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
QUESTIONS 1 of 5 1 2 3 4 5 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.14.66) Which of the following events is likely to occur in the germinal center? QID: 100487 Type & Select Correct Answer 1 Development of early pro-B cells 18% (36/204) 2 Development of immature B cells 24% (49/204) 3 T-cell negative selection 4% (8/204) 4 Isotype switching 50% (101/204) 5 Formation of double-positive T cells 1% (3/204) M 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic (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: QID: 100457 Type & Select Correct Answer 1 B cell class switching 75% (147/196) 2 Stimulates IgA production 8% (15/196) 3 Macrophage and Th1 cell activation 8% (16/196) 4 Neutrophil chemotaxis 5% (10/196) 5 Growth of cytotoxic T cells 1% (2/196) M 1 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic (M1.IM.13.73) The only immunoglobulin found as a dimer has what primary function? QID: 100589 Type & Select Correct Answer 1 Protect against invasive helminth infection 3% (6/206) 2 Protect against viral infections 2% (4/206) 3 Provide an initial humoral immune response to newly presenting bacterial antigens 8% (17/206) 4 Inhibiting bacterial adherance and colonization of mucous membranes 81% (167/206) 5 Provides the most specific recognition to circulating antigens in the bloodstream 4% (8/206) M 1 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic (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? QID: 100477 Type & Select Correct Answer 1 IFN-gamma 4% (6/145) 2 IL-4 89% (129/145) 3 IL-17 5% (7/145) 4 TGF-beta 1% (1/145) 5 IL-22 0% (0/145) M 1 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic
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