Final (cumulative) Flashcards
(349 cards)
1
Q
How many microbial species can be found in humans overall? How many per person?
A
10,000 symbiotic species identified and 1000 per individual
2
Q
About what percentage of human microbiota live in the gut alone?
A
95%
3
Q
What does it mean that human microbes are not homogenous?
A
They all live in different microhabitats that differ in temperature, pH, moisture, [salt], etc
4
Q
Compare microbiota and microbiome
A
Microbiota refers to the microbes in a microhabitat, whereas the microbiome refers to the entire collection of microbiota in a system (human)
5
Q
True/False? The human microbiome is made up of known microbial species due to our extensive knowledge on their culture conditions (we are able to culture them)
A
False. Many are unculturable and thus cannot be characterized
6
Q
What is the dominant microbial species in/on human skin?
A
Propionibacterium
7
Q
What is the dominant microbial species in/on human saliva?
A
Streptococcus
8
Q
What is the dominant microbial species in/on the human urogenital tract?
A
Lactobacillus
9
Q
What is the dominant microbial species in/on the human GI tract?
A
Bacteroidetes (and Firmicutes)
10
Q
Why should we study the human microbiome?
A
The microbiome is essential for growth and development (0-3yo), health, and the immune response
11
Q
What three things is research on the human microbiome focused on?
A
- species composition
- critical organisms that influence health, development, and disease
- therapies to prevent and treat health conditions (reverse symptoms caused by a change in microbiota)
12
Q
What is the trend in oxygen content from the stomach to the colon? Why does this occur?
A
Stomach has high oxygen content and colon has now; caused by facultative anaerobes that use up the oxygen
13
Q
Why is it important to have an anaerobic environment in the GI tract?
A
- fermentation
- reduces growth of aerobic pathogens
14
Q
What is the gram reaction for Bacteroidetes? Firmicutes?
A
Negative, positive respectively
15
Q
What is important about the dominant species in the GI tract?
A
They are also present in every other environment in high amounts (Bacteroidetes and Firmicutes are some of the most prevalent species in the world after Proteobacteria and Actinobacteria)
16
Q
What kind of culture system does the colon represent? How?
A
A continuous culture; many cells are shed with fecal matter every day (~1/3 of the mass) and are continually fed
17
Q
Where is the most microbial diversity within the human microbiome? Why?
A
GI tract; it has a neutral pH, which means the microbes don’t need to be acidophilic to survive
18
Q
What is the trend of pH from the stomach to the intestine?
A
Low pH in stomach, neutral in gut
19
Q
What are the roles of Bacteroidetes and Fermicutes in the gut?
A
Digestion of complex plant materials containing cellulose
20
Q
How does the human digestive system increase its efficiency in nutrient acquisition?
A
The short chain fatty acids produced via fermentation of the gut bacteria make up about 10-15% of our nutrition (we use their waste products)
21
Q
What are the mutualistic symbioses between humans and microbes in the gut?
A
- digestion
- biosynthesis of essential compounds
- microbial warfare
- immune system development
22
Q
What essential compounds may bacteria biosynthesize for us?
A
Vitamins and amino acids
23
Q
What are bacteriocins and lantibiotics?
A
Molecules that form pores in other cell’s membranes used in microbial warfare
24
Q
How do bacteria aid in immune system development?
A
They produce anti-inflammatory molecules that prevent chronic inflammation to train the immune system to accept foods
25
If the immune system developing bacteria were not present at birth, what would happen? How does this happen?
The absence of these bacteria causes the immune system to activate when food is consumed; when babies go on antibiotics and their microbiota is wiped out
26
What is the relevance of the gut-brain axis?
Signals can go either way; form the brain to the gut, or from the gut to the brain. This demonstrates the importance of the gut microbiota in mood
27
How do GI microbiota influence the mood of humans?
The generate neurotransmitter-like metabolic by-products that send signals to the brain that mimic the signals for feelings of happiness, fear, anger, depression, hunger, cravings, and anxiety
28
What evidence suggests the role of the gut microbiota in mood?
The signals resemble neuro-transmitters for those moods and the microbiota of depressed individuals differs from the microbiota of happy individuals
29
The human fetus is _________
sterile
30
When does colonization happen to a newborn?
Begins during and immediately following birth via contact with the mother's skin and feeding
31
Compare the microbiota of a baby birthed naturally versus cesarean section
A baby birthed naturally will be exposed to more of the mother's microbiota, namely her vaginal and epidermal ones. Perhaps some gut microbiota too if the birth is messy (many women poop during delivery!)
32
How does breast milk ensure the health of the baby?
It contains sugars that the infant can't digest to select for "normal" microbiota that can digest it
33
True/False? A naturally birthed and breast-fed baby has the same initial GI microbiota colonizers as a surgically birthed and bottle-fed baby
False. The first baby will start off with a greater diversity of microorganisms, however, as they age, they become more similar (roughly 3 years old)
34
What causes the change in gut microbiota in babies?
The switch to solid food
35
What is a MAMP?
Microbe-associated molecular patterns that aid in the development of the immune system and gut maturation. They can be heavily-repeated cell surface sugars (O-LPS), proteins, and lipids
36
What may result from insufficient exposure to MAMPs?
Reduced colonization resistance and susceptibility to immune-mediated disease. Increased risk of infection, asthma, allergies, diabetes, obesity, IBD, anxiety may result if exposed to bad MAMPs
37
Do you share a relatively similar gut microbiota with people in your city? What about in other continents?
Within the city is more similar than between continents, but the closest degree of similarity is between family members, as you share the same environment, eat the same food, etc
38
What does healthy GI microbiota look like?
Diverse, stable, and resilient to any changes in diet, where short term changes are short lived
39
What does microbial fermentation in the gut produce? Why is this important?
Short chain fatty acids (butyrate, propionate, acetate); they are important signaling molecules that suppress inflammation, strengthen tight junctions between epithelial cells (pathogen resistance), and promote the β-oxidation of fatty acids to create an anaerobic environment to avoid pathogenic growth. Also reduces fatty acid and cholesterol production
40
What is microbial dysbiosis?
A change in the composition of the microbiota due to the inadequate development of "normal" microorganisms
41
What may microbial dysbiosis lead to in the gut?
The immune systems responds to normal gut microbiota as foreign, causing inflammation and an aerobic environment. This allows pathogens access to gut epithelium and leads to IBD
42
What does obesity look like in terms of the microbiota?
The microbiota are less diverse, but have more microorganisms. Caused by a high-fat/low fiber diet
43
How does obesity arise in farm animals?
