Exam 4 Flashcards
1
Q
Adaptive immunity has two branches: ____ and ____-____ immunity
A
humoral, cell-mediated
2
Q
Humoral Immunity
A
- Involves antibodies made by B cells
- Defends against extracellular pathogens
3
Q
Cell-Mediated Immunity
A
- Involves T cells and MHC’s
- Largely defends against intracellular pathogens
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)
5
Q
Antibodies bind antigens to ____ or ____ them
A
neutralize or opsonize
6
Q
Antibody classes include:
A
- IgG
- IgA
- IgM
- IgE
- IgD
7
Q
IgM
A
First responder Ig after antigen exposure
* Pentamer
* Plasma cells that produce them can switch and produce another Ig class
8
Q
IgG
A
Major Ig in blood
* Monomer
* Can cross placenta and activate complement
9
Q
IgA
A
Major Ig in secretions (ex. saliva, breast milk, tears)
* Dimer
* Defends mucosal surfaces
10
Q
IgE
A
Ig in allergic reactions and autoimmune disease
* Monomer
11
Q
IgD
A
Ig found on B cell surfaces, play a role in signaling
* Monomer
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
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
14
Q
VDJ Recombination
A
Rearrangement of antibody gene segments to generate antibody diversity
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
16
Q
Tolerance
A
Removal of self-reactive B cells
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
18
Q
Adaptive immunity has ____ and ____
A
specificity and memory
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
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)
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
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
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
24
Q
The MHC is a ____ encoding cell surface proteins for ____ recognition (Human Leukocyte Antigen complex)
A
collection of genes, self/nonself
25
Human Leukocyte Antigen (HLA) Complex
* 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**)
26
Cell surface proteins encoded by MHC are designated as ____ and ____
* Class I MHC (on all nucleated cells - not erythrocytes
* Class II MHC (only on antigen-presentic cells - dendritic cells, macrophages, B cells)
27
MHC I and II inform the immune system of the ____ by binding and presenting foreign peptides
presence of nonself
28
Class I MHC
* On all nucleated cells
* Present peptides that originate in cytoplasm from intracellular pathogens
* Present peptides to CD8+ (cytotoxic T cells)
29
Class II MHC
* Only found on antigen-presenting cells
* Present peptides from extracellular pathogens taken up by phagocytosis
* Present peptides to CD4+ (helper T cells)
30
Pathogen
Organism that produces disease
31
Opportunistic Pathogen
Infects host with compromised immune system (ex. *Pseudomonas aeruginosa*)
32
Carrier
Infected individual with no observable symptoms, potential source of infection
33
Zoonoses
Diseases transmitted to humans from animals
34
Vectors
Organisms (usually insects) that transmit disease to humans (ex. mosquitoes, ticks, fleas)
35
Pathogenicity
Ability to produce disease
36
Virulence
Degree of pathogenicity
37
Genetic, biochemical, structural features that contribute to virulence (ex. capsule, pigment, toxin)
Virulence Factors (determinants)
38
Latency
Pathogen stops reproducing (dormant), can become active again (ex. varicella-zoster virus, causative agent of chicken pox and shingles)
39
Infectious Dose 50 (ID50)
Number of pathogens required to cause clinical disease in hosts
(increased virulence indicates lower ID50)
40
Pathogens, virulence, and pathogenicity are tested by:
* Model systems - animal models, cell culture
* Epidemiology - examine incidence, distribution, and control of disease
* Human studies - clinical trials, case studies
