1
Q
- How did early inoculation practices in China differ from later European “variolation” techniques?
A
Chinese inoculation (as early as the 10th century) involved blowing powdered smallpox scabs into the nose. European variolation (18th century) involved scratching pus or scabs into the skin. Both aimed to induce mild infection, but Chinese methods were less invasive and likely safer.
2
Q
→ Chinese inoculation (as early as the 10th century) involved blowing powdered smallpox scabs into the nose. European variolation (18th century) involved scratching pus or scabs into the skin. Both aimed to induce mild infection
A
but Chinese methods were less invasive and likely safer.
3
Q
- What risks were associated with variolation
A
and why was it still practiced despite them?
4
Q
→ Risks: full-blown smallpox infection
A
transmission to others
5
Q
- How did Edward Jenner’s cowpox experiments differ scientifically and ethically from earlier inoculation methods?
A
6
Q
→ Jenner used cowpox (a related but mild virus) instead of smallpox
A
creating cross-immunity. Ethically
7
Q
- Why was smallpox uniquely eradicable compared to other infectious diseases?
A
8
Q
→ No animal reservoir
A
visible symptoms for easy tracking
9
Q
A
10
Q
The Immune System: Innate vs. Adaptive
A
11
Q
- What are the main roles of neutrophils
A
macrophages
12
Q
→ Neutrophils: rapid responders that kill pathogens.
A
13
Q
Macrophages: engulf pathogens
A
clean debris
14
Q
Monocytes: circulate in blood and differentiate into macrophages or dendritic cells in tissues.
A
15
Q
- How do innate immune cells act as “first responders” during infection?
A
16
Q
→ They recognize general pathogen patterns (PAMPs)
A
migrate to infection sites
17
Q
**7. What is the process of phagocytosis
A
and how did Metchnikoff’s starfish experiment help define it?
18
Q
→ Phagocytosis: immune cells engulf and digest microbes. Metchnikoff observed starfish larvae cells surrounding foreign particles
A
proving immunity could be cellular.
19
Q
- What techniques do neutrophils use to respond to infection or injury (ex: NETs)?
A
20
Q
→ They release antimicrobial granules
A
produce reactive oxygen species
21
Q
- How do macrophages act as sentinels and help “train” the adaptive immune system?
A
22
Q
→ They detect pathogens
A
secrete cytokines
23
Q
- What are key differences between innate and adaptive immunity in speed
A
specificity
24
Q
→ Innate: fast
A
non-specific
25
Adaptive: slower
highly specific
26
Adaptive Immunity and Immune Memory
27
11. Compare the roles of T cells and B cells.
28
→ T cells: destroy infected cells (cytotoxic) and coordinate immune responses (helper).
29
B cells: produce antibodies to neutralize pathogens.
30
12. Where do T cells and B cells mature?
31
→ T cells mature in the thymus; B cells mature in the bone marrow.
32
13. How do vaccines activate both T and B cells to create long-term immunity?
33
→ Antigens from vaccines are presented by antigen-presenting cells
activating helper T cells (which assist B cells) and cytotoxic T cells
34
14. Why does vaccination often cause mild inflammation (like a sore arm)?
35
→ The immune system’s local inflammatory response recruits immune cells and signals activation — evidence the vaccine is working.
36
Reprogramming the Immune System
37
15. Define immune system reprogramming and give three examples.
38
→ Modifying immune cells to better detect and destroy disease.
39
Examples: CAR-T therapy
checkpoint inhibitors
40
16. How does CAR-T cell therapy work: from T cell collection to infusion?
41
→ 1. T cells collected from the patient
42
→ 2. Genetically modified to express a Chimeric Antigen Receptor (CAR) that targets cancer
43
→ 3. Expanded in lab
44
→ 4. Reinfused to attack tumor cells.
45
17. What makes CAR-T therapy “personalized medicine”?
46
→ It uses a patient’s own immune cells
engineered to target their unique tumor antigens.
