foundation II Flashcards
immunity, microb
Which of the following is an example of a physical barrier against pathogens?
A) Antimicrobial proteins
B) Skin
C) Defensins
D) Acidic pH
B) Skin
* Acidic pH (D) is one of the chemical barriers against pathogens
* antimicrobial pathogens (A) (e.g. defensins (C)) is another type of barrier
Pattern Recognition Receptors (PRRs) recognize Damage-Associated Molecular Patterns (DAMPs).
True or false?
False
* PRRs on innate immune cells recognise PAMPs on pathgens
*
TLR = major class of PRR
specific PAMPs found on gram (-) and gram (+) bacteria respectively
(and which TLRs they each bind to)
gram (-) bacteria: LPS
→ detected by TLR 4
gram (+) bacteria: peptidoglycan
→ detected by TLR2
“4 very 不吉利 so it’s gram (-)
while 2 is 吉利 so it’s gram (+)”
how are Damage-Associated Molecular Patterns (DAMPs) different from Pattern-Associated Molecular Patterns (PAMPs)
pathogen infects cells and cause cellular DAMAGE
-> injured cells produce DAMPs
-> DAMPs bind to PRRs
=> confirms VIRULENCY
and helps to initiate STRONGER inflammatory response
and which cells are they secreted by
what cytokines activate NK cells
- IFN-α and IFN-β
- secreted by infected cells
and which cells is it secreted by
what cytokine helps to increase cytotoxicity of NK cells
- IL-12
- secreted by macrophages
“12 = 1 -> 2 = powering up”
what do NK cells target
intracellular pathogens
* virus (MAIN)
* mycobacteriae
how do NK cells kill infected cells
- via antibody-dependent cellular cytotoxicity (ADCC): release granules containing perforins, granzymes and granulysins
⇒ form pores and enter to trigger apoptosis - release of Fas ligand
→ binds to Fas receptor
⇒ triggers apoptosis
Which type of pathogen is most likely to be processed via the MHC I pathway?
A) Intracellular viruses
B) Fungi
C) Extracellular bacteria
D) Parasites
A) Intracellular viruses
* MHC I: intracellular pathogens (e.g. virus, mycobacteriae)
* MHC II: extracellular bacteria
specify ligands and receptors
how do the ligands secreted by epithelial cells of lymph node guide movement of T cells and dendritic cells
- epithelial cells in lymph nodes secrete CCL19, CCL21 and L-selectin ligand
- T cells express the receptors CCR7 and L-selectin
→ binding to ligands act as a “stay here” signal - DC upregulate expression of receptor CCR7 during MATURATION
→ migrate to (T cell zones) of lymph nodes via chemokine gradient of CCL19/CCL21
what signals are involved in activation of T cells
2 signals
1. MHC-TCR signal
2. co-stimulation signal (B7-CD28)
signal #2 in activation of T cells
what is the ligand and receptor involved in co-stimulatory signal
- ligand: B7 on dendritic cells
- receptor: CD28 on T cells
how does activated T cells promote proliferation
synthesise IL-2 AND IL-2 receptors
→ binding of IL-2 and IL-2R
⇒ stimulates proliferation
what stimulates the differentiation of Th cells
an extra signal (compared to Tc cells)
and which cells is it released by
what cytokine stimulates the differentiation of Th into Th1
- IL-12
- released by DC
and which cells is it released by
what cytokine stimulates the differentiation of Th into Th2
- IL-4
- released by Th2
and which cells is it released by
what cytokine does Th1 secrete
and why
IFN-γ
→ activate macrophages into M1
(pro-inflammatory)
⇒ increase phagocytosis of intracellular pathogens
(mainly viruses)
and which cells are they released by
what cytokines do Th2 secrete
and why
IL-4, IL-5 and IL-13
* IL-4: induces class switching to IgE in B cells
⇒ for allergic reactions
+ to fight off parasites
* IL-5: recruits and activates eosinophils
⇒ to fight off parasites
* IL-4 and IL-13:
activate macrophages into M2
(pro-healing)
⇒ to wall off tissue (containment) and repair the tissue
strategy to fight off parasites (e.g. helminths):
* coat them in antibodies (IgE)
* recruit eosinophils and mast cells to degranulate and damage them externally
is there cross regulation between Th1 and Th2
Yes!
* IFN-γ secreted by Th1
inhibits Th2 proliferation
* TGF-β and IL-10 secreted by Th2
inhibits Th1 proliferation
which 2 immune cells have the same mechanism of killing cells
NK cells and CD8+ Tc cells
how exactly?
recall!
