Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
43 Cards in this Set
- Front
- Back
|
IgG
|
a. Four subclasses (IgG1-4)
b. Half-life 23 days c. 70-80% of serum Ig d. Complement activation e. Opsonization |
|
|
IgG (2)
|
f. ADCC
g. Neutralization i. Toxins ii. Microbes h. Agglutination |
|
|
Placental passage of IgG
|
i. 100% of IgG in a newborn’s serum is of maternal origin
ii. Provides fetus/newborn with passive protection during first 5-6 months of life |
|
|
IgG and anamnestic immune response
|
i. Primary infection: clonal expansion of pathogen-specific B cells
1. IgM early, IgG later ii. Secondary infection: memory B cells immediately differentiate into IgG-secreting plasma cells |
|
|
Elevated serum IgG to infection indicates--
|
i. Past infection
ii. Convalescent phase of a waning infection iii. Chronic infection iv. Prior vaccination |
|
|
IgM
|
a. First antibody class made to all antigens
b. Major class of the primary immune response c. Five IgG-like structures+J chain d. 10% of serum Ig pool e. Complement activation |
|
|
IgM (2)
|
f. Great agglutinator- 10 binding sites
g. Elevated levels= acute phase of infection h. Only class produced by the fetus i. Natural isohemaggutinins to ABO blood groups |
|
|
IgM and fetal production
|
j. IgM is the only class produced by the fetus
i. If a fetus or newborn has elevated IgM to a particular pathogen, this menas the baby is infected by that pathogen ii. If a fetus or newborn has elevated IgG to a particular pathogen, no conclusions can be drawn whether the baby is infected or not, since the IgG is of maternal origin |
|
|
IgA2
|
i. Exists in sermucous secretions→ saliva, colostrum, breast milk, sweat, mucus, tracheobronchial secretions, genitourinary secretions as sIgA
|
|
|
Secretory IgA (sIgA)
|
b. Secretory igA→ protects MALT from bacterial invasion
c. Oral and intranasal vaccines induce IgA synthesis d. 2 IgG-like molecules linked by J chain e. Secretory component protects slgA from proteolytic cleavage f. Secretory component synthesized by epithelial cells |
|
|
IgE
|
a. Similar to IgG in structure, valence of 2-- poor agglutinator
b. Trace serum protein c. Binds to FceR on basophils, mast cells, and eosinophils→ cross-linking causes degranulation d. Interacts with worms and allergens e. Immediate hypersensitivity reactions |
|
|
IgD
|
a. Similar to IgG in structure, valence of 2
b. Less than 1% of serum antibody c. Co-expressed with IgM on surface of mature, naïve B cells (maturation marker) |
|
|
Antibody light chains
|
a. Kappa light chains are found in 60% of human antibody molecules
b. Lambda light chains are found in 40% of human antibodies c. Structures are similar to one another |
|
|
Genetic basis of antibody diversity
|
a. It has been estimated that humans can make antibodies specific for 10^15 different antigens
b. The human genome contains less than 25,000 protein-encoding genes c. Antibodies are encoded by multiple exons that undergo rearrangement in the B cell DNA to generate a multitude of combinations |
|
|
K light chains 1
|
a. The variable region of the K light chain is encoded by V and J exons that are randomly selected and brought adjacent to one another by an enzyme complex called the VDJ recombinase
|
|
|
K light chains RAG-1 and RAG-2
|
b. RAG-1 and RAG-2 components of the VDJ recombinase generate lops in the DNA→ bring together the ends of randomly selected V and J exons
|
|
|
K light chains loop excision
|
c. The loops containing unused exons are removed by nucleasees, and the ends of the V and J exons are ligated together
|
|
|
Persons who lack functional RAG genes...
|
d. Persons who lack functional RAG genes cannot make antibodies or TCR molecules and suffer from SCID
|
|
|
After B cell DNA has rearranged...
|
e. After the B cell DNA has rearranged to bring the V and J segments together, an exact RNA copy is made (primary RNA transcript)
|
|
|
Introns and additional unused exons....
