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exam 2 cramming Flashcards

1
Q

MHC Class I molecule processing and loading

A
  1. MHC a chain and B2m associates with ER-resident proteins, including TAP
  2. proteasome ingests antigen and spits out peptide
  3. TAP brings peptide into ER
  4. ERAP trims the peptide so it’s 8-10 aa
  5. Loaded MHC Class I travels through secretory pathway to present antigen to CD8 T cells
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2
Q

CD3 complex

A

composed of several proteins involved in signal transduction

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3
Q

Th1

A

target intracellular pathogens by activating macrophages through interactions with CD40 ligand and interferon gamma

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4
Q

Th2

A

targets extracellular pathogens (worms) by activating B cells
releases IL-4, 5, and IL-9

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5
Q

Th17

A

targets extracellular pathogens by secreting IL-17. Also makes IL-22 to promote epithelial repair

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6
Q

cytotoxic T cell

A

recognize, target, and destroy cells infected with an intracellular pathogen

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7
Q

Treg

A

inactivate self-reactive T cells to promote peripheral tolerance
-release of IL-10 (infalmmatory) and TGF-B

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8
Q

CD34

A

marker during DN1 (stem cell)
Also what L-selectin in binding to on the T cell during rolling adhesion

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9
Q

CD25

A

marker during DN2-3; receptor for t cell growth factor IL-2

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10
Q

CD4

A

has 4 ig folds; interacts with MHC Class II molecules

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11
Q

CD8

A

has 1 ig fold; interacts with MHC Class I molecules

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12
Q

Follicular helper T cells

A

found in B cell regions (follicles) in the LN and spleen
- provide help to B cells for production of antibodies
- activates B cell thorugh interaction with CD40 ligand and through cyotkine action of IL-4 and IL-21

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13
Q

Instructive Model

A

Co-receptor lineage occurs as follows: binding of TCR and the correct co-receptor to an MHC molecule instructs the cell to express the engaged co-receptor

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14
Q

Kinetic Model

A

Co-receptor lineage occurs as follows: all DP thymocytes express CD4. Continued engagement promotes maintenance. If T cell can’t signal it switches expression from CD4 to CD8

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15
Q

MHC Class II peptide processing and loading

A
  1. MHC Class II associates with invariant chain in the ER to block binding of peptides intended for class I
  2. MHC and invariant chain goes through secretory pathway to a late endosome. Invariant chain is digested here. CLIP (part of chain) remains associated with MHC Class II
  3. Ingestion of antigen via phagoyctosis and phagolysosome fueses with MHC Class II vesicle
  4. Vesicle of HLA-DM fuses with antigen-MHC CLass II vesicle and facilitates loading of peptides, which replace CLIP
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16
Q

What is cross presentation?

A

the capacity of an antigen-presenting cell to acquire exogenous antigen and present the processed peptides in the context of MHC-I

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17
Q

How does cross-presentation work?

A

peptide pumpon phagolysosomal vesicle pumps peptides out of vesicles into the cytoplasm, where TAP pumps them back into the ER

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18
Q

Why do some DCs need to cross-present?

A

Dendritic cells specifically need to cross-present because many viruses avoid detection by infecting non-APC cells, meaning those cells can’t activate CD8+ T cells, which are essential for killing virus-infected cells. By cross-presenting viral antigens, dendritic cells can bridge this gap, allowing the immune system to recognize and target viruses even if they haven’t directly infected the dendritic cells themselves. This is critical for initiating an effective immune response against viruses that don’t directly infect APCs or when the virus is hiding in cells that don’t naturally activate T cells.

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19
Q

Class I MHC molecules include

A

H-2 K, D, L

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20
Q

Class II mouse MHC includes

A

I, A, and E

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21
Q

Human MHC Class I

22
Q

IL-2

A

important for T cell growth and differentiation

23
Q

Human MHC Class II

A

DP, DQ, DR

24
Q

Interferon-y (gamma)

