Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology > Antibodies > Flashcards

Antibodies Flashcards

0
Q

Antibody classes

A

Determined by isotype of heavy chain

mu -> IgM
delta -> IgD
gamma -> IgG
epsilon -> IgE
alpha -> IgA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

General antibody structure

A

2 heavy chains and 2 light chains
H=H and L=L due to allelic exclusion
L-H and H-H di-sulfide bonds hold together

Fab = antigen binding (variable) - H + L
Fc = crystallizable (constant) - only heavy chains
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Membrane antibodies

A

Co-expressed with adhesion molecules

Ig-beta, Ig-alpha (similar to CD3 + TCR) - transduce signals

Membrane antibody + Ig-beta + Ig-alpha = BCR!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Antigen binding site

A

At N-terminus of light and heavy chains
“VL” = variable light loop
“VH” = variable heavy loop

Each loop (VL and VH) contains 3 hypervariable regions aka "CDR" aka "complementarity determining regions"
 - amino acid residues determine specificity of antigen binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Antigenic determinants

A

Antigenic determinant = epitope = region on antigen that binds to antibody

  • may be protein, carb, lipid, etc
  • many antigens have multiple different determinants -> multiple Ab matches

Binding

  • conformational (no affinity when denatured)
  • linear -> either accessible when folded or inaccessible (MUST be denatured for Ab binding)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Fc region

A

Fraction crystallizable
C-terminal of light (1/2) and heavy (3/4) chain
Constant across Ig class and subclass
Determines effector function of antibody!
- CH2 binds complement
- Fc receptors (FcR) bind Fc region of a subclass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Antibody valence

A

Number of Fab regions = number of antigenic determinants that can be bound

“Normal” and membrane = divalent
Secreted IgM and IgA = multivalent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Affinity vs avidity

A

Affinity = strength of binding of antigenic determinant:Fab
Avidity = functional strength of antigen:antibody
- avidity is exponentially increased by valence (ie multivalent, multiple Fab’s can hold antigen exponentially longer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

IgG characteristics

A 
Most abundant in blood
Crosses placenta -> passive immunity
Four subclasses (IgG1, IgG2, IgG3, IgG4)
 - different H chains -> different functions
Simple dimer (2 H, 2 L) -> 2 Fab's
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

IgM characteristics

A

First antibody produced in immune reaction
Expressed on membrane of naive, mature cells as BCR (dimer form) - along with IgD
Released into blood - 5 dimers -> 10 Fab’s
- held together with J chain (not from “J” exon of DNA)
- low affinity but 10 Fab’s -> high avidity -> highly efficient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

IgA characteristics

A

Blood as simple divalent
Secreted (sIgA) = dimer = 4 H + 4 L
- 4 Fab’s -> higher avidity
- J chain + “secretory component” hold together
- made by local plasma cells -> secreted across epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

IgA secretion

A

Produced and secreted in local plasma cells
- secreted as dimer with J chain
Binds to poly-Ig receptor on basal surface of epithelial cell
- dimer + poly-Ig receptor endocytosed
- poly-Ig receptor partially cleaved in endosome ->
- secreted with dimer + J chain + poly-Ig receptor fragment

“Secretory component” = fragment of poly-Ig receptor from epithelial cell
- helps hold together in secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

IgD characteristics

A

Very low levels in blood
Primarily acts as BCR
- expressed with IgM in mature, naive cells (same Fab specificity)
- antigen binding -> internalized -> processed -> present to Th
Important for respiratory, identifying B cell development and type (ie follicular vs marginal zone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

IgE characteristics

A

Very low levels in serum
Important for inflammation and allergies/asthma
Binds to FcER1 receptors on mast cells (via Fc domain)
- antigen -> crosslinking of mast cells -> signal -> histamine release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

“Isotype”

A

Differences between Ig classes

  • sequence in Fc of heavy chain
  • determines function of antibody (ie complement, FcR’s)
  • use in lab to find specific antibody class
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

“Allotype”

A

Genetic polymorphisms in antibodies

  • ex different alleles for H chain of IgM
  • study in Fc region (not affected by recombination)
  • use for paternity
16
Q