* via antibody-dependent cellular cytotoxicity (ADCC): release granules containing perforins, granzymes and granulysins
⇒ form pores and enter to trigger apoptosis
* release of Fas ligand
→ binds to Fas receptor
⇒ triggers apoptosis
what changes in the T cell help with its migration to site of infection
after activation (and differentiation if have)
-
downregulation of receptors CCR7 and L-selectin
=> allows T cells to leave lymph nodes -
upregulation of S1P receptors
AND upregulation of LIGANDS for adhesion molecules and chemokine receptors
(in response to upregulation of adhesion molceules and chemokines at site of infection)
=> helps T cells to migrate to and slow down to a stop at site of infection
All nucleated cells can express MHC II molecules.
True or False?
False!
* MHC I can be expressed in all nucleated cells
← all cells can be infected by intracellular pathogens
* MHC II only expressed by APCs
(i.e. dendritic cells, macrophages, B cells)
← bcos it’s to fight off extracellular pathogens like parasites and thus more specialised
MHC I is present in all nucleated cells = NOT present in RBCs
how is activation of T cells terminated
upregulation of receptor CTLA4 on T cells
→ which binds to B7 with higher affinity than CD28
⇒ delivers inhibitory signals
Which of the following correctly represents the developmental lineage of T and B lymphocytes?
A. Common myeloid progenitor → Lymphoblast → T and B cells
B. Hematopoietic stem cell → Myeloid progenitor → T and B cells
C. Hematopoietic stem cell → Lymphoid progenitor → T and B cells
D. Hematopoietic stem cell → NK progenitor → T and B cells
C. Hematopoietic stem cell (HSC)
→ Lymphoid progenitor
→ T and B cells
both T and B cells originate in bone marrow
myeloid progenitors give rise to other cells like RBCs and phagocytes (macrophages, neutrophils, etc)
where do T cells and B cells mature respectively
- T cells: migrate to Thymus
- B cells: remain in Bone marrow
what does central tolerance involve
-
positive selection: selection of T cells w/ TCR that binds self-peptide presented by self-MHC with some activity (low, mod, high)
(for MHC restriction: TCRs only recognise antigens complexed w/ self-MHCs) - negative selection: elimination of T and B cells w/ receptors that bind self-peptide presented by self-MHC w/ high activity
Autoimmune regulator (AIRE) in the thymus induces transient expression of (…) antigens found in (…),
aiding in negative selection of T cells
Autoimmune regulator (AIRE) in the thymus induces transient expression of self-antigens found in extra-thymic tissues (e.g. skin),
aiding in negative selection of T cells
beore positive (and negative) selection
how is initial TCR and BCR diversity generated during T and B cells maturation
somatic recombination:
* V(D)J recombination
→ for combinatorial diversity
* junctional diversity
enzymes involved:
* V(D)J recombination: RAG
* junctional diversity: TdT
B cell activation
inside follicle:
* B cell acquires antigen via BCR
* processes and presents antigen on MHC II
-> exits follicle:
* activation of B cells by interaction w/ Th cells
-> EITHER enters bloodstream:
* becomes short-lived plasma cells which secrete IgM
OR enters follicle again:
* proliferation
* somatic hypemutation (due to AID in dark zone)
* bind to iccosomes on follicular DCs
* B cells w/ high affinity BCRs rip off and internalise antigen
* present antigen on MHC II
* proliferation
* EITHER presence of blimp signalling:
become plasma cells,
and then undergo isotype switching via stimulation by same Th cell
OR absence of blimp signalling:
become memory cells
Which molecule is most directly involved in determining whether an activated B cell becomes a plasma cell?
a) AIRE
b) T-bet
c) BLIMP
d) GATA3
c) BLIMP
* presence of BLIMP signalling:
become plasma cells,
can then undergo isotype switching (with help of Th cells)
* absence of BLIMP signalling:
become memory cells
activation of B cells:
1. Naive B cells first encounter antigen in the (…), using their membrane-bound (…) to bind the antigen.
2. These B cells internalise, process, and present the antigen on (…) molecules.
3. After this, B cells exit the (…)
and interact with (…) cells which (…) them.
4. Some of these B cells then take the extrafollicular route, becoming (…) plasma cells that secrete (…).
5. Others enter the follicle again,
and in the (…) of the germinal center, B cells rapidly proliferate and undergo (…), mediated by the enzyme (…).