They are pumped with antibiotics, which kills the good bacteria in their system, leading to an overall less diverse microbiota
44
Describe the correlation between GI microbiota and obesity
Sterile mice that underwent fecal transplant from an obese human acquired a comparable microbiota and gained mass. Sterile mice that underwent fecal transplant from a lean human acquired a comparable microbiota and did not gain mass
45
The GI microbiota of obese animals consist of high methanogen counts. Describe why this is significant
Methanogens remove H2, which favours increased fermentation rates, so more short chain fatty acids become available to the host. Thus, more acetate allows for more cholesterol and lipid synthesis in the liver. Lean animals have fewer methanogens, so cannot ferment as easily and thus less SCFA are available for host absorption
46
True/False? Taking antibiotics changes the GI microbiota permanently, unless a fecal transplant is done
False. Shortly after treatment, the microbiota usually return to normal
47
What happens if someone contracts a *C. difficile* infection while their microbiota is recovering from antibiotic use?
The loss of diversity allows antibiotic resistant pathogens like *C. difficile* to colonize the gut, causing diarrhea, abdominal pain, fever, and in severe cases, septic shock and death, which must be treated with the surgical removal of the colon (because *C. difficile* is antibiotic resistant)
48
Why is *C. difficile* able to colonize our gut when on antibiotics? How is this treated in mild cases?
The loss of diversity allows *C. difficile* to outcompete the good microbiota, as it is antibiotic resistant and they are not. Once off antibiotics, the microbiota are allowed to recolonize the gut, especially with help from FMT therapy
49
How do fecal transplants work?
The introduction of healthy microbiota into an unhealthy environment allows for the displacement of pathogenic organisms, such as *C. difficile*
50
What are probiotics?
Live, good bacteria, like *Bifidobacterium, Lactobacillus* ingested through yogurt that may help balance the gut microbiota, although it is not clinically proven. The ingestion of some *Bacillus* species can prevent colonization of pathogenic *S. aureus*, however
51
What are prebiotics?
The injection of nutrients that promote the growth of beneficial bacteria
52
What are synbiotics?
A mix of pre- and probiotics
53
What is a mycobiome?
The collection of fungal symbiotes
54
What is a virome?
The resident eukaryotic viruses and phages
55
What are translocase systems?
Systems that moderate the transport of proteins outside of the cell using ATP, GTP, or PMF for power
56
What are the two universal translocases in prokaryotes?
Sec and Tat
57
What is the Sec pathway used for?
The general secretion of unfolded proteins
58
Tat stands for:
Twin-arginine translocase
59
Describe the two possible outcomes of the Sec pathway
1. Facilitates the co-translation of membrane-associated proteins into the cytoplasmic membrane
- SRP-mediated
- uses GTP to power translocation
2. Transports unfolded extracellular proteins out of the cytosol
- SecA-mediated (chaperone)
- uses ATP to power translocation
60
Describe co-translation
The amino acid sequence is moved into the membrane as it is synthesized
61
What is significant about Sec using GTP to power translocation?
GTP is used in the translation of the translocated protein at the same time, so the reaction is coupled
62
If a protein is to be inserted into the cellular membrane using the Sec pathway, what protein is involved?
SRP (signal recognition particle)
63
Describe the Tat pathway
- transports folded proteins out of the cytosol
- RR-mediated (twin arginine)
- uses PMF
64
Why must the proteins secreted via the Tat pathway be folded prior to secretion?
They require a cofactor or coenzyme for proper function, so they must be folded in order to recognize it
65
Why does Tat use PMF to secrete proteins?
Folded proteins require significantly more energy to be moved across the membrane
66
What are the gram-negative secretion systems? Why are they special?
They are types I-VI. They're special because the secreted molecule must pass at least two membranes
67
What are the two-step GN translocases? How do they work?
Types II and V. They move proteins out of the cell one membrane at a time
68
What are the one-step translocases? How do they work?
Types I, III, IV, and VI. They move proteins across both membranes in one step, some move them across three membranes in one step
69
Describe T2SS
It is a type II secretion system that uses Sec or Tat to move proteins across the inner membrane and then a second translocase moves the folded proteins across the outer membrane by attaching to a secretion pore. Once attached, they are pushed out of the cell by an ATP-mediated pseudopilin extension, which works like a piston
70
What is T2SS commonly used for the secretion of?
AB toxins
71
Describe T5SS
It is a type V secretion system that uses Sec to move autotransporter proteins across the inner membrane. The transporter domain of the autotransporter forms a pore in the outer membrane for the passenger domain to exit the cell (forms its own pore). Autoproteolysis separates the two domains for the transport of the passenger domain
72
What is T5SS commonly used for the secretion of?
Exoenzymes (IgA protease, which destroys antibodies)
73
Describe T1SS
Type I secretion system that uses ABC transporters to move proteins across both bilayers in one step. The IM ABC transporter delivers proteins to a periplasmic membrane fusion protein via ATP hydrolysis, which pushes the protein out an outer membrane pore
74
What is T1SS commonly used for the secretion of?
Secretion of bacteriocins (punch holes in other bacteria), biofilm mediators (LapA), RTX toxins
75
Describe T3SS
A type III secretion system that transports the protein directly from the cytosol of the bacterial cell into the cytosol of a recipient cell, where the recipient has one membrane. Upon contact with a recipient, the tip of the transporter fuses with the host cell membrane and proteins are transported using PMF. Found in both pathogens and symbionts
76
Provide an example of a symbiont that would use a T3SS
Rhizobia inject Nod factors into plant cells
77
What are cells that use TIII secretion?
Injectisomes
78
What is T3SS commonly used for the secretion of?
Cytotoxins and Nod factors
79
What can you infer about the energy use of T3SS and why?
It uses a lot of energy to use this system because it uses the PMF to power it
80
Describe T4SS
A type IV secretion system that transports proteins/DNA directly from the cytosol of the bacterial cell into the cytosol of a recipient cell. It is ATP-mediated and used for conjugation and protein transport. It is the most common type of secretion system
81
What is T4SS commonly used for the secretion of?
DNA for conjugation (F plasmids) and proteins like pertussis toxin
82
Describe T6SS
It is a type VI secretion system that transports proteins directly from the cytosol of the bacterial cell into the cytosol of a recipient cell via an ATP mediated T4 phage-like injection system. When close to the target, contractile sheath proteins undergo a conformational change that extends a spike out of the donor cell and into the recipient, delivering exoproteins
83
What is T6SS primarily used for?
Microbial warfare (competition)
84
Which secretion systems can be used for bacterial to prokaryotic/eukaryotic protein transfer?
Type III, IV, and VI
85
How may signals directly act as effector molecules? Indirectly?
