Lecture 5- Immunoglobulin

Question 1

What are antibodies?

Answer 1

Immunoglobulins that react specifically with the antigen that stimulated their production

Question 2

Antibodies can either be ____ or ______.

Answer 2

soluble; bound to the surface of a B cell

Question 3

What are immunoglobulins?

Answer 3

Glycoprotein molecules that are produced by plasma cells (ex: activated & secreting B cell) in response to an antigenic stimulus

Question 4

What are the 5 immunoglobulins?

Answer 4

IgM, IgD, IgG, IgE, IgA

Question 5

How do the different types of immunoglobulins differ?

Answer 5

• size
• amount of CHO
• biologic function
• heavy chain types

Question 6

What is the cell-bound form of an antibody? What is the soluble form?

Answer 6

The BCR; antibodies (released into the circulation)

Question 7

Once expressed, what Igs signal B-cell maturation & leaving the bone marrow?

Answer 7

IgM and IgD

Question 8

Each B cell produces an antibody of a _____ specificity

Answer 8

single

Question 9

Which Igs are associated with accessory molecules that aid in signal transduction?

Answer 9

Ig-alpha & Ig-beta

Question 10

The specificity of the Ab produced by a B cell is the same as that of its:

Answer 10

BCR

Question 11

Each antibody molecule is made up of ___ and ____ chains. They are joined by ____ bonds.

Answer 11

heavy; light
dipeptide

Question 12

What are Ig-alpha and Ig-beta?

Answer 12

• Sulphide-linked heterodimers
• Contain ITAMS (immunoreceptor tyrosine activation motifs)
  - Are activated by phosphorylation
  - Essential for signal transduction

Question 13

What immunoglobulin subunit binds with the antigen?

Answer 13

The Fab fragment (variable)

Question 14

What subunit of immunoglobulin serves as the immunologic trigger?

Answer 14

Fc fragment (non-variable/constant)

common to all specificities of antibody with an ISOTYPE

Question 15

What are some features of the hypervariable region of Ig?

Answer 15

Found on both heavy & light chains
Responsible for specific binding to antigen
Comprises one domain

Question 16

What are some features of the constant region of Ig?

Answer 16

Responsible for triggering
Comprises three domains

Question 17

What are the functions of the Fab fragment?

Answer 17

• Detect antigen
• Precipitate antigen
• Block the active sites of toxins or pathogen-associated molecules
• Block interactions between host & pathogen-associated molecules

Question 18

What are the functions of the Fc fragment?

Answer 18

• 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

Question 19

What is different between antibody classes?

Answer 19

Variable region NO CHANGE
Heavy chain CHANGED
The effector-end of the antibody molecule is different

Question 20

When is IgM secreted?

Answer 20

ONLY during primary immune response to an antigen

Question 21

What is IgM secreted in the blood called?

Answer 21

pentamer

(5 units joined by a J chain)

Question 22

What is the first antibody secreted after activation?

Answer 22

IgM

Question 23

What is the average life of IgM in serum?

Answer 23

5 days

Question 24

What are the functions of IgM?

Answer 24

Can fix or activate complement
Can cause agglutination of large particles = clumping of particles (ex: RBCs or bacteria)
Neutralization

Question 25

What is the most prevalent Ig?

Answer 25

IgG

Question 26

Which form of each Ig are monomers?

Answer 26

IgM- as a BCR IgD- as a BCR IgG- as BCR IgE- in serum IgA- in serum

Question 27

Which Ig has the longest half-life?

Answer 27

IgG

Question 28

How many subclasses does IgG have?

Answer 28

4 (IgG1-4)

Question 29

What is the average half-life in serum for IgG?

Answer 29

23 days

Question 30

What are some functions of IgG?

Answer 30

- 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

Question 31

Where is IgG found?

Answer 31

- BCR - Intravascular - Interstitial space

Question 32

Where is secretory IgA found?

Answer 32

saliva, tears, milk, mucus important in the respiratory tract, GI tract & urinary tract

Question 33

Where is monomeric IgA found?

Answer 33

In serum

Question 34

Where is dimeric IgA found?

Answer 34

In secretions

Question 35

What are some functions of IgA?