47
18. What are the advantages of CAR-T therapy compared to chemotherapy?
48
→ Targets cancer cells specifically
spares healthy tissue
49
19. How might CRISPR improve CAR-T cell therapy
and what problems does it address?
50
→ CRISPR allows precise
non-viral gene editing — faster
51
20. How does the “Super-Phagocyte Project” merge the functions of innate and adaptive immunity?
52
→ Scientists engineer macrophages with CAR-like receptors
giving innate cells the targeting precision of adaptive ones.
53
Pandemics and Vaccine Development
54
21. Define pandemic and distinguish it from epidemic and endemic diseases.
55
→ Pandemic: global spread of a disease (e.g.
COVID-19).
56
Epidemic: regional outbreak.
57
Endemic: consistently present in a specific area or population (e.g.
malaria).
58
22. How did traditional egg-based vaccine manufacturing work
and what were its limitations?
59
→ Virus grown in chicken eggs
harvested
60
Limitations: slow
limited capacity
61
23. What lessons were learned from the 2009 H1N1 Swine Flu pandemic regarding vaccine delays?
62
→ Egg-based methods couldn’t meet global demand fast enough; emphasized the need for faster
scalable platforms (like mRNA).
63
24. How do recombinant protein subunit vaccines differ from traditional ones?
64
→ Use purified viral proteins produced in cell culture — not whole viruses. Safer but require adjuvants for strong immune responses.
65
25. What are adjuvants
and why are they necessary in subunit vaccines?
66
→ Substances that enhance immune activation by stimulating inflammation and antigen presentation.
67
26. What advantages and limitations do DNA vaccines present
and why did they fail in humans?
68
→ Pros: stable
easy to produce.
69
Cons: low uptake in human cells and potential genomic integration risks — limited immune response.
70
27. How do mRNA vaccines overcome the barriers faced by DNA vaccines?
71
→ mRNA works in the cytoplasm (no nucleus entry)
produces strong protein expression
72
28. How does an mRNA vaccine work inside the body?
73
→ Lipid nanoparticles deliver mRNA into cells → cells make viral protein → immune system recognizes it → memory T and B cells form.
74
29. Why is mRNA inherently safer than DNA for vaccines?
75
→ It can’t alter the genome and degrades naturally after use.
76
30. How do scientists determine which mRNA sequence to use for a new vaccine?
77
→ They analyze pathogen genome data to identify antigens (often spike or surface proteins) that trigger strong immune responses.
78
31. Why can mRNA vaccine platforms be quickly adapted to new pathogens or variants?
79
→ Only the sequence needs to change — the delivery system remains the same
enabling rapid design and production.
80
32. How do mRNA cancer vaccines train the immune system to recognize tumor neoantigens?
81
→ They encode patient-specific tumor antigens
prompting T cells to target and destroy cancer cells displaying those markers.
82
83
[Brain-Computer Interfaces & Neuralink]
84
From Mysticism to Measurement
85
1. How did Harry Houdini contribute to public skepticism about early claims of telepathy and mind reading?
86
→ Houdini exposed fraudulent mediums and psychics
showing that supposed “mind reading” could be faked
87
2. What is meant by describing the brain as a “black box”?
88
→ It means that the brain’s internal processes were unknown — scientists could observe inputs and outputs
but not how thoughts were formed inside.
89
3. How did 20th- and 21st-century technologies change our understanding of the mind as measurable rather than mystical?
90
→ Technologies like EEG
MRI
91
4. How do EEG
ECoG
92
→ EEG is noninvasive and records surface activity; ECoG is invasive with higher precision; MRI is noninvasive and maps brain structure and function.
93
Measuring Thought: EEG and ECoG
94
5. What does an EEG measure
and how does it detect brain activity?
95
→ EEG records electrical signals from neurons through electrodes placed on the scalp.