Direct: inducers or corepressors
Indirect: two-component regulatory systems
86
What are the components (3) of a two-component regulatory system? How do they work?
1. Sensor kinase binds ligand and autophosphorylates histidine residue. Transfers phosphoryl group to response regulator
2. Response regulator is activated by phosphorylation and acts as a TF
3. Phosphatase dephosphorylates response regulator
87
What is quorum sensing?
A density-dependent mechanism for cellular communication to induce a population or community response
88
What is quorum sensing facilitated by?
Extracellular peptide or non-peptide signaling molecules called autoinducers that accumulate as population densities increase
89
When is quorum reached?
When a high enough concentration of the autoinducer is reached
90
What happens when quorum is reached?
Coordinated gene regulation occurs
91
What autoinducers are used by GN bacteria?
Acyl homoserine lactones (AHLs)
92
What happens to AHLs in low cell densities? High cell densities?
Low: the AHLs disperse out of the cell into the surrounding environment
High: AHL concentrations first increase outside of the cells, then inside of the cells, as they are diffusing back into them
93
How do AHLs work?
They may either bind transcription factors as inducers or they can bind to a sensor kinase, which then regulates the TFs. This results in a coordinated up-regulation of quorum-specific genes
94
Which genes would be downregulated in high AHL concentrations? Why?
Flagellation genes; they do not want to move away from the cellular community
95
What autoinducers are used by GP bacteria (and archaea)?
Oligopeptide autoinducers (AIPs)
96
How do AIPs work?
1. Pre-AIPs are transported out of the cell (ABC transporters) into the surrounding environment
2. AIPs bind sensor kinases (2CRS)
3. Results in coordinated up-regulation of quorum-specific genes, some down-regulation
97
What are the two main differences between AHLs and AIPs other than them being GN and GP autoinducers, respectively?
- AHLs diffuse out of the cells while AIPs are transported
- at high cell densities, [AHL] increases both inside and outside the cells, while [AIP] increases only outside
98
What are the two main structural variations seen in AHLs?
- length of the acyl chain (4-18C)
- R group (-OH, =O, -H)
99
What is luciferase? What is its substrate?
A luciferase is an enzyme that uses a luciferin and oxygen to produce light
100
Provide an example of a two-component luciferin. What organism uses this reaction?
RCHO + FMNH2 is the luciferin used by *A. fischeri*
101
Describe how the bobtail squid uses *A. fischeri* as a symbiont
During the day, the bobtail squid "absorbs" *A. fischeri* from the environment. At night, it directs O2 to the light organ that holds the bacteria, which generates light. Augmentation of its ink sacs regulates the intensity of the light. It uses this tactic to reduce its shadow to hide from predators at night, so on bright nights, it produces lots of light and vide versa
102
Describe quorum sensing in *A. fischeri*. What kind of bacteria is it?
1. Expresses LuxI at basal levels
2. LuxI produces an AI-1-type AHL autoinducer (3OC6-HSL)
3. 3OC6-HSL diffuses throughout the squid light organ
4. At high concentrations (quorum), it binds LuxR, which then binds to activator binding sites and induces the Lux operon
Gram negative
103
What is LuxI?
An AHL synthase
104
What is LuxR?
A transcription factor (activator protein)
105
Describe the Lux operon and its components
- components: LuxI, C, D, E, A, B, and G
- positive feedback loop
106
What is the role of LuxC, D, and E?
Synthesis of RCHO (long chain fatty aldehyde that is one component of the luciferin)
107
What is the role of LuxA and B?
Synthesis of the heterodimeric enzyme luciferase
108
What is the role of LuxG?
Produces FMN reductase, which then synthesizes FMNH2 (other component of luciferin)
109
What is *Staphylococcus aureus*?
A ubiquitous bacteria found on our skin that is an opportunistic pathogen if it can bypass the innate immune system. It produces a variety of virulence factors that lead to a variety of infections. Pyogenic (pus-forming)
110
What is the *S. aureus* global control system?
An inducible set of regulons controlled by quorum sensing
111
What are regulons?
Multiple operons under control of the same promoter
112
Describe the *S. aureus* global control system
1. AgrD synthesizes AIP
2. AgrB transports pre-AIP out of the cell (is a membrane transporter)
3. AIP binds AgrC at high concentrations
4. AgrC phosphorylates AgrA
5. AgrA-P binds at activator binding sites within multiple regulons, which upregulates the production of multiple virulence factors
113
What is AgrC?
A histidine kinase that phosphorylates AgrA
114
What is AgrA?
A response regulator (activator)
115
What kind of system is the *S. aureus* global control system?
Two-component system (AgrC and AgrA)
116
If *S. aureus* is present everywhere on our skin, why aren't we under constant infection?
It requires high concentrations to work and must bypass our skin to cause infection. We shed our skin daily, and thus shed the bacteria with it, preventing it from causing infections
117
How is the *S. aureus* global control system inhibited?
Inhibited via microbial warfare, as GI microbiota produce inhibitors that bind ArgC, preventing activation of the two-component system
118
What is the miasma theory of infection? Who replaced it and with what?
Bad smells cause disease; Robert Koch with the discovery of microbes and their links to specific diseases
119
How did Koch disprove the miasma theory?
Formulated postulates for determining the microbial cause of infection
120
What are Koch's postulates?
1. specific organism must be associated with the disease (not present in healthy organisms)
2. specific organism must be isolated
3. pure isolate should produce disease with same symptoms
4. organism should be re-isolated (verify that it is the same organism)
121
What are the issues with Koch's postulates and which issue complicates which postulate?
1. many pathogens are found in asymptomatic carriers or sometimes disease is due to toxins
2. and 4. many pathogens are unculturable
3. many pathogens lack a suitable animal model (only attacks a specific species or produces different symptoms in different species)
122
Describe how Marshall and Warren disproved the existing theory of how stomach ulcers form
They discovered *H. pylori* from tissue biopsies, but lacked an appropriate animal model and no one believed they could survive in the stomach. This met postulates 1 and 2. Eventually, Marshall drank a culture of *H. pylori* and developed gastritis. He then reisolated it, which satisfied postulates 3 and 4.
123
How does *H. pylori* cause stomach ulcers?
It uses its helical shape and polar flagella to penetrate thick mucous lining the stomach epithelium. Epithelial cells naturally secrete carbonate to reduce acidity, and *H. pylori* uses urease to generate ammonia. It then produces toxins (VacA) to damage epithelial cells to gain nutrients
124
How are stomach ulcers treated?
With a strong antibiotic that is capable of killing *H. pylori* in small doses, as most of the drug is degraded in the stomach
125
What is infection?
Growth of a pathogenic microbe in/on a host. May be asymptomatic
126
What is disease?
