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PABI 6100 Immunobiology > 5. Antibody Structure and Effector Functions > Flashcards

5. Antibody Structure and Effector Functions Flashcards

1
Q

What is the basic structure of antibodies?

A
  • 4 polypeptide chains
    > 2 identical light (L) chains/ 2 identical heavy (H) chains
  • each chain has a variable (V) region/ constant (C) region
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2
Q

What region of antibodies defines it?

A
  • constant regions
    > 2x light chain subtypes> κ/ λ
    > 5x heavy chain isotypes > υ/ γ/ α/ δ/ ε
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3
Q

What determines the class of antibody?

A
  • isotype of constant region of heavy chain (υ/ γ/ α/ δ/ ε)
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4
Q

How is each light chain (outer) bound to its partner heavy chain (inner)?

A
  • a disulfide bond
  • non-covalent interactions
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5
Q

How are the 2 heavy chains (inner) brought together?

A
  • disulfide bonds
  • non-covalent interactions
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6
Q

What is the hinge region on antibodies?

A
  • between CH1/ CH2
  • gives flexibility to antigen-binding arms
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7
Q

What is Fab?

A
  • fragment antigen binding region
    > where antibody binds to antigen
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8
Q

What is Fc?

A
  • fragment crystallizable
    > interacts with FcRs that mediate antibody effector functions
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9
Q

What do the amino/carboxy-terminal domains of antibodies do?

A
  • amino-terminal portion (Fab region) binds to antigen
  • carboxy-terminal mediates effector functions (Fc region)
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10
Q

How are antibodies made up of multiple immunoglobulin domains?

A
  • anti-parallel β-pleated strands arranged into a pair of sheets
    > each β sheet contains 3-5 strands
  • loosely folded regions link the strands
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11
Q

What are CDRs?

A
  • complementarity determining regions
    > 3 loops of variable domain with high variation in AAs (hypervariable regions)
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12
Q

What are the 5 major classes of antibodies?

A
  • IgG/ IgD/ IgE/ IgA/ IgM
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13
Q

What joins antibody monomers together?

A
  • J chain (linked by 2 disulfide bonds)
    > serum IgM- pentamer
    > serum IgA- mostly monomer, can be dimer/ trimer/ tetramer
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14
Q

What antibody is always a pentamer?

A
  • serum IgM
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15
Q

What antibodies are multimers?

A
  • Serum IgM > always a pentamer
  • Serum IgA > mostly monomer but can be dimer/ trimer/ tetramer
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16
Q

What determines the class of antibody?

A
  • differences in AA sequences in heavy chain constant regions
    > 5x isotype of heavy chain constant regions
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17
Q

What antibodies do not have a J chain?

A
  • IgG/ IgD/ IgE
  • only IgA/ IgM are multimers (J chain joins monomers together)
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18
Q

Why are there 5 major classes of antibodies?

A
  • 5 basic sequences of heavy-chain constant regions (υ/ γ/ α/ δ/ ε)
  • each different heavy-chain constant region is called an isotype
  • the isotype of the heavy chains of an antibody determines its class
19
Q

What heavy chain isotypes correspond with each class of antibody?

A
  • υ > IgM
  • δ > IgD
  • γ > IgG
  • ε > IgE
  • α > IgA
20
Q

What major classes of antibodies can be further sub-classified?

A
  • α/ γ heavy chain isotypes further classified into sub-isotypes
  • corresponding antibodies IgA/ IgG further classified into subclasses
  • 2 sub-isotypes of α heavy chain: α1/ α2
    > 2 IgA subclasses: IgA1/ IgA2
  • 4 sub-isotypes of γ heavy chain: γ1/ γ2/ γ3/ γ4
    > 4 IgG subclasses: IgG1/ IgG2/ IgG3/ IgG4
21
Q

What is the only antibody that crosses the placenta?
> fetal circulation

A

IgG

22
Q

What is the first antibody produced during a primary immune response?

A

IgM

23
Q

What are antibody isotypes?

A
  • antigenic determinants within constant regions of antibodies
    > shared among all members of species (same for everyone)
24
Q

What are antibody allotypes?

A
  • antigenic determinants within constant regions of antibodies
  • alternative allelic forms of same isotype
    > vary among individuals (different for everyone)
25
Q

What are antibody idiotypes?

A
  • antigenic determinants within antigen-binding site (Fab) of antibodies > sequence of its CDRs
  • characterize a unique antibody
26
Q

What are the 6 main antibody effector functions?

