Week 8

Question 1

important general features of immune responses to microbes?

Answer 1

response is mediated by both innate and adaptive effector mechanisms

response is distinct and specialized to effectively combat specific infectious agents

the ability to evade and resist the effector mechanisms that enable the microbe to survive

tissue injury and disease may be caused by the host response to the microbe

Question 2

what are some ways of direct host damage?

Answer 2

exotoxin secreted by bacteria
endotoxins wall of gram negative bacteria
direct killing of host cells (pathogen replication lyses host cell)
physical blockage
secrete toxins that directly damage host cell
interfere with synthesis of protein metabolism, change signalling pathways in the host cell, produce enzymes that damage host cell

Question 3

some examples of exotoxins?

Answer 3

clostridium tetani = tetanus (interferes with inhibitory neutrons)
staphylococcus aureus = toxic shock syndrome (release of toxins that act as super antigens = non specific T cell cytokine release)
streptococcus pyogenes = tonsillitis

Question 4

some examples of endotoxins?

Answer 4

escherichia coli = gram neg sepsis
haemophilus influenzae = meningitis pneumonia
salmonella type = typhoid fever

Question 5

examples of pathogens that cause direct cytopathic effect:

Answer 5

variola = smallpox
varicella-zoster= chickenpox/shingles
hepatitis B virus
polio virus = poliomyelitis 
measles virus 
influenza virus 
herpes simplex virus = cold sores

Question 6

what are some ways of indirect host damage?

Answer 6

immune complexes (HepB, malaria)
molecular mimicry
aberrant immune responses (T cells)
immune response against pathogen can lead to tissue damage in the host = granulomatous inflammation

Question 7

what is a chemoattract for Th17 cells?

Answer 7

CCL20

Question 8

what is a chemoattractant for monocytes?

Answer 8

CCL2 (produced by Th1)

Question 9

what are some bacterial strategies for avoiding and manipulating host immune responses:

Answer 9

escape epithelial defences - degrade mucous
escape from phagocytes and innate immunity - capsules, Ig binding, opsonization
evade adaptive immunity - resistance to Ab via capsules

Question 10

what are some ways that bacteria resist innate immune responses?

Answer 10

prevention of lysosome-phagosome fusion
escape into the cytoplasm from phagosome
resistance to lysosomal enzymes

Question 11

what are the different serogroups of neisseria meningitides?

Answer 11

A, B, C, X, Z, W135

Question 12

which Neisseria meningitides serogroups have the capsular polysarccharides?

Answer 12

A, C, W135 and Y

capsule used as a conjugate in vaccine

Question 13

why is Nm serogroup B poorly immunogenic?

Answer 13

B capsular polysaccharide is poorly immunogenic because identical to the polysialic acid present in many human glycoproteins

group B vaccine is protein antigen based

Question 14

hydroxyurea?

Answer 14

antimetabolite- urea analogue

- inhibits ribonucleotide reductase, thus interfering with the conversion of ribonucleotides to deoxy ribonucleotides

Question 15

what phase do antimetabolites work at?

Answer 15

S phase

Question 16

pharmacokinetics of alkylating agents?

Answer 16

cyclophosphamide- needs P450 metabolism in liver for activity

Question 17

what phase do alkylating agents work?

Answer 17

not cell specific but predominantly S phase

cell cycle block at G2

Question 18

adverse effects of platinum compounds?

Answer 18

myelosuppression, CINV

cisplatin = nephrotoxic, ototoxic

Question 19

indication for platinum compounds?

Answer 19

primary tx for ovarian and testicular cancer

Question 20

what phase do vinca alkaloids work?

Answer 20

M phase

Question 21

what phase do taxanes work at?

Answer 21

G2-M phase

Question 22

difference between vinca alkaloids and taxanes?

Answer 22

vinca alkaloids binds b tubulin and block polymerization with a-tubulin into MT = prevents spindle formation in dividing cells and causes arrest at M phase

taxanes: stabilize MT in non-functional polymerized state and thus can’t pull part for cell division

Question 23

indications for taxanes?

Answer 23

ovarian cancer

Question 24

at which phase do topoisomerase 1 inhibitors work at?

Answer 24

S phase

Question 25

adverse effect of anthracylcines?

Answer 25

long term therapy can lead to cardiomyopathy

Question 26

which drug is used as a chemical carceration in sex offenders?

