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Immunology > Week 6 > Flashcards

Week 6 Flashcards

1
Q

2 examples of antibacterial enzymes

A

lysozyme (breaks down peptidoglycan bonds), and secretory phospholipase A2.

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2
Q

peptidoglycan structure

A

An alternating polymer of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), strengthened by cross-linking peptide bridges. In bacterial cell walls.

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3
Q

enzymatic activity of lysozyme

A

Selectively cleaves the B-(1,4) linkage between the two different sugars in petidoglycans

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4
Q

What type of bacteria is lysozyme more effective against?

A

Gram-positive bacteria, in which the peptidoglycan cell wall is exposed.

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5
Q

Three important classes of antimicrobial peptides

A

Defensins, cathelicidins, and histatins

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6
Q

Defensins

A

Short, cationic peptides of 30-40 AA long, usually with three disulfide bonds stabilizing a common amphipathic structure

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7
Q

Three subfamilies of defensins

A

alpha, beta, and theta defensins

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8
Q

cryptdins

A

alpha-defensins constitutively produced by Paneth cells of the gut, processed by prteases such as MPM in mice or trypsin in humans

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9
Q

B-defensins

A

Lack the long propiece of alpha-defensins and are generall produced specifically in response to the presence of microbial products.

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10
Q

lamellar bodies

A

lipid-rich secretory organelles that release their contents into the extracellular space to form a watertight lipid sheet in the epidermis and the pulmonary surfactant layer in the lung. Produced by keratinocytes and type II pneumocytes.

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11
Q

C1 protein components

A

C1q (recognition protein), C1r, and C1s (proteases)

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12
Q

Three complement pathways

A

Lectin pathway, classical pathway, and alternative pathway

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13
Q

Lectin pathway initiation of complement

A

initiated by soluble carbohydrate-binding proteins, such as mannose-binding lectin (MBL) and ficolins. Specific proteases called MBL-associated serine proteases (MASPs) that assocaite with these recognition proteins then trigger the cleavage of complement proteins

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14
Q

Classical pathway initiation of complement

A

initiated when the complement component C1 either recognizes a microbial surface protein directly or binds to antibodies bound to a pathogen.

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15
Q

Alternative pathway initiation of complement

A

Can be initiated by spontaneous hydrolysis and activation of C3, which can then bind directly to microbial surfaces.

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16
Q

C3 convertase

A

Shared step in all three complement activation pathways. Multicomponent protease covalently bound to microbial surface that cleaves C3 to form large amounts of C3b and C3a

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17
Q

C3b

A

Main effector protein of the complement system. Opsonin that binds directly to microbial surface.

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18
Q

C3a

A

Small peptide that binds to specific receptors and helps induce inflammation.

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19
Q

C5 convertase

A

Made when C3b binds to C3 convertase. Cleaves C5, liberating the highly inflammatory peptide C5a and generating C5b, which initiates the ‘late’ stages of complement and forms MAC on pathogen surface.

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20
Q

What happens when C3 is cleaved?

A

C3a is released and the remaining C3b undergoes conformational changes that allow its previously hidden thioester bond to react with a hydroxyl or amino group on nearby microbial surfaces.

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21
Q

Components recognized by the lectin pathway of complement

A

Lipotechoic Acid of G+ bacteria, LPS of G- acteria, and mannose ends of glycans of yeast and fungi (as opposed to sialic acid)

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22
Q

Four proteins that can initiate the lectin pathway of complement

A

Mannose-binding lectin (MBL), L-ficolin, M-ficolin, and H-ficolin

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23
Q

What are the shared structural and functional components of MBL and ficolins, and how do they differ?

A

All are composed of a collagen stalk and form trimers or tetramers and have recognition portions that have weak monomeric recognition of microbial components, but high avidity when polymerized.

MBL recognition domains recognize mannose, fucose, and N-acetylglucosamine (GlcNAc), while ficolins have a fibringoen-like domain with a general specificity for oligosaccharides containing acetylated sugars.

All are synthesized and secreted by the liver, with the exception of M-ficolin, which is synthesized and secreted by lung and blood cells.

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24
Q

How does MBL activate complement?

A

MBL is bound with MBL-associated serine proteases (MASPs) in the circulation, which are inactive zymogens. Binding of MBL to microbial surface activates MASP-1, which in turn activates MASP-2, which can cleave and activate C4 and C2.

C4b binds to microbial surface and binds to one C2a molecule, forming C4b2a, which is the C3 convertase of the lectin pathway

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25
Q

C4b2a

A

C3 convertase of the lectin and classical pathway. Formed by the cleavage of C4 and C2 by activated MASP-2 bound to MBL.

Also known as the classical C3 convertase

26
Q

molecules recognized by C1q of the C1 protein

A

polyanionic structures such as lipotechoic acid on G+ bacteria

Also binds to C-reactive protein, which recognizes phosphocholine residues in bacterial surface molecules.

Finally, Fc regions of bound antibodies.

27
Q

How is initiation of complement conserved to the pathogen surface?

A

C4 cleavage is initiated by MBL or ficolin complex that is bound to microbial surface.

C4b is released and the thioester bond that recognizes microbial surface proteins or carbohydrates is rapidly inactivated through hydrolysis if it doesn’t covalently bind with microbe surface.

28
Q

Alternative pathway C3 convertase

A

C3bBb, formed from C3b and portion of the plasma protein Factor B.

29
Q

How can the alternative pathway of complement be activated?

