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Immuno Flashcards

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0
Q

Chemokine signaling? CXCL8?

A
  • MAC produces IL-8
  • Recruits neutrophils with CXCR1/2 (GPCRs); and basophils
  • induces expression of proteins that help with cell entry
  • induce lytic granule release
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1
Q

What pathway do cytokine activate?

A

JAK/STAT- JAK phosphorylates receptor –> STAT recruited, JAK phosphoryates STAT–> STAT dimerizes, goes to nucleus as TF

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2
Q

Defensins- types? and function of each?

A

part of innate immune system
Alpha defensin- neutrophils and paneth cells of intestine
Beta defensin- viral infection induces; prevents viral membrane fusion of non-infected cells

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3
Q

TLR types (5/10)? function?

A 
Found on phagocytic cells and infected cells (induces IFNa/b)
TLR4- recog LPS of gram neg bacteria
TLR3- recog viral dsRNA
TLR7/8- recog viral ssRNA
TLR9- recog unmethylated CpG viral DNA
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4
Q

What cells work through respiratory bursts?

A

Phagocytic cells: MAC, DC, neutrophils

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5
Q

Role of mast cells?

A

Allergies/parasites
Histamine release
IgE binds via FcE receptor

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6
Q

Role of basophils

A

Rare, Allergic response
Cytokine release will impact T cell differentiation (IL-4)
Will bind IgE via FcE receptor

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7
Q

Eosinophils

A

Parasites

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8
Q

Cytotoxic cells?

A

NK and CD8+ T cells

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9
Q

% of each cell type

A

60% neutrophils
30% lymphocytes
<1% basophils

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10
Q

B cell function

A

Recognize free antigen w high specificity (antigen processing)
Received confirmation from T cell (B cell activation)
Proliferates and makes antibody (plasma)
Can also become memory cell

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11
Q

T cell function

A

CD4+
-Activation by APC presentation; highly specificity binding
-Express IL2 and IL2 receptor alpha –> proliferation and differentiation –> Th1,2,17,reg
CD8+: activation by infected cells; effector cells

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12
Q

How do T/B cells enter and leave lymph? Pathogens?

A

Naive T/B cells enter via bloodstream; leave via efferent lymphatics–> heart –> circulation

Pathogen enters with DC via afferent lymphatics

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13
Q

Complement enzymes are what kind of enzymes?

A

Serine proteases

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14
Q

How c3b opsonization –> phagocytosis?

A

CR1 on MAC binds c3b

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15
Q

Role of c3a and c5a

A

Recruit inflammatory cells (c5a help phagocytes adhere to endothelium and increase ability to phagocytosize)
Anaphylotoxins- contract smooth muscle, release histamine from basophil/mast cells, increase blood flow

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16
Q

Where does c3 come from?

A

Liver

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17
Q

Where is mannose found?

A

surface of fungi, bacteria, viruses

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18
Q

Describe lectin complement pathway complex? What does it do?

A

MASP (serine protease) + MBL (mannose binding lecctin)

Cleaves C4 and C2 to make classic C3 convertase (C2aC4b) (C4b embeds on pathogen surface)

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19
Q

How is classical pathway initiated?

A

CRP (c-reactive protein from liver acute phase response) or IgG/IgM (from Th1)
Bind PC of pathogen and C1; cleave C4 and C2 –> C2aC4b classic C3 convertase

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20
Q

How is alternative complement pathway inititated?

A

C3 spontaneous cleaves to iC3
Factor D cleaves Factor B –> iC3Bb (c3 convertase)
iC3Bb cleaves C3 –> C3a and C3b

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21
Q

Describe the convertases (4)

A
  1. iC3Bb- poor C3 convertase (alternative path)
  2. C3bBb- potent C3 convertase
  3. C3b2Bb- alternative C5 convertase (–> direct killing)
  4. C2aC4b- classic C3 convertase (classical and lectin path)
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22
Q

Review complement pathways

A

See notes

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23
Q

Cells in thymus? Function of each?