Injury of host due to infection
127
What is a pathogen?
A microorganism that causes disease
128
What is an opportunistic pathogen?
A pathogen that causes disease only under certain conditions
129
What is pathogenicity?
The ability of a pathogen to cause disease (ranked on severity and how easy it is to develop disease)
130
What is pathogenesis?
The process by which a pathogen causes disease
131
What is virulence?
The relative ability of a pathogen to cause disease (severity of mechanism)
132
What are virulence factors?
Molecules produced by, or strategies used by, a pathogen to cause disease
- achieve attachment and colonization
- evasion of the host immune system
- invasion and dissemination
- acquisition of nutrients and growth
- release into external environment
133
What are some common portals of entry for infection?
- skin (wounds or bites)
- gut (survive stomach and compete against gut microbiota)
- mucous membranes (nose, mouth, eyes)
134
What is mucous composed of?
Mucin (glycoproteins and polysaccharides)
135
What do mucins commonly contain?
sIgA and defensins (punch holes in pathogens)
136
How do microorganisms infect mucous membranes if they're so impermeable?
Require virulence factors such as flagella and enzymes that degrade the mucin
137
What is the role of adhesins? What types are there?
Microbial extracellular glycoproteins or lipoproteins that bind to host receptors; fimbrial and afimbrial
138
What are fimbrial adhesins used for?
Initial attachment via fimbriae or pili
139
What are afimbrial adhesins used for?
Close (intimate) contact
140
What host receptors may adhesins bind to?
Anything! Fibrinogen, elastin, glycoproteins, lectins, cell receptors, the list goes on
141
What are the secretion systems pathogens use for adherence?
T3SS and T6SS, sometimes T4SS to inject proteins/toxins directly into cells
142
Describe *E. coli* host cell recognition
Pathogenic *E. coli* (O157:H7) injects a protein (Tir) into host cells using T3SS. Tir becomes a receptor on the host membrane for an *E. coli* surface adhesin (intimin) that adheres the cells tightly
143
What is an invasin?
A protein that activates host cell signaling pathways that result in reorganization of cytoskeletal actin to form pseudopod-like structures that engulf the bacterium
144
Describe how *L. monocytogenes* gets internalized
It uses invasins called internalins to induce endocytosis and then release lysteriolysin O to dissolve the phagosome membrane
145
Describe how *Salmonella* gets internalized
It uses T3SS to deliver invasins to induce endocytosis and a second T3SS to insert proteins in the phagosome membrane that prevents lysosome fusion
146
How may a pathogen avoid degradation via lysosome after endocytosis?
Escapes phagosome via:
- escape prior to fusion with a lysosome
- prevents lysosome from fusing
147
What are the three ways pathogens evade the immune system?
- immunoglobulin proteases
- antigenic variation
- hide in plain sight
148
How do Ig proteases help pathogens evade the immune system?
- destroys Ig proteins to evade opsonization
- mucin is full of sIgA, IgA protease and Protein A are major virulence factors
149
What is protein A?
A cell surface receptor on pathogens that binds antibodies by their constant regions to avoid recognition by the immune system
150
How does antigenic variation help pathogens evade the immune system?
- change the structure of flagella, pili/fimbriae, or other surface antigens
- change the teichoic acid, LPS, and peptidoglycan layers to evade defensins
151
How do pathogens "hide in plain sight"?
- stop producing flagella, pili, and/or fimbriae
- use polysaccharides found on host cells to build the capsule (use quorum sensing)
- coat cell surface with host proteins (protein A)
152
How do pathogens acquire nutrients?
- degradative enzymes
- elicit minor immune response
- iron acquisition
153
Describe how pathogens acquire nutrients through degradative enzymes
They use lipases, proteases, glycosidases, and phospholipases to rupture host cell membranes to release nutrients into the environment
154
Describe how pathogens acquire nutrients through eliciting a minor immune response
They cause damage of host cells by tricking the immune system into doing so, which releases nutrients
155
Describe how pathogens acquire nutrients through iron acquisition
- siderophores bind iron with high affinity
- receptors for host iron-binding proteins (or exoenzymes that destroy them), such as lactoferrin, transferrin, ferritin, and heme
- iron abstinence (substitutes iron with other cofactors)
156
What are pathogenicity islands? What is their function?
A cluster of genes for chromosomal virulence factors; facilitates their complete spread to other organisms by horizontal gene transfer
157
Where are most VF genes located?
Plasmids (also aids in horizontal gene transfer)
158
Where may some VF genes that are not bacterial in origin be located?
Prophage DNA within the pathogen's chromosome (permanent and cannot leave host genome, like a provirus)
159
Why do pathogens cause disease in the first place?
They do so to acquire nutrients for growth, replication, and spread
160
What is toxicity?
Pathogens that damage cells and tissues
161
What are the three major mechanisms of toxicity?
1. enzymes that break down components of host cells
2. protein molecules that affect host cell function
3. endotoxins
162
How may toxic enzymes cause cell damage?
- exoenzymes are secreted into the surroundings (T1SS and T5SS)
- enzymes can be delivered directly into host cells via T4SS or T6SS
163
How may toxins cause cell damage?
- exotoxins are secreted into the surroundings
- toxins can be delivered directly into host cells
- enterotoxins are active in the GI tract
164
What are the cellular components of endotoxins that cause cell damage?
- Lipid A portion of LPS in GN cells
- lipoteichoic acids in GP cells
- not secreted (part of the cell membrane)
165
What are tissue-destroying enzymes? Provide 6 examples
Enzymes that break down components of the extracellular matrix, opening paths for microbes to spread below the epithelium
- hyaluronidase
- collagenase
- elastase
- protease
- lipase
- nuclease
166
How does hyaluronidase work?
It breaks down hyaluronic acid, which is a polysaccharide that maintains the organization of cells in tissues and glues cells together
167
What are the clot forming and dissolving enzymes?
Coagulase and streptokinase (staphylokinase)
168
What is coagulase?
A clot-forming enzyme that causes clots to form around the infection site to protect the pathogen from immune cells
169
What is streptokinase?
A clot-dissolving enzyme that dissolves clots to allow the pathogen to move deeper into the tissue
170
How do pyogenic infections occur?
*Staph. aureus, epidermis*, and *Strep. pyogenese* make their way through the skin. Coagulase walls off the infected tissue to slow immune response. Hemolysins and leucocidins destroy RBC and WBC, resulting in pus formation
171
What is pus made of?
Dead and dissolved bacteria, host cells, RBC, and WBC
172
What does *Staph. aureus* use to aid in pyogenesis? How does it work?