6. In the light zone, B cells then test their new BCRs by trying to bind antigens displayed on (…) held by (…) cells.
7. Those with high-affinity receptors internalise the antigen again, present it on (…), and start proliferating.
8. If the transcription factor (…) is expressed, B cells differentiate into (…) cells, and can then undergo (…) with the help of Th cells (the same ones as before).
9. However, if (…) is not expressed, B cells become (…) cells.
- Naive B cells first encounter antigen in the follicle, using their membrane-bound BCR to bind the antigen.
- These B cells internalise, process, and present the antigen on MHC II molecules.
- After this, B cells exit the follicle
and interact with Th cells which activate them. - Some of these B cells then take the extrafollicular route, becoming short-lived plasma cells that secrete IgM
- Others enter the follicle again,
and in the dark zone of the germinal center, B cells rapidly proliferate and undergo somatic hypermutation mediated by the enzyme AID - In the light zone, B cells then test their new BCRs by trying to bind antigens displayed on iccosomes held by follicular dendritic cells.
- Those with high-affinity receptors internalise the antigen again, present it on MHC II and start proliferating.
- If the transcription factor Blimp is expressed, B cells differentiate into plasma cells, and can then undergo isotype switching with the help of Th cells (the same ones as before).
- However, if Blimp is not expressed, B cells become memory cells.
What is the recommended treatment for Herpes Simplex Virus (HSV) infections?
A) Doxycycline
B) Acyclovir
C) Benzylpenicillin
D) Rifampicin
B) Acyclovir
Violet recycling bin
=> Treatment of Acyclovir
or Valacyclovir
NOT mouth
The hallmark symptom of Herpes Simplex Virus (HSV) affecting the lips is known as (…).
gingivostomatitis
(i.e. inflammed lips)
What type of DNA is characteristic of HSV?
double-stranded linear DNA
* Blue background + Boy wearing blue shirt
=> DNA virus
* Double white lines on road
=> double-stranded linear DNA
Aseptic Meningitis is more common with HSV-1 than HSV-2.
True or False?
False
* HSV-1: encephalitis (with (necrosis and haemorrhage) is more common
← Hermes is wearing a black helmet which has red wings attached to it
* HSV-2: aseptic meningitis is more common
← Herpes wearing neckbrace
Which of the following is a symptom of Varicella-Zoster Virus?
A) Herpetic whitlow
B) Herpes genitalis
C) Snake-like pattern on cornea
D) Lesions in different stages of healing all simultaneously present
D) Lesions in different stages of healing all simultaneously present
← Sign that says “All ages welcome!”
The latent form of VZV remains in the (…) ganglia.
dorsal root
← Roots of tree at dorsal part of picture
The vaccine for VZV is safe for all HIV patients.
True or False?
False!
Vaccine only given to HIV patients if their CD4 count < 200
← shade has sign that says “Max Occupancy: 200”
for which virus will the patient develop a maculopapular rash if given aminopenicillin?
A) Leptospira interrogans
B) Epstein-Barr Virus
C) Varicella-Zoster Virus
D) Herpes Simplex Virus
B) Epstein-Barr Virus (EBV)
Mischievous boy using red pen to draw red circles on sleeping archer’s face
→ if mistakenly give aminopenicillin (ampicillin/amoxicillin),
Patient can develop maculopapular rash
EBV envelope glycoprotein binds to (…) to infect B cells.
CD21
Sign stating “Must B 21”
→ EBV envelope glycoprotein binds CD21 to infect B cells
In patients with EBV, monospot test can be used to detect IgG antibodies.
True or False?
False!
Star-shaped darts clumped at one spot of dartboard
→ Monospot test detecting for IgM antibodies can be used for rapid DIAGNOSIS
What are some neoplasms which are associated with EBV
-
Nasopharyngeal carcinoma,
(associated with asian patients)
← asian man, whose nose is being pinched by a crab, sitting at bar -
Burkitt lymphoma,
(mainly the endemic African form)
← Bar keep’s child, who is dressed in African clothes and eating crab, also sitting at the bar - Hodgkin’s lymphoma
(which has Reed-Sternberg cells that look like “owl’s eyes”)
← Picture of a stern owl sitting among reeds
hanged up on the wall
recall!
burkitt lymphoma involves t(8;14) translocation
← burkitt has 7 letters abd 7 + 1 = 8
what is the triad of symptoms commonly associated with Rickettsia species infections
-
fever (in early infection) and headache
← sweating tennis player, holding head in frustration, after losing the match -
rash
← the tennis player who lost throwing racket on ground after losing, resulting in it breaking and forming red bumps on the floor of the court
Rickettsial rashes typically spare the trunk of the body.