41
Pathogen ____ and ____ properties initiate disease
adherence and invasion
(allow for evasion of immune response)
42
____ and ____ spike proteins mediate viral attachment
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)
43
Viruses can spread via ____, ____, or ____ systems
blood, neuronal, or lymphatic
44
Syncytia
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))
45
Viruses can evade both innate and adaptive immune responses by
Innate - block complement and interferon (cytokine) production
Adaptive - block antigen processing and presentation, evade Abs through **antigenic variation**
46
Antigenic Variation
Amino acid changes in virion spikes, common in RNA viruses (ex. SARS-CoV-2 Omicron subvariants BA.2,3,4,5)
47
Bacterial attachment occurs via:
* Pili
* Capsules (ex. *S. pneumoniae*, *H. influenzae*, *N. meningitidis*, and sometimes *P. aeruginosa*)
48
Mucoid Strains
Strains of *Pseudomonas aeruginosa* that make capsules, are opportunistic pathogens in burn victims and cystic fibrosis patients
49
Bacterial virulence determinants:
* Coagulase
* Streptokinase
* IgA Proteases
* Hemolysins
* Siderophores
* DNase
All can lead to spread of bacteria to bloodstream (**bacteremia**)
50
Coagulase
Clots fibrinogen in plasma, clot protects pathogens
51
Streptokinase
Activates **plasmin**, digests **fibrin** clots, pathogen moves from clotted area (used in medical procedures to remove blood clots therapeutically)
52
IgA Proteases
Destroy antibody
53
Hemolysins
Digest erythrocytes, releases iron
54
Siderophores
Released by microbes, bind available iron needed by the host
55
DNase
Degrades extracellular DNA used in Neutrophil Extracellular Traps (NETs), lowers viscosity of secretions, leading to spread of bacteria
56
Neutrophil Extracellular Traps (NETs)
Comprised of DNA and antimicrobial proteins and enzymes
* Traps pathogens
* **DNase enzyme** (virulence factor) contributes to bacteria escaping NET
57
Bacteria can evade both innate and adaptive immune responses
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
58
Bacterial intracellular pathogens include:
* *Chlamydia*
* *Rickettsia*
* *Mycobacterium tuberculosis*
* *Salmonella*
* *Listeria*
59
*Listeria monocytogenes*
* Gram +, food-borne pathogen found in produce, raw (unpasteurized) milk, cheese, deli meat
* Psychrophile
* Can cross placenta
* Movement via **actin tail**
60
Actin Tail
*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
61
Encapsulated, causative agent of Otitis Media (infection of middle ear) and bacterial meningitis
*Streptococcus pneumoniae*
62
*Staphylococcus* and *Enterococcus* are both causative agents of ____ infections (endocarditis)
heart valve
63
*Streptococcus mutans* (et. al)
Dental plaque biofilms
64
Bacteria can evade innate and adaptive immunity by forming biofilms, rendering antibiotics ineffective and leading to ____ ____
"frustrated phagocyte"
65
Toxins
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)
66
Exotoxin Types
* Superantigens
* AB (A = toxin, B = cell targeting)
* Membrane-disrupting
67
Membrane-disrupting exotoxins (such as ____ and ____) function by ____
forming pores, causing swelling/lysis
(ex. leukocidins, hemolysins)
68
Superantigens
* 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
69
AB Exotoxins
* 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)
70
Diphtheria toxin (*Corynebacterium diphtheriae*)
* 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)
71
Many AB toxins are also ____ ____ specific (ex. cholera toxin, botulinum toxin, tetanospasmin)
host site
72
Cholera toxin
* Produced by *Vibrio cholerae*
* Enterotoxin (intestinal tract)
* ADP-ribosyl transferase
73
Botulinum Toxin