Answer 35

Mucosal immunity Neutralization of body surfaces Blocks attachment of pathogen Intestinal immunity in suckling neonates

Question 36

What is the average half-life in serum for IgA?

Answer 36

6 days

Question 37

What are some features of dimeric IgA?

Answer 37

- it is similar to IgG - joined by J chain - has a secretory portion that aids in transfer across epithelial cells 4 binding sites

Question 38

Which Ig is the primary trigger of "allergic" reactions?

Answer 38

IgE

Question 39

Which Ig is a trigger for mast cells and basophils? How?

Answer 39

IgE - Stimulates the release of cytokines that mediate allergies (ex: histamine) - Mast cell sensation

Question 40

What Ig is the primary defense against multicellular parasites (Mainly helminths/worms)? How?

Answer 40

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)

Question 41

Where is IgG found?

Answer 41

found in serum Subcutaneous Submucosal

Question 42

Which is the mystery Ig? Where is it found?

Answer 42

IgD -Small amounts of IgD are found free in the serum - Exists on the surface of B cells as a receptor

Question 43

Which Ig acts mainly as a receptor on the Naive B-cell surface?

Answer 43

IgD- marker of a mature B cell

Question 44

Which Igs take assist in agglutination?

Answer 44

IgM, IgG & IgA -Enhances phagocytosis & reduces the number of infectious units

Question 45

Which Ig assists in opsonization?

Answer 45

IgG -Coating antigen w/ antibody enhances phagocytosis

Question 46

Which Igs assist in the neutralization of a microbe?

Answer 46

IgG, IgA, IgM

Question 47

Which Igs assist in toxin neutralization?

Answer 47

IgG, IgA, IgM

Question 48

Which Igs assist in complement activation?

Answer 48

IgM, IgG

Question 49

What are allotypes?

Answer 49

Genetically determined differences in antibodies between different species

Question 50

What are idiotypes?

Answer 50

Antibodies that recognize different specific epitopes

Question 51

What is avidity?

Answer 51

The functional affinity (Measure of the total binding strength of an antibody at every binding site)

Question 52

What is affinity?

Answer 52

the strength of the interaction between the antigen epitope & antibody-antigen binding site

Question 53

What causes antigen-antibody interactions to occur?

Answer 53

-Electrostatic interactions - Hydrogen bonds - Van der Waal forces - Hydrophobic interactions - Receptor-ligand (similar to enzyme-substrate)

Question 54

Antigen-antibody interactions are extremely:

Answer 54

specific

Question 55

Are there covalent bonds between antigens and antibodies?

Answer 55

No- they would be **too strong**

Question 56

What determines specificity?

Answer 56

The shape of the antigen, complimented by the shape of the binding site - Binding site formed from the amino acids in the variable region

Question 57

When does cross-reactivity occur?

Answer 57

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

Question 58

Why is antibody detection used for the diagnosis in many infectious diseases?

Answer 58

Specificity - Antibody-detection utilized b/c each is specific for an antigen & trigger cascade of other measurable aspects

Question 59

What type of antibodies are mainly tested against?

Answer 59

monoclonal (mAb)

Question 60

Define monoclonal antibodies:

Answer 60

Antibodies derived from a single clone of B cells that will have specificity for a single antigen of the infectious agent

Question 61

Define polyclonal antibodies:

Answer 61

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

Question 62

How are B cells capable of such wide diversity when the whole human genome is much smaller?

Answer 62

gene rearrangements

Question 63

When does somatic hypermutation (SMH) occur?

Answer 63

Once the antigen stimulates the B-cells because it is encouraged to clone (increase) and fight.

Question 64

In somatic hypermutation (SMH), what gives the antibody its diversity?

Answer 64

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)

Question 65

What is responsible for **fine tuning** the antibody response in B-cells?

Answer 65

Affinity maturation -because a better affinity for an antigen makes the B cell more likely to clone (proliferate).

Question 66

A plasma cell may switch/change the heavy chain of the antibody it _______.

Answer 66

secretes

Question 67

If the class of antibody changes IgM to IgG, does the specificity to the antigen change too?

Answer 67

No