Lecture 6 - Ab structure Flashcards

1
Q

What is adaptive immunity?

A

“acquired immunity”, specific response to antigenic challenge

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1
Q

What is adaptive immunity?

A

“acquired immunity”, specific response to antigenic challenge

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2
Q

What is it mediated by?

A

antigen-specific lymphocytes and/or their products

-two arms: humoral and cell-mediated immunity

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2
Q

What is it mediated by?

A

antigen-specific lymphocytes and/or their products

-two arms: humoral and cell-mediated immunity

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3
Q

What is also associated with adaptive immunity?

A

immunologic memory

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3
Q

What is also associated with adaptive immunity?

A

immunologic memory

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4
Q

True or False: adaptive immunity doesn’t coordinate with innate immunity

A

False

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4
Q

True or False: adaptive immunity doesn’t coordinate with innate immunity

A

False

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5
Q

Describe different pathways of immunity activation

A
  • Innate –> infection –> recognition by non-specific effectors –> pathogen clearance
  • Early induced –> infection –> recruitment of effector cells –> activation of effector cells –> pathogen clearance
  • late adaptive –> infection –> Ag transport to lymphoid organs –> recognition by naive B and T cells –> clonal expansion of B and T cells –> pathogen clearance
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5
Q

Describe different pathways of immunity activation

A
  • Innate –> infection –> recognition by non-specific effectors –> pathogen clearance
  • Early induced –> infection –> recruitment of effector cells –> activation of effector cells –> pathogen clearance
  • late adaptive –> infection –> Ag transport to lymphoid organs –> recognition by naive B and T cells –> clonal expansion of B and T cells –> pathogen clearance
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6
Q

What is protective immunity?

A

re-infection –> recognition by preformed Ab and effector T cells –> pathogen clearance

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6
Q

What is protective immunity?

A

re-infection –> recognition by preformed Ab and effector T cells –> pathogen clearance

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7
Q

What does immunological memory look like?

A

re-infection –> recognition by memory B and T cells –> rapid expansion to effector cells –> pathogen clearance

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7
Q

What does immunological memory look like?

A

re-infection –> recognition by memory B and T cells –> rapid expansion to effector cells –> pathogen clearance

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8
Q

When is Ab production initiated?

A

3-7 days after initial exposure to Ag and only if innate immune processes fail to clear it rapidly

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8
Q

When is Ab production initiated?

A

3-7 days after initial exposure to Ag and only if innate immune processes fail to clear it rapidly

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9
Q

What are Ab?

A

also called immunoglobulins; antigen-specific products of B cells

  • principle mediators of adaptive immunity and production of appropriate Ab response to infection (major contributor to immunity)
  • secreted proteins found in plasma and on mucosal surfaces at varying concentrations
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9
Q

What are Ab?

A

also called immunoglobulins; antigen-specific products of B cells

  • principle mediators of adaptive immunity and production of appropriate Ab response to infection (major contributor to immunity)
  • secreted proteins found in plasma and on mucosal surfaces at varying concentrations
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10
Q

What do Ab do?

A
  • interact with Ag non-covalently
  • heterodimeric proteins produced by B bells
  • divalent
  • bifunctional
  • fn in many environments
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10
Q

What do Ab do?

A
  • interact with Ag non-covalently
  • heterodimeric proteins produced by B bells
  • divalent
  • bifunctional
  • fn in many environments
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11
Q

What do different constant regions divide Ig into?

A

classes or isotypes (IgMM, IgG, IgE, IgA)

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11
Q

What do different constant regions divide Ig into?

A

classes or isotypes (IgMM, IgG, IgE, IgA)

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12
Q

What is the Ab structure?

A
  • all have same basic structure: 2 Identical light chains and 2 Identical heavy chains
  • subunits are covalently linked
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12
Q

What is the Ab structure?

A
  • all have same basic structure: 2 Identical light chains and 2 Identical heavy chains
  • subunits are covalently linked
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13
Q

What does heavy subunit determine?

A

Ig class (isotype)

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13
Q

What does heavy subunit determine?

A

Ig class (isotype)

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14
Q

How are distinct Ab regions determined?

A

by protease digestion
Fc portion - contains heavy chain constant region
Fab portion - contain Ag finding site

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14
Q

How are distinct Ab regions determined?

A

by protease digestion
Fc portion - contains heavy chain constant region
Fab portion - contain Ag finding site

15
Q

Different regions of the Ab molecule have been defined by what?

A

proteolytic digestion and function; VH, VL, CH, CL

16
Q

What is the Ag binding pocket formed by?

A

variable regions of the Ab H and L chains –> encoded by multiple gene segments

17
Q

What does this variable region that forms the binding pocket undergo?

A

mutation to generate Ag binding pockets of varying strength

18
Q

What does the binding pocket interact with?

A

an epitope in a non-covalent manner

19
Q

True or False: all Ab are multivalent

A

True

20
Q

If Ab are multivalent, what can happen?

A

Ab can bind two of the same epitopes on a signle Ag or two of the same epitopes on two different Ags

21
Q

Ab differences are denoted based on what?

A

the nature of the differences

22
Q

Give examples of Ab differences?

A
  • Isotypic differences: IgG vs IgA - could be same binding pocket but Ab end up in diff place
  • Allotypic differences: different alleles of the Ab chains - two IgG1 mols
  • Idiotypic differences: diff specificities for epitopes they bind (come together differently) - two IgG mol, different Ag specificities
23
Q

What’s the difference btw B cells and plasma cells?

