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Immuno Flashcards

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
Q

where do T cells devo?

A

Progenitor made in bone marrow

Differentiate/mature in thymus

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25
Q

what goes through VDJ rearrangement?

A

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
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26
Q

Review T cell development

A

See notes

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27
Q

When does T cell express CD8/CD4?

A

After first chain rearrangement (beta)

“uncommittd double positive thymocyte”

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28
Q

Positive selection in T cell devo? in B cell devo?

A

T cell: select for T cells that can recognize MHC (off of stromal cells)

B cell devo: does not have positive selection

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29
Q

Differences between gamma chain and alpha/beta chain T cells?

A

Gamma chains do not require MHC presentation (positive selection); are mature after rearrangement

Gamma chains have less diverse receptors

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30
Q

what % comitted alpha/beta T cells will recognize MHC?

A

2%

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31
Q

When does T cell become single positive?

A

During positive selection; binding to MHCI–> CD8+, binding MCHII–> CD4+

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32
Q

Where does T cell positive selection occur?

A

cortex of thymus

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33
Q

Negative selection in T cell devo? In B cell devo?

A

T cell: DC presents self-antigen; strong binding –> apoptosis

B cell: same, remove cells that bind self

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34
Q

What is AIRE?

A

TF in thymus that promotes expression of all tissue types; negative selection during T cell devo

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35
Q

how does naive T cell enter lymph node?

A

CCR7 signaling

CCR7 from T cell binds CCL19/21 of stromal cell and DC of lymph tissue

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36
Q

where do B cells devo?

A

bone marrow

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37
Q

What is RAG1/RAG2?

A

involved in initiating rearrangement during B cell devo

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38
Q

What contributes to MHC diversity?

A

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)

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39
Q

Genetics of HLA?

A

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)

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40
Q

hematopoiesis: where does it occur in each stage of devo?

A

first trimester, after first month: yolk sac
Second trimester: fetal liver/spleen
third trimester: bone marrow

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41
Q

EPO

A

erythropoietin (promote erythrocyte differentiation)

cytokine; type I short chain

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42
Q

TPO

A

Thrombopoietin- promote thrombocyte differentiation (platelet)
cytokine; type I short chain

43
Q

GM-CSF

A

granulocyte macrophage colony stimulating factor - (promote granulocyte and monocyte differentiation)

44
Q

M-CSF

A

Macrophage colony stimulating factor

45
Q

G-CSF

A

granulocyte colony stimulating factor

46
Q

Interleukins that promote differentiation?

A

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
Q

MAC/DC ligand and receptor? Result? bact or viral?

A

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
Q

infected celll activation ligand and receptor? result? bact or viral?

A

Ligand: antigen
Receptor: TLR of infected cell

Result: IFNa/b release –> autocrine and paracrine effects (and other stuff)

VIRAL

49
Q

Antigen processing: exogenous vs endogenous

A

exogenous: MHCII presentation of peptide via DC/MAC/Bcell (internalize first)

Endogenous: infected cell presentation via MHC-I (pathogen already inside)

50
Q

How does neutrophil get recruited to site of infection?

A

IL-8 signaling. neutrophil has CXCR1/2 (a GPCR)–> degranulation of proteins that help cell enter

51
Q

Alternative complement: viral or bacterial?

A

mostly bacterial

52
Q

What cytokines induce fever?

A

IL-1, TNFa, IL6

53
Q

What cytokines promote vascular permeability?

A

IL-1 and TNFa

54
Q

What cytokines induce acute phase response? what is made?

A

IL1, IL6, TNF a

hepatocytes make: CRP, MBL

55
Q

How do NK cells get activated? what happens?

A
  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
Q

What cytokine helps NK cells? where does this cytokine come from?

A

IFNa/b makes much more effective (20-100x more effective)

From MAC/DC and infected cells

57
Q

What cytokine does NK produce? what induces this? what does this cytokine do?

A
  1. IL-12, TNFa (from MAC/DC) –> NK produce IFN gamma

2. IFN gamma promotes Th1 differentiation; makes MAC more effective

58
Q

T cell activation ligand and receptor? result?

A

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
Q

How is IgM produced? what is it effective against?

A

independent of T cells in lymph node

LPS antigen

60
Q

What promotes Th1 differentiation? what does Th1 produce?

A

IFN gamma/IL-2

Th1 produces IFN gamma

61
Q

What does Th1 cell do? receptor and ligands involved?

A

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
Q

What promotes Th2 differentiation? What does Th2 produce?

A

IL-4; IL-4

63
Q

B cell activation receptor/ligand? what is the result?

A

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
Q

Four ways aB functions

A
  1. Neutralizing: bind aB
  2. Opsonizing: phagocytic cells have Fc receptors
  3. ADCC: NK cell has Fc receptor (mostly cancer)
  4. Complement:
65
Q

Types of antiodies and features of each

A
  • 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
Q

CSR

A 
class switch recombination
aka isotype switching
constant region (Fc) is changed (thus, C region determines isotype)
67
Q

Th cell influence on recombination?

