Exam 3: Humoral Immune I Flashcards

1
Q

Passive humoral immune response
artificial
natural

A

artificial - immunoglobulins

natural - transplacental, colostrum, egg

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2
Q

Active humoral immune response
artificial
natural

A

artificial - vaccination

natural - diseases

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3
Q

B lymphocyte antigen receptors

characteristics (4)

A

200,000 - 500,000 BCRs on cell membrane

antibodies are soluble BCRs

all BCRs are antibodies

BCR and antibodies belong to superfamily of proteins: immunoglobulins

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4
Q

BCR strucutre

A

2 light chains and 2 heavy chains

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5
Q

what attaches light chain to heavy chain

A

light chain protein attached to heavy chain protein by disulfide bonds

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6
Q

what attaches heavy chains together

A

disulfide bonds attach heavy chains together

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7
Q

how many constant domains and variable domains in heavy and light chains

A

Light chain: 1 constant domain, 1 variable domain

Heavy chain: 3-4 constant domains, 1 variable domain

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8
Q

Fab and Fc

A

Fab is fragment antigen-binding
part of BCR above hinge region

Fc is fragment crystallization
part of BCR below hinge region

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9
Q

what is hinge region

A

part of heavy chain where disulfide bond is that connects the heavy chain

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10
Q

what enzyme causes fragmentation of antibody

A

papain or pepsin

breaks antibody into Fab and Fc

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11
Q

which fragment is more antigenic

A

Fc - because bigger and more constant

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12
Q

which fragment is used to avoid immune reaction in a receptor animal

A

Fab - smaller, has variable portions

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13
Q

Light chain domains

A

constant domain C1 (CL)
variable domain V1 (VL)
Light kappa chain (k)
Light lambda chain (λ)

Both light chains are the same, either both lambda or both kappa

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14
Q

Heavy chain domains

A

4-5 chains domain
always 1 variable, domain 3-4 constant domains

variable domain VH
Constant domain CH

five different types of heavy chain domains
     alpha (α) -- IgA
     gamma (γ) -- IgG
     delta (δ) -- IgD
     epsilon (ε) -- IgE
     mu (μ) -- IgM

both heavy chains are the same - both alpha, both gamma, both delta, both epsilon, or both mu

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15
Q

variable domain - hypervariable regions

A

AKA complementary determining regions (CDR)

3 regions (CDR1, CDR2, CDR3)

highly variable areas of variable domain

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16
Q

variable domain - framework regions

A

between hypervariable regions

relatively constant areas of variable domain

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17
Q

epitope-variable domain interaction

A

complementary determining regions come together with epitope

when epitope not there the space is called a paratope

like a lock and key
key is the epitope, lock is the receptor
need correct epitope for a specific receptor

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18
Q

what part of the antibody does the antigen bind to

A

the variable domain

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19
Q

differences between different types of heavy chains

A

alpha, gamma, and delta heavy chains – 3 constant domains –> CH1, CH2, CH3

mu and epsilon heavy chains – 4 constant domains –> CH1, CH2, CH3, and CH4

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20
Q

what part of antibody is the antigen binding site

A

VH + VL

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21
Q

what part of antibody stabilizes the antigen binding site

A

CH1 + CL

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22
Q

Why do IgG and IgM antibodies have complement activating regions

A

IgG and IgM can activate the classical pathway of the complement system

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23
Q

Which part of the antibody can move

A

Fab part can move in order to have better interaction with the antigen

both Fab parts can move

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24
Q

what “CD” is present on all B cells and not present on T cells

A

CD 79

if want to find only B cells can use antibody against CD 79

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25
Q

CD 21 and CD 19 interaction

A

CD 21 - complement receptor for C3d

CD 19 - signaling component

CD21 binds to C3d

Signaling through CD19, it generates a potent costimulatory signal to enhance B cell responses

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26
Q

B cell crosslinking

A

Activates B cells

Triggers cell division, differentiation, and immunoglobulin synthesis

both NF-kB and NF-AT are involved in B cell signal transduction

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27
Q

what must happen for B cell to respond to antigen

A

B cell must be stimulated by antigen

B cell must receive co-stimulation from T helper cells and their cytokines

28
Q

what do B cells differentiate into

A

Plasma cells that produce antibodies

or memory cells

29
Q

what do memory cells do

A

memory cells produce primary immune response and are APC in secondary immune response

30
Q

what does Th2 promote

A

humoral immune response

31
Q

IL - 4 (3 things)

A

Increased growth and differentiation of B cells

Increased expression of MHC II

Induces Ig class switching

32
Q

IL-5 (4 things)

A

B cell differentiation into plasma cells

Stimulates IgM and IgG production

IL-5 + IL-4 induced IgE production

Selectively stimulates IgA production

33
Q

IL-6 (3 things)

A

Needed for final differentiation of B cells into plasma cells

IL-6 + IL-5 promotes IgA production

IL-6 + IL-1 promotes IgM production

34
Q

IL-13 (2 things)

A

Similar to IL-4

Required for optimal induction of IgE

35
Q

what happens during primary immune resposne

A

antigen is processed by a dendritic cells and presented to the helper T cell

36
Q

what happens during the secondary immune response

A

the B cell itself can act as an APC

Co-stimulators (CD154, CD28) engage serially to trigger IL-4 secretion by the T cell and IL-4R production by the B cell

37
Q

CD154 and CD 40 interaction

A

CD 154 on T cell

CD40 on B cell –> proliferation, Ig production, Ig class switching

CD40 on dendritic cell –> antigen presentation, cytokine production, cell survival