96
6. What are the main types of brain waves (delta
theta
97
→ Delta = deep sleep
Theta = drowsy
98
7. What are the key uses of EEG in medicine and neuroscience?
99
→ EEG helps diagnose epilepsy
sleep disorders
100
8. How does the P300 Speller system allow communication without muscle movement?
101
→ It detects a brainwave spike (P300) when a user recognizes the desired letter flashing on a screen
turning brain responses into text.
102
9. How does electrocorticography (ECoG) differ from EEG
and what advantages does it offer?
103
→ ECoG places electrodes directly on the cortex
giving clearer
104
10. What did UCSF’s ECoG experiments reveal about mapping speech and imagined words to brain activity?
105
→ They showed distinct brain patterns correspond to specific spoken and imagined words
making thought-based speech decoding possible.
106
11. What accuracy rates did researchers achieve in matching brain activity to spoken words?
107
→ Around 90% accuracy in decoding words and sentences from neural signals.
108
Visualizing the Mind: MRI and “Videos of Thought”
109
12. How does functional MRI (fMRI) detect brain activity?
110
→ fMRI measures changes in blood oxygen levels
which indicate active brain regions.
111
13. What is a voxel
and how does it correspond to neural activity in the brain?
112
→ A voxel is a 3D pixel that represents the smallest unit of brain volume measured in an MRI scan.
113
14. What did Dr. Jack Gallant’s lab at UC Berkeley achieve with “videos of the brain”?
114
→ They reconstructed rough visual scenes people were watching using brain activity data.
115
15. What is a “cognitive dictionary
” and how does it relate to thought decoding?
116
→ It’s a map linking specific words or ideas to brain activity patterns
allowing researchers to interpret what someone is thinking.
117
16. What are the main limitations of MRI-based decoding (speed
resolution
118
→ fMRI is slow
has limited temporal resolution
119
Neuralink: Engineering the Brain-Computer Interface
120
17. What problems in existing BCIs was Neuralink designed to solve (signal distortion
rigidity
121
→ Neuralink aimed to fix low signal quality
rigid electrodes that damage tissue
122
18. What are the key design features of Neuralink’s electrode “threads”?
123
→ They are ultrathin
flexible
124
19. What is the function of the neurosurgical robot
and how does it avoid blood vessels during insertion?
125
→ It precisely inserts threads while using imaging to avoid blood vessels
reducing bleeding and inflammation.
126
20. How does Neuralink achieve high channel counts while minimizing tissue damage?
127
→ By using many fine
flexible electrodes that record thousands of signals with minimal invasiveness.
128
21. What does impedance measure
and why is it important for neural signal clarity?
129
→ Impedance measures electrical resistance; lower impedance gives clearer neural recordings.
130
22. What materials did Neuralink test to lower electrode impedance (PEDOT:PSS vs. IrOx)
and how did they compare?
131
→ PEDOT:PSS performed better than IrOx
offering lower impedance and stronger signal quality.
132
23. What was Neuralink’s first successful animal experiment
and what did it demonstrate?
133
→ A pig implant demonstrated safe recording and removal of neural data without harming the animal.
134
24. What was the significance of the 2021 “monkey playing Pong” demonstration?
135
→ It proved that a primate could control a computer directly through brain activity
showing real-time neural control.
136
Neuralink’s Clinical Transition & Human Trials
137
25. What are the main steps Neuralink took from research prototype to clinical device?
138
→ They miniaturized the implant
improved safety
139
26. How did the system evolve from USB-C wired data transfer to fully wireless operation?
140
→ Neuralink replaced wired ports with a wireless chip that transmits data via Bluetooth-like signals.
141
27. What is the FDA’s medical device classification system
and where does Neuralink fall within it?
142
→ It’s Class III
the highest-risk category
143
28. What are Neuralink’s major regulatory challenges and controversies?
144
→ Ethical issues
animal testing scrutiny
145
29. Who were Neuralink’s first human patients
and what abilities did the implant restore for them?
146
→ Paralyzed patients regained digital communication and cursor control through thought alone.