A
  1. Thymocytes- devo to T cells
  2. Epithelial cells (thymic stroma)- express MHC for positive selection; produces IL-7
  3. DC- negative selection (present self-peptide)
  4. MAC-clears dead lymphocytes
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24
where do T cells devo?
Progenitor made in bone marrow | Differentiate/mature in thymus
25
what goes through VDJ rearrangement?
DJ pairs first!! then DJ-V 1. beta chain of T cell- (first rearrangement); Alpha chain goes to VJ pairing only 2. Heavy chain of B cell (first) Light chain goes to VJ pairing only
26
Review T cell development
See notes
27
When does T cell express CD8/CD4?
After first chain rearrangement (beta) | "uncommittd double positive thymocyte"
28
Positive selection in T cell devo? in B cell devo?
T cell: select for T cells that can recognize MHC (off of stromal cells) B cell devo: does not have positive selection
29
Differences between gamma chain and alpha/beta chain T cells?
Gamma chains do not require MHC presentation (positive selection); are mature after rearrangement Gamma chains have less diverse receptors
30
what % comitted alpha/beta T cells will recognize MHC?
2%
31
When does T cell become single positive?
During positive selection; binding to MHCI--> CD8+, binding MCHII--> CD4+
32
Where does T cell positive selection occur?
cortex of thymus
33
Negative selection in T cell devo? In B cell devo?
T cell: DC presents self-antigen; strong binding --> apoptosis B cell: same, remove cells that bind self
34
What is AIRE?
TF in thymus that promotes expression of all tissue types; negative selection during T cell devo
35
how does naive T cell enter lymph node?
CCR7 signaling | CCR7 from T cell binds CCL19/21 of stromal cell and DC of lymph tissue
36
where do B cells devo?
bone marrow
37
What is RAG1/RAG2?
involved in initiating rearrangement during B cell devo
38
What contributes to MHC diversity?
MHC-I: isotypes A, B, C, E, F, G (ABC are polymorphic) (MHC-I has 3 heavy domain chains and 1 beta2 microglobulin) MHC-II: isotypes DM, DO, DP, DQ, DR (PQR are polymorphic) (MHC-II has alpha and beta chain only)
39
Genetics of HLA?
MHC diversity Chromosome 6 2 alleles for each isotype (multiple isotypes of HLA make up a MHC) (ex. HLA-A1, A7, B....C...) then each serotype has additional heterogeneity)
40
hematopoiesis: where does it occur in each stage of devo?
first trimester, after first month: yolk sac Second trimester: fetal liver/spleen third trimester: bone marrow
41
EPO
erythropoietin (promote erythrocyte differentiation) | cytokine; type I short chain
42
TPO
Thrombopoietin- promote thrombocyte differentiation (platelet) cytokine; type I short chain
43
GM-CSF
granulocyte macrophage colony stimulating factor - (promote granulocyte and monocyte differentiation)
44
M-CSF
Macrophage colony stimulating factor
45
G-CSF
granulocyte colony stimulating factor
46
Interleukins that promote differentiation?
IL-7 promotes T cell differentiation (from CD34+ cell to T cell progenitor) IL-3 promotes myeloid differentiation from stem cell (myeloid--> granulocytes and monocytes)
47
MAC/DC ligand and receptor? Result? bact or viral?
Ligand: antigen Receptor: TLR of MAC/DC (recognize PAMP) Result: incr MHC-II, incr B7, incr cytokine release (IFNa/b, TNFa, IL6, IL12, IL1) (IL8 is MAC only) VIRAL
48
infected celll activation ligand and receptor? result? bact or viral?
Ligand: antigen Receptor: TLR of infected cell Result: IFNa/b release --> autocrine and paracrine effects (and other stuff) VIRAL
