chapter 4

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The Immune System
Chapter 4
updated 6 years ago by ednalznd
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1

Antibodies are a class of glycoproteins called

immunoglobulins

2

Antibodies are produced by

plasma cells (stimulated B cells)

3

IgM

First antibody produced in blood and lymph in a primary antibody responce

8% Ig pool

4

IgG

makes up the vast majority of antibody in blood and lymph

Principal antibody in secondary antibody response against the antigen

80% of Ig pool

5

IgA

found in body cavities where it binds bacteria and viruses before they can infect tissue.

12% of Ig pool

6

IgE

important in allergic reactions. Trace amount in serum

7

IgD

normally bound to B cells as a cell surface receptor. Trace amounts in serum

8

Plasma cells secrete antibody of the same antigen specificity as the membrane bound immunoglobulin expressed by

b-1 precursor

9

IgM

is a pentameric antibody

10

IgA

is a dimeric antibody

11

IgG, IgD, IgE

monomeric antibodies

12

Antibodies are composed of

polypeptides with variable and constant region

13

Epitope recognition requires antibodies to have special structure of

2 identical heavy chains

2 identical light chains

14

Each light and heavy chains has

constant region

variable region

antigen binding site

15

Constant regions

determines the location and functional class of antibody

16

Variable region

which contains different amino acids for the many antibodies produced

17

An antigen- binding site is formed from

the hypervariable regions of a heavy chain V domain and a light chain V domain

The variability allows formation of the specific antigen binding site

18

Immunoglobulin chains are folded into

compact and stable protein domains

19

Treatment of IgG with enzyme papain results in

proteolytic cleavage of the hinge of each heavy chain

reduction of the disulfide bonds that connects the two hinges

20

The flexible hinge of the IgG molecule allows it to bind with both arms to many

different arrangements of antigens on the surface of pathogens

21

The antigen-binding site of an immunoglobulin is formed from?

Paired V regions of a single heavy chain and a single light chain

22

Antigen-binding sites vary

in shape and physical properties

23

Epitopes can bind to

pockets, grooves, extended surfaces, or knobs in antigen-binding sites.

24

A liner epitope of a protein antigen is

formed from contiguous amino acids

25

A discontinuous epitope is formed from

amino acids from different parts of the polypeptide that are brought together when the chain folds

26

Monoclonal antibodies produced from

a clone of an antibody-producing

27

Rituximab used for

non-hodgkin b cell lymphoma

28

Adalimumab for rheumatoid arthritis

anti TNF alpha

29

Production of a mouse monoclonal antibody

Lymphocytes from a mouse immunized with the antigen are fused with myeloma cells by using polyethyleneglycol.

The cells are then grown in the presence of drugs that kill myeloma cells but permit the growth of hybridoma cells. unfused lymphocytes also die.

Individual cultures of hybridoma are tested to determine whether they make the desired antibody. The cells are then cloned to produce a homogeneous culture of cells making a monoclonal antibody.

30

Myelomas are tumors of

plasma cells; those used to make hybridomas were selected not to express heavy and light chains

31

Hybridomas only express

the antibody made by the b-cell partner

32

Generation of immunoglobulin diversity in B cells before encounter with antigen

Generation of immunoglobulin diversity in B cells before encounter with antigen

33

The DNA sequence encoding a V region is assembled from two or three gene segments

...

34

The two types of gene segment that encode the light chain V region are called

variable- V

joining -J

segments

35

Two light-chain loci version

kappa or lambda only one is used

Each kappa or lambda has two types of gene segment (V,J)

36

The heavy chain locus includes an additional set of

diversity (D) gene segment for a total of three segments

37

Random somatic recombination of gene segment produces

diversity in the antigen-binding sites of immunoglobulins.

38

enzyme responsible for recombining V,D,J

V(D) J recombinase

39

Gene segments encoding the variable region are joined by recombination signal sequences recognized by the

RAG complex

40

Developing and naive B cells use

alternate mRNA splicing to make both IgM and IgD

41

The isotype of an antibody is determined

by its heavy chain

42

The only heavy chains made by mature B cells before they encounter antigen are

mu μ and delta δ corresponding to IgM and IgD, respectively,on B cell surfaces

43

Simultaneous expression by both forms from the same heavy chain locus is accomplished by

differential splicing of the same primary RNA transcript (no gene rearrangement)

44

Each B cell produces immunoglobulin of

a single antigen specificity

45

Allelic exclusion

in developing b-cells ensures that only one heavy chain and one light chain are expressed, which results in B cells producing antibodies of a single antigen specificity.

46

B cells are

monospecific

47

monospecific

an encounter with a given pathogen engages a subset of B cells that will make antibodies of a single antigen specificity

----- this is clonal selection. Focus of B cell/ antibody response to a specific antigen

48

Immunoglobulin is first made in a

membrane- bound form that is present on the B cell surface

49

When B cells first make IgM and IgD, they are

associated with cell membrane. they need anchors to stick to the plasma membrane

50

Igβ and Igα invariant chains are trans membrane

proteins that anchor the antibody heavy chain, constant region, to the plasma membrane

51

Diversification of antibodies after B cells

encounter antigen

52

Secreted antibodies are produced by alternative pattern of heavy chain

RNA processing

53

Gene rearrangement with immature B cells leads to the expression of functional heavy and light chain and to the

production of membrane-bound IgM and IgD on the mature B cells

54

After an encounter with antigen,

the secreted antibodies are produced by the B-cell ( now known as the plasma cell)

55

HOW? ^^^

Alternative RNA splicing (no gene rearrangement going on here) The membrane bound has a hydrophobic anchor sequence at the end of the heavy chain, where the secreted one has a hydrophilic one.

56

The surface and secreted forms of an immunoglobulin are derived from the same

heavy-chain gene by alternative RNA processing

57

Rearranged V-region sequences are further diversified by

somatic hypermutation

58

Once a B cell has been activated by antigen

further diversification of the whole V-domain coding sequences occurs thru somatic hyper mutation

59

There is random point mutation at

a very high rate throughout the V-region of the heavy chain and light chain genes

Constant regions are not affected

60

Somatic hypermutation results in B cells bearing mutant antibodies at the

variable region

61

somatic hypermutation is dependent on the enzyme

activation-induced cytidine deaminase (AID)

also converts cytosine to uracil normally

62

Some of these mutant antibodies will bind antigen

better (higher affinity)

63

B cells containing these mutant receptors will compete for the antigen and are

preferentially selected to mature in to plasma cells

64

The almost random variation produced by somatic hypermutation allows

selection of variant immunoglobulins with improved antigen-binding sites.

65

Somatic hypermutation targets the rearranged gene segments encoding the

variable region

66

IgM and igD are coexpressed on naive cells by a process called

aleternative mRNA splicing

67

Isotype switching produces immunoglobulins with different

C regions but identical antigen specificities

68

Like somatic hypermutation isotype switching is dependent on the enzyme

activation-induced cytidine deaminase (AID)

69

Further DNA recombination allows V regions to be joined with

different C regions

70

Isotype switching only occurs in

B cells that have been activated

71

isotype switching involves

recombination between specific switch regions

72

Antibodies with different C regions have

different effector functions

73

identify which of the following is associated with activation induced cytidine deaminase activity?

diversification of the VH domain but not the VL domain

74

The derivation of antibodies from a single clone of B lymphocytes that have identical antigen specificity is reffered to as

monoclonal antibody production