“Idiotype”

A

Changes to variable domains

  • directly determines antigen binding site specificity
  • use for targeting therapies to destinations or pathogens
17
Q

Overview of antibody diversity

A

Multiple exons in different gene segments
- V = variable, D = diversity, J = joining, C = constant
->rearrange DNA so VDJ (or VJ) is encoded in a single uninterrupted exon
- unique DNA rearrangement -> unique Fab
Similar process at each of three gene loci (H chain, lambda, kappa)

18
Q

DNA recombination process

A

Requires combined expression/activity of “recombination-activating genes” - RAG1, RAG2 - limited to lymphocyte dev’t
H chain first
- DJ join
- V joins -> VDJ
- C region not rearranged (spliced in mRNA)
Either kappa or lambda (not both in same cell)
- VJ join

19
Q

DNA - antibody structure

A

V = variable exon
- determines general shape of antigen binding site
- contains complementarity determining region (CDR) 1, 2
VDJ junction -> CD3 (most variability!)

20
Q

Light chain components

A

Either kappa or lambda expressed in each cell
VJ exons splice -> determine variable region
Each allele also has constant region at C-terminal end

21
Q

Constant region DNA

A

Located at 3’ (C-terminus) of allele
Not recombined!
Isotype and class switching determined by splicing
- “switch”/S sequences between C-regions
C-region exons: alpha (1,2), delta, epsilon, mu, gamma (1-4)

22
Q

Membrane vs secreted antibodies

A

Determined by splicing and poly’A of constant DNA region of H chain
Membrane - includes transmembrane (hydrophobic) and cytoplasmic exons - at 3’ end of mu and delta C regions
Secreted - transmembrane and cytoplasmic exons spliced off

23
Q

Mechanisms of antibody diversity

A

Most are antigen-independent -> inc likelihood of antigen match

  • variation in germ line alleles (V, D, J, V, J)
  • variation in exon combination (which V, which D…)
  • imprecise joining -> junctional diversity
  • CD3 -> extra nucleotides added -> frameshift
  • terminal deoxynucleotidyl transferase (TDT) addes “N” nucleotides to 5’ end of exons
  • “P” nucleotides added during recombination

Also have antigen-dependent affinity maturation during clonal expansion

24
Q

Affinity maturation

A

Within germinal center (ie during clonal expansion)
Somatic point mutations develop in V region
Mutations accumulate if they increase binding affinity (compete for antigen:BCR binding)

-> decrease in binding coefficient/increased affinity of final plasma and memory cells

25
Q

Allelic exclusion

A

Each mature B cell only expressed one H chain and one L (either kappa or lambda)
If first is successful -> second is silenced and never recombines

26
Q

Stages of B cell maturation

A

Does NOT require foreign antigen
Heavy chain rearrangement -> mu expressed + surrogate light chain -signal> stop heavy rearrangement ->
Start light chain rearrangement -(if successful)>
IgM expressed -> “immature” -> tolerance induction ->
IgM signals survival, expansion -> IgD expressed -> “mature naive”

27
Q

BCR co-receptors

A

Most active when stimulated by same complex as BCR (ex antigen + complement)

Stimulatory (-> activation)
 - CD21 = complement receptor 2
 - CD19
 - CD81
Inhibitory (slows activation or requires more antigen)
 - CD32 = receptor for Fc region of IgG
28
Q

CD19 deficiency

A

Form of “common variable immunodeficiency”
CD19 is co-stimulator for B-cell activation

If Cd19 missing -> no co-stimulation -> more bacterial infections
Treat with IV-Ig -> passive immunity

29
Q

Isotype switching

A

Induced by T-cell cytokines: IL-4, TGF-beta, INF-gamma

Via differential splicing of VDJ to different C regions

30
Q

B cell tolerance

A

Multiple mechanisms
Apoptosis - either central or peripheral
Anergy
Receptor editing - “tries” a second time to make light chain -> new antigen specificity
T cells - don’t activate self or produce Treg (T cell tolerance is more robust)

Immunology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions