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91
Q

Heat microbe control

A

Moist heat more effective than dry
* Steam under pressure (autoclave) sterilizes after 15 mins at 121 C under 15lbs/sq in of pressure

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92
Q

Pasteurization

A

Doesn’t sterilize but kills most pathogens including Listeria, Salmonella, Campylobacter
* 63 C - 30 min., rapid cool (beer, fruit juice)
* 72 C - 15 sec., rapid cool (milk)

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93
Q

Antimicrobial agents are used to ____

A

treat disease, destroy pathogenic microbes, or inhibit growth
* Most are antibiotics (microbial products - ex. Penicillin from Penicillium)

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94
Q

Streptomyces requires over ____ enzymatic reactions to make ____

A

70, tetracycline

95
Q

Paul Ehrlich

A

(1904) Hypothesized selective toxicity of drugs (selectively targets pathogen, non-toxic to human taking drug)

96
Q

Alexander Fleming

A

(1928) Accidentally rediscovered penicillin

97
Q

Purified penicillin, injected into mice infected with Staphylococcus, mice survived

A

(1940) Florey, Chain, and Heatley

98
Q

Cultured over 10,000 strains of soil bacteria, discovered streptomycin

A

(1944) Selman Waksman

99
Q

Considerations for developing a clinically useful antibiotic

A
  • $300 million, 15-20 yrs
  • Allergenic? Toxic?
  • 20 and 2 rule (20 yrs to develop, 2 for antibiotic resistance)
  • Broad vs. narrow
  • Reach effective conc. at target site?
  • Not inactivated
  • Doesn’t eliminate microflora
100
Q

Pseudomembranous colitis

A

Prolonged antibiotic use and destruction of microflora, results in Clostridium difficile infection - C. diff (anaerobic, spore-forming, toxin-producing bacillus)

101
Q

Targets of antimicrobial agents:

A
  • Cell wall
  • Plasma membrane
  • Neucleic acid synthesis
  • Metabolic enzymes
  • Protein synthesis
102
Q

Cell wall synthesis inhibitors

A
  • Penicillins (b-lactams)
  • Cephalosporins (b-lactams)
  • Vancomycin
  • Bacitracin
103
Q

Penicillins

A
  • Most are narrow-spectrum (Gram +) and cidal
  • Alteration-derived Penicillins include Ampicillin, Amoxicillin (broad, Gram + and -)
  • Structural features include b-lactam ring and R group
104
Q

Bacterial enzymes called ____ catalyze the transpeptidation reaction that cross-links peptidoglycan

A

Penicillin Binding Proteins (PBPs)

105
Q

Penicillins and cephalosporins ____ PBPs

A

inhibit bacterial (peptidoglycan synthesis stops, osmotic lysis occurs)

106
Q

Vancomycin

A

Binds terminal D-ala, blocks transpeptidation

107
Q

Bacitracin ____ the carrier of the peptidoglycan subunit responsible for transporting it across the plasma membrane to the cell wall

A

blocks

(bacitracin is often used topically as Neosporin)

108
Q

Polymyxins - Plasma Membrane Inhibitor

A

Cidal, narrow Gram -

Ex. Colistin (binds outer membrane LPS)

109
Q

Antifungal agents often target ____ ____

A

plasma membrane (treat Candida yeast infections, athletes foot)

110
Q

Fluconozole and Miconazole

A

Inhibit ergosterol synthesis (ex. Micatin, Monistat brands)

111
Q

Nystatin and Amphotericin

A

Bind ergosterol

112
Q

Nikkomycin

A

Chitin synthesis inhibitor

113
Q

Metabolic Enzyme Inhibitors

A

Metabolic pathways are catalyzed by enzymes (bind substrates to lower Ea)

Ex. Sulfonamides and Trimethoprim

114
Q

Sulfonamides and Trimethoprim

A

Synthetic, static antimetabolites

  • Structurally similar to substrates for folic acid synthesis, tricking bacterial enzymes
  • Blocks folic acid needed for purine and pyrimidine (DNA) synthesis
115
Q

Nucleic Acid Inhibitors

A

Drugs that inhibit DNA replication (ex. Quinolones, Nalidixic Acid, Ciprofloxacin) and transcription (ex. Rifampin)

116
Q

Quinolones

A

Nucleic acid inhibitor that targets DNA replication

  • Synthetic, cidal
  • Inhibits bacterial DNA gyrase
117
Q

Rifampin

A

Nucleic acid inhibitor that targets transcription

  • Broad spectrum, cidal
  • Inhibits RNA polymerase
118
Q

Protein synthesis inhibitors are ____ spectrum antibiotics, take advantage of differences between eukaryotic and prokaryotic ____ and ____ synthesis machinery

A

broad, ribosomes, protein

119
Q

Aminoglycosides

A
  • Cidal
  • Binds to 30S component of ribosome, causing misreading of mRNA codons

Ex. Streptomycin, Kanamycin

120
Q

Tetracyclines

A
  • Static
  • Binds 30S component block tRNA and amino acid binding to A site
  • Low toxicity, widely prescribed

Ex. Doxycycline (Lyme disease, pneumonia, acne)

121
Q

Macrolides

A
  • Static
  • Binds 23S rRNA of 50S ribosomal subunit, blocking peptide bond formation

Ex. Erythromycin (Whooping cough), Azithromycin (Chlamydia, Z-Pak)

122
Q

Chloramphenicol

A
  • Same mode of action as Macrolides (inhibits peptide bond formation)
  • Toxic, only used in life-threatening situations
123
Q

Why are antiviral drugs difficult to develop?

A

Because viruses rely on the biochemical processes of the host cell to reproduce

124
Q

Acyclovir

A

Antiviral drug that inhibits DNA polymerase of herpesvirus

125
Q

Influenza antiviral drugs

A

Xofluza - blocks RNA replicase inhibiting replication and translation of viral RNA

Tamiflu - blocks neuraminidase

126
Q

For anti-HIV drugs, the major goal of antiretroviral therapy (ART) is to reduce the ____ ____, not to cure

A

viral load

127
Q

Anti-HIV Drugs:

A

Azidothymidine (AZT) - reverse transcriptase, copies viral RNA into DNA

Integrase inhibitors - integrase integrates DNA copy into host DNA (provirus)

Ritonavir - targets protease (processes viral polypeptides into proteins for virion assembly)

128
Q

PrEP Anti-HIV Drugs

A

Pre-exposure Prophylaxis

  • Contain compounds that function as analogs (like AZT)
  • Taken by people who do not have HIV but are at risk of contracting it

Ex. Descovy, Truvada

129
Q

Paxlovid

A

COVID-19 treatment

Two medications that target SARS-CoV-2 protease (ritonavir and nirmatrelvir)

130
Q

Chloroquine

A

Treatment for malaria by blocking heme (toxic) polymerization

131
Q

Malarone

A

Treatment for malaria by blocking e- transport, pyrimidine synthesis

132
Q

Metronidazole (Flagyl)

A

Treatment for Giardia and some bacteria (Helicobacter), enters pathogen, activates, and nicks its DNA

  • Prodrug - harmless until activated
133
Q

Vancomycin Resistant Enterococcus (VRE)

A

vanA gene - encodes enzyme that replaces terminal D-alanine with D-lactate (vancomycin rendered ineffective)

134
Q

Methicillin Resistant Staphylococcus aureus (MRSA)

A

mecA gene - encodes Penicillin Binding Protein (PBP) resistant to penicillin

Resistant to numerous antibiotics

135
Q

One mechanism of drug resistance is the transfer of an ____ ____ by transformation/conjugation

A

R plasmid

136
Q

Methods for confronting drug resistance

A
  • Antibiotics create environments that select for resistant mutants
  • Use only when necessary, take in high concentrations for prescribed course
  • Don’t treat viral infection with antibacterials
  • Give two or more drugs at once (ex. Augmentin = Amoxicillin (cell wall inhibitor) + Clavulanic Acid (target for penicillinase to attach to)
137
Q

Future possible treatments for viral and bacterial infections? Antibiotic, Vaccine, Other?

A
  • New antibiotic sources
  • New antibiotic targets (ex. two component signaling/ quorum sensing)
  • New vaccines (cholera, malaria, HIV)
  • Bacteriophage therapy
138
Q

Viral diseases fall into five categories:

A
  1. Airborne
  2. Arthropod-borne
  3. Direct contact
  4. Food and water-borne
  5. Zoonotic
139
Q

Chickenpox origin and features

A

Caused by the Varicella-Zoster virus in family Herpesviridae

  • Enveloped DNA virus, icosahedral
  • Contracted through inhalation or conjunctiva
  • Spreads in blood, neuronal
  • ~10 days after infection leads to vesicular rash
140
Q

