Exam 2 Flashcards

1
Q

What is the solution that explains antibody diversity?

A

genes for both chains come from multiple discontinuous genetic segments

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2
Q

How many constant regions does a kappa chain gene have?

A

1

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3
Q

Describe the differences of the J and C region between kappa and lambda chain genes

A
  • kappa: one C region with J regions grouped separately

- lambda: J and C are grouped together; before every C region there is a J region

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4
Q

What cells express these chain genes and can they express both kappa and lambda at the same time?

A
  • B cells
  • express one or the other; once one is expressed, the other will be permanently silenced
  • this gives 300 possible variable regions and 5 different isotypes (4 from lambda, 1 from kappa)
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5
Q

Which chromosome are kappa chain genes located?

A

chromosome 2

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6
Q

Which chromosome are lambda chain genes located?

A

chromosome 22

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7
Q

Which chromosome are heavy chain genes located?

A

chromosome 14

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8
Q

How many constant region does a lambda chain gene have?

A

4-5

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9
Q

How many constant region does a heavy chain gene have?

A

9

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10
Q

Where can VDJ recombinase be found?

A

only in B cell and T cell

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11
Q

What does VDJ recombinase do in B cells?

A

rearrangement of Ig genes

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12
Q

What does VDJ recombinase do in T cells?

A

rearrangement of T cell receptor

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13
Q

How does VDJ recombinase change the genome?

A

2 RAG subunits on the linear chain come together to form a loop which gets budded off; I remember RAG as Re Arrange Genome (not sure what it really stands for)

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14
Q

IgM producing cells

A

produce both IgM and IgD; this happens via how they process RNA transcript viav alternate splicing

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15
Q

Stages of B cell development

A
  • Stem cell
  • Early pro-B cell
  • Late pro-B cell
  • Large pre-B cell
  • Small pre-B cell
  • Immature B cell
  • Mature B cell
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16
Q

What happens in the bone marrow after B cell generation before those B cells are activated?

A

the B cells that are self-reactive are eliminated

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17
Q

What happens during pro-B cell phase?

A

heavy chain starts to assemble; light chain is still in the germline

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18
Q

What happens during pre-B cell phase?

A

heavy chain is rearranged; light chain starts to rearrange but not expressed yet; surrogate light chain serves as quality control to make sure that the heavy chain that has been expressed is not useless

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19
Q

What happens during immature B cell phase?

A

both heavy and light chain are rearranged; will express lambda or kappa but not both; have mature antibody appear on the surface

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20
Q

What happens during mature B cell phase?

A

IgD and IgM antibody both appear on the surface

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21
Q

Define antibody

A

protein produced in response to an immunogen; specifically binds to immunogen that stimulated its formation

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22
Q

composition of immunoglobulin

A
  • two identical heavy chains (H)

- two identical light chains (L)

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23
Q

What are examples of secondary activities of Ig?

A
  • activation of complement
  • opsonization
  • transport across placental barrier into fetal circulation
  • secreted in external secretions of the body
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24
Q

Where are the N-termini and C-termini region on the antibody?

A
  • N-termini are located on the antigen binding region

- C-termini are at the C region of the heavy chain where Fc receptors are

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25
Q

What does gamma globulin refer to?

A

total collection of immunoglobulin or antibody molecules present

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26
Q

Where is the hypervariable region and what is its purpose?

A
  • near the variable region end

- give each CDR its properties

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27
Q

How is cleft formed and what is its purpose?

A
  • formed by folded Vh and Vl regions

- plays a role in antigen binding

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28
Q

What is the purpose of the intermolecular disulfide bonds that link the heavy and light chains?

A

stabilize the structure

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29
Q

What is the purpose of the intramolecular disulfide bonds? (in antibody)

A

stabilize constant and variable region

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30
Q

What are advantages of using pepsin instead of papain?

A
  • crosslinking tumor antigens can trigger apoptosis

- penetrate tissue better

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31
Q

T/F: If you undergo class switch, classes will change but CDR remains the same.

A

True

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32
Q

How many different heavy chain isotypes are there in humans?

A

9: four IgG, two IgA, IgM, IgD, IgE

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33
Q

Why is IgE so low in concentration in the serum?

A

they are not free floating; they are tied up to mast cells; their half life is 2 days

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34
Q

What are the two forms of IgM and how do you get them?

