Updated: 6/2/2020

Antibodies

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Overview
 

 
Introduction
  • Antibodies are immunologically active circulating proteins that
    • are composed of two heavy chains paired with two light chains
    • serve as a primary component of humoral immunity
    • are produced by B-cells that can further
      • differentiate into plasma cells that specialize in secreting antibodies
      • mature to make antibodies with higher affinity
      • remain dormant as memory cells
    • bind antigens from a wide variety of pathogens
    • are also known as immunoglobulins (Ig)
  • Antibodies are able to fight infections through multiple mechanisms including
    • opsonization of the surface of the pathogen leading to
      • phagocytosis by innate immune cells like macrophages
      • cytotoxicity by triggering release of toxic compounds by innate immune cells
    • neutralization of pathogens and viruses by
      • blocking interaction of pathogenic proteins with host receptors
      • inactivating virulence factors expressed by pathogens
    • activation of the complement cascade through the classical pathway
Antibody Structure
  • Antibodies are composed of two heavy chains paired with two light chains
  • Together these chains create distinct regions of the antibody such as
    • the constant fragment (Fc)
    • two identical variable antigen binding fragments (Fab)
  • These regions differ in both structure and function
Differences Between Antibody Regions
Feature Antibody Binding (Fab)
Constant (Fc)
Composition
  • One heavy and one light chain
  • Linked by disulfide bonds
  • Two heavy chains
  • Linked by disulfide bonds
  • Attached to carbohydrate chains
Terminus
  • N-terminus of protein chains
  • C-terminus of protein chains
Function
  • Binds to antigen in specific manner      
  • Binds to complement proteins 
  • Binds to effector regions of innate immune cells       
Variability
  • Site of idiotype diversity
  • Changed in affinity maturation
  • Unique for every antibody
  • Site of isotype diversity
  • Changed in isotype switching 
  • 5 types that are shared among all antibodies
Antibody Variation and Diversity
 

 
  • Antibodies are able to fight an incredible range of infections because of 
    • idiotype diversity which
      • governs what antigens can be recognized by antibodies
      • is generated by multiple diversity mechanisms including
        • random recombination of VDJ regions of antibody coding regions
        • random addition of nucleotides to hypervariable regions by TdT
        • random assortment of heavy chains with light chains
        • affinity maturation through somatic hypermutation after antigen exposure
      • ensures that any moiety can be recognized by the variable region of an antibody
    • isotype diversity through five types of constant regions
 
Antibody Isotypes
Feature IgA IgD
IgE IgM
IgG
Constant chain type
  • α chain
  • δ chain
  • ε chain
  • μ chain
  • γ chain
Concentration
  • High in mucus membranes and in secretions
  •  Low
  •  Low
  • High in serum during early response
  • High in serum during late response
Valence
  • Dimer
  • Monomer
  • Monomer
  • Pentamer
  • Monomer 
Function
  • Mucosal immunity
  • Transported into mucosal lumens by poly Ig
  • Present on B-cell surfaces
  • Unclear role
  • Defense against parasites 
  • Mediates allergies
  • Low affinity
  • Main antibody in early response 
  • High affinity
  • Main antibody in late reponse
Recognized by
  • Innate immune cells
  • Complement
  •  Unknown
  • Mast cells 
  • Basophils
  • Innate immune cells
  • Phagocytes 
  • Complement

Reference

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(M1.IM.13.8) A 19-year-old male is found to have Neisseria gonorrhoeae bacteremia. This bacterium produces an IgA protease capable of cleaving the hinge region of IgA antibodies. What is the most likely physiological consequence of such a protease?

QID: 100429
1

Membrane attack complex formation is impaired

11%

(37/339)

2

Opsonization and phagocytosis of pathogen cannot occur

12%

(40/339)

3

Impaired adaptive immune system memory

2%

(6/339)

4

Impaired antibody binding to mast cells

3%

(9/339)

5

Impaired mucosal immune protection

70%

(237/339)

M 1 E

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(M1.IM.13.20) In which location is dimeric IgA most likely to be found in highest concentrations?

QID: 100441
1

Colostrum

85%

(115/135)

2

Blood from the fetus

5%

(7/135)

3

Blood from the mother

6%

(8/135)

4

Fetal bone marrow

1%

(2/135)

5

Fetal thymus

1%

(2/135)

M 1 E

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