A

macrophage activation, upreg in MHC Class I and class II

25
IL-4
Activation and growth of B cells T cell growth and survival
26
IL-5
makes hematopoietic cell increase eosoniphil growth and differentiation
27
IL-13
increased produciton of mucus
28
IL-17
1. stimulates neutrophil recruitment 2. Stimulatesfibroblasts, and epithelial cells to secrete chemokines
29
IL-22
stimulates mucosal epithelium and skin to produce antimicrobial peptides
30
TGF-B
inhibits growth of B cells; inhibits Th2 and Th2 and encourages TH17 and Itreg differentiation
31
IL-10
inhibits inflammatory cytokine release by macrophages
32
TNF-alpha
activates, induces, NO production by macrophages
33
How do cytotoxic cells induce apoptosis?
1. perforin to create holes and release of granzymes, which activates caspase 3. caspase 3 induces apoptosis 2. Granule protien, FasL interacts with Fas on target cell. This activates caspase-8 which activates caspase 3 and induces apoptosis
34
How do T cells migrate into lymphoid tissue?
1. Rolling Adhesion: Interaction of L-selectin on the T cell with Cd34 or GLyCAM-1 on the endothelial cell 2. Tight Binding: T cell tightly binds to ICAM-1 using cell-surface molecule LFA1 3. Diapedesis: T cells squeeze through the endothelial wall of the high endothelial venule 4. Migration into lymphoid tissue
35
How do we initiate adaptive responses?
Activated DCs leave the tissue and go to LNs. The activated DCs express the CD28 ligand and produce IL-12, which directs T cell differentiation.
36
CD28
Expressed after PRR stimulation of the DC Binds to B7 on dendritic cell!
37
Broad overview of T cell priming, activation, and differentiation (think of the 3 signals)
Naive T cells are activated through stimulation by TCR/CD3 copmlex (signal 1) Also costimulation by CD28 (signal 2) Without signal 2, there's anergy UNLESS there's exogenous IL-2 introduced Cytokines drive differentiation of T cells (signal 3)
38
Signaling events inducing T cell activation (all)
1. Clustering of proteins together 2. CD45 phosphatase dephosphorylates Lck and activates it 3. Lck phosphorylates ITAMs on the CD3 complex 4. ITAMS allow for binding of ZAP-70 5. Lck phosphorylates ZAP-70 6. ZAP - 70 activates and phosphorylates PLC 7. Production of IP3 and DAG 8. IP3: release of calcium from ER activates calcineurin, allowing for NFAT translocation (allowing for activation of T cell activating genes) 9. DAG: allows NFkb to go to the nucleus and activate T cell genes, activation of MAP kinase cascade. Early activation genes include IL-2 and IL-2ra. Downregulation of sphingosine-1-phosphate receptor promotes retention in the LN
39
JAK/STATs pathway | how cytokines signal
1. cytokines bind to cytokine receptor, leading to dimerization of receptors and JAKS phosphorylating each other as well as the receptors 2. transcription factor STAT is recruited to receptor and JAK phosphorylates STAT 3. Phosphorylated STATs dimerize and translocate to the nucleus, activating transcription
40
STAT 6 is activated by
IL-4 and IL -13
41
STAT 3 is activated by
IL -6 and IL-10
42
STAT 1 is activated by
interferon a,b,gamma
43
TH1 cells: cytokine signal, transcription factors, effector function
Signal: IL-12 Transcription factor: Tbet Effector function: produciton of interferon gamma (intracellular pathogen defenses and macrophage activation)
44
TH2 cells: cytokine signal, transcription factors, effector function
cytokine signal: IL-4 transcription factor: GATA 3 effector: production of more IL-4 (B cell production and defense against extracellular pathogens)
45
Th17 cells: cytokine signal, transcription factors, effector function
Cytokine signals: IL-23, IL-1B, IL-6 Transcription factor: ROR gamma t Effector: production of IL-17 which activates neutrophils
46
Group 1 ILCs: cytokine signal, transcription factor, effector function
same as TH1: signaling from IL-12 , tbet transcription factor, IFN-y
47
Group 2 ILCs: cytokine signal, transcription factor, effector function
cytokine signaling: IL-25, IL-33, TSLP transcription factor: GATA-3 effector function: IL-4 production
48
Group 3 ILCs: cytokine signal, transcription factor, effector function
cytokine signaling: IL-23, IL-1B transcription factor: RORgt effector function: IL-17
49
What is required for naive CD8 activation
CD4 help!! CD4 cells can provide IL-2 CD4s can also signal to DCS via CD40 to upregulate B7 AND to activate cross presentation
50
What are cytotoxic T cells doing?
monitor MHC Classs I molecules on the surface of cells to scan for presence of antigen their TCR can bind to. This drive in activation of effector function (destroy by apoptosis and monitor other cells)
51

Immunobiology (4 decks)

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