A

IFN gamma (Th1) –> IgG2a (complement, opsonizing)

IL-4 (Th2) –> IgG1 (neutralizing)

68
Q

B cell antigen processing ligand and receptor?

A

signal 1: antigen binds BCR (clustering from multiple antigen binding)
signal2: CD19 on B cell phosphorylation

Result: ITAM phosphorylation –> TK signaling –> endocytosis

69
Q

cytokines –> vascular permeability?

A

IL-1beta

TNF-alpha

70
Q

Cytokines –> fever, APR

A

IL-1 beta
IL-6
TNF-a

71
Q

[cytokines] induce NK cells to produce [cytokines]

A

IL12, TNFa

NK cell produces IFN gamma

72
Q

cytokines that promote th1 differentiation

A

IFN gamma

IL-12

73
Q

MAC/DC produce what cytokines?

A

IL-1, IL-6, IL-12, TNF-a, IFNa/b, IL-8 (MAC only)

74
Q

Stromal cells produce what cytokines/chemokines?

A

IL-7: promotes T cell differentiation (progenitor)

CCL19/21: recruits naive T cells to lymph node

75
Q

IL-1: producer and effector?

A

P: MAC/DC
E: vascular permeability, fever, APR

76
Q

IL-2: producer and effector

A

P: Activated T cell
E: autocrine; clonal expansion of T cells

77
Q

IL-3: producer and effector

A

P: ?
E: promotes myeloid progenitor differentiation (granulocytes and monocytes)

78
Q

IL-4: producer and effector

A

P: Th2 cells and basophils
E: Th2 differentiation

79
Q

IL-6: producer and effector

A

P: MAC/DC
E: Fever, APR

80
Q

IL-7: producer and effector

A

P: stromal cells (thymus)
E: promotes differentiation to double negative T cell progenitor

81
Q

IL-12: producer and effector

A

P: MAC/DC
E: induces NK cellss to produce IFN-gamma; induces Th1 cell differentiation

82
Q

IFNa/b: producer and effector

A

P: MAC/DC/infected cellls
E: autocrine/paracrine effects on infected cells (MHC-I express); induces lytic granule release form NK cells (cosignal)

83
Q

IFN gamma: producer and effector

A

P: NK cells and Th1 cells
E: promote Th1 cell differentiation; increase MAC fxn (upregulate MHC-II expression)

84
Q

TNF-a: producer and effector

A

P: MAC/DC
E: vascular permeability, fever, APR, induce NK cell to produce IFN gamma

85
Q

IL-8: producer and effector

A

P: MAC
E: recruit neutrophil and basophils, induce release of lytic granules that help cell entry

86
Q

CCL19/21: producer and effector

A

P: stromal cells in lymph noode
E: CCR7 of naive T cells; allows entry to lymph node

87
Q

cytokines –> vascular permeability?

A

IL-1beta

TNF-alpha

88
Q

Cytokines –> fever, APR

A

IL-1 beta
IL-6
TNF-a

89
Q

[cytokines] induce NK cells to produce [cytokines]

A

IL12, TNFa

NK cell produces IFN gamma

90
Q

cytokines that promote th1 differentiation

A

IFN gamma

IL-12

91
Q

MAC/DC produce what cytokines?

A

IL-1, IL-6, IL-12, TNF-a, IFNa/b, IL-8 (MAC only)

92
Q

Stromal cells produce what cytokines/chemokines?

A

IL-7: promotes T cell differentiation (progenitor)

CCL19/21: recruits naive T cells to lymph node

93
Q

IL-1: producer and effector?

A

P: MAC/DC
E: vascular permeability, fever, APR

94
Q

IL-2: producer and effector

A

P: Activated T cell
E: autocrine; clonal expansion of T cells

95
Q

IL-3: producer and effector

A

P: ?
E: promotes myeloid progenitor differentiation (granulocytes and monocytes)

96
Q

IL-4: producer and effector

A

P: Th2 cells and basophils
E: Th2 differentiation

97
Q

IL-6: producer and effector

A

P: MAC/DC
E: Fever, APR

98
Q

IL-7: producer and effector

A

P: stromal cells (thymus)
E: binds CD127 receptor on progenitor; promotes differentiation to double negative T cell progenitor

99
Q

IL-12: producer and effector

A

P: MAC/DC
E: induces NK cellss to produce IFN-gamma; induces Th1 cell differentiation

100
Q

IFNa/b: producer and effector

A

P: MAC/DC/infected cellls
E: autocrine/paracrine effects on infected cells (MHC-I express); induces lytic granule release form NK cells (cosignal)

101
Q

IFN gamma: producer and effector

A

P: NK cells and Th1 cells
E: promote Th1 cell differentiation; increase MAC fxn (upregulate MHC-II expression)

102
Q

TNF-a: producer and effector

A

P: MAC/DC
E: vascular permeability, fever, APR, induce NK cell to produce IFN gamma

103
Q

IL-8: producer and effector

A

P: MAC
E: recruit neutrophil and basophils, induce release of lytic granules that help cell entry

104
Q

CCL19/21: producer and effector

A

P: stromal cells in lymph noode
E: CCR7 of naive T cells; allows entry to lymph node

Foundations2 (17 decks)

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