Chickenpox treatment and prevention

A
  • Treatment is largely supportive, no aspirin (linked to Reye’s Syndrome/liver and brain swell), acyclovir - inhibits DNA polymerase only in infected cells
  • Prevention through an attenuated vaccine
141
Q

Vaccines can either be ____ (killed) or ____ (live but avirulent)

A

inactivated, attenuated

142
Q

Inactivated Vaccines

A

Killed using chemicals or heat, induce humoral immune system (B cells)

  • Requires booster
    Ex. Rabies, flu (shot)
143
Q

Attenuated Vaccines

A

Specific genes are inactivated, the virus can reproduce but is weakened

  • Humoral and cell-mediated responses induced
  • May revert into pathogenic type
    Ex. Chickenpox, MMR, flue (intranasal)
144
Q

Herd immunity protects ____ people in a largely vaccinated population to lessen risk of transmission

A

unvaccinated

145
Q

What percent of the population vaccinated is necessary to achieve herd immunity?

A

Depends on pathogen, highly contagious diseases (Pertussis, Measles) require 80-90%

146
Q

Shingles (Zoster)

A

Viral DNA can remain inside nuceli of nerves, sensory neurons (dorsal root ganglion) via latency

  • Immunocompromised state can reactivate virus (same virus)
147
Q

Shingles Vaccines

A

Zostavax - live attenuated vaccine (same as chickenpox w/ high PFUs)

Shingrix - viral glycoprotein vaccine

148
Q

Influenza (Flu)

A

In family Orthomyxoviridae, enveloped, -ssRNA, and segmented genome
* Brings RNA replicase (converts to +ssRNA that is used as mRNA)

149
Q

Influenza replication cycle

A

Attachment - hemagglutinin to sialic acid
Entry - endocytosis
Release - via budding (neuraminidase cleaves)

150
Q

Influenza Antigenic Drift

A

Minor, mutations in viral genes in single strain, based on viral RNA replicase as error-prone, can cause epidemic (sudden increase in disease)

151
Q

Influenza Antigenic Shift

A

Major, different strains (animal/human) infect cell simultaneously, genomes sort to form new strain which humans have no immunity to, can cause pandemic (increase in disease worldwide)

Ex. 1918 Spanish Flue (50 million dead)

152
Q

COVID-19

A

In large family Coronaviridae that infects many animal hosts (7 strains infect humans)

  • SARS-CoV-2 strain, primarily spread via respiratory droplets
  • Enveloped, linear +ssRNA
153
Q

COVID-19 interacts with ____ host receptor to enter cell

A

ACE-2

154
Q

COVID-19 testing methods

A

RT (Reverse Transcriptase)-PCR, serology (antibody), and antigen testing

155
Q

COVID-19 Vaccines

A

Moderna and Pfizer - both mRNA vaccines, encode SARS-CoV-2 spike protein, enclosed in lipid nanoparticles

Johnson & Johnson - Adenovirus (non-replicating) vector with genome edited to encode spike

156
Q

Measles, Mumps, and Rubella

A

RNA viruses, treated with MMR attenuated vaccine

Measles has raised bumps on skin, Mumps leads to salivary gland swelling, and Rubella produces large rashes

157
Q

Arthropod-borne (mosquito vector) diseases include:

A

West Nile Fever
Yellow Fever
Dengue Fever (400 million/yr)
Zika

All are enveloped, icosahedral, and +ssRNA

158
Q

Zika Virus background

A

From Zika forest in Uganda (1947), most people are asymptomatic

Transmitted by mosquito (Flaviviridae), sexually, mother to fetus, blood transfusion

159
Q

Zika symptoms

A

Fever, rash, joint pain, red eyes

Linked to microcephaly in newborns, other brain and birth defects

160
Q

Direct contact viral diseases include:

A

Common cold
Mononucleosis
Warts
AIDS
Ebola

161
Q

Common Cold

A

Caused by Rhinovirus, as well as coronaviruses and adenoviruses

Rhinovirus - +ssRNA, naked, icosahedral, >100 serotypes! –> wash your hands

162
Q

Mononucleosis (Mono)

A

Caused by Epstein-Barr virus (Herpesviridae), transmitted via saliva

  • Initially replicates in throat epithelial cells before infecting B cells (utilizes MHC Class II receptor to enter), becomes latent
  • Can cause cancer (Burkitt’s B cell lymphoma), primarily in Africa, in children with malaria
163
Q

Downey cells

A

Enlarged T cells, responding to infected B cells

164
Q

Warts are caused by ____ ____, a ____ virus with ____ genome

A

Human Papillomavirus, naked, DNA

165
Q

Some strains of HPV are ____ (cervical cancer)

