Humoral Immunity Flashcards
complement system
set of interacting proteins released into the blood after production in the liver.
has two pathways of activation, enhances inflammation, enhances phagocytosis by opsonization, causes lysis of particles by membrane pore formation, removes extracellular pathogens
both pathways produce anaphylatoxins (C3a, C4a C5a). C5a is also chemotactic.
alternative pathway of complement activation
completely innate, does not require antibody to initiate, C3 spontaneously lysis in serum and C3b finds surface of bacteria, forms membrane attack complex, major opsonin
classical pathway of complement activation
activated by antigen-antibody complexes (ex. IgM or IgG)
cleavage of C3 results in recruitment of inflammatory cells, opsonization of pathogens, and perforation of pathogen cell membranes
Inappropriate activation of the complement cascade is controlled at the level of
C1, C3, and C5
Contact between B and T helper cells involves
MHC class 2/peptide presentation, costimulatory molecules (B7/CD28), CD40/CD40L binding, and cytokine production (IL-2, IL-4, IL-5, IL-6)
cytokines induce differentiation, memory cell, class switching
costimulatory molecules (B7:CD28)
needed for T-cell activation
CD40/CD40 Ligand binding
needed for B cell class switching and memory response
Papain cleavage
results in 2 Fab and 1 Fc, cannot agglutinate, each part can only bind to single antigen
Pepsin cleavage
results in one divalent molecule, can bind 2 antigen, can still agglutinate
avidity
increases with number of binding sites. IgM has greater avidity than IgG because it is secreted as a pentamer
idiotype
defines antigen specificity, determined by variable region
isotype
dictates effector functions, constant region
IgM
first antibody made, secreted as pentamer that is joined together by J chains, can bind 10 antigens, traps free antigen, activates complement, low affinity (weaker binding strength) to antigen compared to IgG, cannot act as opsonin
class switching (what it requires, when it occurs, where it occurs)
requires: T-cell, CD40 Ligand, Cytokines, occurs only during immune response, happens in germinal center in secondary lymphoid tissues
result of recombination within constant region. antigen specificity unchanged. dependent on AID (activation induced cytidine deaminase).
somatic hypermutation
random mutations in the coding of the variable domain region, creates single point mutations in the antibody idiotype which can increase affinity
occurs after b cell is activated by antigen, does not affect constant region, dependent on AID (activation induced cytidine deaminase) enzyme
TH2 cell release of cytokine
induces the differentiation of B cells into fully differentiated, antibody-secreting cells and memory cells and induce class switching
thymus-independent antigens
antigens contain no peptides, stimulates secretion of IgM antibodies only and does not result in immunologic memory
germinal centers
clones of proliferating antigen specific B cells, where somatic hypermutation occurs, follicles of the lymph nodes and spleen
clonal selection
results in affinity maturation, predominance of clones capable of producing antibodies with increasing affinity for the antigen
isotype switching
changing the heavy chain constant domains to classes of antibodies with new and different effector functions. rearranges the DNA encoding the constant region of the heavy chain. one way reaction.
IgG
activates complement, opsonizes, mediates ADCC, can be transported across placenta which protects fetus during gestation
has a gamma heavy chain,
IgA
exists as dimer, protective defense of the mucosal surfaces of the body, not opsonin
neutralization, crosses epithelium, present in urinary and gut, predominate class in secretions
B cell activation requires
needs to enter lymphoid follicles and be stimulated by antigen with T cell help to become activated
thymus independent 1 (TI-1) antigen
such as LPS can activate a B cell by replacing T-cell signals with TLR4 (toll receptor). This results in antibodies specific for LPS.
no immunologic response, no memory B cells, no IgG, only IgM response, responses are short lived
thymus independent 2 (TI-2) antigen
can activate a B cell by cross linking receptors to produce a strong signal, enough to activate a B cell.
no immunologic response, no memory B cells, no IgG, only IgM response, responses are short lived
follicular dendritic cell
holds antigen without processing them so B cells can examine antigen and become activated
endotoxin
heat stable, toxicity not destroyed by sterilization techniques, detected using Limulus Amebocyte Lysate
opsonization
enhances phagocytosis, occurs when specific antibodies are present
eosinophil
clears parasitic worms, releases granule contents to kill antibody coated parasites
neutrophils
engulf and kills bacteria in infected tissue, does not undergo cell division, enters tissue during inflammation, contains granules with bacterial and hydrolytic enzymes
macrophage
derived from bone marrow, circulates in blood, capable of intracellular and extracellular killing
natural killer cells
kills cells that don’t present MHC class I, large granular lymphocytes, kills cells infected with certain viruses
common lymphoid progenitor
B cell, T cell, NK cells
myeloid progenitor
neutrophil, eosinophil, basophil
lag (inductive/latent) phase
period of time before any antibodies are made/detected
steady state
when peak antibody concentration is reached
secondary response vs primary response
faster response, higher rate of antibody synthesis, increased response, increased half life of antibodies, mostly IgG, antibodies have higher affinities, less antigen needed to provoke response
clonal expansion
when a single B-cells proliferates with T cell help
clonal selection theory
each naive B cell produces an immunoglobin of unique specificity
RAG 1 and RAG 2
recombinase genes that are needed to recombine V, D, J segments. cleaves heptamer from D and J segments, opens up DNA hairpins. RAG is sloppy and leaves pieces of DNA
no RAG means no T or B cells. no rearrangement of genes to express immunoglobins
TdT (terminal deoxynucleotidyl transferase)
randomly adds nucleotides, only exists at certain times of the life cycle
no TdT means less diversity, antibodies with lower affinities to antigen (no random mutations)
Antibodies expressed on naive B cell that has never encountered antigen
IgM and IgD only
somatic recombination
occurs during development of B cells. arrays of V, D, and J segments are cut and spliced by DNA recombination
heavy chain
heavy chain locus on chromosome 14. requires 2 recombinations. 1st D and J, then DJ and V.
light chain
kappa on chromosome 2, gamma on chromosome 22. single recombination needed. V and J.
junctional diversity
addition of P and N nucleotides with help of TdT and RAG
diversity in V region sequences
random combination of VJ in light chain and VDJ in heavy chain, junctional diversity (introduction of nucleotides at junctions between segments during recombination), association of heavy and light chain in different combinations
less mature B cell
only one of the following is rearranged (light and heavy chain)
IgE
sensitization of mast cells, immediate hypersensitivity
