Updated: 12/20/2018

Humoral-Mediated Immunity

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Overview

Introduction
  • Humoral immunity is based upon the production and activity of antibodies that
    • defend against extracellular threats such as bacteria via
      • 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
  • The main effector cell of humoral immunity B-cell that
    • is activated by displaying peptides to helper T-cells
    • undergoes affinity maturation to make higher affinity antibodies
    • undergoes class switching to develop new classes of antibodies
    • differentiates into plasma cells that are specialized to produce antibodies
  • Humoral immunity occurs in multiple phases including
    • the primary response that occurs immediately after B-cell activation
    • the secondary response after further differentiation of B-cells
Activation of Humoral-Mediated Immunity
  • Humoral immunity can be activated by two classes of antigens including
    • thymus independent antigens that do not require T-cell help
    • thymus dependent antigens that require T-cell help
Activation of Humoral Mediated Immunity
Feature Thymus Independent
Thymus Dependent
Function
  • Detect conserved non-peptide antigens
  • Identify pathogens that are missed by T-cells
  • Detect peptide antigens
  • Cooperate with T-cells to clear pathogens
Activation steps
  • Crosslinking of B-cell receptors by polymeric antigens
  • Examples include bacterial cell wall or lipopolysaccharide
  • Activation by mitogens to promote general B-cell activity 
  • Endocytosis of protein antigens that are detected by the B-cell receptor
  • Processing of these antigens in endosomes and presentation on MHC class 2
  • Recognition of MHC complexes by activated helper T-cells
  • Interaction of costimulatory CD40 on B-cells with CD40 ligand
  • Differentiation after cytokine stimulation
Limitations
  • Does not lead to class switching or affinity maturation
  • Does not produce immunological memory (require adjuvent)     
  • Requires peptide antigen
  • Must have functional helper T-cells
 
Affinity Maturation and Isotype Switching
  • After B-cells are activated they can undergo two main processes including
    • affinity maturation to increase receptor affinity
    • isotype switching to produce different antibody isotypes
  • Affinity maturation is a coordinated process with distinct stages including
    • migration of B-cells to secondary lymphoid organs where
      • B-cells proliferate in germinal centers to form a colony
      • the B-cell receptor is randomly mutated in different cells
    • selection of the cells with the highest affinity receptors within the colony by
      • providing a limited number of survival signals
      • allowing mutated B-cells to compete for these signals
      • pruning less effective B-cells through apoptosis
  • Isotype switching is stimulated after activation and
    • occurs in germinal centers of secondary lymphoid organs
    • is the process of irreversibly switching constant regions by DNA rearrangement with 
      • removal of μ (IgM) and δ (IgD) type constant regions
      • addition of other constant regions making IgG, IgE, and IgA
    • is controlled by stimulation with specific cytokines
      • no specific IL required for IgG production
      • IL-4 produces IgE  
      • IL-5 produces IgA
Primary and Secondary Responses
  • Upon activation distinct populations of B-cells will develop including
    • effector B-cells that mediate the primary response by
      • secreting antibodies
      • secreting cytokines
    • proliferating B-cells that mediate the secondary response after
      • undergoing affinity maturation and class switching
      • differentiating into plasma cells
  • These responses differ in a variety of key aspects
Primary versus Secondary Responses
Feature Primary Response
Secondary Response
Function
  • Immediately secrete antibodies
  • Contain infection while secondary response develops
  • Develop into a more effective response with higher affinity
  • Clear infection after development
Antibody type
  • Low affinity IgM
  • High affinity IgG
  • IgA in mucosal infections
  • IgE in parasitic infections
Timing
  • Early in infection
  • Late in infection
 

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Questions (5)
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.73) The only immunoglobulin found as a dimer has what primary function? Review Topic

QID: 100589
1

Protect against invasive helminth infection

7%

(3/44)

2

Protect against viral infections

0%

(0/44)

3

Provide an initial humoral immune response to newly presenting bacterial antigens

7%

(3/44)

4

Inhibiting bacterial adherance and colonization of mucous membranes

70%

(31/44)

5

Provides the most specific recognition to circulating antigens in the bloodstream

9%

(4/44)

M1

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PREFERRED RESPONSE 4

(M1.IM.66) Which of the following events is likely to occur in the germinal center? Review Topic

QID: 100487
1

Development of early pro-B cells

21%

(10/48)

2

Development of immature B cells

21%

(10/48)

3

T-cell negative selection

6%

(3/48)

4

Isotype switching

42%

(20/48)

5

Formation of double-positive T cells

4%

(2/48)

M1

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PREFERRED RESPONSE 4

(M1.IM.56) A 12-year-old African American is exposed to pollen while playing outside. The allergen stimulates TH2 cells of his immune system to secrete a factor that leads to B-cell class switching to IgE. What factor is secreted by the TH2 cell? Review Topic

QID: 100477
1

IFN-gamma

7%

(2/28)

2

IL-4

86%

(24/28)

3

IL-17

7%

(2/28)

4

TGF-beta

0%

(0/28)

5

IL-22

0%

(0/28)

M1

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PREFERRED RESPONSE 2

(M1.IM.36) Immunology researchers attempt to characterize the role of several cytokines in a 5-year-old male’s allergic reaction to peanuts. Months after initial exposure to peanuts, the child was brought to the ER with symptoms of anaphylaxis that resolved following epinephrine injection and supportive therapy. Which of the following best describes the role of IL-4 in the child’s response: Review Topic

QID: 100457
1

B cell class switching

62%

(54/87)

2

Stimulates IgA production

6%

(5/87)

3

Macrophage and Th1 cell activation

14%

(12/87)

4

Neutrophil chemotaxis

10%

(9/87)

5

Growth of cytotoxic T cells

2%

(2/87)

M1

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PREFERRED RESPONSE 1
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