|
f. Introns and additional unused exons are spliced from the primary RNA, which brings the Ck constant region exon adjacent to the VJ construct in the mature mRNA molecule
|
|
|
mRNA is translated into....
|
g. The mRNA is translated into a K light chain polypeptide by ribosomes
|
|
|
Heavy chain gene encoding
|
a. The variable region of the heavy chain is encoded by V, D(diversity) and J exons that are randomly selected and joined together by the action of the VDJ recombinase/RAG enzymes
|
|
|
Junctional diversity
|
b. After the RAG enzymes have generated loops in the DNA, the nuclease that removes loops is imprecise in it selection of cleavage sites
c. This can lead to hcnages in the codons (and thus the amino acids) that are expressed at the junctions between the exons, leading to JUNCTIONAL DIVERSITY |
|
|
N-region diversity
|
d. Terminal deoxynucleotidyl transferase (TdT) randomly inserts nucleotides at the VDJ jucntions (and at the VJ junction in light chains), leading to N-REGION DIVERSITY
|
|
|
Heavy chain primary RNA
|
e. Rearranged DNA is transcribed to primary RNA
|
|
|
C u exon
|
f. Cu(mew) exon is brought adjacent to the VDJ
|
|
|
Primary RNA is...
|
g. Primary RNA is transcribed to mRNA
|
|
|
mRNA is translated to....
|
h. mRNA is translated to H chain polypeptide
|
|
|
Further steps of heavy chain expression
|
i. Two u chains associated with two light chains (either K or lambda)
j. Molecule is expressed on B cell surface or secreted k. AS the B cell matures further, it will simultaneously express both surface-bound IgM and IgD through alternative RNA splicing l. Because they share the same VDJ construct, the IgM and IgD molecules expressed by a single B cell will have the same antigen specificity |
|
|
Heavy chain class switching
|
a. Helper T cells stimulate the progeny of IgM and IgD-expressing B cells to produce antibodies of different heavy chain isotypes
|
|
|
Class switching inducement
|
b. Heavy chain class switching is induced by a combination of CD40L-mediated signals and cytokines secreted by the TH cell
|
|
|
B cell activation in class switching
|
c. CD40-CD40L interaction activates B cells to make activation-induced (cytidine) deaminase (AID)
|
|
|
AID
|
d. AID recognizes switch regions preceding each heavy chain C region exon (except C delta)
|
|
|
AID brings rearranged VDJ construct....
|
e. Brings rearranged VDJ construct adjacent to a downstream C region exon
|
|
|
Looped out introns and unused C region exons
|
f. Looped out introns and unused C region exons are excised
|
|
|
B cell that has class-switched....
|
g. B cell that has class-switched from IgM to another class cannot go back to IgM synthesis: Cu is gone
|
|
|
IgM predomination in primary response
|
g. B cell that has class-switched from IgM to another class cannot go back to IgM synthesis: Cu is gone
h. Explains why IgM predominates during primary response and other classes predominate during secondary response |
|
|
CD40, CD40L, or AID deficiency
|
i. Persons deficient in CD40, CD40L, or AID suffer from hyper-IgM syndrome
|
|
|
B-cell class switching determination
|
j. Exactly which antibody class the B cell will switch to is determined by the cytokines made by the TH cell
i. TH2-derived Il-4 and IL-13→ IgE ii. TH2-derived IL-5→ IgA iii. TH1-derived IFNy→ IgG3 |
|
|
Somatic hypermutation and affinity maturation
|
a. AID enzyme → point mutaitons in V exons of H and L chains
|
|
|
Somatic hypermutation
|
i. Point mutations occurring at a high rate lead to somatic hypermutation
|
|
|
Affinity maturation
|
i. Somatic hypermutation leads to affinity
|
|
|
Sources of antibody diversity
|
a. Random recombination of VJ and VDJ exons
b. Random combination of heavy chains with light chains c. Somatic hypermutation mediated by AID d. Junctional diversity e. N-region diversity mediated by TdT |
