:)))) Flashcards

Question

describe the structure of two motors in ATP synthase what are they used for?

Answer 1

function: converting ion gradients to ATP in ATP synthase: - 2 motors - one electrical, one chemical - one motor location: membrane - powered by flow of protons - one motor location: intermembrane space: powered by ATP WHEN ONE TURNS, CAUSES THE OTHER TO TURN

Answer 2

- myosin has two heads: one binds to ATP, one binds to actin. - when ATP binds to myosin. ATP is hydrolysed as a result. - change in 3D shape of myosin. - changes the position between actin and myosin filaments - = muscle contracts

Answer 3

- thermogenin (uncoupling protein): found in the mitochondria of Brown adipose tissue - allows passage of protons back into mt matrix - generates HEAT - do not have enzyme activity to catalyse production of ATP - so H+ move down energy gradient without using this energy for synthesis of ATP = NON SHIVERING HEAT PRODUCTION **with ATP synthase:** - ATP synthase and thermogenin / uncoupling protein work in parrallel - both in mitochondria membrane - uncoupling protein generates HEAT - ATP synthase generates ATP - last step in ox. phosphorylation

Answer 4

* *stores:** - ATP - Phosphate - PMF * *uses:** - anabolism (synthesis of x) - transport (primary / secondary AT) - motility - heat

Answer 5

- extreme resistance to antiobiotics and other anti-microbrial agents - high resistance to host immune defences

Answer 6

bacterial patogens often produce degradative enzymes - aka spreading factors: facilitate growth and spread of pathogen (dont kill host cells) * *1. hyaluronidase:** - breaks down hyaluronic acid (intracellular cement of CT). e.g. Strept. spp, Staph aureas. allows invasion further into tissues * *2. collagenase:** - breaks down collagen network - gives access to deeper tissues. E.g. Clostridium spp.

Answer 7

* *1. triggered invasion:** - bacteria inject virulence factors into host cell cytoplasms to activate uptake by cell - bacteria force the cell to extend local protrusion that engulf the bacterium - = type 3 secretion system-dependent - Salmnoella spp, Shigella flexneri * *2. Zippered invasion:** - bacteria produce outer membrane protein, with extracellular part exposed - recognises receptor on target cell - taken up by the cell - specifc high affinity interaction between bacteria molecule and host cell receptor.

Answer 8

Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. **Type II:** IgG/IgM to patients own RBCs due to M. pneumonia **Type III:** complement activation causing inflammation e.g. S. pyogenes causing glomerulonephritis **Type IV:** T cell mediated e.g. TB granulomas

Answer 9

**non specific**: Force of attraction e.g. Van der Waals forces * *specific:** - Proteins on microbe cell surface binds to host cells e.g. Hemagglutinin - Fimbriae interact with cell surface receptors - Pili transfers DNA between Bacteria all creates a dense biofilm that protects pathogen

Answer 10

innate immune response

Answer 11

opsonisation: **(C3b and IGG):** membrane attack complex (MAC): **(C5b)** inflammation: **(C5a & C3a)**

Answer 12

microbiocidal effects 1. escape from endosome-phagosome and grow in cytoplasm: Listeria / Shigella 2. inhibition of phagosome-lysosome fusion: Leigonella pneumophilia 3. survive within phagolysosome 4. replicate within phagolysosome: Salmonella

Answer 13

detoxifcation of oxygen derived harmful substances from the host: e.g. some microbes have: - superoxide dismutase (SOD): neutralises free radicals such as O2 - catalase (breaks down H2O2): e.g. Staph. aureas

Answer 14

- create **IgA proteases** - these destroy IgA (IgA coat foreign microbes with mucous)

Answer 15

1. toxins that damage membranes: **cytolysines and pore forming toxins.** help spread of bacteria 2. toxins that act as enzymes: **A/B toxins,** more diverse group of toxins - 2 subunits: A&B - _A = enzymatic activity_ - _B = binds to cell membrane_ (allows A to go into cell( 3. toxins that activate immune response: **superantigens**

Answer 16

**gram negative bacteria** **location**: outer membrane of bacteria cell wall **structure**: lipid A, core polysaccharide, O antigen lipid A = toxic activates complement and stimualtes producion of **cytokines**: results in _septic shock, ferver, intravascular coagulation = haemorrage and endotoxin shock._

Answer 17

detoxifcation of oxygen derived harmful substances from the host: e.g. some microbes have: - superoxide dismutase (SOD): neutralises free radicals such as O2 - catalase (breaks down H2O2): e.g. Staph. aureas

Answer 18

* *superantigens:** - induces _non-specific class II MHC and T cell receptor binding: w_idespread binding stimulation of T cells. - **Excessive cytokine release:** fever, vomiting, diarrhea, organ failure * *- 20 / 30% T cells activated**

Answer 19

- some microbes can cause development of chronic inflam processes: **H. pylori (**stomach cancer) - some **viruses incorp. nucleic acids into host genome:** cause development of cancers - **Hep B:** hepatocellular carcinoma - **HIV**: lymphoma - **HPV**: cervical carcinoma - **Epstein Bar** - Burkitt’s lymphoma

