Lecture 5- Immunoglobulin Flashcards
What are antibodies?
Immunoglobulins that react specifically with the antigen that stimulated their production
Antibodies can either be ____ or ______.
soluble; bound to the surface of a B cell
What are immunoglobulins?
Glycoprotein molecules that are produced by plasma cells (ex: activated & secreting B cell) in response to an antigenic stimulus
What are the 5 immunoglobulins?
IgM, IgD, IgG, IgE, IgA
How do the different types of immunoglobulins differ?
- size
- amount of CHO
- biologic function
- heavy chain types
What is the cell-bound form of an antibody? What is the soluble form?
The BCR; antibodies (released into the circulation)
Once expressed, what Igs signal B-cell maturation & leaving the bone marrow?
IgM and IgD
Each B cell produces an antibody of a _____ specificity
single
Which Igs are associated with accessory molecules that aid in signal transduction?
Ig-alpha & Ig-beta
The specificity of the Ab produced by a B cell is the same as that of its:
BCR
Each antibody molecule is made up of ___ and ____ chains. They are joined by ____ bonds.
heavy; light
dipeptide
What are Ig-alpha and Ig-beta?
- Sulphide-linked heterodimers
- Contain ITAMS (immunoreceptor tyrosine activation motifs)
- Are activated by phosphorylation
- Essential for signal transduction
What immunoglobulin subunit binds with the antigen?
The Fab fragment (variable)
What subunit of immunoglobulin serves as the immunologic trigger?
Fc fragment (non-variable/constant)
common to all specificities of antibody with an ISOTYPE
What are some features of the hypervariable region of Ig?
Found on both heavy & light chains
Responsible for specific binding to antigen
Comprises one domain
What are some features of the constant region of Ig?
Responsible for triggering
Comprises three domains
What are the functions of the Fab fragment?
- Detect antigen
- Precipitate antigen
- Block the active sites of toxins or pathogen-associated molecules
- Block interactions between host & pathogen-associated molecules
What are the functions of the Fc fragment?
- Acts as a receptor for complement proteins & a ligand for cellular binding sites
- Transplacental passage of antibody
- Enhanced phagocytosis by macrophages & PMN
- Triggers inflammatory reactions
What is different between antibody classes?
Variable region NO CHANGE
Heavy chain CHANGED
The effector-end of the antibody molecule is different
When is IgM secreted?
ONLY during primary immune response to an antigen
What is IgM secreted in the blood called?
pentamer
(5 units joined by a J chain)
What is the first antibody secreted after activation?
IgM
What is the average life of IgM in serum?
5 days
What are the functions of IgM?
Can fix or activate complement
Can cause agglutination of large particles = clumping of particles (ex: RBCs or bacteria)
Neutralization
What is the most prevalent Ig?
IgG
Which form of each Ig are monomers?
IgM- as a BCR
IgD- as a BCR
IgG- as BCR
IgE- in serum
IgA- in serum
Which Ig has the longest half-life?
IgG
How many subclasses does IgG have?
4 (IgG1-4)
What is the average half-life in serum for IgG?
23 days
What are some functions of IgG?
- Activate complement (IgG1 and IgG3)
- Can cross the placenta and confer immunity to developing fetus
- Opsonization = bind & coat to large antigens, marking for phagocytosis
- can bind to Fc receptors on macrophages and neutrophils and facilitate phagocytosis
Where is IgG found?
- BCR
- Intravascular
- Interstitial space
Where is secretory IgA found?
saliva, tears, milk, mucus
important in the respiratory tract, GI tract & urinary tract
Where is monomeric IgA found?
In serum
Where is dimeric IgA found?
In secretions
What are some functions of IgA?
Mucosal immunity
Neutralization of body surfaces
Blocks attachment of pathogen
Intestinal immunity in suckling neonates
What is the average half-life in serum for IgA?
6 days
What are some features of dimeric IgA?
- it is similar to IgG
- joined by J chain
- has a secretory portion that aids in transfer across epithelial cells
4 binding sites
Which Ig is the primary trigger of “allergic” reactions?
IgE
Which Ig is a trigger for mast cells and basophils? How?
IgE
- Stimulates the release of cytokines that mediate allergies (ex: histamine)
- Mast cell sensation
What Ig is the primary defense against multicellular parasites (Mainly helminths/worms)? How?
IgE
- It binds to antigens on the surface of the worm
- then binds to eosinophils causing them to degranulate on the surface of the worm (and in turn, the worm’s surface itself degranulates)
Where is IgG found?
found in serum
Subcutaneous
Submucosal
Which is the mystery Ig? Where is it found?
IgD
-Small amounts of IgD are found free in the serum
- Exists on the surface of B cells as a receptor
Which Ig acts mainly as a receptor on the Naive B-cell surface?
IgD- marker of a mature B cell
Which Igs take assist in agglutination?
IgM, IgG & IgA
-Enhances phagocytosis & reduces the number of infectious units
Which Ig assists in opsonization?
IgG
-Coating antigen w/ antibody enhances phagocytosis
Which Igs assist in the neutralization of a microbe?
IgG, IgA, IgM
Which Igs assist in toxin neutralization?
IgG, IgA, IgM
Which Igs assist in complement activation?
IgM, IgG
What are allotypes?
Genetically determined differences in antibodies between different species
What are idiotypes?
Antibodies that recognize different specific epitopes
What is avidity?
The functional affinity
(Measure of the total binding strength of an antibody at every binding site)
What is affinity?
the strength of the interaction between the antigen epitope & antibody-antigen binding site
What causes antigen-antibody interactions to occur?
-Electrostatic interactions
- Hydrogen bonds
- Van der Waal forces
- Hydrophobic interactions
- Receptor-ligand (similar to enzyme-substrate)
Antigen-antibody interactions are extremely:
specific
Are there covalent bonds between antigens and antibodies?
No- they would be too strong
What determines specificity?
The shape of the antigen, complimented by the shape of the binding site
- Binding site formed from the amino acids in the variable region
When does cross-reactivity occur?
If the antibody can bind to similarly shaped but different antigens
- Avidity will ALWAYS be higher for the original antigen
- If there is competition, the original antigen will win
Ex: circle binding site = circle antigen vs oval antigen = circle will bind better
Why is antibody detection used for the diagnosis in many infectious diseases?
Specificity - Antibody-detection utilized b/c each is specific for an antigen & trigger cascade of other measurable aspects
What type of antibodies are mainly tested against?
monoclonal (mAb)
Define monoclonal antibodies:
Antibodies derived from a single clone of B cells that will have specificity for a single antigen of the infectious agent
Define polyclonal antibodies:
Different antibodies produced against various antigens of a single infectious agent
Infectious agent can have several components that make it “infectious” & the immune response can be target to towards that
How are B cells capable of such wide diversity when the whole human genome is much smaller?
gene rearrangements
When does somatic hypermutation (SMH)
occur?
Once the antigen stimulates the B-cells because it is encouraged to clone (increase) and fight.
In somatic hypermutation (SMH), what gives the antibody its diversity?
Point mutations in genes that code the Variable region → This results in progeny B cells producing BCR/antibodies w/ different affinities for the SAME antigen
(b/c the variable region is being further altered = hypermutation)
What is responsible for fine tuning the antibody response in B-cells?
Affinity maturation
-because a better affinity for an antigen makes the B cell more likely to clone (proliferate).
A plasma cell may switch/change the heavy chain of the antibody it _______.
secretes
If the class of antibody changes IgM to IgG, does the specificity to the antigen change too?
No