A

there are two polyadenylation site encoded in the gene and the primary transcript looks the same; depending on the processing steps and which polyadenylation site gets recognized, you can get transmembrane or secreted IgM

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35
Q

Properties of IgM

A
  • 10% of serum
  • decavalent pentamer [macroglobulin]
  • efficient complement activator
  • major receptor on B cells
  • natural antibody to A and B blood group antigens
  • diffuses poorly
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36
Q

Properties of IgG

A
  • 75% of serum Ig
  • longest half life
  • complement activator (G3 best, no G4)
  • cross placenta (G2 poor)
  • opsonizing antibody
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37
Q

Properties of IgG4

A
  • can swap half of its molecule with another IgG4 antibody molecule
  • compete with IgE to bind to allergens
  • help dampen allergic immune response
  • tie up antigen because cannot crosslink
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38
Q

Properties of IgA

A
  • 15% of serum
  • high concentration in external secretions
  • dimeric IgA via J chain
  • tetravlent dimer
  • serum IgA is monomer
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39
Q

What is the secretory piece?

A
  • synthesized by epithelial cells
  • protein that reacts with IgA
  • when IgA binds, it triggers receptor mediated endocytosis
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40
Q

Properties of IgD

A
  • interacts with basophils

- surface receptor with IgM

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41
Q

Properties of IgE

A
  • cytophilic for mast cells and basophils via Fc receptors

- may be involved in immunity against some parasites

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42
Q

Why does allergic response happen so fast?

A

once IgE on mast cells is attached to its antigen, it triggers degranulation of mast cells and gets dumped out into surrounding tissues; IgE already primed on mast cells

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43
Q

Define allotypes

A

Genetically-determined differences in the proteins (antigens) between individuals in the same species; usually differ by 1 aa

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44
Q

Effect on immunogenicity in allotype variation.

A

Variant C regions can be immunogenic in some circumstances

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45
Q

What are the different types of Fc receptors and their function?

A
  • FcγRI – Binds IgG
  • FcεRI – Binds IgE
  • FcRn – Transports IgG across epithelia
  • FcγRIIB1 – Negative feedback mechanism to limit antibody synthesis
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46
Q

What are Fc receptors on NK cells good for?

A

to detect virally infected cells

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47
Q

Immunity in prenatal stage: 8 weeks

A

B cells in fetal liver

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48
Q

Immunity in prenatal stage: 10 weeks

A

Small amounts of immunoglobulin may be detected in this order
IgM > IgD > IgG > IgA

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49
Q

When do you have transport of maternal antibody during pregnancy?

A

16th week but more than 50% happens after the 34th week

50
Q

How can you determine if the fetus has been exposed to an infection?

A

presence of IgM and IgA in cord blood

51
Q

Immunity in neonatal stage

A

immuno-competent

52
Q

How long does maternal IgG antibodies last?

A

6 months; side note: mother must be immune in order to protect child against a specific pathogen and there is no memory to this passive immunity

53
Q

Immunity in childhood stage

A

immune response is mature but child is immunologically inexperienced

54
Q

Immunity in adult stage

A

immunologically developed and experienced

55
Q

What does SIgA-antigen complex do?

A
  • excreted with mucus

- block bacteria from binding to host cell

56
Q

Which antibody helps with opsonization?

A

IgG

57
Q

What is toxin neutralization?

A

Physical binding of an antibody (IgG is most plentiful) to prevent a protein toxin from binding to its receptor site and thereby inhibit the toxic activity

58
Q

What are types of antibody-mediated immunity?

A
  • molecular antigens
  • extracellular infections
  • viremia
  • transfusion reactions
59
Q

What are types of cell-mediated immunity?

A
  • intracellular infections
  • cellular antigens
  • molecular antigens that causes things such has contact dermatitis
60
Q

B cell binding with epitopes

A

bind to epitopes on complete immunogens

61
Q

T cell binding with epitopes

A

bind to epitopes from metabolized immunogen; usually associated with MHC; surface of an APC

62
Q

T cell always attached to the surface of the cell. Why?

A

if it’s not attached, it can act like an antagonist

63
Q

T cell recognition characteristics

A
  • requires antigen processing
  • requires APC
  • MHC restricted
64
Q

Surface molecules of T cells

A
  • TCR, CD3
  • CD4 if MHC class II
  • CD8 if MHC class I
65
Q

What does a double negative T cell have on its surface?

A

TCR, CD3

66
Q

What does a double positive T cell have on its surface?

A
  • Both CD4 and CD8 expressed —TCR increases
67
Q

What does a single positive cell have on its surface?

A

TCR, CD3, and their choice of CD4 or CD8

68
Q

What happens to single positive cells after they become single positives?