Answer 26

cyproterone (anti-androgen) - has prosgestogenic effects that decrease production of testosterone

Question 27

actions of mTOR1?

Answer 27

``` protein synthesis ribosome biogenesis cell survival proliferation angiogenesis invasion migration/ metastases ```

Question 28

actions of mTOR2?

Answer 28

cell survival cell cycle progression actin remodelling

Question 29

indications for nivolumab?

Answer 29

NSCLC, melanoma

Question 30

indications for ipilimumab?

Answer 30

metastatic melanoma

Question 31

mechanism of cytotoxic drug resistance: transport?

Answer 31

decreased accumulation of cytotoxic drugs in the cells due to increased expression of drug transport efflux pumps (P-glycoprotein) decreased amount of drug uptake in cell

Question 32

mechanism of cytotoxic drug resistance: metabolic?

Answer 32

decreased metabolic activation of drug (5-FU) increased inactivation of the drug (anti-metabolites) increased concentration of target enzymes (methotrexate - DHFR) decreased requirement for substrates/ utilization of alternative metabolic pathways

Question 33

mechanism of cytotoxic drug resistance: targets?

Answer 33

mutations leads to altered/ resistant target molecules increased repair of drug induced dNA damage inhibition of apoptosis

Question 34

difference between cocaine and methamphetamines?

Answer 34

cocaine: shorter duration of action; blocks reuptake of DA meth: longer duration of action; blocks reuptake of DA and stimulates the release of DA from VMAT2

Question 35

what are some physical harms with stimulants?

Answer 35

``` OD renal failure cardiac failure seizure MI rhabdomyolosis malnutrition ```

Question 36

long term effects of amphetamine use

Answer 36

chronic insomnia psychosis - lasting up to weeks HTN, abnormal HB, MI risk self medication with psycho depressants malnutrition, less resistant to infections (BBV) brain damage: memory impairment, cognitive/ motor impairment, impaired thinking violent, aggressive behaviour

Question 37

what are the 3 phases of amphetamine withdrawal and what is the onset and durations?

Answer 37

crash phase: 12-24 hrs after use, subsides 2-4 days withdrawal phase: 2-4 days after use; subsides over 2-4 weeks extinction phase: weeks to months

Question 38

what are some characteristics of the crash phase of amphetamine withdrawal?

Answer 38

low cravings fluctuations in mood disturbed sleep, exhaustion, fatigue generalized aches and pain

Question 39

what are some characteristics of withdrawal phase of amphetamine withdrawal?

Answer 39

strong cravings increased appetite fluctuating mood disturbed sleep, vivid dreams, insomnia, poor concentration/ attention disturbed thoughts/ perceptions that can re-emerge but were masked in crash phase

Question 40

what are some characteristics of extinction phase of amphetamine withdrawal?

Answer 40

gradual resumption to normal mood with periodic episodes of mood changes disturbed sleep episodic cravings

Question 41

more prominent effects of cocaine when compared to amphetmaines?

Answer 41

hyperthermia pulmonary edema seizures muscle rigidity

Question 42

the effects of GHB?

Answer 42

seizures, resp depression, coma, N&V, aggression hypnotic with narrow therapeutic window so ID is common

Question 43

what is the safe level of caffeine for adults?

Answer 43

<400mg/day for adults

Question 44

specific opiate withdrawal symptoms?

Answer 44

goosebumps, yawning, runny nose, abdo cramps, diarrhea

Question 45

specific withdrawal symptoms for alcohol?

Answer 45

tremors, confusion (seizures, delirium, hallucination), fever

Question 46

onset and duration of alcohol withdrawal?

Answer 46

3-24 hours | 4-10days

Question 47

mechanism of dependance and withdrawal for cocaine?

Answer 47

increase expression of DAT increased presynaptic DA receptors presynaptic DA is depleted

Question 48

what is the safe level of caffeine per day?

Answer 48

<400mg/day

Question 49

Th1 functions in IC bacteria: | IL3 and GM-CSF?

Answer 49

IL3 and GMCSF= stimulate production of monocytes in BM

Question 50

Th1 functions in IC bacteria: | TNFa and LTa

Answer 50

act on local BV, activates endothelium to induce macrophage binding and exit from BV at the site of infection

Question 51

what is the chemoattractant for monocytes and where does it come from?