A

oncogenic

166
Q

HPV protein ____ targets ____ human tumor suppressor protein (controls cell cycle and apoptosis) for destruction

A

E6, p53

167
Q

Gardasil is a ____ - ____ ____ (VLP) vaccine with only the ____ of the virus, no genome

A

virus-like particle, capsid

168
Q

Ebola Hemorrhagic Fever

A

Caused by the Ebola virus (Ebola river in DRC), an enveloped, filamentous, RNA virus

*Family Filoviridae
* Viral proteins block interferon, clot blood

169
Q

Ebola is transmitted by

A

direct contact with blood or body fluids of an infected and symptomatic person

Evidence for zoonotic transmission (fruit bats, primates)

170
Q

Gastroenteritis

A

Food and water-borne illness causing inflammation of stomach and intestine

Major causes include Rotavirus and Norovirus (naked RNA viruses, pass via fecal-oral transmission or person to person)

171
Q

Polio (infantile paralysis)

A

Food and water-borne disease caused by Poliovirus (serotype of Enterovirus, RNA genome)

  • Stable in food and water, multiplies in throat and intestine following ingestion
  • Targets motor nerve cells in spinal cord - paralysis
172
Q

Salk vs. Sabin polio vaccines

A

Salk is killed (shot), Sabin is live (oral)

80% of world’s pop. now lives in polio-free areas

173
Q

Rabies is a viral, ____ disease caused by Rabies virus, a ____ shaped, enveloped virus with a ____ genome

A

zoonotic, bullet, RNA

174
Q

Rabies Transmission Pathway

A
  • First multiplies in animal salivary glands (foaming at the mouth)
  • Animal bites person, where virus has a tropism for muscle and neuronal cells, spreads to brain via CNS - causing paralysis and death
175
Q

Since incubation of rabies is slow (2-16 weeks), pre-exposure vaccine (____ virus) can also be used ____-____

A

killed, post-exposure

176
Q

Viruses move by hijacking the neurons’ own ____ pathways, moving along ____ tracks and using ____ and ____ motor proteins

A

transport, microtubule, dynein and kinesin

177
Q

Diphtheria

A

Caused by Corynebacterium diphtheriae via airborne transmission (specifically tox gene, found on a prophage)

  • AB toxin produced, targets EF-2 used in protein synthesis (ADP-ribosyl transferase)
  • Causes destruction of cardiac, kidney, and nervous tissue
178
Q

Tuberculosis (TB) is caused by ____, that are ____ and ____ in the lung (not killed due to protective ____ acids in membrane), forms ____

A

Mycobacterium tuberculosis, inhaled and phagocytosed by macrophages, mycolic acids), tubercles

179
Q

In response to M. tuberculosis infection of macrophages, host forms ____, in which the bacteria become ____

A

tubercles (bacteria, macrophages, T cells, and proteins), latent

180
Q

____% of the world’s population have latent TB, which is ____ ____

A

25, not infectious

181
Q

Tubercles can liquify, spreading bacteria to blood and organs, becomes ____

A

transmissable

182
Q

Mantoux Tuberculin Skin Test (TST)

A

Standard method of determining whether a person has had TB or been exposed to M. tuberculosis

  • Bacterial proteins injected in forearm, immune response measured in mm (48-72hrs later)
  • Antigen presenting macrophages attract and activate sensitized memory T cells
183
Q

What individual tried to develop tuberculin as a vaccine?

A

Robert Koch

184
Q

Bacille Calmette-Geurin (BCG) TB Vaccine

A

Live, avirulent M. bovis, not recommended in US

185
Q

TB Diagnosis

A

Diagnosed based on bloody sputum symptom, chest x-ray (tubercle identification in lung), acid fast staining, or cell culture

186
Q

TB Antimicrobial Therapy

A

Rifampin (targets RNA polymerase, transcription) and Isoniazid (inhibits mycolic acid synthesis to prevent protection from phagolysosome) – Daily for 6-9 months

187
Q

Antibiotic resistance emerging in TB strains such as

A

Multidrug resistance (MDR) and extensive drug resistance (XDR) TB

188
Q

Streptococcal diseases/infections, such as ____ (skin), throat, lung (____), and ear (____ ____) are caused by ____ ____ (group A, beta hemolytic) or S. pneumoniae

