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BLD + Pharm > BLD434 Section 2 > Flashcards

BLD434 Section 2 Flashcards

Immunology

1
Q

Immunoglobulin (Ig) - BCR vs. Ab

A

protein/gene secreted by plasma cells to create a unique antigen receptor on each naive B cell.

BCR when presented on the B cell membrane

Antibody (Ab) when secreted as an effector protein

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2
Q

CDR

A

Complementarity Determining Regions
- The exposed amino acid loops at the end of the V Ig-like domain of a heavy chain

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3
Q

Hypervariable region

A

(same as CDR) the part that is complementary to the Ag-binding site with the target Ag.
This is what changes during somatic hypermutation.

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4
Q

RSS

A

(Recombination Signaling Sequence)
Heptamer + Nonamer + spacer (12 or 23 nucleotides)
During somatic recombination – Controls where RAG cuts and joins the dsDNA of the light and heavy chains

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5
Q

TdT

A

Terminal deoxynucleotidyl transferase
- Enzyme that randomly adds N nucleotides to increase diversity during junctional diversity

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6
Q

RAG

A

Recombination Activating Gene
Two RAG-1 enzymes bind on heptamer and nonamer to pull gene segments together between the V and J. RAG-2 cuts as the border of RSS so V and J can be joined together.

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7
Q

Combinatorial diversity

A

(Pt. 1 of somatic recombination)
Creates different combinations of different gene segments to increase diversity (L-V-(D)-J-C)

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8
Q

Junctional diversity

A

(Pt. of somatic recombination)
TdT puts random P and N nucleotides in between the gene segments to create a unique Ag-binding domain (increases diversity in the a.a. seq of the light and heavy chain CDR3s)
Occurs in B & T cells

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9
Q

P nucleotides

A

short Palindromic sequences formed by cleavage of hairpins that form at the blunt end cut sites

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10
Q

N nucleotides

A

Non-templated nucleotides stuffed in coding joints.

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11
Q

Somatic Recombination

A

(Combinatorial Diversity + Junctional Diversity)
Recombine genes within a cell to create its unique antigen receptor to increase diversity of the lymphocyte pool
- changes the variable regions
- initiated by RSS
- enzymes = RAG complex, TdT
- Occurs in B & T cells - if failed, neither will be produced

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12
Q

Effector function of B lymphocytes

A

Antibody production and secretion

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12
Q

Why are Ig-like domains commonly found in immune system proteins?

A

Because they are very stable in the harsh conditions of infection sites (pH, salt, proteases)
B-sheet antiparallel - very stable

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13
Q

Gene segments for light chain vs heavy chain

A

Light = L-V-J-C
Heavy = L-V-D-J-C

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14
Q

2 Types of light chains

A

Kappa and Lambda

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15
Q

Functions of VL, VH, CL, and CH protein domains

A

VL and VH: form CDR and allow for diversity and specificity
CL and CH: structural support for Ab - don’t change

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16
Q

What 2 C gene segments are closest to the variable gene segments in the Ig heavy chain locus

A

C-mu and C-delta are closest to the variable gene segments, so it is convenient for the naive B cells to transcribe here so IgM and IgD can be expressed on their cell surface.

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17
Q

What proteins compose a complete BCR?

A

2 light chains, 2 heavy chains, Ig-alpha and Ig-beta (signaling molecules)

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18
Q

Ig-alpha an Ig-beta

A

Signaling molecules that transduce signal that Ag has been bound by BCR, leading to change and cell differentiation

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19
Q

Affinity

A

The strength of binding between a Ag-binding site and its target epitope on an antigen.

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20
Q

Avidity

A

Added up affinity
Ex: IgM has 2 Ag-bs per Ab (pentamer)

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21
Q

Somatic Hypermutation

A

Single nucleotide DNA point mutations (sub) in the Ig hypervariable regions to improve BCR binding affinity for Ag.
- initiated by AID
- high rate of mutation
Only occurs in B cells

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22
Q

Clonal selection

A

The B cells that bind to Ag better will be selected for in the population while those that don’t will be lost from the population.

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23
Q

Affinity maturation

A

An improvement in the responding (affinity) B cell pool – achieved by somatic hypermutation then clonal selection
Only occurs in B cells

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24
Q

Surface vs secreted immunoglobulins

A

Surface (BCR) - have hydrophobic a.a. which embed well into the plasma membrane
Secreted (Ab) - have hydrophilic a.a. which are stable in solution

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25
Q

AID

A

Activation-induced cytidine deaminase
- initiates somatic hypermutation and isotype switching

26
Q

What factors control which isotype of Ab the B cell will produce?

A

Cytokines secreted by CD4 Helper T cells

27
Q

Isotype switching

A

Change function of Ab by
- changes the BCR constant heavy chain
- initiated by switch sequences
- enzymes = AID, UNG, APE1
- if failed, can only make IgM
Only occurs in B cells

28
Q

BCR structure

A

2 heavy chains, 2 light chains
2 Ag binding domains
12 Ig-like domains minimum
Associated with Ig-a and Ig-B signaling molecules

29
Q

TCR structure

A

Single TCR-a (VJ) and single TCR-b (VDJ)
1 Ag binding domain
4 Ig-like domains minimum
CD3 complex
CD4 or CD8 co-receptors

30
Q

What antigen is recognized by TCR aB?

A

peptide fragments presented on MHC I and MHC II

31
Q

What antigen is recognized by TCR gamma delta?

A

Lipids - through direct binding

32
Q

Proteins that compose TCR-aB?

A

Va, VB, Ca, CB
CD3 complex
CD4 or CD8 co-receptors

33
Q

Proteins that compose TCR gamma delta?