Answer 51

CCL2 made from Th1 cells

Question 52

how does escaping epithelial defences help -bacteria avoid immune response?

Answer 52

interfere with physical barrier - degrade mucus attachment and colonization evasion of immune recognition (antigenic variation and LPS)

Question 53

how do bacteria escape from phagocytes and innate immunity?

Answer 53

capsules, Ig binding, opsonization, complement | interfere with phagocytosis and phagocyte recruitment (degrades chemokine)

Question 54

how do bacteria evade adaptive immunity?

Answer 54

resistance to bacteria | interfere with cytokine secretion, Ag presentation

Question 55

what is the characteristic pathological feature tb?

Answer 55

tb cavity formed when caseated and liquefied centre of tubercular pulmonary lesion is discharged into a bronchus

Question 56

how is dx of tb made?

Answer 56

chest x ray sputum is stained with stain for acid and alcohol fast bacilli immune based tests (mantoux test)

Question 57

prevalence of lynch syndrome?

Answer 57

1:660 - 1:2000

Question 58

prevalence of hereditary breast and ovarian cancer?

Answer 58

1:1600

Question 59

prevalence of familial adenomatous polyposis?

Answer 59

1:8000

Question 60

prevalence of cowed syndrome?

Answer 60

1: 20 000 | very rare

Question 61

prevalence of li-fraumeni syndrome?

Answer 61

very rare

Question 62

prevalence of von-hippel lindau syndrome?

Answer 62

1: 36 000

Question 63

difference between septic shock and toxic shock syndrome?

Answer 63

septic shock = mediated by macrophages and endotoxin (LPS) | toxic shock syndrome = mediated by T cell cytokines and endotoxin (staph aureus)

Question 64

What is the consequence of the immune suppression seen in severe sepsis?

Answer 64

The cytokine storm seen in sepsis can cause activation-induced cell death (T cells, dendritic cells, etc.) and suppression of antigen presentation leading to the loss of adaptive immune responses. Immunosuppressed patients are then at increased risk of opportunistic infection. Anti-inflammatory cytokines (e.g. IL-10) released to allow return to homeostasis also impair APC/T cell function. Immunosuppression in severe sepsis predisposes patients to secondary infection that can delay recovery of organ function following the initial pro-inflammatory response. It also has important implications in the care of the elderly septic patients, as elderly patients exhibit increased susceptibility to both infection and septic shock.

Question 65

septic shock?

Answer 65

Septic shock: sepsis is the presence of an infection in the bloodstream that results in the excessive release of TNF-alpha from macrophages throughout the body. The systemic release of TNF-alpha into the blood causes vasodilation and increased vascular permeability, this, in turn, leads to loss of plasma volume and eventual shock, also known as septic shock. This damage to capillary endothelium and vessel wall vasodilation which may also lead to multiple organ failure due to ischaemia.

Question 66

how does neisseria meningitides evade immune response?

Answer 66

polysaccharide capsule changes surface proteins (evade adaptive immunity) This pathogen also produces IgA1 proteases which serve as a virulence factor by overriding mucosal immunity

Question 67

how does meningococcal present? (Nm)

Answer 67

septecemia and meningitis

Question 68

what class of bacteria is TB?

Answer 68

classified as acid fast bacteria due to their impermeability by certain dyes and stains.

Question 69

how does Tb spread?

Answer 69

M. tuberculosis primarily infects alveolar macrophages but can infect other cell types. It then transits to lung parenchyma where it can infect resident macrophages or other phagocytes like neutrophils. Have the ability to replicate inside macrophages. Immune signals produced by infected macrophages provide additional target for infection. Bacteria can also be taken up by DCs to circulate to thoracic lymph node, where they activate T cells. These T cells return to the infectious site and organise around infected macrophages to form granulomas, which serves as a reservoir for bacteria.

Question 70

Anti-TB drug resistance is a major public health problem that threatens TB care and control worldwide. Why has TB drug resistance emerged?

Answer 70

Spontaneous gene mutations in TB render the bacteria resistant to anti-TB drugs thereby increasing their chance of survival and consequent transmission to other people when not adequately treated. Because the standard treatment for TB calls for a strict six-month drug regime, compliance with the treatment is very often very challenging and rates of non-compliance or premature treatment interruption can be high, allowing for the development of drug-resistant bacteria that can then be transmitted to other people.