* Produced by *Clostridium botulinum*
* Neurotoxin (brain/CNS)
* Blocks release of acetylcholine at neuromuscular junctions, resulting in flaccid paralysis (ex. Botox)
74
Exotoxins are ____ proteins
antigenic
75
Antibodies can ____ toxicity of the toxin (antitoxin)
neutralize
76
Exotoxins are generally unstable, can lose ____ but remain ____
toxicity, antigenic
(ex. toxoid)
77
Toxoid
Inactivated toxin that can still illicit an immune response (bases of toxoid vaccines, ex. DTaP)
78
Endotoxin component of Gram - Lipopolysaccharide (LPS) and 2 things about it
Lipid A
*heat stable
*toxic in nanogram amounts but weakly immunogenic
79
During infection, bacterial LPS binds TLR4, activates NF(Kappa)B to transcribe genes for cytokine, leading to:
fever, inflammation, and blood vessel leakage (hypotension), **Septic Shock**
80
Sepsis
Systemic response to microbial infection, elevated temperature, heart, and respiratory rate, leukocyte count
81
Shock
Sepsis with hypotension (low bp)
82
Septic shock causes ____ (red blotches on skin caused by hypotension), and in severe cases ____ (shut off blood to extremities)
petechiae, gangrene
83
Cidal
Kills microbes
84
Static
Inhibits microbial growth
85
Sterilization
Processes by which all living cells, spores, and viruses are destroyed or removed
86
Disinfection
Reduction of microbial population, destruction of pathogens
87
Sanitization
Reduction of microbial contamination to levels safe by public health standards
88
Antiseptic
Chemical agent applied to tissue to prevent infection by inhibition or killing
89
Microbial control methods include:
mechanical removal (ex. filtration), chemical reagents (ex. gases), and physical agents (ex. radiation and heat)
90
Radiation microbe control
* UV - can sterilize, but poorly penetrates, mostly used to disinfect
* Ionizing (X, gamma ray) - penetrates, sterilizes
91
Heat microbe control
Moist heat more effective than dry
* Steam under pressure (autoclave) sterilizes after 15 mins at 121 C under 15lbs/sq in of pressure
92
Pasteurization
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)
93
Antimicrobial agents are used to ____
treat disease, destroy pathogenic microbes, or inhibit growth
* Most are antibiotics (microbial products - ex. Penicillin from *Penicillium*)
94
Streptomyces requires over ____ enzymatic reactions to make ____
70, tetracycline
95
Paul Ehrlich
(1904) Hypothesized **selective toxicity** of drugs (selectively targets pathogen, non-toxic to human taking drug)
96
Alexander Fleming
(1928) Accidentally rediscovered penicillin
97
Purified penicillin, injected into mice infected with *Staphylococcus*, mice survived
(1940) Florey, Chain, and Heatley
98
Cultured over 10,000 strains of soil bacteria, discovered streptomycin
(1944) Selman Waksman
99
Considerations for developing a clinically useful antibiotic
* $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
Pseudomembranous colitis
Prolonged antibiotic use and destruction of microflora, results in *Clostridium difficile* infection - *C. diff* (anaerobic, spore-forming, toxin-producing bacillus)
101
Targets of antimicrobial agents:
* Cell wall
* Plasma membrane
* Neucleic acid synthesis
* Metabolic enzymes
* Protein synthesis
102
Cell wall synthesis inhibitors
* Penicillins (b-lactams)
* Cephalosporins (b-lactams)
* Vancomycin
* Bacitracin
103
Penicillins
* 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
Bacterial enzymes called ____ catalyze the transpeptidation reaction that cross-links peptidoglycan
Penicillin Binding Proteins (PBPs)
105
Penicillins and cephalosporins ____ PBPs
inhibit bacterial (peptidoglycan synthesis stops, osmotic lysis occurs)
106
Vancomycin
Binds terminal D-ala, blocks transpeptidation
