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)
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(M1.IM.14.66) Which of the following events is likely to occur in the germinal center? Tested Concept

QID: 100487
1

Development of early pro-B cells

17%

(15/87)

2

Development of immature B cells

22%

(19/87)

3

T-cell negative selection

6%

(5/87)

4

Isotype switching

48%

(42/87)

5

Formation of double-positive T cells

2%

(2/87)

M 1 B

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(M1.IM.13.73) The only immunoglobulin found as a dimer has what primary function? Tested Concept

QID: 100589
1

Protect against invasive helminth infection

5%

(5/96)

2

Protect against viral infections

1%

(1/96)

3

Provide an initial humoral immune response to newly presenting bacterial antigens

7%

(7/96)

4

Inhibiting bacterial adherance and colonization of mucous membranes

76%

(73/96)

5

Provides the most specific recognition to circulating antigens in the bloodstream

6%

(6/96)

M 1 D

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(M1.IM.13.56) 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? Tested Concept

QID: 100477
1

IFN-gamma

6%

(3/52)

2

IL-4

83%

(43/52)

3

IL-17

10%

(5/52)

4

TGF-beta

2%

(1/52)

5

IL-22

0%

(0/52)

M 1 E

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(M1.IM.13.36) 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 due to repeat exposure 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: Tested Concept

QID: 100457
1

B cell class switching

64%

(66/103)

2

Stimulates IgA production

7%

(7/103)

3

Macrophage and Th1 cell activation

14%

(14/103)

4

Neutrophil chemotaxis

9%

(9/103)

5

Growth of cytotoxic T cells

2%

(2/103)

M 1 E

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