A

impetigo, pneumonia, otitis media, Streptococcus pyogenes

189
Q

Streptococcal disease diagnosis, treatment, and prevention

A
  • Diagnosed via culture and strep test (uses labeled Abs to detect cell wall carbohydrates)
  • Treated with penicillin (beta lactam, targets peptidoglycan) and erythromycin (targets protein synthesis)
  • Prevented using pneumococcal vaccine (Prevnar), bacterium polysaccharide based
190
Q

Streptococcal virulence factors that promote adherence (two of them)

A

Capsule and M protein

191
Q

Antibody to M protein (strep virulence factor) can cross react with heart tissue, causing ____ ____ (autoimmune disease)

A

Rheumatic Fever

192
Q

Group A streptococci can cause ____ ____, some strains make tissue-destroying proteases resulting in ____ ____ by “flesh-eating bacteria”

A

invasive infections, necrotizing fasciitis

193
Q

Streptococcus is also associated with ____ ____ (dental)

A

tooth decay (Streptococcus mutans, part of dental plaque (biofilm))

Fermentation of sugars –> acid –> enamel decay

194
Q

Whooping Cough (Pertussis) is caused by Gram - bacteria ____ ____, which colonizes the ciliated cells of the respiratory tract

A

Bordetella pertussis

195
Q

Stages of Pertussis

A

Stage 1: Cold-like symptoms
Stage 2: Prolonged cough followed by inspiratory gasp or whoop

196
Q

Bordetella pertussis virulence factors include:

A

Pili (adherence), siderophores (acquire iron), and Pertussis toxin (AB toxin, same MOA as cholera toxin)

197
Q

B. pertussis Vaccination and Treatment

A

Subunit Vaccine DTP (1940) - DT (deactivated toxoid proteins, elicit immune response), P (killed Bordetella bacteria)

DTaP (current) - DT (deactivated toxoid proteins - elicit immune response), aP (acellular, toxoid, and other protein antigens (purified componentes))

  • Tdap booster also available
198
Q

Meningitis

A

Inflammation of brain and spinal cord meninges (membranes)

  • Caused by bacteria, viruses, and fungi
199
Q

Bacteria that cause meningitis include

A

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae

200
Q

Neisseria meningitidis

A
  • Gram - diplococcus, leading cause of meningococcal disease in children, young adults
  • Spread person to person via respiratory secretions
  • Can cross mucosal barrier into blood
  • Serogroups - groups of strains with common surface antigens (A, B, C, Y, and W)
201
Q

N. meningitidis virulence factors include:

A

Pili, capsules, endotoxin

202
Q

N. meningitidis meningitis diagnosis, treatment, and prevention

A
  • Symptoms include sore throat, vomiting, confusion, stiffness in neck, rash, diagnosed by Gram stain of spinal fluid, bacterial culture
  • Antibiotics (cell wall. protein synthesis inhibitors)
  • Prevention includes the MCV4 vaccine (based on capsular polysaccharide, protects against A, C, Y, and W serogroups) and the Bexsero vacccine (protects agains group B, which differs in outer membrane protein)
203
Q

The Plague

A

Caused by Yersinia pestis (Gram -), results in large Buboes (swollen black/purple lymph nodes)

204
Q

The Plague comes in two forms, the ____ (flea) and the ____ (person to person)

A

Bubonic, Pneumonic (flu-like, almost 100% fatal if not treated early, category A bioweapons agent)

205
Q

Yersinia pestis can inject toxins into human cells (macrophages), which ____

A

block actin polymerization, inhibits phagocytosis

206
Q

Only ____ cases of human plague in US each year (usually all bubonic), concentrated in west where animals such as ____ can be infected

A

7, rodents and rabbits

207
Q

Lyme Disease

A

Most commonly reported (~30,000 cases/yr) tick-borne disease in US, caused by spirochete Borrelia burgdorferi, using deer tick (Ixodes genus) as a vector

208
Q

Stages of Lyme Disease

A
  1. Localized (7-10 days) - Bullseye rash (erythema migrans), flu-like symptoms, treatable with doxycycline and penicillins
  2. Disseminated (weeks/months) - Muscle pain, arthritis, antibody to Borrelia proteins may cross react with human MHC
  3. Late (years) - Nervous system involvement
209
Q

Direct contact bacterial diseases include:

A

anthrax (also airborne/zoonotic routes of transmission), staphylococcal disease

210
Q

Anthrax is caused by ____ with virulence factors ____ and ____, the genes encoding which are on separate plasmids