A

Either by the activation of the classical or lectin pathway, as it is an amplification of C3b production. Alternatively, it can be spontaneously activated by C3 hydrolysis called C3 tickover, forming a transient or fluid-phase C3(H2O)Bb C3 convertase

30
Q

Properdin

A

Released by activated neutrophils (stored in 2ary granules). Stabilizes the short-lived alternative pathway C3 convertases of the complement system, leading to amplification of C3b production.

31
Q

Negative regulatory proteins of complement system

A

Decay accelrating factor (CD55), Membrane cofactor of proteolysis (CD46), Cell-surface complement receptor 1 (CR1, CD35)

32
Q

Which are the only TLRs to not only use MyD88 for intracellular signaling?

A

TLR2 dimers and endosomal TLR4, TLR3

33
Q

How does MyD88 interact with TLRs?

A

Through TIR (Toll/Interleukin-1 receptor) domains

34
Q

General makeup of the proteasome

A

20S catalytic core and two 19S regulatory caps, one on each end

35
Q

Makeup of the 20S catalytic core of proteasome

A

Four stacked rings of seven subunits each. Two end rings are made from alpha subunits and are not catalytic. The two center rings are composed of catalytic Beta subunits, among which B1, B2, and B5 are constitutively expressed.

36
Q

How does the immunoproteasome differ from the proteasome?

A

Beta subunits are replaced with interferon-induced subunits (i.e. B1 is replaced with B1i and so on). These preferentially degrade peptides with increased cleavage after hydrophobic residues and decreased cleavage after acidic residues.

The resulting peptides more easily bind to MHC I and have better activity for TAP proteins that transport peptides into the ER

37
Q

What are some proteins involved in antigen presentation that are upregulated in response to interferon gamma?

A

MHC I molecules, Beta-i subunits for the immunoproteasome, and TAP proteins for peptide transport into the ER, ERAAP

38
Q

calnexin

A

general-purpose protein chaperone that retains the MHC I molecule in a partially folded state before B2 microglobulin association

39
Q

peptide loading complex (PLC)

A

binds to MHC I molecule after it forms a heterodimer with B2 microblobulin. Maintains the MHC I molecule in a state receptive to peptide loading by forming a bridge to TAP protein complex via tapasin

40
Q

tapasin

A

component of the peptide loading complex for MHC I that forms a bridge between the MHC I and the TAP proteins in the ER membrane.

41
Q

Acid proteases of the endosome

A

cathespins B, D, S and L

42
Q

Three class I genes in humans

A

HLA-A, HLA-B, and HLA-C (all alpha chains)

43
Q

Three pairs of class II MHC genes in humans

A

HLA-DP,
HLA-DQ
HLA-DR

Some HLA-DR clusters contain an additional Beta gene

44
Q

What are the three amino acids usually phosphorylated by protein kinases?

A

Serine, threonine, and tyrosine

45
Q

What are three ways in which protein scaffolds regulate intracellular signaling?

A

By specifying which proteins are recruited, by recruiting specific substrates, or by changing the conformation of a recruited protein. They can also promote membrane localization of the signaling complex.

46
Q

In what form are GTPases inactive?

A

Generally, small GTPases are inactive if they are bound to GDP, and active if they are bound to GTP.

47
Q

What proteins facilitate the exchange of GDP for GTP in small GTPases?

A

Guanine-nucleotide exchange factors (GEFs)

48
Q

What is the stoichiometry of the TCR thought to be?

A

TCR alpha chain interacts with a CD3[delta]􏰅:CD3[epsilon]􏰆 dimer and one [zeta]􏰇 dimer, while the TCR Beta􏰀 chain interacts with one CD3[gamma]􏰄:CD3[epsilon]􏰆 dimer

49
Q

Number of ITAMs in TCR

A

One ITAM in each CD3[epsilon], CD3[delta], CD3[gamma], and three ITAMs in each zeta chain, for a total of 10 ITAMs per TCR.

50
Q

Canonical ITAM sequence for signaling motifs

A

YXX[L/I] X(6–9)YXX[L/I]

Y = tyrosine
L = Leucine
I = Isoleucine
X = any amino acids
51
Q

What does mTOR activation lead to?

A

increased lipid production, ribosome biosynthesis, mRNA synthesis, and protein translation.

52
Q

Which CD markers make up the B cell co-receptor?

A

CD21, CD19, and CD81.

53
Q

What are the ligands for LFA-1 and where are they expressed?

A

ICAM-1 (HEVs), ICAM-2 (all endothelial cells) and ICAM-3 (APCs)

54
Q

Through which receptors do T cells bind to activated DCs?

A

LFA-1 and CD2 on T cells

ICAM-1, ICAM-2 and CD58 on DCs

55
Q

CD25

A

alpha chain of IL-2 receptor. Induced in naive T cells along with IL-2 upon activation.

56
Q

Three cytotoxic proteins produced by CD8+ CTLs

A

perforin, granzymes, and granulysin

57
Q

calprotectin

A

AMP produced by ECs and neutrophils that sequesters free zinc and manganese to ‘starve’ microbes.

58
Q

What are the ‘secondary cytokine’ signals needed for effective Th1 and Th17 differentiation?

A

IL-23 for Th17 and IL-12 for Th1. They share structural similarities and share a common subunit (p40)

59
Q

Subunits of IL-23

A

one p40 (IL-12 p40) and one p19 (IL-23 p19). p40 subunit is shared between IL-12 and IL-23

60
Q

subunits of IL-12

A

one p40 (IL-12 p40) and one p35 (IL-12 p35). p40 subunit is common between IL-12 and IL-23

61
Q

CD152

A

CTLA-4

Immunology (17 decks)

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