107
Bacitracin ____ the carrier of the peptidoglycan subunit responsible for transporting it across the plasma membrane to the cell wall
blocks
(bacitracin is often used topically as Neosporin)
108
Polymyxins - Plasma Membrane Inhibitor
Cidal, narrow Gram -
Ex. Colistin (binds outer membrane LPS)
109
Antifungal agents often target ____ ____
plasma membrane (treat *Candida* yeast infections, athletes foot)
110
Fluconozole and Miconazole
Inhibit ergosterol synthesis (ex. Micatin, Monistat brands)
111
Nystatin and Amphotericin
Bind ergosterol
112
Nikkomycin
Chitin synthesis inhibitor
113
Metabolic Enzyme Inhibitors
Metabolic pathways are catalyzed by enzymes (bind substrates to lower Ea)
Ex. Sulfonamides and Trimethoprim
114
Sulfonamides and Trimethoprim
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
Nucleic Acid Inhibitors
Drugs that inhibit DNA replication (ex. Quinolones, Nalidixic Acid, Ciprofloxacin) and transcription (ex. Rifampin)
116
Quinolones
Nucleic acid inhibitor that targets DNA replication
* Synthetic, cidal
* Inhibits bacterial **DNA gyrase**
117
Rifampin
Nucleic acid inhibitor that targets transcription
* Broad spectrum, cidal
* Inhibits **RNA polymerase**
118
Protein synthesis inhibitors are ____ spectrum antibiotics, take advantage of differences between eukaryotic and prokaryotic ____ and ____ synthesis machinery
broad, ribosomes, protein
119
Aminoglycosides
* Cidal
* Binds to 30S component of ribosome, causing misreading of mRNA codons
Ex. Streptomycin, Kanamycin
120
Tetracyclines
* Static
* Binds 30S component block tRNA and amino acid binding to A site
* Low toxicity, widely prescribed
Ex. Doxycycline (Lyme disease, pneumonia, acne)
121
Macrolides
* Static
* Binds 23S rRNA of 50S ribosomal subunit, blocking peptide bond formation
Ex. Erythromycin (Whooping cough), Azithromycin (*Chlamydia*, Z-Pak)
122
Chloramphenicol
* Same mode of action as Macrolides (inhibits peptide bond formation)
* **Toxic**, only used in life-threatening situations
123
Why are antiviral drugs difficult to develop?
Because viruses rely on the biochemical processes of the host cell to reproduce
124
Acyclovir
Antiviral drug that inhibits DNA polymerase of herpesvirus
125
Influenza antiviral drugs
Xofluza - blocks RNA replicase inhibiting replication and translation of viral RNA
Tamiflu - blocks neuraminidase
126
For anti-HIV drugs, the major goal of antiretroviral therapy (ART) is to reduce the ____ ____, not to cure
viral load
127
Anti-HIV Drugs:
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
PrEP Anti-HIV Drugs
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
Paxlovid
COVID-19 treatment
Two medications that target SARS-CoV-2 protease (ritonavir and nirmatrelvir)
130
Chloroquine
Treatment for malaria by blocking heme (toxic) polymerization
131
Malarone
Treatment for malaria by blocking e- transport, pyrimidine synthesis
132
Metronidazole (Flagyl)
Treatment for *Giardia* and some bacteria (*Helicobacter*), enters pathogen, activates, and nicks its DNA
* Prodrug - harmless until activated
133
Vancomycin Resistant *Enterococcus* (VRE)
*vanA* gene - encodes enzyme that replaces terminal D-alanine with D-lactate (vancomycin rendered ineffective)
134
Methicillin Resistant *Staphylococcus aureus* (MRSA)
*mecA* gene - encodes Penicillin Binding Protein (PBP) resistant to penicillin
Resistant to numerous antibiotics
135
One mechanism of drug resistance is the transfer of an ____ ____ by transformation/conjugation
R plasmid
136
Methods for confronting drug resistance
* 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
Future possible treatments for viral and bacterial infections? Antibiotic, Vaccine, Other?