A

Bacillus anthracis (spores), capsule, toxin (AB but in 3 parts, targeting macrophages and leading to cell death)

211
Q

Forms of Anthrax

A

Cutaneous - bacterium enters via cut or abrasion (“wool-sorter’s disease)

Pulmonary - spores inhaled, enter macrophages in lung and germinate, producing toxin within macrophages that kills them. Active bacteria spread, fatal if they reach the bloodstream

212
Q

Early treatment of anthrax is critical using ____

A

ciprofloxacin (inhibits DNA gyrase)

Spores used in bioterrorism in 2001 causing 17 cases of pulmonary anthrax, 5 deaths

213
Q

Staphylococcal diseases are caused by two major species, ____ and ____, which are differentiated using the ____ test

A

S. aureus (invasive, virulent), S. epidermidis (less invasive and virulent), coagulase (S. aureus +, S. epidermidis -)

214
Q

Staphylococcal diseases include:

A

Boils, carbuncles, toxic shock syndrome, food poisoning

215
Q

Staphylococcus aureus has an arsenal of virulence factors, including:

A
  • Superantigens (TSST-1)
  • Enterotoxins (food poisoning)
  • Capsules
  • IgA protease
  • Coagulase
  • DNase

Virulence genes often controlled by quorum sensing and 2-component systems

216
Q

Food and water-borne bacterial diseases such as ____, ____, ____, ____, and ____ are generally prevented and controlled by ____ measures, ____, and ____ therapy

A

Cholera, Listeriosis, Botulism, E. coli, and S. typhimurium infections

sanitation measures, antitoxins (preformed Abs), and antibiotic therapy

217
Q

E. coli O157:H7, or Enterohemorrhagic E. coli (EHEC), have an incredibly low ID of < ____, carried by cattle and swine and produce a ____ toxin (AB toxin)

A

100, Shiga

218
Q

EHEC Shiga toxin

A

An AB toxin that binds glycolipid receptors on kidney and intestinal cells and enters, cleaves human rRNA to block protein synthesis

  • Infection may cause Hemolytic Uremic Syndrome (HUS, kidney failure)
  • Toxin genes are from a prophage
  • Certain stressors on bacteria can activate the prophage (ex. antibiotics)
219
Q

Foods such as kimchi and sauerkraut are made using ____, while natto is made using ____

A

Leuconostoc, Bacillus natto

220
Q

Major fermentations used in food production include:

A

lactic, propionic, and ethanolic fermentative pathways

221
Q

Yogurt production via lactic acid bacteria begins with ____ of ____ and ____ bacteria, which hydrolyze the ____ in milk to form ____, which is then fermented into lactic acid

A

Lactobacillus, Streptococcus, lactose, glucose

222
Q

In yogurt production, contamination with ____ is a major concern

A

bacteriophages

223
Q

Cheese is produced by adding a ____ starter and ____ enzyme to promote coagulation, and ____ involves adding more microbes (____ for Swiss cheese, ____ for Blue and Brie cheeses)

A

Lactobacillus, renin, ripening, Propionibacterium, Penicillium

224
Q

Probiotics

A

Microbes added to diet to improve health (ex. Lactobacillus, Bifidobacterium)

225
Q

Probiotic Benefits

A

Vitamin production, improved digestion, pathogen inhibition, scientific evidence not well established

226
Q

Prebiotics

A

Compounds (fiber) that promote growth of beneficial microbes

227
Q

Kombucha

A

Fermented tea using bacteria (Bacillus) and Yeast (Saccharomyces) in SCOBY (Symbiotic Colony of Bacteria and Yeast)

228
Q

Beer is made via ____ and ____, plant enzymes breakdown complex starches and proteins in barley, hops are added for antibacterial and flavor benefits

A

malting and mashing

229
Q

Ginger Beer

A

Non-alcoholic, fermentation of ginger spice and sugar with Saccharomyces and Lactobacillus

230
Q

Wine

A

Grape juice (must) with sugars, fermented with yeast (Saccharomyces) via ethanolic pathway

231
Q

Biofuels from biological material are formed with ____ and ____ used to ferment the material and form ethanol biofuel

A

bacteria, yeast

232
Q

Antibiotics are ____ ____, not required for growth and made by microbes under limiting conditions, therefore formed in the ____ phase of the growth curve

A

secondary metabolites, stationary

233
Q

NF(Kappa)B

A

Nuclear Factor Kappa B

Protein transcription factor responsible for regulating genes responsible for innate immunity function

MICB 3301 Lecture (5 decks)

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