Antibodies and Receptor Diversity

Four polypeptide chains

- 2 identical heavy chains (H)

- 2 identical light chains (L)

What is the basic structure of an antibody molecule?

antigen

Both "arms" of the antibody must bind the same ______________

- Variable Domains (Ag Binding Sites)

- Constant Domains (Effector Function

- Hinge Region (Allows variable domains flexibility)

What are the 3 functional domains/regions of an antibody molecule?

species

The constant domains of antibody molecules are ___________ specific (ex. humanized antibodies from animals = change the constant region)

- Kappa

- Lambda

What are the two different light chains that may be used with any of the heavy chains?

class

Both light chains on an antibody are of the same ____________ (2 kappa or 2 lambda)

functional

There is no _____________ difference between the different light chains, but the ratio varies with species

- IgM = Mu

- IgD = Delta

- IgG = Gamma

- IgE = Epsilon

- IgA = Alpha

What are the 5 antibody isotypes and what is the heavy chain that gives them their names?

IgY

What is the bird and reptile major antibody?

- Camelids (smaller, allows for better tissue penetration, but less diversity)

- Sharks

What species can have antibodies that consist of only heavy chains?

B cell

Individuals can produce up to 5*10^13 different ____________ receptors

Somatic DNA recombination

What is the process that allows the generation of different light and heavy chains?

variable

The pairing of light and heavy chains allows the _________________ end of both chains to combing and form the antigen binding site

Somatic hypermutation

What occurs after B cell activation where the binding sites can change to bind antigens better (contributes to diversity)?

- V

- D

- J

What are the 3 different types of variable gene segments for formation of the heavy chain for antibodies (picks one of each kind)?

- V

- J

What are the 2 different types of variable gene segments for formation of the light chain for antibodies (picks one of each kind)?

Combinatorial

_______________ diversity of antibodies is produced when the variable gene segments are connected end to end to make a single long DNA strand (each different combination of segments yields a different product)

Junctional

_________________ diversity of antibodes is produced by the addition and subtraction of nucleotides at the junctions of the genes begin spliced and connected together

change

Once a lymphocyte has made selections of variable genes and recombined them, it cannot ____________ them again

affinity

Somatic hypermutation increases antibody diversity to improve _______________ for antigens

After B cell activation

When does somatic hypermutation occur?

amino acids

Somatic hypermutation introduces changes in the __________ ___________ of the variable region

cytidine deaminase (AID)

What enzyme initiates the mutations in somatic hypermutation?

germinal center

AID is expressed by the _______________ __________ B cells

Converts cytidine (C) to uridine in the DNA encoding the variable region

What does AID actually do?

- Combinatory diverstiy of V-D-J (heavy chain) or V-J (light chain) joining

- Junctional diversity

- Combinatoral diverstiy of light and heavy chain pairing

- Somatic hypermutation after activation

What are the four main processes that contribute to the immunoglobulin repertoire (diversity)?

switching

Isotype or class _____________ involves a "cut and connect" mechanism very similar to that used in the variable regions

discarded

Once a B cell undergoes isotype switching, the intervening heavy chain DNA is ___________________ = why it cannot switch backwards

IgM

A B cell that starts producing IgG cannot make __________ again

forwards

Isotype switching can go ________________ though = meaning that a B cell that produces IgG can later produce IgA (but can't go back to IgG)

constant

Isotypes are distinguished by their heavy-chain _________ regions

- IgM

- IgE

What isotypes lack a hinge region but contain an extra heavy chain domain?

- Differences in the number and location of disulfide bonds

- Differences in the distribution of linked sugar molecules

What are additional differences that can distinguish isotypes?

- Neutralization

- Opsonization

- Antibody dependent cell-mediated cytotoxicity (ADCC)

- Lysis of microbes/abnormal cells

- Activation of other effector cells (mast cells, eosinophils)

What are the potential effector functions of antibodies?

Neutralization

______________ through antibodies involves binding that blocks a structure critical for microbe invasion or toxin function

opsonization

Antibodies can work through ______________ by coating microbes and making them easier to grab

- Activates the classical complement pathway

- NK cells can bind antibody to kill bound cells

What are methods that antibodies can contribute to the lysis of microbes/abnormal cells?

IgM

What is the first antibody produced during a primary immune response (can also be produced in secondary responses)?

pentamer

The secreted form of IgM consists of 5 subunits, forming a large ______________ that rarely enters tissue even during inflammation

- First antibody produced

- Greate at complement activation

What are the major functions of IgM?