* New antibiotic sources
* New antibiotic targets (ex. two component signaling/ quorum sensing)
* New vaccines (cholera, malaria, HIV)
* Bacteriophage therapy
138
Viral diseases fall into five categories:
1. Airborne
2. Arthropod-borne
3. Direct contact
4. Food and water-borne
5. Zoonotic
139
Chickenpox origin and features
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
Chickenpox treatment and prevention
* 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
Vaccines can either be ____ (killed) or ____ (live but avirulent)
inactivated, attenuated
142
Inactivated Vaccines
Killed using chemicals or heat, induce **humoral** immune system (B cells)
* Requires booster
Ex. Rabies, flu (shot)
143
Attenuated Vaccines
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
Herd immunity protects ____ people in a largely vaccinated population to lessen risk of transmission
unvaccinated
145
What percent of the population vaccinated is necessary to achieve herd immunity?
Depends on pathogen, highly contagious diseases (Pertussis, Measles) require 80-90%
146
Shingles (Zoster)
Viral DNA can remain inside nuceli of nerves, sensory neurons (dorsal root ganglion) via **latency**
* Immunocompromised state can reactivate virus (same virus)
147
Shingles Vaccines
Zostavax - live attenuated vaccine (same as chickenpox w/ high PFUs)
Shingrix - viral glycoprotein vaccine
148
Influenza (Flu)
In family *Orthomyxoviridae*, enveloped, -ssRNA, and segmented genome
* Brings RNA replicase (converts to +ssRNA that is used as mRNA)
149
Influenza replication cycle
Attachment - hemagglutinin to **sialic acid**
Entry - endocytosis
Release - via budding (neuraminidase cleaves)
150
Influenza Antigenic Drift
Minor, mutations in viral genes in single strain, based on viral RNA replicase as error-prone, can cause **epidemic** (sudden increase in disease)
151
Influenza Antigenic Shift
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
COVID-19
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
COVID-19 interacts with ____ host receptor to enter cell
ACE-2
154
COVID-19 testing methods
RT (Reverse Transcriptase)-PCR, serology (antibody), and antigen testing
155
COVID-19 Vaccines
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
Measles, Mumps, and Rubella
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
Arthropod-borne (mosquito vector) diseases include:
West Nile Fever
Yellow Fever
Dengue Fever (400 million/yr)
Zika
All are enveloped, icosahedral, and +ssRNA
158
Zika Virus background
From Zika forest in Uganda (1947), most people are asymptomatic
Transmitted by mosquito (*Flaviviridae*), sexually, mother to fetus, blood transfusion
159
Zika symptoms
Fever, rash, joint pain, red eyes
Linked to microcephaly in newborns, other brain and birth defects
160
Direct contact viral diseases include:
Common cold
Mononucleosis
Warts
AIDS
Ebola
161
Common Cold
Caused by **Rhinovirus**, as well as coronaviruses and adenoviruses
Rhinovirus - +ssRNA, naked, icosahedral, >100 serotypes! --> wash your hands
162
Mononucleosis (Mono)
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
Downey cells
Enlarged T cells, responding to infected B cells
164
Warts are caused by ____ ____, a ____ virus with ____ genome
Human Papillomavirus, naked, DNA
165
Some strains of HPV are ____ (cervical cancer)
oncogenic
166
HPV protein ____ targets ____ human tumor suppressor protein (controls cell cycle and apoptosis) for destruction
E6, p53
167
Gardasil is a ____ - ____ ____ (VLP) vaccine with only the ____ of the virus, no genome
virus-like particle, capsid
168
Ebola Hemorrhagic Fever
Caused by the Ebola virus (Ebola river in DRC), an enveloped, filamentous, RNA virus
*Family *Filoviridae*
* Viral proteins block interferon, clot blood
169
Ebola is transmitted by
direct contact with blood or body fluids of an infected **and** symptomatic person
Evidence for zoonotic transmission (fruit bats, primates)
170
Gastroenteritis
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
Polio (infantile paralysis)
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
Salk vs. Sabin polio vaccines
Salk is killed (shot), Sabin is live (oral)
80% of world's pop. now lives in polio-free areas
173
Rabies is a viral, ____ disease caused by Rabies virus, a ____ shaped, enveloped virus with a ____ genome
zoonotic, bullet, RNA
174
Rabies Transmission Pathway
* 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
Since incubation of rabies is slow (2-16 weeks), pre-exposure vaccine (____ virus) can also be used ____-____
killed, post-exposure
176
Viruses move by hijacking the neurons' own ____ pathways, moving along ____ tracks and using ____ and ____ motor proteins
transport, microtubule, dynein and kinesin
177
Diphtheria
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
Tuberculosis (TB) is caused by ____, that are ____ and ____ in the lung (not killed due to protective ____ acids in membrane), forms ____
*Mycobacterium tuberculosis*, inhaled and phagocytosed by macrophages, mycolic acids), tubercles
179
In response to *M. tuberculosis* infection of macrophages, host forms ____, in which the bacteria become ____
tubercles (bacteria, macrophages, T cells, and proteins), latent
180
____% of the world's population have latent TB, which is ____ ____
25, not infectious
181
Tubercles can liquify, spreading bacteria to blood and organs, becomes ____
transmissable
182
Mantoux Tuberculin Skin Test (TST)
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
What individual tried to develop tuberculin as a vaccine?