α-toxin; it is a pore-forming cytotoxin that targets surrounding cells, resulting in cell lysis
173
How may pyogenic infections be treated?
With antibiotics and drainage
174
How do surface-level bacterial infections become more serious?
Colonize subcutaneous tissues using multiple adhesins to attach to the extracellular membrane and hyaluronidase. May eventually infect the blood, leading to septicemia or sepsis
175
Septicemia vs. sepsis
Septicemia is when bacteria grow in the bloodstream, where sepsis is when toxins produced by bacteria get into the bloodstream
176
What are AB-type exotoxins?
Two-component toxins, where the B-subunit binds host cell receptors and facilitates the transport of the A-subunit into the cell, where it has toxic activity such as enzymatic inhibition
177
What is Diphtheria? What is it caused by and how is it treated?
A respiratory disease that results when *Corynebacterium diphtheriae* colonizes the throat and upper respiratory tract via exposure to aerosolized droplets or direct contact with infected individuals. Treated with antibiotics
178
What are the molecular symptoms of Diphtheria?
Buildup of fibrin clots, dead cells, and an immune response result in typical welling of the neck and pseudomembrane formation in the throat (protect the infection)
179
What are the components of the DTaP vaccine?
Diphtheria, Tetanus, and acellular Pertussis
180
How does Diphtheria produce its toxin, DT? What kind of toxin is it?
Produced via the Tox gene on the lysogenic bacteriophage; AB-type exotoxin
181
What are the functions of the A and B subunits of DT?
B: binds host cell receptor and translocates A into cell
A: ADP-ribosylates EF-2, which stops translation, leaving to host cell death
182
What is the overall reaction DT uses to deactivate EF-2?
NAD+ + EF-2 + DT > nicotinamide + EF-2-ADP + DT
183
What is Botulism? What is it caused by and how is it treated?
A neuromuscular disease that results when *Clostridium botulinum* either colonizes the GI tract or the toxin is ingested. Treatment with antibiotics and antitoxin, but once the toxin is bound to its target, there is no treatment and damage is permanent if the neuron isn't replaced
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Why is Botulism especially dangerous in children?
Their microbiota is underdeveloped and thus cannot outcompete *C. botulinum* in the GI tract, causing neuromuscular damage
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What are the molecular symptoms of Botulism?
Once the toxin is absorbed in the stomach and enters the bloodstream, it targets motor neurons at neuromuscular junctions, It causes flaccid paralysis
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How does Botulism produce its toxin, BoNT? What kind of toxin is it?
Produced via the Bot genes on the chromosome, plasmids, and prophage; AB-type neurotoxin
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What are the functions of the A and B subunits of BoNT?
B: binds host cell membrane receptor on motor neurons and translocates A into cell
A: endoproteases that cleave SNARE proteins, preventing synaptic vesicles from merging with cell membrane and releasing acetylcholine into the synaptic cleft for muscle contraction initiation
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What is Tetanus? What is it caused by and how is it treated?
A neuromuscular disease that results when *Clostridium tetani* colonizes a deep tissue wound (anaerobic). Treatment with antibiotics and antitoxin, but once the toxin is bound to its target, there is no treatment and damage is permanent if the neuron isn't replaced
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What are the molecular symptoms of Tetanus?
Toxin diffuses into the bloodstream where it targets the inhibitory neurons of motor neurons, causing spastic paralysis (lockjaw)
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How does Tetanus produce its toxin, TeNT? What kind of toxin is it?
Produced via Tet genes on a plasmid; AB-type neurotoxin
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What are the functions of the A and B subunits of TeNT?
B: binds host cell membrane receptor on inhibitory neurons and translocates A into cell
A: endoprotease that cleaves a SNARE protein (synaptobrevin-VAMP), preventing synaptic vesicles from merging with the cell membrane and releasing glycine into the synaptic cleft (glycine inhibits motor neurons)
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What is Pertussis? What is it caused by and how is it treated?
A respiratory disease that results when *Bordetella pertussis* colonizes ciliated cells of the lower respiratory tract. Treated with antibiotics
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What are the molecular symptoms of Pertussis?
Toxins kill ciliated cells that keep lungs free of debris, causing a buildup of debris and a violent cough that can last over 6 weeks
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What are the toxins produced in Pertussis? What kind of toxins are they?
PT: AB-type exotoxin secreted through T4SS
TCT: endotoxin
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What is Cholera? What is it caused by and how is it treated?
An intestinal disease that results when *Vibrio cholerae* colonizes the small intestine. Treatment via rehydration and antibiotics, although antibiotics aren't super effective because they are constantly being flushed out the system
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What are the molecular symptoms of Cholera?
Severe diarrhea and vomiting caused by the secretion of electrolytes into the intestines, causing water to follow
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How does Cholera produce its toxin, CT? What kind of toxin is it?
Produced via ctx gene on the prophage; hexameric AB-type toxin
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If *V. cholerae* hasn't been infected with a phage carrying the ctx gene, can it produce the symptoms of Cholera?
No, as the gene is located on the prophage, so it must be infected with a lysogenic phage first
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What are the functions of the A and B subunits of CT?
B: Bind host cell receptor on intestinal epithelial cells and translocates A into cell
A: ADP-ribosylates the α-subunit of Gs proteins
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Describe the molecular pathway caused by CT
1. A-subunit ADP-ribosylates the α-subunit of Gs
2. Gs constitutively activates adenylate cyclase
3. cellular cAMP levels increase
4. cAMP activates PKA signaling pathways
5. cells stop absorbing Na and Cl from the intestinal lumen, actively pump Cl and HCO3 into the lumen
6. osmosis causes water to follow the ions into the intestinal lumen
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What are superantigens? How do they work?
Excreted toxins that induce a massive immune response that damages the host itself by binding and indiscriminately activating Th cells (about 20% of all immune cells)
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What are the bacterial species that use superantigens?
*Staph. aureus* causes toxic shock syndrome via TSST-1, and *Strep. pyogenes* causes scarlet fever via exotoxin A
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What are endotoxins?
Permanent components of the pathogen's outer surface that elicit immune response (not excreted)
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How does the immune system respond to endotoxins?
Release of pyrogenic cytokines, increased heart rate, diarrhea, low blood pressure, and inflammation
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How is septic shock caused?
High concentrations of endotoxins
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Provide 2 examples of endotoxins
Lipid A (component in LPS), and lipoteichoic acids
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What is innate immunity? How does it prevent infection?
The automatic ability to recognize and destroy a pathogen (or its products) by reducing exposure, adherence, colonization, and invasion of pathogenic organisms
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How fast does the innate immune system act? What does this say about its target specificity?
Fast-acting (within hours), but non-specific
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What are the seven components of the human body that contribute to innate defense?
