Updated: 10/11/2018

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
  • Defence 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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Questions (6)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.IM.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? Review Topic

QID: 100429
1

Membrane attack complex formation is impaired

13%

(28/222)

2

Opsonization and phagocytosis of pathogen cannot occur

13%

(29/222)

3

Impaired adaptive immune system memory

2%

(4/222)

4

Impaired antibody binding to mast cells

2%

(5/222)

5

Impaired mucosal immune protection

66%

(147/222)

M1

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PREFERRED RESPONSE 5

(M1.IM.20) In which location is dimeric IgA most likely to be found in highest concentrations? Review Topic

QID: 100441
1

Colostrum

87%

(52/60)

2

Blood from the fetus

3%

(2/60)

3

Blood from the mother

3%

(2/60)

4

Fetal bone marrow

3%

(2/60)

5

Fetal thymus

2%

(1/60)

M1

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PREFERRED RESPONSE 1
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