Antibodies Part II- Diebel Flashcards

1
Q

What is the Ig supergene family?

A

It is a large group of cell surface proteins that are involved in recognition, binding, adhesion, etc…..

Antibody are part of this…
Also, ICAM, VCAM, TCR, MHC molecules

All members have one or more immunoglobin domains, beta pleated sheets arranged in opposite directions so it kinda forms a barrel like structure.

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2
Q

What isotype has the highest serum concentration?

A

IgG

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3
Q

What isotype has the longest half life in the serum?

A

IgG

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4
Q

Does IgG cross the placenta? Do any other isotypes cross?

A

IgG does cross!

No other isotypes cross….

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5
Q

Which isotype is best at complement fixation?

A

IgM

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6
Q

Which isotype is best at bacterial lysis?

A

IgM

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7
Q

Which isotypes are best at toxin neutralization?

A

IgG and IgA

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8
Q

Which isotype facillitates Mast Cell/basophil degranulation?

A

IgE

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9
Q

Isotype IgA is pretty good at two things, what are they?

A

Antiviral activity

Toxin Neutralization

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10
Q

Biological functions of IgM????

A
  • Virus neutralization
  • bacterialcidal
  • agglutination of antigens
  • complement fixation
  • first aby in response to antigen exposure

Does NOT bind to macrophage Fc receptors

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11
Q

Biological functions of IgG?

A
  • Virus neutralization
  • Toxin neutralization
  • Bactericidal
  • Agglutination/precipitation of antigens
  • Complement fixation
  • Binds to macrophage Fc receptors
  • Crosses the placenta
  • Present in interstitial fluids
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12
Q

Some therapeutic uses of IgG?

A
  • protecting immunocompromised individuals (gamma globins)
  • blocking aby for TNF production (rheumatoid arthritis)
  • blocking aby to block allergens (desensitization to hypersensitivity)
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13
Q

Biologic functions of IgA?

A
  • Viral neutralization
  • toxin neutralization
  • agglutination/precipitation of antigens
  • Highest daily production of all isotypes
  • secreted by b cells in subepithelial tissues of most mucosal epithelial and glandular epithelia
  • Present in breastmilk, protects newborn against respiratory and intestinal infections

Does NOT bind to macrophage Fc receptors

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14
Q

Biological functions of IgE?

A
  • Cross-linking of IgE on surface of mast/basophil cells causes release of histamine; synthesis of prostaglandins, leukotrienes, and other chemokines and cytokines
  • Parasitic infections
  • pulmonary fungal infections
  • Type I hypersensitivity
  • Role in asthma
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15
Q

Keys to antibody diversity?

A
  • Genetic rearrangement by mixing and matching gene segments for light and heavy chains
  • Variation at the joining sites
  • Hypermutation in the variable region of the light and heavy chains during proliferation of B cells
  • Mixing and matching light and heavy chains
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16
Q

What is clonal selection theory?

A

Basically that a B cell makes only one specific antibody, this preexists randomly before exposure to antigen (so we’re not making them to adjust to environment we just have ‘em already!) When an antigen comes around the best fitting one is selected by the antigen….these then proliferate….

17
Q

Explain allotypic exclusion?

A

We have two copies of kappa and lambda and also heavy chain genes since we’re diploid (one from mom and one from dad)…..we only express one H chain, and one L chain….all other genes are silenced….this allows us to have a lot more diversity

18
Q

How to make heavy chains?

A
  • B cell brings random D segment close to J segment
  • DNA is cut, intervening DNA is discarded
  • V segment is brought next to recombined DJ segment (junk is spliced out)
  • VDJ segment is transcribed with the constant region into RNA
  • These primary RNA transcripts are processed to make IgM right away….later then can CSR to make IgG
19
Q

What determines whether or not IgM is secretory or membrane bound?

A

There is a secretion signal and membrane bound signal in the DNA…whichever one is expressed will result in either secretion or membrane boundness…

20
Q

How to make light chains?

A

-Same as heavy chains but there is no D region….random V and J segments are selected and spliced together (junk is removed)……you either use kappa or lambda, but not both

21
Q

What do RAG recombinases do? What happens if they get knocked out?

A

RAG-1 and RAG-2 are enzymes that do the recombination of antibody and TCR DNA. They bind to splice signals on the right of D segments and the left of J segmnet, pull them together and then cut and splice. THey then go to the right of V segment and do it again.

If knocked out you don’t get B or T cells….Omenn Syndrome (really rare in humans)

22
Q

What do exonucleases do?

A

Chews away nucleotides inbetween VDJ regions after DNA is cut and before they are put together…..leads to more diversity.

23
Q

What does terminal deoxynucleotidyl transferase (TdT) do?

A

Adds nucleotides in between VDJ regions….more variability

24
Q

What is the N region?

A

This is the joining regions between VDJ, they’re really sloppy which leads to a lot of diversity……about 2/3 of these receptors are no good because of this and are trashed as a result.

25
Q

What Ig molecules are expressed on Mature (but not activated) B cells?

A

They can express IgD and IgM…..as they are activated it’ll switch to secretory IgM and later on it can class switch to IgG, IgE, IgA…..this happens at the level of rearrangements of DNA

26
Q

What does a hypermutable VDJ region mean?

A

It means that every time a B cell divides after antigenic stimulation this region changes slightly….

27
Q

what is affinity maturation?

A

After B cells are stimulated by antigen the daughter cells that are proliferating make slighlty different VDJ regions….the best-fitting mutants will be selected for….

T-Cells DON’T DO THIS!!!! After contact with antigen they do not change….

28
Q

How does somatic hypermutation work at the DNA level?

A

Activation-Induced Deaminase (AID) randomly converts cytosines to uracil so it goes from C:G to U:G which is a mismatch

These mismached U:G are excised by repair enzyme uracil-DNA glycosylase.

  • Error prone DNA polymerase then fills in the gaps
  • End up with variability in the daughter cells antibody…could be better or worse
29
Q
What stays the same in class switching? 
What changes in class switching? 
Can you class switch from M--->G? G----A? G----->M?
A

The L chain and the VH domain stays the same

The C region of the H chain changes (so cell subs in G, A, or E….cells cannot go backwards, ie from G back to M because the info for that has been spliced out forever)

30
Q

In Heavy Chains how many V, D, J segments are there to choose from?

In light chains how many V and J segments are there to choose from?

A

Heavy:
V-65 D-27 J-6

Light:
V-35 J-5
-Light chains can be kappa or lambda

31
Q

What are all of the key cytokines for proliferation?

A

IL-2, IL-4, and IL-5

32
Q

What are all of the key cytokines for differentiation?

A

IL-2, IL-4, IFN-gamma, and TGF-beta

33
Q

What are all of the key cytokines for class switching?

A

IFN-gamma —–> IgG2a
IL-4—————–> IgG1, IgE
IL-5—————–> IgE