- tears (lysozymes inhibit peptidoglycan)
- cilia in nasopharynx
- skin
- stomach acidity
- GI microbiota
- blood and lymph
- flushing of urinary tract
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What is the function of the blood and lymphatic systems?
They distribute immune cells and molecules throughout the body
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What happens to blood in capillary beds?
Lymph drains across the surrounding tissue and into the lymph capillary beds, where it is pumped by lymph ducts through the lymph nodes and back into the blood
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What does lymph consist of?
Everything in blood minus RBC
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What are the secondary lymph organs?
- lymph nodes
- spleen
- mucosa-associated lymphoid tissue (MALT)
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What is the function of the lymph nodes?
Lymphocyte-filled tissues that sample the lymph for pathogens, toxins, and activated immune cells
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What is the function of the spleen?
Lymphocyte-filled tissues that sample the blood for pathogens, toxins, and activated immune cells
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What is the function of MALT?
Patches of lymphocyte-filled tissue that sample the mucosa for pathogens, toxins, and activated immune cells
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What are the primary lymphoid organs? What happens here?
Bone marrow and thymus; development of lymphocytes
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What is hematopoiesis?
The process by which hematopoietic stem cells in the bone marrow differentiate into specific cell types
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What are the two lineages that hematopoietic stem cells differentiate into?
Lymphoid cells (adaptive) and myeloid cells (innate)
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How is hematopoiesis activated?
Cytokines released by the immune response
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Which cell is found more often in circulation, RBC or WBC?
RBC make up >99% of the cells, while WBC make up 0.1%
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Lymphoid cells use ______ and _________-mediated immunity
Cell-; antibody
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What are myeloid cells used for?
Phagocytosis and inflammation
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True/False? All innate immune cells come from myeloid cells
False. NK (natural killer) cells differentiate from the lymphoid precursor but are innate
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What are the two APC cell types?
Dendritic and macrophage
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What are the four granulocyte cell types?
Neutrophil, eosinophil, basophil, and mast cell
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What are the four phagocytic cell types?
Dendritic, macrophage, neutrophil, eosinophil
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What are the two inflammatory response cell types?
Basophils and mast cells
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What are the two cell-mediated immunity cell types?
Natural killer and T cells
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What is the antibody-mediated immunity cell type?
B cells
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What are the two adaptive immunity cell types?
T cells and B cells
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What tissues do macrophages associate with? What happens to them when they encounter a pathogen?
Tissues and organs (lungs, skin, etc); phagocytose pathogen and present antigens on MHC II receptors. Stay in the tissues to fight off infection
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What are the phagocytic granulocytes? What is their function?
Neutrophils and eosinophils; both release antimicrobials (defensins, proteases, lipases), cytokines, and chemokines and phagocytose pathogens
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What tissues do dendritic cells associate with? What happens to them when they encounter a pathogen?
Epithelial cells (skin, mucosa); phagocytose pathogen and present antigens on MHC II receptors, then migrate to lymphoid tissues to activate the adaptive immune response after passed through lymph capillaries
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Which WBC is the most abundant in our circulatory system?
Neutrophils
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If the host is being attacked by a parasite, which WBC is used to fight it off?
Eosinophils
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What are the inflammatory granulocytes? What is their function?
Basophils and mast cells; release histamine, cytokines, and chemokines
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Where are basophils located?
Blood
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Where are mast cells located?
Mucosal tissues
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What are histamines?
Molecules that cause vasodilation and increase vascular permeability to allow for increased blood flow (WBC) to the site of infection
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What do damaged cells release? What are the functions of these molecules?
Cytokines (signaling peptides) and chemokines (chemoattractant for immune cells) which activate immune cells and induce inflammation
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What are proinflammatory cytokines?
The promote hematopoiesis, induce fever, attract and activate immune cells, induce vasodilation, and increase vascular permeability
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What are the localized responses to injury? What is this a result of?
Redness (rubor), heat (calor), swelling (tumor), and pain (dolor); lymph flows through the tissues
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Describe the steps to diapedesis following phagocyte activation
1. phagocytes arrive at infection site following chemokine gradient
2. cytokines have loosened the junctions between capillary endothelial cells
3. phagocytes squeeze between the cells and enter the damaged tissue
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What are the other names for diapedesis?
Extravasation, transmigration, exudation
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What are PAMPs?
MAMPs specifically for pathogens (MAMPs are more general)
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What are PRRs?
Pattern recognition receptors found on phagocytes that bind PAMPs
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What happens following PAMP-PRR binding?
Activation of a signaling cascade that results in the microbes being internalized into a phagosome, which fuses with a lysosome, forming a phagolysosome
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What do lysosomes contain? What does this result in for the phagocytosed microbe?
Lysozymes, defensins, myeloperoxidase, nucleases, proteases, lipases, ROS; lysis of the microbe
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What is purulence?
The release of antimicrobials (lysosomal contents) into extracellular space via activated neutrophils
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How does purulence contribute to pyogenesis?
Because it releases lysosomal contents, both microbes and WBCs at the area are at risk for lysis, The build-up of dead cells, lymph, and coagulation factors form the pus
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What is a cytokine storm? What is it a result of?
A mass release of cytokines, histamines, etc following toxic shock via septicemia, superantigen toxins (TSST), and endotoxins (LPS)
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A cytokine storm causes:
Systemic inflammation
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What is systemic inflammation?
Blood pressure drops due to mass dilation of vasculature and lymph exiting circulation, so the heart pumps harder to compensate for the slow blood flow. Organ systems fail due to lack of oxygen
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What are interferons?
Molecules released by infected host cells that activate expression of antiviral genes to limit viral spread (surrounding cells are harder for the pathogen to infect)
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What are a couple of factors that make pathogens harder to kill? What is used to remedy this?
- capsules resist phagocytosis
- exoenzymes allow pathogens to get to endothelial layers
- some pathogens are intracellular and thus cannot be detected by innate system
Adaptive immune system used
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What is adaptive immunity?
The acquired ability to recognize and destroy a specific pathogen or its products
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What is the trade-off with using adaptive immunity?
Takes longer to react and create an output, but specific and has long-lasting effects by conferring protection against subsequent exposure
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Does the adaptive immune system have the potential to harm the host?
Yes, if the host has an autoimmune disease. Otherwise, no, because they are high-specificity responses
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What are lymphocytes?
Differentiated lymphoid precursors used in the adaptive and innate immune systems
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What are B lymphocytes?
B cells that mature in the bone marrow and await activation in the secondary lymphoid organs. Confer humoral immunity
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What are T lymphocytes?
T cells that mature first in the bone marrow and then in the thymus, then await activation in the lymphoid tissue. Confer cell-mediated immunity
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What are NK cells?
Cells that differentiate from lymphoid precursors by partaking in innate immunity by identifying and destroying infected and cancerous cells
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What are antigens?
Molecules that interact with components of the immune system. More specific than PAMPs. Includes microbes, viruses, toxins, self molecules
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What are epitopes?
Specific parts of an antigen that interacts with the immune system with specific binding sites
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True/False? Each antigen has a single epitope
False. Antigens can (and usually do) have multiple epitopes
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What is the negative selection T cells must undergo in the thymus?
T cells must react with MHC molecules, destroyed if they don't
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What is the positive selection T cells must undergo in the thymus?
T cells must not react with self antigens, destroyed if they do
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Where do mature T cells migrate after clonal deletion?
Secondary lymphoid tissues (lymph nodes, spleen, MALT)
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How are B cells selected?
Tested for their ability to react with self antigens, destroyed if they do
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Where do mature B cells migrate after selection?
Secondary lymphoid tissues (lymph nodes, spleen, MALT)
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Which immune cells first make contact with pathogens?
Macrophages and dendritic cells
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Describe the steps between pathogen encounter to MCHII presentation
1. pathogen encounters macrophages and dendritic cells
2. PAMPs (pathogen) bind to PRRs (APC) and the pathogen is phagocytosed
3. antigens are processed and presented on MHCII cell surface receptors
4. dendritic cells migrate to secondary lymphoid tissues to activate B and T cells, macrophages stay in the infected site
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Which types of cells can present MHCII?
APC cells (macrophages, dendritic cells, B cells)
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How many versions of MHCII are there? What does this allow for?
6 versions; many different MHCII-antigen binding opportunities
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What type of cells recognize MHCII? How are the antigens presented?
Naive Th cells; antigens are presented on MHCII type receptors on APC cells with epitopes facing outwards
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True/False? Every Th cell recognizes multiple epitopes thanks to its thousands of TCRs
False. One Th cell binds one epitope, and each Th cell has thousands of receptors that can only recognize a single epitope
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What is CD4?
A Th cell coreceptor that also binds MHCII to strengthen the association
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What is clonal expansion?
Activated Th cells undergo clonal expansion, which is the replication to form multiple copies of the epitope-specific cell
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What types of cells result from clonal expansion of Th cells?
Th1, Th2, and Tm cells
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What are Th1 cells?
Cells that result from clonal expansion that enter circulation to migrate to infection sites and release cytokines that activate phagocytes
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What are Th2 cells?
Cells that result from clonal expansion that stay in the lymphoid tissue and release cytokines that activate B cells
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Where does clonal expansion occur?
Secondary lymphoid tissues
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Describe the function of Th1 cells once they migrate to the infection site
1. interact with macrophages displaying epitope on MHCII
2. release cytokines to activate phagocytes (enhances phagocytosis and stimulates them to release their own cytokines)
3. results in a positive feedback loop of cross activation
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How do superantigens force activation of Th cells?
It forced MHCII + TCR + antigen together even if they are not specific to each other
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What results from the effects of superantigens?
A massive wave of immune cell activation that has the potential to harm the host (toxic shock)
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What are BCRs?
B cell receptors are membrane-bound antibodies (immunoglobulin) that act as receptors (variable regions face outwards)
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True/False? Every B cell recognizes multiple epitopes thanks to its thousands of BCRs
False. One B cell binds one epitope, and each B cell has thousands of receptors that can only recognize a single epitope
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Describe the steps for T cell-dependent B cell activation
1. during infection, antigens are swept into the lymph, which passes through MALT and lymph nodes (where mature, naive B cells await)
2. when an antigen binds to a BCR, the antigen is internalized and phagocytosed (like a macrophage or dendritic cell)
3. antigens are processed and presented on MHCII
4. if a Th cell binds the MHCII-epitope complex, the Th cell releases cytokines that activate the B cell (strengthens independent B cell response)
5. B cells undergo clonal expansion into plasma cells and Bm cells
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What are plasma B cells?
Differentiated B cells (post-antigen exposure) that produce and release antibodies specific to the antigen recognized by the Th2 cell
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What kind of immunity do plasma cells provide?
Antigen-specific humoral immunity
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True/False? Memory B cells still require re-exposure of the antigen via Th2 cell to activate the immune response
False. They do not require Th2 cells to be activated upon re-exposure
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Describe the structure of an antibody
- 2 heavy 2 light chains
- symmetrical Y shape
- variable regions are specific to epitopes
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What is the Fab region?
The antigen epitope binding site
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How many antigens may one antibody bind at a time? What is this called?
Two of the same antigen (must recognize the same epitope); bivalence
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What is the Fc region?
The constant region that allows antibodies to interact with other immune effectors
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What are the immunoglobulin classes?
- IgM
- IgG
- IgA
- IgD
- IgE
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What is IgM? Describe monomeric and serum forms
An antibody class secreted by B cells during initial exposure. Monomeric IgM functions as a BCR and serum IgM forms a pentamer in the blood
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What function does pentameric IgM serve?
Clumps antigens together in the blood
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What is IgG? Describe monomeric and serum forms
An antibody class secreted by B cells during subsequent exposure. Serum form is monomeric (in the blood)
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What is IgA? Describe serum, monomeric, and other forms
Involved in preventing pathogens from reaching the epithelium. Serum form is monomeric; dimeric IgA is secreted at mucosal surfaces (sIgA) to trap pathogens before they get into the system
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What does IgA bind? What can you infer about this?
Mucin found in tears, sweat, and colostrum; they are found in and around mucous membranes
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What is IgD? Describe monomeric and serum forms
Function is not known, although it is hypothesized to be involved in Bm cell activation; serum IgD is monomeric and acts as a BCR
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What is IgE? Where is it displayed and what is its function?
Displayed on basophils and mast cell membranes, triggers the release of histamine and proinflammatory cytokines. Two antibodies may bind a singular antigen via crosslinkage
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What are the three functions of antibodies?
1. opsonization
2. agglutination
3. neutralization
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What is opsonization?
The coating of an antigen with antibodies, which marks it for phagocytosis, complement activation, or antibody-dependent cell-mediated cytotoxicity (ADCC)
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Phagocytes that react to opsonized antigens have what cellular membrane structure? What does this allow for?
C3b (complement) receptors and Fc receptors; allows for the efficient phagocytosis of opsonized pathogens
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How may pathogens avoid phagocytosis via opsonization?
They carry a special protein (Protein A) that recognizes the Fc portion of antibodies so that they disguise themselves as "self" cells to avoid recognition by the immune system (antibodies are basically put on the wrong way so they look like immune cells themselves)
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What is agglutination?
