Immune Responses Flashcards
IgG
Main antibody in 2° response to an antigen. Most abundant isotype in serum. Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses. Only isotype that crosses the placenta (provides infants with passive immunity).
IgA
Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement. Monomer (in circulation) or dimer (with J chain when secreted). Crosses epithelial cells by transcytosis. Produced in GI tract (eg, by Peyer patches) and protects against gut infections (eg, Giardia). Most produced antibody overall, but has lower serum concentrations. Released into secretions (tears, saliva, mucus) and breast milk. Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases
IgM
Produced in the 1° (immediate) response to an antigen. Fixes complement. Cannot cross the placenta. Antigen receptor on the surface of B cells. Monomer on B cell, pentamer with J chain when secreted. Pentamer enables avid binding to antigen while humoral response evolves.
IgD
Unclear function. Found on surface of many B cells and in serum
IgE
Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine. Contributes to immunity to parasites by activating eosinophils. Lowest concentration in serum
Classic Complement Pathway
IgG or IgM mediated
Alternative Complement Pathway
microbe surface molecules
Lectin Complement Pathway
mannose or other sugars on microbe surface
C3b functions
opsonization
C3a, C4a, C5a functions
anaphylaxis
C5a functions
neutrophil chemotaxis
C5b-9 functions
cytolysis by MAC
Opsonins functions
C3b and IgG are the two 1° opsonins in bacterial defense; enhance phagocytosis. C3b also helps clear immune complexes.
Inhibitors functions
decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells (eg, RBCs).
Early complement deficiencies (C1-C4)
Increased risk of severe, recurrent pyogenic sinus and respiratory tract infections. Increased risk of SLE
Terminal complement deficiencies (C5–C9)
Increased susceptibility to recurrent Neisseria bacteremia
C1 esterase inhibitor deficiency
Causes hereditary angioedema due to unregulated activation of kallikrein ->
bradykinin.
Characterized by decreasedC4 levels.
ACE inhibitors are contraindicated.
Paroxysmal nocturnal hemoglobinuria
A defect in the PIGA gene preventing the formation of anchors for complement inhibitors, such as decay-acclerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59). Causes complement-mediated lysis of RBCs
IL-1
SECRETED BY MACROPHAGES
Causes fever, acute inflammation. Activates endothelium to express adhesion molecules. Induces chemokine secretion to recruit WBCs. Also known as osteoclast-activating factor.
IL-6
SECRETED BY MACROPHAGES
Causes fever and stimulates production of acutephase proteins
IL-8
SECRETED BY MACROPHAGES
Major chemotactic factor for neutrophils
IL-12
SECRETED BY MACROPHAGES
Induces differentiation of T cells into Th1 cells. Activates NK cells
Tumor necrosis factor-alpha
SECRETED BY MACROPHAGES
Activates endothelium. Causes WBC recruitment, vascular leak
IL-2
SECRETED BY ALL T CELLS
Stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells
IL-3
SECRETED BY ALL T CELLS
Supports growth and differentiation of bone marrow stem cells. Functions like GM-CSF
INF-gamma
FROM Th1 CELLS
Secreted by NK cells and T cells in response to antigen or IL-12 from macrophages; stimulates macrophages to kill phagocytosed pathogens. Inhibits differentiation of Th2 cells
IL-4
FROM Th2 CELLS
Induces differentiation of T cells into Th (helper) 2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG
IL-5
FROM Th2 CELLS
Promotes growth and differentiation of B cells. Enhances class switching to IgA. Stimulates growth and differentiation of eosinophils.
IL-10
FROM Th2 CELLS
Attenuates inflammatory response. Decreases expression of MHC class II and Th1 cytokines. Inhibits activated macrophages and dendritic cells. Also secreted by regulatory T cells
Interferon-α and -β
A part of innate host defense against both RNA and DNA viruses. Interferons are glycoproteins synthesized by virus-infected cells that act on local cells, “priming them” for viral defense by downregulating protein synthesis to resist potential viral replication and upregulating MHC expression to facilitate recognition of infected cells.