Antibodies & Immunoglobulins Flashcards
Regions of antibody
Fab
- Fragment, antigen binding
- determines idiotype (unique Ag-binding pocket/ only 1 antigenic specificity expressed per B cell)
Fc (Four Cs)
- Constant
- Carboxy terminal
- Complement binding
- Carbohydrate side chains (macrophage binding)
- Determines isotype (IgM, IgD…)
Which is dependent on the type of antigen:
- generation of antibody diversity or generation of antibody specificity?
Generation of antibody specificity
What is generation of antibody diversity?
Antigen independent
- Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
- Random addition of nucleotides to DNA (by TdT terminal deoxynucleotidyl transferase)
- Random combination of heavy chains with light chains
TdT (terminal deoxynucleotidyl transferase) is used as a marker for early stage T cell & B cell development in which disease?
Acute lymphoblastic leukemia
What is generation of antibody specificity?
Antigen dependent
- Somatic hypermutation & affinity maturation (variable region)
- Isotype switching (constant region)
Functions of antibodies
OPSONIZATION
Antibody promotes phagocytosis
NEUTRALIZATION
Antibody prevents bacterial adherence
COMPLEMENT ACTIVATION
Antibody activates complement → enhancing opsonization & lysis
Somatic hypermutation & affinity maturation & isotype switching are antibody specificity or diversity?
Antibody specificity
Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
& random addition of nucleotides to DNA (by TdT terminal deoxynucleotidyl transferase) is part of antibody specificity or diversity?
Antibody diversity
Which immunoglobulins do mature, naïve B cells express prior to activation?
IgM
IgD
Which immunoglobulin is the main antibody in 2° (delayed) response to an antigen?
IgG
Which immunoglobulin is the most abundant isotype in serum?
IgG
IgG function
Fixes complement
Passive immunity in infants (crosses placenta)
Opsonizes bacteria
Neutralizes bacterial toxins & viruses
Which immunoglobulin is most produced antibody overall?
IgA
Which immunoglobulin has the lowest serum concentration?
IgA
Which immunoglobulin is released into secretions (tears, saliva, mucus) & breast milk?
IgA
IgA function
Prevents attachment of bacteria & virus to mucous membranes
Protects against gut infections (eg by Peyer patches against Giardia)
Protects Fc portion from luminal proteases (picks up secretory component from epithelial cells)
How does IgA cross epithelial cells?
Transcytosis
(receptor-mediated uptake of a ligand on one side of the cell →
vesicular transport across the cell →
exocytosis of the vesicle contents on the opposite side. ‘trans: across/ through’)
Which antibodies can fix complement?
IgM
IgG
Which is the only antibody that can cross placenta?
IgG
Which antibody has highest avidity?
IgM
Monomer on B cell → pentamer with J chain when secreted → ↑binding to antigen while humoral response evolves
Antibody deficiency in babies whose mothers who don’t breastfeed them?
Which infections are common?
Treatment?
IgA
↑GI infections / diarrhea
Fortify milk/feed with IgA
IgE function
Binds mast cells & basophils
Cross-links when exposed to allergen
→ immediate type I hypersensitivity
→ release of inflammatory mediators (histamine)
Activates eosinophils
worm immunity against helminths (ascaries, strongyloides, hookworms, trichinella)
Which type of autoimmune hemolytic anemia is IgG associated with?
WARM autoimmune hemolytic anemia
(Warm: anti-RBC autoantibodies trigger extravascular hemolysis at body temp or higher. direct antiglobulin test is +ive at 37° C)
*cold hemolytic anemia is < 37° C (cold agglutinin disease)
What are isotypes?
Differences in heavy chains
(IgG vs IgA vs IgE vs IgD vs IgM)
Different Fc region
What are allotypes?
Allelic variation resulting in subtle differences in a single amino acid on the same antibody
Difference in species
What are idiotypes?
Differences that happen between two of the same type of antibody in the same person within the variable region
Each idiotype recognizes a different part or different type of antigen
What is meant by allelic exclusion?
Why is it important?
Expression of heavy chain gene product of either the maternal or paternal chromosome, but not both
-BCR is the product of a chromosomal rearrangement: only one allele is expressed and the other is shut down
(All of the B cell receptors on a given B cell are identical)
Ensures clonal specificity - each B cell produces only a single, unique receptor
What is clonal specificity?
Each B cell produces only a single, unique receptor
Which cytokine leads to the proliferation and expansion of immature T and B cell progenitors?
IL-7