True or False?
False!
* R. prowazekii: rash that STARTS AT TRUNK,
and spreads outwards towards extremities
← gameplay involves players spreading out
* R. rickettsii: rash eventually spreads centrally from extremities
← 3 climbers representing presentation of rash at different time periods of infection,
with climber at the top having redness everywhere
what is the treatment for Rickettsia infections?
doxycycline
← all 3 cases have a banner which says that event is sponsored by “Ricketts Tires”
Which bacteria contains spores found in animal feces and causes pneumonia and headache?
Choices
A) Leptospira interrogans
B) Coxiella burnetii
C) Campylobacter jejuni
D) Borrelia burgdorferi
B) Coxiella burnetii
Picture: Curly Q the ram
* bag of walnuts lying beside poop
⇒ contained in spores found in animal faeces
* after breathing in dust cloud that ram kicks up,
farmer coughs and also hits his head
⇒ pneumonia and headache
Weil’s disease is associated with Borrelia burgdorferi.
True or False?
False!
* Weil’s diseases is associated with Leptospira interrogans
← whale
* Borrelia burgdorferi is instead associated with Lyme disease
← archers dressed in lime-coloured clothes for the archery competition
Which bacteria is transmitted by ticks and causes relapsing fever?
A) Borrelia recurrentis
B) Leptospira interrogans
C) Borrelia duttoni
D) Coxiella burnetii
C) Borrelia duttoni
* both Borrelia duttoni and Borrelia recurrentis involve relapsing fever
* Borrelia duttoni is transmitted by ticks while Borrelia recurrenti is transmitted by louse
Which of the following interactions is essential for initiating isotype switching in B cells?
A) CD28 on CD8+ T cell binding B7 on B cell
B) CD40L on CD4+ T cell binding CD40 on B cell
C) CD28 on CD4+ T cell binding B7 on B cell
D) CD40L on CD8+ T cell binding CD40 on B cell
B) CD40L on CD4+ T cell binding CD40 on B cell
binding triggers cytokine release
→ which then stimulate gene arrangement
Which antibody isotype switch(es) is/are mediated by IL-4?
A) IgM → IgG
B) IgG → IgA
C) IgA → IgE
A) IgM → IgG
and C) IgA → IgE
IgG → IgA (B) is mediated by TGF-β
Match the hypersensitivity type with its corresponding mechanism:
- Type I: Allergy
- Type II: antiBody-mediated cytotoxicity
- Type III: immune Complex deposition
- Type IV: Delayed reaction
both type II and III hypersensitivity reactions involves binding to specific antigen target.
what’s the difference between the 2 types of reaction?
- type of antigen:
bind to antigen FIXED on cell or ECM in type II,
but bind to soluble antigens in circulation in type III - effect (after binding to antigen):
killing of cell or tissue via complement activation or opsonisation and phagocytosis in type II,
while forming immune complexes which circulate and then deposit in blood vessels in type III
think of the different T cell subtypes activated: 1) Th1 2) Th2 3) Tc
examples of type IV hypersensitivity
-
tuberculin skin test:
screen for latent TB via triggering inflammation (Th1) - contact dermatitis:
body try to remove small chemicals skin come into contact with
via killing it (Tc) and inflammation (Th1) -
chronic asthma:
eosinophil survival (Th2)
→ persistent inflammation
⇒ airway remodeling
how do regulatory T cells (Treg) suppress immune responses?
1. express (…)
→ constitutive expression of (…)
⇒ binds to (…)
and (…) upon binding
2. secrete (…) cytokines
- express Foxp3
→ constitutive expression of CTLA-4
⇒ binds to B7 on DCs with higher affiinty than CD28
and delivers inhibitory signals upon binding - secrete inhibitory cytokines
(e.g. TGF-B and IL-10 which inhibit Th1)
part of peripheral tolerance!
Programmed cell death protein 1 (PD-1) is primarily expressed on which immune cell type, and what is its role?