49
Antigen processing: exogenous vs endogenous
exogenous: MHCII presentation of peptide via DC/MAC/Bcell (internalize first) Endogenous: infected cell presentation via MHC-I (pathogen already inside)
50
How does neutrophil get recruited to site of infection?
IL-8 signaling. neutrophil has CXCR1/2 (a GPCR)--> degranulation of proteins that help cell enter
51
Alternative complement: viral or bacterial?
mostly bacterial
52
What cytokines induce fever?
IL-1, TNFa, IL6
53
What cytokines promote vascular permeability?
IL-1 and TNFa
54
What cytokines induce acute phase response? what is made?
IL1, IL6, TNF a hepatocytes make: CRP, MBL
55
How do NK cells get activated? what happens?
1. MHC-I binds to inhibitory receptor; no binding --> activation 2. MIC of infected cell binds NKG2D receptor of NK --> activation lytic granule release
56
What cytokine helps NK cells? where does this cytokine come from?
IFNa/b makes much more effective (20-100x more effective) | From MAC/DC and infected cells
57
What cytokine does NK produce? what induces this? what does this cytokine do?
1. IL-12, TNFa (from MAC/DC) --> NK produce IFN gamma | 2. IFN gamma promotes Th1 differentiation; makes MAC more effective
58
T cell activation ligand and receptor? result?
Signal 1: MHC of APC/infected cell binds TCR Signal 2: B7(CD80/86) APC/infected cell binds CD28 receptor release IL2 and IL2R-alpha (and CLTA4) --> autocrine receptor act --> JAK/STAT --> clonal expansion
59
How is IgM produced? what is it effective against?
independent of T cells in lymph node | LPS antigen
60
What promotes Th1 differentiation? what does Th1 produce?
IFN gamma/IL-2 | Th1 produces IFN gamma
61
What does Th1 cell do? receptor and ligands involved?
optimizes MAC Signal 1: TCR binds MHC-II/antigen Signal 2: CD40L of T cell binds CD40 of MAC Signal 3: IFN gamma from Th1 binds IFN gamma receptor on MAC
62
What promotes Th2 differentiation? What does Th2 produce?
IL-4; IL-4
63
B cell activation receptor/ligand? what is the result?
Signal1: MHC-II of B cell binds TCR Signal2: CD40L of Th2 cell binds CD40 of B cell Signal3: IL-4 binds IL-4 receptor of B cell Proliferation and differentiation (isotype switching, somatic hypermutation, affinity maturation)
64
Four ways aB functions
1. Neutralizing: bind aB 2. Opsonizing: phagocytic cells have Fc receptors 3. ADCC: NK cell has Fc receptor (mostly cancer) 4. Complement:
65
Types of antiodies and features of each
- IgM: first, low affinity - IgG: opsonizing/neutralizing/complement; most abundant; crosses placenta - IgD: never secreted, disappears after activation; second to be made - IgA: mucosal - IgE: histamine; mast cells have Fc receptors
66
CSR
``` class switch recombination aka isotype switching constant region (Fc) is changed (thus, C region determines isotype) ```
67
Th cell influence on recombination?
IFN gamma (Th1) --> IgG2a (complement, opsonizing) IL-4 (Th2) --> IgG1 (neutralizing)
68
B cell antigen processing ligand and receptor?
signal 1: antigen binds BCR (clustering from multiple antigen binding) signal2: CD19 on B cell phosphorylation Result: ITAM phosphorylation --> TK signaling --> endocytosis
69
cytokines --> vascular permeability?
IL-1beta | TNF-alpha
70
Cytokines --> fever, APR
IL-1 beta IL-6 TNF-a
71
[cytokines] induce NK cells to produce [cytokines]
IL12, TNFa | NK cell produces IFN gamma
72
cytokines that promote th1 differentiation
IFN gamma | IL-12
73
MAC/DC produce what cytokines?
