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IMMUNOLOGY VDMP817 > lecture 4 exam 2 > Flashcards

lecture 4 exam 2 Flashcards

1
Q

adaptive immunity relies on APC to process antigen and present it to T cells via

A

peptides on MHC molecules

MHC molecules are on the surface of antigen presenting cells (DC, B cells, macrophages)

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2
Q

cytosolic pathogens

A

obligate intracellular
viruses
some bacteria

any cell

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3
Q

extracellular (vesicular pathogen)

A

bacteria
protozoa
infected apoptotic cells

macrophage

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4
Q

extracellular pathogens

A

bacteria
toxins

b cell

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5
Q

macrophage as pro APC

A

main function is to trap and destroy
phagosomes are very acidic
cannot engage in prolonged interactions w t cells
present antigens to effector and memory t cells but NOT naive t cells

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6
Q

b cell as pro APC

A

process and present protein antigens in blood and lymphoid organs to helper t cells to activate immune response

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7
Q

dendritic cell as pro APC

A

most important full time professional APC
ONLY cell w ability to present to naive T cell
100x more effective at presenting antigen than macrophage and B cell

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8
Q

dendritic cells

A
  1. derived from bone marrow
  2. found in most tissues and blood
  3. long thin cytoplasmic processes called dendrites
    - increase cell SA -> increased efficiency in trapping and presenting ag
  4. immature DC are good at capturing antigen (phagocytosis, pinocytosis)
  5. mature DC are best at processing the internalized antigen and presenting antigens to naive T cells in lymph nodes
  6. can produce diff cytokines depending on binding to PAMPs and alarmins that lead to activation of various T cell subsets
  7. act as sentinel cells
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9
Q

classical DC

A

langerhans cells - immature DC in skin
origin of histiocytomas in dogs

interdigitating, thymic, follicular

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10
Q

interdigitating DC

A

mature DC interacts w T cells in the lymph node

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11
Q

thymic DC

A

in thymus important for presenting self antigens to developing T cells

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12
Q

follicular DC

A

confined to follicles of lymph nodes

present antigen to B cells as immune complexes (antigen + fdc)

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13
Q

plasmacytoid DC

A

derived from plasma cell rather than myeloid precursor
long lived cells
found in blood, bone marrow and lymphoid organs
not as effective at APC
essential in anti-viral responses
-rapidly activated by viral nucleic acids
-professional producers of type 1 IFN
-activate NK cells

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14
Q

immature vs mature DC

A

as they mature they change their function

immature: specialized antigen trapping cells - increased tolerance, decreased immunity
mature: specialized antigen processing cells - increased immunity, decreased tolerance
- increase surface epression of MHC 2, upregulate costimulatory molecules tat are needed for T cell activation (CR3), secrete cytokines needed for T cell proliferation and differentiation

through maturation interact w pathogens, PAMPS, DAMPS, inflammation
produce CD80, CD40, CD86

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15
Q

processing and presentation of cytosolic (endogenous) antigens to MHC 1

A

intracellular
proteasome cleaves proteins into peptides (8-10aa)
ubiquitin - recycles proteins and targets viral proteins to proteasome
transporter proteins (TAP) carry the antigen peptides to ER
approx 200 MHC 1 to stimulate a CD8+ t cell
MHC antigen complex get imbedded in cell membrane

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16
Q

presentation of vesicular or exogenous antigens to MHC 2

A

extracellular (vesicle or normal)
invariant chain prevents peptide from binding to MHC 2 in the ER
infected cell enters and fuses w lysosome
antigenic peptide exchanges for invariant chain and creates complex w MHC 2
MHC 2 ag complex goes to membrane

approx 200-300 peptide MHC complexes required to activate CD4+ t cell

17
Q

MHC 1

A

intracellular antigens
CD8+ T cells
cell mediated immunity

18
Q

MHC 2

A

extracellular antigens
CD4+ T cells
humoral immunity

19
Q

T cell subsets

A 
alpha beta:
- CD4+: t helper 1, 2, 17, tregulatory
- memory t cells 
-CD8+: cytotoxic/cytolytic
gammadelta
innate lymphoid - NK
20
Q

naive t cells and dc migrate to lymph node for priming

A

chemokines signal movement to ln
selectins & integrins support migration across endothelial cells (vessels & lymphatics)
DC enter afferent lymphatic
naive t cells enter HEV
-interact w thousands of DC in paracortex
-TCR recognizes specific antigenic peptide/MHC of DC
-adhesion molecules cause firm binding (immunological syapse)

21
Q

T cell activation requires 3 signals

A
  1. antigen specific - TCR & CD3 (TCR complex), CD4& CD8 (coreceptor) - CD3 helps signal transduction
  2. costimulatory - CD28 binds to B7 (CD80/86)
  3. cytokines - IL 2 for proliferation, others for differentiation of thelper cells
22
Q

signal 2 costimulatory signals

A

CD40L on T cell binds to CD40 on APC
-DC releases cytokines
-upregulates CD28 on T cell
CD28 on t cell binds costimulatory molecule B7 (CD80/86) on APC
-CD80 on macrophages and DC
-CD86 on B cells
-enhances cytokine expression and survival genes in T cell
-upregulates CTLA-4 (CD152) expression
CD152 binds CD80/86 after 2-3 days to STOP activation

23
Q

CD152 bound to CD80/86 bw T cell and APC does what?

A

stops activation of costimulatory signals

24
Q

immunological synapse

A

t cell and DC must be in contact for 12-24 hours to complete T cell activation
co receptors and adhesion molecules strengthen T cell:APC interactions via this synsapse
SMACs

after complete, the synapse is endocytosed and degraded terminating the cell interactions

25
Q

supramolecular activation clusters (SMAC)

A

concentric rings of molecular complexes that add co receptors and adhesion molecules to strengthen APC:T cell bond
peripheral SMAC: LFA1, ICAM1, adhesion molecules present on lipid rafts that aggregate around cSMAC stabilize interaction bw the T cell & APC
central SMAC: TCR, CD28 (CD80/86)

26
Q

IL2 signals proliferation

A

has 3 chains - alpha chain required for high affinity, happens after activation of T cell

binding of IL2 sends autocrine signal to T cell to induce proliferation

27
Q

Th1 cell development from classical DC

A

when encounter certain bacteria, viruses, tumors cDC1 presents MHC2 and releases IL12 cytokines

28
Q

Th2 cell development from classical DC

A

when encounter allergens, parasites, intestinal bacteria cDC2 presents MHC2 and releases IL6 cytokines

29
Q

Th17 cell development from classical DC

A

when encounter allergens, parasites, intestinal bacteria cDC2 presents MHC2 and releases IL23

30
Q

anergic

A

when APC has specific peptide:MHC complex bu no costimulatory molecule the t cell is

31
Q

naive t cell

A

formed when both specific peptide: MHC complex and costimulatory molecule is present

IMMUNOLOGY VDMP817 (22 decks)

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