A

go to lymphoid tissue waiting to be stimulated by APC; die is not stimulated by immunogen

69
Q

What happens in negative selection?

A

makes sure that t cells are not auto immune; don’t want it to attack self; if it does, it becomes anergic and die

70
Q

What is the major product from T cells?

A

cytokine; NOT the same thing as antibody

71
Q

structure of TCR

A
  • α chain and β chain (like heavy and light chain in Ig)
  • variable and constant domain
  • variable region contribute to antigen binding site
  • monovalent and monospecific
  • anchored by transmembrane protein
72
Q

With respect to antigen binding site, what is the difference between α β chains and γ δ chains?

A
  • α β chain bind to peptide

- γ δ chain pick up patterns / classes of antigen; link between innate and acquired immunity

73
Q

What is the importance of CD3 in the TCR complex?

A

it’s the wiring; you have to have all four chains in order for signal transduction to occur

74
Q

T cell acticvation

A
  • MHC class II binds to receptor -> first signal
  • dendritic cell upregulates B7 -> T cell brings in CD28 to attach to B7 -> second signal -> proliferation and differentiation
75
Q

What happens without B7?

A

no costimulation -> no proliferation -> cell becomes anergic -> shuts off due to lack of signal

76
Q

Superantigen pathology

A

immunostimulation -> dendritic cells release cytokines -> cytokine storm -> toxic shock

77
Q

Profound paradoxical immunosuppression

A

patient survives toxic shock but is super immunosuppressed; t cells shut off

78
Q

MHC II Presentation

A
  • antigen endocytosed
  • chopped up
  • associated with MHC in the cell
  • goes to surface of cell
79
Q

MHC I Presentation

A
  • protein gets chopped up in the cell
  • goes to golgi
  • associates with MHC
  • goes to cell surface
80
Q

How does T cell interact with APC?

A
  • adhesion molecules
  • all T cells express LFA-1
  • all dendritic cells present ICAM-1
  • LFA and ICAM interact and change conformation to increase affinity
81
Q

CTLA-4

A

when B7 tries to stimulate a T cell that’s already been stimulated, CTLA-4 is upregulated; CD28 looks for overstimulation in order to suppress itself by making suppressive cytokines

82
Q

suppression binding affinity

A

CTLA-4 bind to B7 twenty times the affinity than it does to CD28

83
Q

What are the results of T cell cell-cell interaction?

A
  • CD8 kills viral cell
  • CD4 stimulates macrophage to make cytokines
  • TH2 (also CD4) causes B cell to produce cytokines and also to differentiate into plasma cell
84
Q

TH1

A
  • mainly antiviral
  • can be anti-tumor, anti-fungal, and anti-parasite
  • can activate macrophages to fight bacteria
85
Q

TH2

A
  • mainly anti-parasitic
  • also involved in allergies
  • promote basophil, eosinophil, mast cell proliferation, class switch to IgE, B cell proliferation, Ig production, humoral immunity
86
Q

Treg

A
  • mucosal immunity
  • anti-inflammatory
  • broadly immunosupressant
  • inhibit response so that you stay healthy without having inflammatory response
  • suppress other effector T cells
  • protective role in autoimmunity; pathogenic role in cancer
87
Q

TH17

A
  • inflammatory T cell response
  • associated with fungal and mycobacterial surviellience
  • main effector in auto-immune disease
  • enhance neutrophil response
88
Q

What can TH0 cells differentiate to?

A
  • TH1
  • TH2
  • Treg
  • TH17
89
Q

Balance between TH1 and TH2

A
  • TH1 cells make cytokines that inhibit TH2 responses

- TH2 cells make cytokines that inhibit TH1 responses

90
Q

γδ T cells

A
  • majority in lymphoid tissue
  • doesn’t use CD4 or CD8
  • doesn’t need MHC
  • ligands are not short peptides
  • help tissue repair
  • main function is homeostasis
  • cytotoxic to tumor cells
91
Q

Natural killer cells

A
  • 10-15% of circulating lymphocytes
  • contain lots of inhibitory receptors
  • possess Fcγ receptors—ADCC [can bind Fc portion of IgG]
  • antiviral first line of defense
92
Q

pleiotropy

A

when cytokines have different biological effects on different target cells

93
Q

redundant (with respect to cytokines)

A

when two or more cytokines have the same effect on a target cell

94
Q

Since cytokines have a wide range of activities, how do you keep specificity in the immune response?

A
  • Regulation of cytokine receptor expression.
  • Limited radius of effectiveness.
  • Short half lives.
95
Q

Clinical signs of inflammation

A
  • redness
  • swelling
  • heat
  • pain
  • loss of function
96
Q

What happens during initiation of inflammatory response?