IL-1, IL-6, IL-12, TNF-a, IFNa/b, IL-8 (MAC only)
74
Stromal cells produce what cytokines/chemokines?
IL-7: promotes T cell differentiation (progenitor) | CCL19/21: recruits naive T cells to lymph node
75
IL-1: producer and effector?
P: MAC/DC E: vascular permeability, fever, APR
76
IL-2: producer and effector
P: Activated T cell E: autocrine; clonal expansion of T cells
77
IL-3: producer and effector
P: ? E: promotes myeloid progenitor differentiation (granulocytes and monocytes)
78
IL-4: producer and effector
P: Th2 cells and basophils E: Th2 differentiation
79
IL-6: producer and effector
P: MAC/DC E: Fever, APR
80
IL-7: producer and effector
P: stromal cells (thymus) E: promotes differentiation to double negative T cell progenitor
81
IL-12: producer and effector
P: MAC/DC E: induces NK cellss to produce IFN-gamma; induces Th1 cell differentiation
82
IFNa/b: producer and effector
P: MAC/DC/infected cellls E: autocrine/paracrine effects on infected cells (MHC-I express); induces lytic granule release form NK cells (cosignal)
83
IFN gamma: producer and effector
P: NK cells and Th1 cells E: promote Th1 cell differentiation; increase MAC fxn (upregulate MHC-II expression)
84
TNF-a: producer and effector
P: MAC/DC E: vascular permeability, fever, APR, induce NK cell to produce IFN gamma
85
IL-8: producer and effector
P: MAC E: recruit neutrophil and basophils, induce release of lytic granules that help cell entry
86
CCL19/21: producer and effector
P: stromal cells in lymph noode E: CCR7 of naive T cells; allows entry to lymph node
87
cytokines --> vascular permeability?
IL-1beta | TNF-alpha
88
Cytokines --> fever, APR
IL-1 beta IL-6 TNF-a
89
[cytokines] induce NK cells to produce [cytokines]
IL12, TNFa | NK cell produces IFN gamma
90
cytokines that promote th1 differentiation
IFN gamma | IL-12
91
MAC/DC produce what cytokines?
IL-1, IL-6, IL-12, TNF-a, IFNa/b, IL-8 (MAC only)
92
Stromal cells produce what cytokines/chemokines?
IL-7: promotes T cell differentiation (progenitor) | CCL19/21: recruits naive T cells to lymph node
93
IL-1: producer and effector?
P: MAC/DC E: vascular permeability, fever, APR
94
IL-2: producer and effector
P: Activated T cell E: autocrine; clonal expansion of T cells
95
IL-3: producer and effector
P: ? E: promotes myeloid progenitor differentiation (granulocytes and monocytes)
96
IL-4: producer and effector
P: Th2 cells and basophils E: Th2 differentiation
97
IL-6: producer and effector
P: MAC/DC E: Fever, APR
98
IL-7: producer and effector
P: stromal cells (thymus) E: binds CD127 receptor on progenitor; promotes differentiation to double negative T cell progenitor
99
IL-12: producer and effector
P: MAC/DC E: induces NK cellss to produce IFN-gamma; induces Th1 cell differentiation
100
IFNa/b: producer and effector
P: MAC/DC/infected cellls E: autocrine/paracrine effects on infected cells (MHC-I express); induces lytic granule release form NK cells (cosignal)
101
IFN gamma: producer and effector
P: NK cells and Th1 cells E: promote Th1 cell differentiation; increase MAC fxn (upregulate MHC-II expression)
102
TNF-a: producer and effector
P: MAC/DC E: vascular permeability, fever, APR, induce NK cell to produce IFN gamma
103
IL-8: producer and effector
P: MAC E: recruit neutrophil and basophils, induce release of lytic granules that help cell entry
104
CCL19/21: producer and effector
P: stromal cells in lymph noode E: CCR7 of naive T cells; allows entry to lymph node

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