Cd40 on macrophage –> cytokine production, activation

38
Q

what happens when PAMPs bind to TLR on B cell (5)

A

B cell activation and proliferation

No participation of helper T cells

Only IgM response

No memory cells

No immunoglobulin class switching

39
Q

what kind of antigen can BCRs bind to

A

free soluble antigens

recognizes “native” epitopes as opposed to processed epitopes

40
Q

antigen + BCR and presence of helper T cell causes (3)

A

increased IgM BCR

Increased MCH II

increased IL-4, IL-5, IL-6, TNF-a, TGF-B receptors

41
Q

Ig class switching

A

IL-4 –> IgG, IgE

IFN- γ –> IgG

TGF-B –> IgA

Il-5, IL-6 –> IgG, IgM, IgA

42
Q

plasma cells

A

short lived population - 1 or 2 weeks
spleen and lymph nodes after immunization

long lived population - months to years
accumulate in bone marrow

43
Q

memory cells

A

long lived resting memory cells
survival do not depend on antigen contact

large and dividing memory cells
survival depends on antigen contact

memory cells survival in humans - 60 years

44
Q

germinal center

A

antigen derived cell proliferation

somatic hypermutation

positive and negative B cell selection

stimulated B cells + Th cells migrate to germinal center around 6 days after response begins

45
Q

antibodies fight against?

A

viruses

protozoa

bacteria

toxins

46
Q

local and general specific protection by antibodies

A

milk

body surfaces

blood circulation

47
Q

antibodies - multiple immunoglobulin classes

A
IgM
IgG
IgA
IgE
IgD
48
Q

serum concentration of immunoglobulin classes

A
IgG - highest 
IgM
IgA
IgD
IgE - lowest
49
Q

where does IgA have a high concentration

A

saliva, milk, GI fluids

50
Q

IgG (4)

A

plasma cells in spleen, lymph nodes, bone marrow

important in inflammation

agglutination, opsonization

activate classical complement pathway

51
Q

IgM (5)

A

plasma cells in secondary lymphoid organs

complement activation site is on CH4

major Ig produced in primary immune response

opsonization, virus neutralization, agglutination

not very important in inflammation

52
Q

IgA (3)

A

plasma cells in body surfaces: intestines, respiratory tract, urinary system, skin, mammary gland

transported through intestinal epithelial cells into external secretions

major Ig in external secretions of non ruminants

53
Q

IgE (6)

A

Produced by plasma cells located under body surfaces

IgE attached to FceRI on mast cells and basophils

IgE + antigen –> inflammation –> enhances local defense

release inflammatory molecules from mast cells

immunity against parasites

shortest half life of all Igs

54
Q

IgD (4)

A

not present in cats, chickens, rabbits

IgD mainly attached to B cells

some circulating IgD binds to basophils = IL-4, IL-1, cathelicidins, and B cell activator factor

mediated link between innate and adaptive immune response

55
Q

what do all cattle possess

A

a complete set of classes and sub classes (isotypes)

56
Q

within a population what do individual cattle possess

A

different allotypes

Example: IgG2(A1) or IgG2(A2)

57
Q

what does each individual animal have

A

a very large number of different idiotypes

58
Q

exons vs introns

A

Intron - don’t code for protein and are deleted from gene

Exon - each exon codes for a different component of the constant domain of the heavy chain

example: exon 1 may code for CH1 while exon 2 codes for CH2 and exon 3 codes for CH3

a different set of genes codes for the variable domain

59
Q

Antibody production

A
V(D)J recombination = antigen binding site
     variable part
     V = variable gene
     D = diversity gene
     J = joining gene

Antigen activation of B cells = switch in the class of antibody –> constant part

60
Q

class switching

A

genes that code for different Ig classes are deleted and the variable gene and correct Ig class gene are joined

Example: want IgA
V – Cmu – Cdelta – Cgamma – Cepsilon – Calpha
Delete Cmu, Cdelta, Cgamma, Cepsilon to get
V – – – – – Calpha
join these to make IgA –> V–Calpha

61
Q

IgM serving as BCRs have a choice as to which C terminal domain they will use

A

Membrane bound form uses hydrophobic transmembrane domain (CmuM)

Secreted form deletes this sequence and uses CmuS gene

difference between the 2 forms is determined by RNA splicing following transcription

62
Q

antibody levels at first and second doses of antigen

A

first dose - IgM is higher

second dose - IgG is higher

at second dose total Ig is much higher than at first dose

63
Q

primary vs secondary immune response - levels of Ig

A

Primary immune response – IgM

Secondary immune response – IgG
secondary immune response - antigen is
recognized by memory cells

64
Q

Which Ig has the most subclasses

A

IgG has the most subclasses (all species in chart)

IgA has a few subclasses in some species (sheep, mice, humans)

IgM has 2 subclasses in humans

IgE has 2 subclasses in dogs (might have 2 in cats)

Cats do not have IgD (or it hasn’t been found yet?)

65
Q

What are each of the Ig classes involved in

A

**IgM and IgG activate classical complement pathway

IgA1 activate lectin complement pathway

**IgG - placental transfer

IgG1, IgG3, IgG4, IgA1, IgA2, IgE - binding to macrophages and other phagocytes

**IgE - high affinity binding to mast cells and basophils

IgE - lowest serum content

66
Q

Where can each Ig be found

A

IgA - provides immunity in mucosa
including urinary, reproductive tract, gut,
respiratory

IgE - skin and mucosa (linings?)

IgG - provides systemic protection

IgM and IgG - blood circulation
Can’t find IgM in other parts of body because it is too big