A
  1. Neutralization > inactivate/ prevent binding to cells
  2. Agglutination > enhances neutralization/ pathogen clearance
  3. Opsonization > phagocytosis
  4. Complement activation > formation of MAC > kill microbe
  5. ADCC- (Antibody-Dependent Cell-Mediated Cytotoxicity) > NK cell-induced apoptosis
  6. Degranulation > triggers mediator release from granulocytes
27
Q

What are neutralizing antibodies?

A
  • antibodies that bind pathogens/ prevent them from binding to other cells
    > can prevent pathogen from ever initiating an infection
28
Q

What are the first antibodies produced during a primary immune response?

A

IgM
- low-affinity antibodies (since B cells that make them have not yet undergone affinity maturation)
- very effective at binding pathogen since decavalent (can bind 10 antigens) since are pentamers

29
Q

What are the effector functions of IgM antibodies?

A
  • fixing complement > lysis of pathogens they bind to
  • agglutination of pathogens > phagocytosis by macrophages
30
Q

What are known as “natural antibodies”?

A
  • IgM antibodies produced by B-1 cells (most circulating IgM antibodies)
  • B-1 cells constitutively produce IgM cells without being exposed to pathogen > protect from common gut/ mucosal pathogens
31
Q

What is the most common antibody class in the serum?

A
  • IgG antibodies (most abundant)
    > also most diverse class (4 subclasses- IgG1 > IgG4)
32
Q

What are the effector functions of IgG antibodies?

A
  • all variants bind to Fc receptors
  • opsonization > enhance phagocytosis by macrophages
33
Q

What is the major antibody isotype found in secretions?

A

IgA
- mucus in gut/ respiratory and reproductive tracts/ milk from mammary glands/ tears/ saliva

34
Q

What are the effector functions of IgA antibodies?

A
  • neutralization of pathogens
  • interact with commensal bacteria/ prevent from entering bloodstream
  • IgA can not fix complement
  • mediate ADCC by binding FcRs on NKT cells
  • trigger degranulation of granulocytes
35
Q

What are the effector functions of IgE antibodies?

A
  • best known for role in allergy/ asthma
  • protection against parasitic helminths (worms)/ protozoa
  • induce degranulation of eosinophils/ basophils
36
Q

What are the effector functions of IgD antibodies?

A
  • minor immunoglobulin in blood (0.2%) > respiratory tract
  • degranulation > bind to basophils/ mast cells > release antimicrobial peptides/ cytokines/ chemokines
37
Q

What are FcRs?

A
  • Fc receptors > on innate cells/ APCs (most immune cells)
  • mediate effector functions of antibodies
38
Q

Why are Fc receptors important/ how do they work?

A
  • mediate effector functions of antibodies
  • multiple FCRs must be cross-linked to initiate signal
    > positive signal- enhances effector function
    > negative signal- inhibits effector function
  • outcome depends on whether receptor associated with ITAM/ ITIM
    > immunoreceptor tyrosine activation/ inhibition motif
  • most FCRs are activating receptors/ associated with ITAM
39
Q

What is the most diverse group of FcRs?

A
  • FcγR
  • 4 families > 3 activating/ 1 inhibiting family of receptors
  • main mediators of Ab functions in the body
40
Q

What antibody effector functions are mediated by FcγR?

A
  • main mediators of Ab functions in the body
  • induce phagocytosis if expressed by macrophages
  • induce degranulation if expressed by cytotoxic cells
41
Q

What antibody effector functions are mediated by FcεR?

A
  • expressed by granulocytes (mast cells/ basophils/ eosinophils)
  • triggers inflammation cascade > release histamines/ proteases/ inflammatory mediators
    > associated with allergy symptoms
42
Q

What antibody effector functions are mediated by FcαR?

A
  • expressed by myeloid cells
  • trigger ADCC/ phagocytosis > contribute to pathogen destruction
  • stimulate myeloid cells to release inflammatory cytokines/ generate superoxide free radicals > kill internalized pathogens
43
Q

What is the neonatal Fc receptor?

A

FcRn
- expressed on epithelial/ endothelial cell types
- helps carry Ab ingested in milk across epithelial cells > bloodstream
- in adults > help recycle IgG taken up through endothelial cell pinocytosis

44
Q

What antibody effector functions are mediated by PolyIgR?

A
  • expressed by epithelial cells
  • initiates transport of IgA/ IgM from blood to lumen of tissues in gastrointestinal/ respiratory/ reproductive tracts
    > transports IgA across epithelial borders
  • carries antibody into secretions
  • populates gut mucosa with IgA to protect against ingested microbes

PABI 6100 Immunobiology (6 decks)

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