The function of antibodies that clumps multiple pathogens together for phagocytosis
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What is neutralization?
A function of antibodies that prevents toxins, viruses, and microbial adhesins from interacting with their targets by binding their recognition sites
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Which antibody is secreted during primary immune response?
IgM (first exposure to pathogen)
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Describe the secondary antibody exposure. Which antibodies are produced?
Upon subsequent exposure to the same antigen, Bm cells rapidly differentiate into plasma cells without assistance from Th2 cells. The antibodies produced are IgG (serum) and IgA (mucosal surfaces) at 10-100x the concentration of the primary response
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What is antibody class switching?
The switch from IgM to IgG and IgA after secondary exposure to a pathogen
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True/False? Third and fourth exposures elicit an even faster immune response than secondary exposure
False. All the same speed
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Compare the speed and antibody concentration between primary and secondary responses
Secondary occurs much faster and antibody concentration is much higher (mostly IgG)
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What is vaccination?
Deliberate antigen exposure to illicit a primary immune response to develop Bm and Tm cells so that secondary exposure allows for a faster response
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What may vaccines be developed from? Provide an example for each
- live-attenuated pathogens (MMR - measles, mumps, and rubella)
- heat/chemically "killed" pathogens (polio/influenza)
- altered toxins (toxoids) (DTaP)
- subunit vaccines: inject spike proteins (HepB)
- viral vector (DNA) or lipid nanoparticle (mRNA)
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What two criteria must vaccines meet?
- safe (few side effects and no autoimmunity)
- efficacious (must produce memory cells)
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How was smallpox treated?
Jenner took pus from cowpox pustules and injected it intravenously into a "young boy", which protected him from smallpox because cowpox is antigenically similar to smallpox
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Has smallpox been eradicated?
Yes and no. Eliminated from natural spread but it still exists in 2 research labs
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How may pathogens evade the innate immune system and antibodies?
They may become intracellular
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How do our cells protect against intracellular pathogens?
There are intracellular PRRs that detect PAMPs in the cytosol
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How do cells notify the immune system that they have an intracellular invader?
They process pathogenic proteins in proteasomes and present them on MHC I receptors
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What is important to note when considering MHC I receptors?
Every cell regularly degrades self proteins in proteasomes and presents self antigens on MHC I
325
Where may MHC I receptors be found?
On all nucleated cells (including APCs, excluding RBC)
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How are antigens bound to MHC I displayed on the cell surface? Why?
With their epitopes sticking outwards so they may be recognized by Tc cells
327
True/False? Every Tc cell recognizes multiple epitopes thanks to its thousands of TCRs
False. One Tc cell binds one epitope, and each Tc cell has thousands of receptors that can only recognize a single epitope
328
Describe Tc cell initial activation
TCRs on naive Tc cells interact with MCH I-epitope complexes on APCs. CD8 strengthens the association by binding MHC I too
329
What is CD8?
A Tc cell coreceptor responsible for strengthening the interaction between the TCR and MHC I
330
What two pathways may APCs take depending on the MHC class bound with an antigen?
If MHC II: humoral response and inflammation
MHC I: cellular response and cell lysis
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The MHC I-epitope-TCR-CD8 interaction is not enough to activate Tc cells. Why?
It prevents self-reactive Tc cells from killing self cells
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How must Tc cells be further activated to cause cell lysis?
The CD28 on the Tc cell must bind B7 on the APC, as B7 is unique to APCs
333
True/False? Every Tc cell must bind B7 to be activated, even after other cells have already been activated for that specific epitope
False. CD28 to B7 is only required once per epitope, as once the Tc cell is activated by this interaction, it undergoes clonal expansion. This allows for a rapid response as newly formed Tc cells only need to recognize the MHC I antigen and not B7
334
What are perforins?
Proteins secreted by Tc cells post-activation that form pores in the target membrane
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What are granzymes?
Proteins secreted by Tc cells post-activation that induce apoptosis in the target cell
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What four things do Tc cells do once activated?
- release perforins
- release granzymes
- release cytokines
- undergo clonal expansion
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What are complement proteins?
A set of proteins that "complement" the innate and adaptive immune systems that enhance inflammation, phagocytosis, and pathogen lysis
338
Complement proteins are part of the (adaptive/innate) immune system
Innate
339
True/False? Complement proteins are only present when antigens are present
False. They are constantly circulating in blood and associating with tissues
340
How are complement proteins activated?
- bind opsonized pathogens (requires B cell activation)
- bind pathogens directly
341
Describe the steps in the complement cascade (MAC Attack)
1. C1 complex binds to the Fc portion of antibodies coating a pathogen
2. C1 recruits and activated C2 and C4
3. C2 splits into C2a and C2b
4. C4 splits into C4a and C4b
5. C2a and C4b bind the cell surface in close association with C1
6. C2b and C4a float away and act as chemokines to attract other cells
7. the C2a/C4b complex recruits C3 and C5
8. C3a and C5a float away and act as chemokines
9. C3b and C5b bind the cell surface
10. the C3b/C5b complex recruits C6, C7, C8, and multiple C9 proteins that form a membrane attack complex (MAC) in the pathogen membrane, causing cell lysis
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Why does the formation of MAC cause cell lysis?
It punches a hole in the pathogen's cell membrane, causing an intracellular imbalance that ends in cell lysis
343
What is a secondary function of C3b?
It can directly opsonize pathogens (if cleaved in the blood)
344
How do complement proteins enhance opsonization?
C3b proteins opsonize pathogens. Phagocytes have C3b receptors (C3R) in addition to antibody receptors (FcR) which allows for the amplification of phagocytosis by 10x
345
Natural killer cells are part of the (adaptive/innate) immune system
Innate
346
Describe how NK cells differentiate between targets
They sample MHC I receptors on host cells. Presence (with or without self antigen) inhibits NK cell activation while absence activates them. The presence of stress proteins on the unhealthy cell surface activates them further, allowing them to release perforin and granzyme to kill the cell
347
Which cells don't display MHC I? Why?
Infected or cancerous cells; they have enzymes that degrade MHC I proteins to avoid Tc response
348
NK cells act similarly to what other kind of immune cell when activated?
Tc cells, except they don't produce memory cells as they are non-specific
349
What is antibody-dependent cell-mediated cytotoxicity (ADCC)?
Antibodies coating infected or cancerous host cells can bind to Fc receptors on NK cells. This triggers the release of messengers that induce apoptosis in the infected cancerous cell via perforin and granzyme (if antibodies are bound to the cell it must be infected, so the NK cell kills it non-specifically)