IgG

What antibody is the highest in the blood and plays a major role in Ab-mediated defense (esp. secondary responses)?

- Can mediate ANY of the major antibody functions

- Smallest (good mobility into tissue)

- Can cross the placenta (in some species = neonatal immunity)

What are the major functions of IgG?

sub-isotypes

There are also ____________________ of IgG with slightly different functions

IgA

What antibody is secreted by plasma sells in MALT that can pass through epithelial cells into mucus secretions (+lots go into circulation)?

dimers

IgA is normally secreted onto mucousal surfaces as ______________ attached by a "joining chain" and "secretory component" which protects against digestion

monomer

IgA can also circulate in the blood and tissue as _______________

Critical for mucosal immunity

What is the major function of IgA?

IgE

What antibody is present in extremely low concentrations in the serum and tissues, where most is already bound to high affinity receptors on mast cells and basophils?

degranulation

What occurs if antigen crosslinks to a bound IgE on a mast cell or basophil?

• Immunity to parasites

• Type I hypersensitivity / allergies

What are the major functions of IgE?

IgM

Which is described: first produced, large, form pentamer, rarely enter tissues, great complement activator?

IgG

Which is described: highest concentration in blood, small, can perform all antibody functions, comes in sub-classes?

IgA

Which is described: secreted onto mucosal surfaces as dimers, critical for mucosal immunity?

IgE

Which is described: low concentrations in serum, bound to high-affinity receptors on mast cells, immunity to parasites, allergies?

B. IgD Function in cell-mediated cytotoxicity

Which of the following statement is not true?

A. IgA Defense at mucosal sites

B. IgD Function in cell-mediated cytotoxicity

C. IgE Defense against parasites and involved in allergic diseases

D. IgG Provide a high level of passive immunity at birth

E. IgM First one produced after B-cell activation

D. IgG

Which of the following is the most abundant immunoglobulin class in healthy adult humans and mice?

A. IgA

B. IgD

C. IgE

D. IgG

E. IgM

D. Endogenous antigen presentation

Which of the following is not an antibody effector function?

A. Opsonization

B. Neutralization

C. Complement activation

D. Endogenous antigen presentation

E. NK-cell cytotoxicity

F. Mast-cell degranulation

C. Affinity maturation

Somatic hypermutation of Ig genes accounts for:

A. Allelic exclusion

B. Class switching from IgM to IgG

C. Affinity maturation

D. All of the above

E. None of the above

A. 2 identical heavy and 2 identical light chains

The basic Ig unit is composed of:

A. 2 identical heavy and 2 identical light chains

B. 2 identical heavy and 2 different light chains

C. 2 different heavy and 2 identical light chains

D. 2 different heavy and 2 different light chains

E. Non-covalently bound polypeptide chains

B. Constant domains of heavy chain

Which of the following gene clusters do not contribute to antigen binding:

A. Variable domain of light chain

B. Constant domains of heavy chain

C. Variable segments (V)

D. Diversity segments (D)

E. Joining segments (J)

A. Appears early in the primary immune response

Which of the following statements does not apply to IgG?

A. Appears early in the primary immune response

B. Neutralizes bacterial toxins

C. Can fix complement

D. Crosses the human placenta

E. Opsonizes bacteria

B. Binding to antigen

The Fab region of an Ig is responsible for:

A. C1q fixation

B. Binding to antigen

C. Binding to Fc receptors

D. Binding to macrophages

E. The ability of Ig to cross the human placenta

C. Restricted to the variable region

Somatic hypermutation is:

A. Commonly found in both Ig and T-cell receptor genes

B. Restricted to the constant region

C. Restricted to the variable region

D. Found only in Ig heavy chains

E. Found only in lambda light chains

B. IgA

B lymphocytes in the lamina propria secrete large amounts of:

A. IgD

B. IgA

C. MHC molecules

D. Bile acids

E. Secretory T-cell receptor

A. Somatic hypermutation

High affinity B-cell clones in mammals are usually generated by:

A. Somatic hypermutation

B. Somatic DNA recombination

C. Pairing light and heavy chains

D. Class switching

E. Apoptosis

C. IgM and IgD

Prior to class switching, B-cells express:

A. IgA alone

B. IgA and IgG

C. IgM and IgD

D. IgD alone

E. No surface Ig

B. Antibody

Toxins are neutralized by:

A. Complement

B. Antibody

C. Antimicrobial peptides

D. Lipid inflammatory mediator like PGE2

E. Proteolytic enzymes