147
30. What types of conditions (ALS
spinal cord injury) are the current focus of Neuralink’s trials?
148
→ ALS and spinal cord injuries
where patients lose voluntary movement or speech.
149
31. How do C4–C5 spinal injuries differ from other levels of injury in terms of function and prognosis?
150
→ They cause paralysis below the shoulders but often preserve some arm or neck movement.
151
32. How does ALS affect the nervous system
and why is it a key target for BCIs?
152
→ ALS destroys motor neurons
leading to paralysis but leaving the brain intact — allowing BCIs to restore communication.
153
154
The Biology of Aging and Longevity
155
1. What are the hallmarks of aging?
156
→ The hallmarks include genomic instability
telomere attrition
157
2. What is cellular senescence
and how do “zombie” cells drive inflammation and tissue decline?
158
→ Cellular senescence is a state in which damaged or stressed cells permanently stop dividing. These “zombie” cells secrete inflammatory molecules (the SASP—senescence-associated secretory phenotype) that damage nearby cells and promote chronic inflammation.
159
3. What evidence shows that senescent cells cause aging rather than just accompany it?
160
→ Studies in mice show that selectively removing senescent cells extends lifespan and improves tissue function
demonstrating a causal role in aging.
161
4. What does antagonistic pleiotropy mean
and how does it explain the persistence of senescence in evolution?
162
→ Antagonistic pleiotropy refers to genes that are beneficial early in life (e.g.
for wound healing or tumor suppression) but harmful later (e.g.
163
5. What happens to a cell when its telomeres become critically short?
164
→ The cell undergoes replicative senescence or apoptosis
as the DNA damage response halts further division to prevent genomic instability.
165
6. What is telomerase
and which cells does it function in?
166
→ Telomerase is an enzyme that elongates telomeres. It is active in germ cells
stem cells
167
7. How is telomere shortening linked to organismal aging and age-related diseases?
168
→ Telomere erosion limits cell renewal capacity
leading to tissue dysfunction and increased risk for diseases like fibrosis
169
170
Immune & Genetic Strategies to Combat Aging
171
11. How does CAR-T cell therapy work
and how might it be adapted to eliminate senescent cells instead of cancer cells?
172
→ CAR-T cells are engineered immune cells that recognize specific antigens. Modified CAR-Ts could target markers unique to senescent cells (e.g.
uPAR) to clear them selectively.
173
12. What is the concept of a “senescence vaccine”?
174
→ A vaccine could train the immune system to recognize and destroy senescent cells using antigens specific to their surface
reducing age-related inflammation.
175
13. How are LINE-1 retrotransposons (“jumping genes”) linked to inflammation and genomic instability?
176
→ LINE-1 elements can copy and insert themselves into new DNA sites
causing mutations and triggering innate immune responses that promote inflammation.
177
14. Why does LINE-1 activation increase with age
and how does it amplify DNA damage and immune signaling?
178
→ Epigenetic silencing of LINE-1 weakens with age
leading to uncontrolled activation that causes DNA breaks and chronic interferon signaling.
179
15. How can reverse-transcriptase inhibitors (originally HIV drugs) reduce inflammaging and restore tissue health?
180
→ These drugs block LINE-1 replication
lowering DNA damage and inflammatory signaling
181
16. Why does Sinclair argue that aging may be treated like a chronic viral infection from within?
182
→ Because aging involves persistent activation of endogenous elements like LINE-1 that behave like internal “viruses
” driving inflammation and cellular damage.
183
184
Information Theory of Aging and Cellular Reprogramming
185
17. What is Sinclair’s “Information Theory of Aging”?
186
→ It proposes that aging results from the loss of epigenetic information—the cellular “software” controlling gene expression—while the genetic “hardware” remains intact.
187
18. What is the difference between digital and analog information in Sinclair’s framework?
188
→ Digital information = DNA sequence (stable).
189
→ Analog information = epigenetic regulation (flexible and damage-prone).