A

Plasma cells are B cells; B cells have Ab on their cell surface; plasma cells secrete Abs
-B cells mature into plasma cells, some proliferate into B memory cells –> store in lymphoid tissue

24
Q

What’s the first Ab to be secreted by B cells?

A

IgM; immature B cells secrete IgM (in bone marrow) as monomers –> after maturing and being activated by an Ag, IgM are secreted as pentamers

25
Q

B cells leave lymphoid tissues secreting what?

A

IgM

26
Q

What Abs are secreted onto mucosal surfaces?

A

IgM and IgA

27
Q

IgM and IgA (on mucosal surfaces) are protected from degradation by what?

A

by binding to J chain; IgM forms a pentamer, while IgA forms a dimer

  • This covalent link with the J chain occurs within the B cell
  • This occurs after being activated by an Ag
28
Q

Since the covalent link with the J chain occurs within the B cell, what does this mean?

A

the Ag specificity of each Ag-binding site is identical for a give IgM pentamer of IgA dimer (respectively)

29
Q

What is the J chain used for?

A

transporting dimeric IgA across epithelial barriers to coat mucosal surfaces

30
Q

What determines the Ab class or isotype?

A

constant region of the heavy chain

31
Q

What does the variable region confer?

A

epitope specificity

32
Q

What does the constant region confer?

A

functional capacity

33
Q

Give examples of functional capacities

A

IgG and IgM activate pathway for complement

IgE bidns to mast cells and basophils

34
Q

True or False: relative expression of each isotype varies

A

True; depends on location for what Ab has highest [ ]

35
Q

What’s the ratio of relative expression of Ab isotypes

A

IgG>IgM>IgA in blood

IgA»IgM>IgG on mucosal surfaces

36
Q

What does allelic exclusion result in?

A

only one chromosome rearrangement per cell

37
Q

Describe the major Ab isotype for each fn/activity (neutralization, opsonization, NK cell activation, mast cell activation, complement activity, crosses epithelium crosses placenta, extravascular diffusion, highest in serum level/half-life)

A
Neutralization - IgG and IgA
Opsonization - IgG
NK cell activation - IgG
Mast cell activation - IgE
Complement activity - IgM and IgG
Crosses epithelium - IgA
Crosses placenta  - IgG
Extravascular diffusion - IgG and IgA
Serum level - IgG
Serum half-life - IgG
38
Q

When are other isotypes (besides IgM) secreted?

A

later depending on what cytokines it interacts with –> can rearrange and make other isotypes other than IgM

39
Q

What Ab isotypes do these cytokines induce production of (IL-4, IL-5, IFN-gamma, TNF-alpha)?

A

IL-4 –> induces IgG and IgE
IL-5 - augments production of IgA
IFN-gamma - induces IgG and IgG
TNF-alpha - induces IgG and IgA

40
Q

Different Ab isotypes have different what?

A

functionalities for immune response

ex: heavy chain of IgG is recognized by receptors on phagocytes
- mast cells have receptors for IgE
- IgA is secreted across epithelial layers to provide protection at mucosal surfaces

41
Q

What is a well documented Ab deficiency in humans?

A

IgA deficiency; no surface Ab in lungs –> susceptible to URI
-similar condition identified in laboratory beagles and a colony of cocker spaniels

42
Q

What does the “hinge” covalent bond btw constant heavy regions help with?

A

giving flexibility

43
Q

Define major functional properties of these Ab (IgM, IgG, IgA and IgE)

A

IgM - antigen receptor of naive and some memory B cells
IgG - transfer of adaptive immunity to offsprign, regulation of Ab production
IgA - protection of mucosa, protection of newborn mucosa via milk
IgE - activation of mast cells and basophils

44
Q

Each B cell makes a unique receptor generated via what?

A

rearrangement and mutation of the germline DNA

45
Q

what is agglutination?

A

reduces number of infectious untis to be dealt with (Ab bind multiple antigens)

46
Q

What is opsonization?

A

coating Ag with Ab enhances phagocytosis (several Ab on 1 Ag)

47
Q

What is activation of complement?

A

complement cascade –> causes inflammation and cell lysis

48
Q

What is Ab-dependent cell-mediated cytotoxicity?

A

Abs attached to target cell cause destruction by macrophages, eosinophils and NK cells

49
Q

What is neutralization?

A

blocks adhesion of bacteria and viruses to mucosa (Ab blocks all attachment sites on Ag)

50
Q

What is structure of IgG, IgM and IgA?

A

monomer, pentamer, dimer

51
Q

What is percentage of total serum Ab for IgG, IgM and IgA?

A

80%, 5-10%, 10-15%

52
Q

What is half-life in serum of IgG, IgM and IgA?

A

23 days, 5 days, 6 days

53
Q

Is there placental transfer for IgG, IgM and IgA?

A

yes, no, no

54
Q

known functions of IgG, IgM and IgA?

A

enhances phagocytosis, 1st Ab production in response to initial infection,, localized protection on mucosal surfaces

55
Q

How do B cells develop receptors (Abs) that can bind to almost any epitope?

A

Region of Ab gene that binds the epitope is generated by a semi-random rearrangement of gene segments, thus creating different exons for the Ab chains within each B cell