A
  • increased blood supply
  • increased vascular permeability
  • migration of leukocytes out of capillaries into the area
97
Q

What are the stages of inflammatory response?

A
  • initiation
  • amplification
  • termination
98
Q

What happens during amplification of inflammatory response?

A

Activated immune system cells secrete cytokines and chemokines that amplify the response.

99
Q

What is the difference between acute and chronic inflammatory response?

A
  • acute: accumulation of innate immune cells; toxins cleared; response terminated
  • chronic: persistent presence of T cell and macrophage
100
Q

Principle cellular mediators. What are the tissue residents and what do they recruit?

A
  • Tissue: mast cells, macrophages

- Recruit: neutrophils, eosinophils, basophils, lymphocytes, monocytes

101
Q

What are the first type of leukocytes that leave circulation to go to site if injury and what do they do?

A

neutrophils; they spit out their chromatin to trap bacteria which keeps infection local

102
Q

Macrophages’ role in inflammation

A
  • secrete cytokines
  • activate other leukocytes
  • phagocytose microbes
  • present antigen to T cells
  • secrete factors that are important in regulating fibroblasts and endothelial cells
103
Q

What are the main transcription factors for production of inflammatory mediators?

A

AP-1 and NF-kB

104
Q

What are the soluble inflammatory mediators?

A
  • cytokines
  • complement components
  • chemokines
  • C-Reactive Protein
  • histamine
  • platelet activating factor (PAF)
  • arachidonic acid metabolites
105
Q

complement components as an inflammatory mediator

A

Found in serum. C5a and C3a are “anaphylatoxins.” Activate mast cells to release histamines. C5a is a chemoattractant.

106
Q

C-Reactive Protein as an inflammatory mediator

A

CRP is made in liver in response to TNFa, IL-1, and IL-6. Binds to LPS in bacterial cell walls and acts as opsonin. Binds to C1q and activates complement.

107
Q

histamine as an inflammatory mediator

A

Released by mast cells and causes vasodilation, vascular permeability, and release of arachidonic acid.

108
Q

platelet activating factor as an inflammatory mediator

A

Causes platelets to release serotonin (similar to histamine in effects). PAF is a strong chemoattractant for neutrophils.

109
Q

arachidonic acid metabolites as an inflammatory mediator

A
  • Leukotrienes and prostaglandins: cause capillary endothelial leakiness and edema during inflammation
  • Thromboxanes: vasoconstrictors
  • Prostacylins: vasodilators
110
Q

Define margination

A

Leukocytes adhere to vascular endothelium (via selectin and integrin binding) near sites of infection or injury.

111
Q

Define transmigration

A

Leukocytes migrate through the endothelium. Vasodilation aids this process.

112
Q

Define chemotaxis

A

Leukocytes follow a gradient of chemical attractants to the site of infection or injury.

113
Q

Selectin-mediated adhesion

A

weak; allows neutrophil to roll along the vascular endothelial surface

114
Q

What causes chronic inflammation?

A
  • genetic traits
  • autoimmunity due to improper lymphocyte development
  • persistent irritation or injury
115
Q

Characteristics of chronic inflammation

A
  • Persistence of T cell and macrophage activity
  • Presence of high levels of inflammatory cytokines
  • Pain
  • Swelling
  • Unnecessary scarring
  • High levels of matrix metalloproteinases (MMPs)
  • Elevated levels of reactive oxygens
  • Tissue destruction
116
Q

What are the types of chronic inflammation?

A
  • cellular mediated immunity: psoriasis, RA

- immune complexes: glomerulonephritis, uveoretinitis

117
Q

What does it mean if a T cell has CD4 on its surface?

A
  • makes up 65% of T cells
  • it is a T helper cell
  • helps TCR interact with MHC class II
  • doesn’t recognize antigen
118
Q

What does it mean if a T cell has CD8 on its surface?

A
  • makes up 35% of T cells
  • it is a T killer cell / cytotoxic T lymphocyte
  • helps stabilize complex between TCR and MHC class I
119
Q

Response of T cell vary depending on what?

A
  • type of APC

- type of T cell

120
Q

Superantigen properties

A
  • Bacterial toxins and retroviral proteins
  • Specific for Vb
  • Activate 1-10%
  • Leads to toxic shock syndrome
  • Cross link TCRβ and MHC II
121
Q

What happens after APC activation?

A

cytokine production

122
Q

Tfh

A
  • activate B cells

- maturation of antibody response