Robert Koch
184
Bacille Calmette-Geurin (BCG) TB Vaccine
Live, avirulent *M. bovis*, not recommended in US
185
TB Diagnosis
Diagnosed based on bloody sputum symptom, chest x-ray (tubercle identification in lung), acid fast staining, or cell culture
186
TB Antimicrobial Therapy
Rifampin (targets RNA polymerase, transcription) **and** Isoniazid (inhibits mycolic acid synthesis to prevent protection from phagolysosome) -- Daily for **6-9 months**
187
Antibiotic resistance emerging in TB strains such as
Multidrug resistance (MDR) and extensive drug resistance (XDR) TB
188
Streptococcal diseases/infections, such as ____ (skin), throat, lung (____), and ear (____ ____) are caused by *____ ____* (group A, beta hemolytic) or *S. pneumoniae*
impetigo, pneumonia, otitis media, *Streptococcus pyogenes*
189
Streptococcal disease diagnosis, treatment, and prevention
* 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
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Streptococcal virulence factors that promote adherence (two of them)
Capsule and M protein
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Antibody to M protein (strep virulence factor) can cross react with heart tissue, causing ____ ____ (autoimmune disease)
Rheumatic Fever
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Group A streptococci can cause ____ ____, some strains make tissue-destroying proteases resulting in ____ ____ by "flesh-eating bacteria"
invasive infections, necrotizing fasciitis
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Streptococcus is also associated with ____ ____ (dental)
tooth decay (*Streptococcus mutans*, part of dental plaque (biofilm))
Fermentation of sugars --> acid --> enamel decay
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Whooping Cough (Pertussis) is caused by Gram - bacteria *____ ____*, which colonizes the ciliated cells of the respiratory tract
*Bordetella pertussis*
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Stages of Pertussis
Stage 1: Cold-like symptoms
Stage 2: Prolonged cough followed by inspiratory gasp or whoop
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*Bordetella pertussis* virulence factors include:
Pili (adherence), siderophores (acquire iron), and Pertussis toxin (AB toxin, same MOA as cholera toxin)
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*B. pertussis* Vaccination and Treatment
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
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Meningitis
Inflammation of brain and spinal cord meninges (membranes)
* Caused by bacteria, viruses, and fungi
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Bacteria that cause meningitis include
*Neisseria meningitidis*, *Haemophilus influenzae*, and *Streptococcus pneumoniae*
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*Neisseria meningitidis*
* **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)
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*N. meningitidis* virulence factors include:
Pili, capsules, endotoxin
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*N. meningitidis* meningitis diagnosis, treatment, and prevention
* 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)
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The Plague
Caused by *Yersinia pestis* (Gram -), results in large Buboes (swollen black/purple lymph nodes)
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The Plague comes in two forms, the ____ (flea) and the ____ (person to person)
Bubonic, Pneumonic (flu-like, almost 100% fatal if not treated early, category A bioweapons agent)
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*Yersinia pestis* can inject toxins into human cells (macrophages), which ____
block actin polymerization, inhibits phagocytosis
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Only ____ cases of human plague in US each year (usually all bubonic), concentrated in west where animals such as ____ can be infected
7, rodents and rabbits
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Lyme Disease
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
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Stages of Lyme Disease
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
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Direct contact bacterial diseases include:
