humoral immunity Flashcards
in which infections is there a humoral immune response?
- exotoxin mediated diseases (tetanus, diptheria, etc…)
- bugs with polysaccharide capsules
- some viral infections
effector functions of antibodies
- neutralization of toxins (IgG, IgA)
- blocking entry of pathogens across mucosa and into cells (IgA)
- activating complement cascade via classical pathway (IgG and IgM)
- opsonization (IgG)
- antibody dependent cell-mediated cytotoxicity => sensitization for killing by NK cells (IgG)
- sensitization of mast cells (IgE)
- immunity against helminths via eosinophil activation (IgE)
describe the steps of IgE mediated immunity against helminths
- IgE binds helminths
- Eosinophils bind to IgE Fc via FceRI
- IgE binding leads to release of eosinophil mediators of death
- Th2 CD4+ T cells release IL-5 that enhances eosinophil activity
induction of a humoral antibody response to a TI antigen
- naive B cells (in marginal zone or mucosa) recognize antigen via IgM BCR
- Co-stimulation through complement receptors (CD21) or TLRs
- Antigen specific B cells differentiate to short-lived plasma cells
- IgM produced, with limited isotype switching to to IgG and IgA
*no memory or affinity maturation
induction of a humoral antibody response to a TD antigen
- naive B cells (outside germinal centers) recognize antigen via IgM BCR
- Antigen is internalized and degraded
- Peptide presented on MHC class II
- CD40 and B7 expressed
- Second singal from complement, TLR, CD4+ T cells, or cytokines
- Activated B cells migrate toward B cell-T cell zone border and interact with antigen-activated CD4+ T helper cells
- Differentiate to plasmablasts and secrete IgM with low affinity for antigen
- Other antigen activated B cells in germinal centers interact with antigen specific activated CD4+ T helper cells via CD40/CD40L
- Rapid proliferation, isotype switching, and somatic hypermutation (IL4 and IL5)
- Interaction with follicular dendritic cells and APCs to select for high affinity antibody
- B cells with high affinity antibodies differentiate into memory B cells or plasma cells and live in bone marrow.
primary antibody response
- 5-10 days
- early: specific, but low affinity IgM produced first
- later: germinal centers => isotype switching and somatic hypermutation => differentiation into memory B cells and plasma cells
what is the genetic mechanism of isotype switching?
genetic recombination via activation induced cytidine deaminase AID (mu subunit is removed)
secondary antibody response
- 1-3 days after exposure
- relies on memory B cells and T cells
- further affinity maturation => stronger, class-switched response
how does antigen exposure affect antibody affinity
more exposure => more B/T cell interactions in the germinal center => more mutations and more specificity
feedback inhibition of humoral immunity
FcgammaRIIB on B cell surface binds IgG Fc region => signaling through an immunomodulatory tyrosine-based inhibition motif (ITIM) => termination of B cell response to antigen
how much of the different antibody classes are present in the peripheral blood?
IgG»_space; IgA > IgM > IgD, IgE
x-linked agammaglobulinemia
- deficiency in bruton’s tyrosine kinase required for B cell development
- no antibodies or secondary lymphatic tissues
- life threatening infections by: encapsulated bugs, enterovirus, vaccine associated poliomyelitis
IgA deficiency
- most common immunodeficiency and often asymptomatic
- increased risk for mucosal (esp viral) infections
- autoimmune association
- blood transfusion risk
common variable immunodeficiency
- multiple causes => defect in B cells or T helper cells => low immunoglobulins and decreased memory B cells
- increased risk for bacterial, enteroviral, and giardia infections in late childhood/adulthood
- increased autoimmune and lymphoma risk