Answer 20

a) Th1: **IL-12** b) Th2: **IL-4**

Answer 21

mycobacterial infections

Answer 22

glycopeptide antibiotics: **gram postive** polymyxins: **gram negative**

Answer 23

- inhibition of **bacterial cell wall synthesis** - inhibition of **bacterial protein synthesis** - inhibition of **DNA transcription and replication** - inhibition of **RNA synthesis and replication** _most successful hit:_ - rb - cell wall synthesis - DNA gyrase or DNA toposiomerase

Answer 24

**quinolones / fluoroquinolones:** - broad spectrum - bind to topoisomerase II (DNA gyrase) and topoisomerase IV and inhibit DNA synthesis. **Rifampicin**: - acts on RNA transcription: inhibits RNA polymerase on gram postive - treats TB

Answer 25

**susceptibility**: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a high likelihood of therapeutic success **intermediate**: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a uncertain therapeutic success **resistant**: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a high likelihood of therapeutic failure **breakpoint concentration:** A breakpoint is a chosen concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic. changes all the time

Answer 26

- **aminglycosides**: change shape of 30S portion & disrupt the structure (Gentamicin, tobramycin and amikacin). Gram-negative bacteria. can cause hearing loss and renal impairment. IV drugs - **tetracyclines**: bind to 30S. interfere with attachment of tRNA to rb. oral drugs - **macrolides**: bind to 50s subunit. prevents translocation - **chloramphenicol**: bind to 50S, inhibit formation of peptide bond

Answer 27

effect of drug regarding its antimicrobial activity can differ regarding PD indices: * *- Cmax / MIC ratio** - concentration depending killing: most importnat is getting high conc above MIC. - **T\>MIC - t**ime dependent killing - most important is time above MIC. with minimal prolonged antibiotic effect * *- AUC24 / MIC ratio** - combo of above time dependent killing with prolonged antibiotic effect

Answer 28

normally used to pump out metabolic waste: - undergo mutations - **pump out drug instead** - high level of resistance provided - genes for **multidrug resistance** efflux pumps integrate into plasmids can **transfer between bacteria: can be acquired or intrinsic**

Answer 29

1. drug inactivation 2. activation of drug pumps (pump out) 3. modification of target: e.g. acquire new gene that methylates Rb, so is resistant to drugs that target Rb. 4. alternative metabolic pathways: e.g. with FA production, get mutations which mean that enzymes change structure so cant be targeted

Answer 30

**B-lactamases** (aka penicillinase): Beta-lactamases are enzymes (EC 3.5. 2.6) produced by bacteria that provide multi- resistance to β-lactam antibiotics such as penicillins - beta-lactamase hydrolyse the b-lactam antibiotics and make it ineffective beat this by: use inhibitors of b-lactamases.

Answer 31

the highly cirtical ones are all **gram negative: have multi drug resistance.** BUT THERE ARE NO NEW DRUGS IN THE PIPELNE :(

Answer 32

1. **gram-negative bacteria**: outer membrane forms a permability barrier - drugs cannot cross 2. **efflux** **pumps**: active transporter. Efflux systems function via an energy-dependent mechanism (active transport) to pump out unwanted toxic substances through specific efflux pumps.

Answer 33

Reverse transcriptase – turns +ssRNA into DNA Integrase – integrates viral DNA with host genome Protease – help create viral building blocks RNA polymerase – forms mRNA before going to ribosome

Answer 34

* *Latency**: Dormancy that reactivates when host is immunocompromised e.g. HIV, Herpes * *Phagocyte** **evasion**: Prevention of phagosome and lysosome fusion e.g. HIV * *Antigenic shift and drift:** Genetic shuffling and random mutation makes immune system naïve again * *Hiding**: Within cells: HSV, VZV, malaria

Answer 35

* *Ro =** av. number of new transmissions per case over infectious period in sus or non vaccinated pop * *1/ Ro** = proportion of the population sus. to virus (aka epidemic threshold) * *Ro \< 1** infection dies out * *Ro \> 1** infection will spread * *Ro = 1** infection stable ## Footnote **proportion of pop. that needs to be vaccinated to eliminate virus: 1-1/Ro**

Answer 36

Targets viral **replication process:** **• Reverse transcriptase:** RNA to DNA * **Integrase**: integration of viral genetic material into host genome * **Protease**: cleave precursor proteins

Answer 37

- the **virus life cycle** is tied to **host** **cell**: difficult to target virus alone - viruses are **difficult** to **grow** - most virus infections are **short lived** - compound must block virus replication compelely otherwise the virus will **mutate and become resistant**

Answer 38

- dsDNA viruses - stays **latent** in body after infection: - **chickenpox** **infection**: virus goes into **dorsal root ganglia** and stays **latent** and can reemrge later in life as **shingles**

Answer 39

**acyclovir**: - reduces symptoms but doesnt cure **- mimics one of the 4 bases for DNA (but misses OH group): terminates DNA sythesis** _- prodrug mechanism:_ - has to be activated by HSV enzyme **thymdine kinase** to **add P** - cellular kinases add 2nd and 3rd P - chain termiantes - can get resistance - need to treat IC patients

Answer 40

**Antigenic shift**: combination of different viral RNA in the host cell to produce a new variant **Antigenic drift:** accumulation of random mutations during viral replication

Answer 41

drugs: **HAART** (Highly Active ART) Uses a variety of inhibitors in from different classes of anti-viral drugs to reduce the viral load. * Entry inhibitors * Reverse transcriptase inhibitors (NRTI, NNRTI) * Integrase inhibitors * Protease inhibitors * Fusion inhibitors