A

Vgamma, Vdelta, Cgamma, Cdelta
CD3 complex and two zeta chains

34
Q

Gene segments used to create Va and VB

A

Va: V and J
VB: V, D, J

35
Q

Features and functions of gamma delta T cells

A
  • rare (alternate TCR heterodimer)
  • mostly in epithelial cells/CT
  • involved in homeostasis
  • must signal through CD3 complex and zeta chains
  • recognize lipids
36
Q

Endogenous

A

intracellular proteins produced within cell cytosol
MHC I carries peptide fragments from endogenous proteins

37
Q

Exogenous

A

extracellular proteins picked up by pinocytosis (DC), endocytosis (BCR), and phagocytosis (macrophage + DC)

38
Q

B2-microglobulin

A

The soluble light chain of MHC I that provides structural support and is required for MHC I expression

39
Q

Calnexin

A

Chaperone protein that keeps the heavy chain of MHC folded (stabilized until B2m binds)

40
Q

Calreticulin

A

Chaperone protein that keeps the heavy chain of MHC I folded properly until peptide binds (replaces calnexin once peptide binds)

41
Q

TAP

A

(Transporter associated with Antigen Processing)
Heterodimeric protein that transports peptides produced in the cytosol, so they can be loaded in MHC I.
proteasome –> ER.

42
Q

ERp57 enzyme

A
  • Associates the MHC I heavy chain with TAP
  • Facilitates peptide loading into MHC I
43
Q

Tapasin

A
  • Associates the MHC I heavy chain with TAP
  • Facilitates peptide loading into MHC I (assembly)
44
Q

Proteasome

A

Protein complex that degrades ubiquitinated proteins into peptide fragments

45
Q

Invariant chain

A

Covers the peptide binding groove so MHC II doesn’t get loaded with peptides in the ER.
Shuttles MHC II into outgoing endosomes, so it’s released from the ER w/o peptide

46
Q

CLIP

A

(Class II-associated invariant-chain peptide)
24-residue fragment that
fills and blocks binding of peptides to MHC II in vesicles

47
Q

HLA-DM

A

Human Leukocyte Antigen Complex that is contained within the endosome.
Releases CLIP, so peptides can bind to MHC II

48
Q

MHC I

A
  • CD8 (cytotoxic) co-receptor
  • Present on all nucleated cells
  • Presents endogenous (mostly viral) peptides (capable of the other during cross pres.)
  • Pita pocket (small) peptide-binding groove
  • Calnexin, B2m, calreticulin, TAP, tapasin, ERp57
  • HLA –> A,B,C
49
Q

MHC II

A
  • CD4 (helper) co-receptor
  • Present on surfaces of APCs (B cell, macrophage, DC)
  • Presents exogenous peptides
  • Hot dog (large) peptide-binding groove
  • Invariant chain, CLIP, HLA-DM
  • HLA –> D (DP, DQ, DR (2,3,4))
50
Q

How do the APCs obtain antigens & what type of antigens?

A

B lymphocytes: endocytosis (receptor-mediated) – soluble, viral?
Macrophages: phagocytosis – bacteria, yeast, etc.
Dendritic cells: pinocytosis & phagocytosis (can activate naive T cells) – viral

51
Q

Cross presentation

A

MHC I can present exogenous antigens to activate CD8 T cells to respond to viral infections.

DCs take anitgen from apoptotic debris outside cell and process them and put them into MHC I, activating CD8+ in secondary lymphoid tissues (to go kill virus-infected cells in the body)

52
Q

HLA

A

Human Leukocyte Antigens
Genes in MHC that help code for proteins to differentiate between self and non-self

53
Q

Polygeny

A

Several genes are expressed to perform the same function in a cell

54
Q

Polymorphism

A

Having multiple forms - HLA gene sequences (alleles) vary from person to person

55
Q

Relative numbers of alleles that exist for each HLA gene in the human population

A

Monomorphic: DR-alpha
Oligomorphic (1-10): E, F, G, DM, DO, B2
Polymorphic (hundreds): DP, DQ
Highly polymorphic (thousands): A, B, C, DRB1, DRB3-5

56
Q

How are HLA haplotypes inherited?

A

Each person inherits a complete haplotype from each parent and expresses all alleles form each parent.
Ex: heterozygote expresses 2 haplotypes

57
Q

How many MHC I and MHC II isoforms can compose an individual’s haplotype?

A

Minimum = 3 MHC I, 3 MHC II
Maximum = 6 MHC I, 8 MHC II
Most people = 6 MHC I, 6 MHC II

58
Q

How can interferons modify the level of MHC on cells?

A

Type I interferons (alpha & beta) enhance antigen expression of MHC I during viral infections
- uses immunoproteasome
Type II interferons (gamma) enhance antigen expression of MHC II heavy and invariant chains
- induced by CIITA (MHC II transcription factor)

59
Q

Immunoproteasome

A
  • Generates peptides that can fit MHC I molecules.
  • Has LMP 2 and LMP 7 which increase nonamer production, TAP, B2m, and expression og MHC I heavy chain
60
Q

CIITA

A

Class II Trans Activator Protein
- Transcription factor for MHC II to increase its expression

61
Q

HLA-E function

A
  • expressed on all nucleated cells
  • binds peptide fragments of MHC I leader peptides and presents them to inhibitory receptors on NK cells
  • prevent NK cells from attacking self
62
Q

HLA-G function

A
  • restricted to fetal cells that lack HLA-A,B,C
  • provides a NK cell ligand
  • Prevents NK cells from attacking self
63
Q

Anchor residues

A

A.A. residues on the floor/wall of peptide-binding groove of MHC I & II
- The points where antigen peptides bind (anchor) to the MHC

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