A) B cells; enhances antibody production
B) Dendritic cells; increases antigen presentation
C) Natural killer cells; promotes cytotoxicity
D) T cells; downregulates immune responses
E) Mast cells; triggers histamine release
D) T cells; downregulates immune responses
* expressed on chronically activated T cells
* sends negative signal which inhibits T cell activation
upon binding to its ligands PD-L1 and PD-L2
does so by inhibiting TCR and CD28 signalling
part of peripheral tolerance!
How does the absence of co-stimulation (Signal #2) affect T cells?
results in anergy
(i.e. inactivation of T cells FOREVER)
part of peripheral tolerance!
is ignorance (at signal 1) due to
absence of interaction or interaction being too weak?
due to interaction being too weak
to trigger activation
which antibodies are responsible for immune complex formation
IgM and IgG
Trap and remove pathogens
which antibodies are responsible for opsonisation
IgG
Promotes phagocytosis of pathogen
which antibodies are responsible for complement activation
IgM
Activation of the classical pathway involving C1q
which antibodies are responsible for neutralisation
IgG and IgA
Prevent pathogen or toxin interaction with targets
which antibodies are responsible for ADCC
IgG
Activate NK cell killing of targets
which antibodies are responsible for mast cell degranulation
IgE
Release of toxic granules against parasites
via IgE coating parasite -> mast cells bind to IgE via specialised Fc receptor (FcER1)
e.g. constitutively expressed, expressed in specfic situations
describe the expression of COX-1 and COX-2
- COX-1: constitutively expressed
← head coach who is always on field managing players - COX-2: expression induced by inflammation
← assistant coach who appears when there is trouble
main functions of COX-1
-
TXA2 causes vasoconstriction and
promotes platelet aggregation
← head coach angry at pitching box A2 where batter and catcher are supposed to be in and thus twisting red hat in anger -
prostaglandins has gastroprotective function
← “pro-slugger” batter protecting catcher
(who is wearing GIT-looking protective pads)
from coach’s fury
main functions of COX-2
-
prostacyclin (PGI2) causes vasodilation and
inhibits platelet aggregation
← assistant coach has to deal with the “pro-cycler” pitching machine,
which has a wide tube and is pitching out balls which disperses people,
being activated -
prostaglandins mediate signs of inflammation
(increased permeability, fever, pain)
← assistant coach also has to deal with the 3 “pro-slugger” batters,
in which 1 has accidentally activated leaky sprinkler,
another has set his cap on fire
and the last one is in pain from hitting his foot
what is the effect of NSAIDs on kidney
inhibit production of COX-1 and COX-2
-> inhibit production of prostaglandins
(produced by BOTH COX)
-> prevent dilation of afferent arteriole
=> decrease GFR and thus exacerbate AKI
“BOTH coaches ushering in “pro-slugger” batters through afferent tunnel”
what disease can aspirin be used to treat
aspirin can be used to treat Kawasaki disease
← umpire driving KAWASAKI car around field
aspirin = umpire
as it irreversibly inhibits both COX-1 and COX-2
= kicking both coaches off permanently
what situation and what disease can it lead to if used
when is aspirin contraindicated in children
usage in children with viral illness
can lead to Reye’s syndrome
← umpire in car picking up sniffling lost child
who is wearing a shirt with rays
are NSAIDs contraindicated in pregnancy
yes!
* in 3rd trimester of pregnancy
* due to premature closure of ductus arteriosus
“very pregnant lady exiting stadium as she cannot stand the mess”
on the other hand, can be USED to close ductus arteriosus in premature infants
what is the use of paracetamol
- inhibits COX-2
- acts as analgesic and anti-pyretic,
but NOT anti-inflammatory
“guy tries to help assistant coach by using icy-medicine spray on him,
but the spray only *cools him down *and relieves his pain
and does not actually put out the fire”
effect of toxic levels of paracetamol
deplete glutathione
→ acetaminophen metabolised to NAPQI
⇒ hepatotoxicity
“icy-medicine spray scares away goat w/ the liver spot”
paracetamol = acetaminophen
as glutathione usually conjugates NAPQI
to turn it into a harmless cpd that can be excreted in urine
what can be used to treat paracetamol overdose
N-acetylcysteine
as it restores glutathione
← N-flower seeds attract goat which was scared away
Which of the following non selective NSAIDs has a stronger anti-inflammatory profile?
A) aspirin
B) ibuprofen
C) naproxen
D) indomethacin
D) indomethacin
not only a non-selective inhibitor of COX
but also inhibits PLA2
→ thus reduces production of leukotrienes
in addition to prostanoids,
⇒ broader spectrum anti-inflammatory effect