anthrax (also airborne/zoonotic routes of transmission), staphylococcal disease
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Anthrax is caused by ____ with virulence factors ____ and ____, the genes encoding which are on separate plasmids
*Bacillus anthracis* (spores), capsule, toxin (AB but in 3 parts, targeting macrophages and leading to cell death)
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Forms of Anthrax
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
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Early treatment of anthrax is critical using ____
ciprofloxacin (inhibits DNA gyrase)
Spores used in bioterrorism in 2001 causing 17 cases of pulmonary anthrax, 5 deaths
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Staphylococcal diseases are caused by two major species, ____ and ____, which are differentiated using the ____ test
*S. aureus* (invasive, virulent), *S. epidermidis* (less invasive and virulent), coagulase (*S. aureus* +, *S. epidermidis* -)
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Staphylococcal diseases include:
Boils, carbuncles, toxic shock syndrome, food poisoning
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*Staphylococcus aureus* has an arsenal of virulence factors, including:
* Superantigens (TSST-1)
* Enterotoxins (food poisoning)
* Capsules
* IgA protease
* Coagulase
* DNase
Virulence genes often controlled by quorum sensing and 2-component systems
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Food and water-borne bacterial diseases such as ____, ____, ____, ____, and ____ are generally prevented and controlled by ____ measures, ____, and ____ therapy
Cholera, Listeriosis, Botulism, *E. coli*, and *S. typhimurium* infections
sanitation measures, antitoxins (preformed Abs), and antibiotic therapy
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*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)
100, Shiga
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EHEC Shiga toxin
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)
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Foods such as kimchi and sauerkraut are made using ____, while natto is made using ____
*Leuconostoc*, *Bacillus natto*
220
Major fermentations used in food production include:
lactic, propionic, and ethanolic fermentative pathways
221
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
*Lactobacillus*, *Streptococcus*, lactose, glucose
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In yogurt production, contamination with ____ is a major concern
bacteriophages
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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)
*Lactobacillus*, renin, ripening, *Propionibacterium*, *Penicillium*
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Probiotics
Microbes added to diet to improve health (ex. *Lactobacillus*, *Bifidobacterium*)
225
Probiotic Benefits
Vitamin production, improved digestion, pathogen inhibition, scientific evidence not well established
226
Prebiotics
Compounds (fiber) that promote growth of beneficial microbes
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Kombucha
Fermented tea using bacteria (*Bacillus*) and Yeast (*Saccharomyces*) in SCOBY (Symbiotic Colony of Bacteria and Yeast)
228
Beer is made via ____ and ____, plant enzymes breakdown complex starches and proteins in barley, hops are added for antibacterial and flavor benefits
malting and mashing
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Ginger Beer
Non-alcoholic, fermentation of ginger spice and sugar with *Saccharomyces* and *Lactobacillus*
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Wine
Grape juice (must) with sugars, fermented with yeast (*Saccharomyces*) via ethanolic pathway
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Biofuels from biological material are formed with ____ and ____ used to ferment the material and form ethanol biofuel
bacteria, yeast
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Antibiotics are ____ ____, not required for growth and made by microbes under limiting conditions, therefore formed in the ____ phase of the growth curve
secondary metabolites, **stationary**
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NF(Kappa)B
Nuclear Factor Kappa B
Protein transcription factor responsible for regulating genes responsible for innate immunity function
