Humoral Immunity Flashcards Preview

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Flashcards in Humoral Immunity Deck (49):
1

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.

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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

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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

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Inappropriate activation of the complement cascade is controlled at the level of

C1, C3, and C5

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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

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costimulatory molecules (B7:CD28)

needed for T-cell activation

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CD40/CD40 Ligand binding

needed for B cell class switching and memory response

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Papain cleavage

results in 2 Fab and 1 Fc, cannot agglutinate, each part can only bind to single antigen

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Pepsin cleavage

results in one divalent molecule, can bind 2 antigen, can still agglutinate

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avidity

increases with number of binding sites. IgM has greater avidity than IgG because it is secreted as a pentamer

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idiotype

defines antigen specificity, determined by variable region

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isotype

dictates effector functions, constant region

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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

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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).

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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

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TH2 cell release of cytokine

induces the differentiation of B cells into fully differentiated, antibody-secreting cells and memory cells and induce class switching

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thymus-independent antigens

antigens contain no peptides, stimulates secretion of IgM antibodies only and does not result in immunologic memory

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germinal centers

clones of proliferating antigen specific B cells, where somatic hypermutation occurs, follicles of the lymph nodes and spleen

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clonal selection

results in affinity maturation, predominance of clones capable of producing antibodies with increasing affinity for the antigen

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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.

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IgG

activates complement, opsonizes, mediates ADCC, can be transported across placenta which protects fetus during gestation

has a gamma heavy chain,

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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

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B cell activation requires

needs to enter lymphoid follicles and be stimulated by antigen with T cell help to become activated

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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

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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

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follicular dendritic cell

holds antigen without processing them so B cells can examine antigen and become activated

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endotoxin

heat stable, toxicity not destroyed by sterilization techniques, detected using Limulus Amebocyte Lysate

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opsonization

enhances phagocytosis, occurs when specific antibodies are present

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eosinophil

clears parasitic worms, releases granule contents to kill antibody coated parasites

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neutrophils

engulf and kills bacteria in infected tissue, does not undergo cell division, enters tissue during inflammation, contains granules with bacterial and hydrolytic enzymes

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macrophage

derived from bone marrow, circulates in blood, capable of intracellular and extracellular killing

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natural killer cells

kills cells that don't present MHC class I, large granular lymphocytes, kills cells infected with certain viruses

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common lymphoid progenitor

B cell, T cell, NK cells

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myeloid progenitor

neutrophil, eosinophil, basophil

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lag (inductive/latent) phase

period of time before any antibodies are made/detected

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steady state

when peak antibody concentration is reached

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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

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clonal expansion

when a single B-cells proliferates with T cell help

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clonal selection theory

each naive B cell produces an immunoglobin of unique specificity

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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

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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)

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Antibodies expressed on naive B cell that has never encountered antigen

IgM and IgD only

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somatic recombination

occurs during development of B cells. arrays of V, D, and J segments are cut and spliced by DNA recombination

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heavy chain

heavy chain locus on chromosome 14. requires 2 recombinations. 1st D and J, then DJ and V.

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light chain

kappa on chromosome 2, gamma on chromosome 22. single recombination needed. V and J.

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junctional diversity

addition of P and N nucleotides with help of TdT and RAG

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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

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less mature B cell

only one of the following is rearranged (light and heavy chain)

49

IgE

sensitization of mast cells, immediate hypersensitivity