190
19. How does epigenetic noise act like “scratches on a DVD
” and what is meant by resetting the biological code?
191
→ Epigenetic noise disrupts gene regulation
like scratches disrupting playback. Resetting the code restores proper epigenetic patterns
192
20. What did early cloning experiments (frog tadpoles
Dolly the sheep) prove about the persistence of youthful genetic information?
193
→ They showed that old or differentiated nuclei still contain all the information needed to generate a young organism—aging affects expression
not the DNA code itself.
194
21. What is somatic cell nuclear transfer (SCNT)
and why is it central to the idea that aging can be reversed?
195
→ SCNT transfers an adult cell’s nucleus into an egg cell
reprogramming it to an embryonic state—proving cellular youthfulness can be restored.
196
22. What are induced pluripotent stem cells (iPSCs) and Yamanaka factors?
197
→ iPSCs are adult cells reprogrammed into stem-like cells using four transcription factors—Oct4
Sox2
198
23. What risks arise from full reprogramming of adult cells
and why is partial reprogramming a safer approach?
199
→ Full reprogramming erases cell identity and may cause tumors. Partial reprogramming rejuvenates cells without losing their specialized function.
200
24. How did Sinclair’s team restore vision in mice using Oct4
Sox2
201
→ They reactivated OSK genes in retinal cells
reversing age-related damage and restoring optic nerve function—evidence that cellular age can be reset in vivo.
202
25. What does it mean that aging is a loss of access to information
not a loss of information itself?
203
→ The genetic data remains
but the cell loses proper control over which genes to express—aging results from corrupted regulation
204
205
The Mitochondrial Theory of Aging
206
32. What is the Mitochondrial Theory of Aging
and how has it evolved over time?
207
→ Originally
it held that accumulation of mitochondrial DNA damage and ROS leads to aging. Modern versions emphasize mitochondrial signaling
208
33. How does the electron transport chain (ETC) create both ATP and reactive oxygen species (ROS)?
209
→ As electrons pass through the ETC
some leak to oxygen prematurely
210
34. What are free radicals
and how can they be both beneficial and harmful?
211
→ Free radicals (ROS) are reactive molecules that can signal adaptive responses at low levels but cause oxidative stress and damage at high levels.
212
35. How do antioxidant systems neutralize free radicals
and why can excess antioxidants be counterproductive?
213
→ Enzymes like superoxide dismutase and glutathione peroxidase convert ROS into harmless molecules. Too many antioxidants can blunt beneficial stress responses (hormesis).
214
36. What is the “vicious cycle” of mitochondrial aging
and how does apoptosis prevent greater damage?
215
→ ROS damages mitochondrial DNA
impairing the ETC and generating more ROS. Apoptosis removes severely damaged cells to protect the organism.
216
37. What is mitophagy
and how does it preserve cellular health?
217
→ Mitophagy selectively removes dysfunctional mitochondria
maintaining energy balance and reducing oxidative stress.
218
38. What makes bird mitochondria more efficient than mammalian ones
and how does this explain avian longevity?
219
→ Bird mitochondria have tighter coupling and fewer ROS leaks
supporting high metabolism without equivalent oxidative damage—contributing to long lifespan.
220
39. How does uncoupling reduce ROS
and why is mild uncoupling protective while excessive uncoupling is fatal?
221
→ Mild uncoupling lowers membrane potential
reducing electron leakage and ROS formation. Excess uncoupling halts ATP production
222
40. What examples show the dangers of excessive mitochondrial uncoupling (DNP
MDMA)?
223
→ Drugs like DNP and MDMA overstimulate metabolism and heat production
causing hyperthermia and potentially fatal energy failure.
224
41. Why can’t standard CRISPR tools currently edit mitochondrial DNA?
225
→ CRISPR requires guide RNA
which mitochondria cannot import efficiently. Current tools can’t target or repair mtDNA with standard CRISPR components
bioengineering
flashcards
Decks in class (1)
# Cards
