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Molecules and Cells II > Cellular Basis of the Immune Response T and B Cell Activation > Flashcards

Cellular Basis of the Immune Response T and B Cell Activation Flashcards

1
Q

Where do superantigens bind?

A

Both to the Vbeta region of the TCR and to the alpha region of the MHC

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2
Q

What are the phases of the Primary Humoral Response?

A
  1. Lag Phase - time required for B cell division, differentiation; release of IgM followed by release of both IgM and IgG; memory B cell subset formed (4-5 days before antibody detection in serum; varies with nature of antigen – soluble antigen takes 7 days).
  2. Logarithmic Phase – antibody production increases logarithmically reaches peak levels (day 7-10) (day 14 for soluble protein antigen)
  3. Plateau Phase – equal synthesis and decline of antibody
  4. Decline Phase – more rapid degradation and decline of antibody

memory B cells stop dividing and enter G0 phase of the cell cycle

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3
Q

What are the gene products of T cell Activation?

A
  1. Immediate Genes - expressed within 30 min of

antigen recognition

  • encode transcription factors,

c-fos, c-Jun, c-Myc, NF-AT and NF-κB

  1. Early Genes - expressed within 1-2 hrs

encode IL-2, IL-2R(receptor),

IL-3, IL-6, IFNγ

  1. Late Genes - expressed >2 days after

antigen recognition

encode adhesion molecules

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4
Q

What are the three signals required for T cell activation?

A

Signal 1: Interaction of MHC: Peptide with TCR: CD3 Complex

Signal 2: Interactions between CD28 on T cell and B7 on APC

Signal 3: Cytokines

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5
Q

What effectors are produced by cytotoxic T cells?

A

Soluble effectors

  • Cytotoxins (perforins and granzymes)
  • IFNy
  • TNF- b

Membrane bound

  • Fas ligand
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6
Q

What happens after signals 1,2,and 3 occur?

A

The resting cell enters the cell cycle and begins to profilerate and differentiate into effector and memory cells.

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7
Q

What effectors are produced by Th2 cells?

A

Soluble

  • IL-3, IL-4,IL-5,IL-6. IL-10, IL-13, GM-CSF (low)

Membrane bound effectors

  • CD40 Ligand
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8
Q

Only ___________% of the many B cells that are produced will enter the recirculating pool of B cells.

A

10

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9
Q

Cytokines act on their target cells by _____________

A

binding to specific membrane receptors

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10
Q

Naïve cells are activated exclusively by___________

Memory cells can be activated by ______________

A

dendritic cells

all 3 APCs; made possible by the large amounts of adhesion molecules

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11
Q

____________increases in response to activation signals

___________adhesion protein (homing to secondary sites)

___________chemokine (homing to secondary sites)

A

CD44

CD62L

CCR7

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12
Q

Bacterial superantigens have been implicated in ___________ and ___________.

A

food poisoning, toxic shock syndrome

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13
Q

What are the phases of the Secondary Humoral Response?

A
  1. Lag Phase – much shorter
  2. Logarithmic Phase – greater and longer lasting
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14
Q

_________ plays an important role in T cell homeostasis

A

CTLA-4

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15
Q

In addition to the stimulatory coreceptor, ___________delivers a negative signal that inhibits continuous B cell activation

A

CD22

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16
Q

Antibody cell signaling

A
  1. Binding antigen results in phosphorylation of tyrosines within the ITAMs (immunoglobulin Tyrosine-based activation motifs) of the Ig-α and Ig-β chains
  2. This creates docking sites for other molecules such as Syk
  3. Activated Syk phosphorylates the adaptor protein BLNK , creating docking sites for PLCγ2 and Btk
  4. Activated Btk phosphorylates and activates PLCγ2
  5. PLCγ2 cleaves PIP2 into DAG and IP3
  6. DAG and Ca2+ activate PKC which activates NF-кB which regulates gene expression, differentiation, activation and causes functional changes in the cell
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17
Q

Proinflammatory cytokines

A

TNF

IL-1

IL-6

Chemokine

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18
Q

What is the characteristic of cells in effector memory?

A

Some travel to tertiary sites of original infection

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19
Q

What effectors are produced by Th1 cells?

A

Soluble effectors

  • IL-2, IL-3, TNF-B, IFNy, GM-CSF

Membrane bound effectors

  • TNF B
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20
Q

Which cytokine receptors are used by the HIV virus?

A

CCR5 and CXCR4

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21
Q

What are the three signals of Thymus-dependent B cell response?

A

Signal 1 – multivalent antigen cross links Ig molecules

Signal 2- CD40L on T cell binds CD40 on B cell

Signal 3 – T cell cytokines bind and induce B cell proliferation

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22
Q

Antiinflammatory Cytokines

A

IL-10

IL-1a

TGF-b

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23
Q

Eosinophil/ Mast Cell Activating Cytokines

A

IL-3

IL-4

IL-5

IL-13

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24
Q

In what ways are natural killer cells similar to cytotoxic cells? In ways are they different?

A

Natural killer cells release perforins and granulozymes in the same manner as Tc cells

Natural killer cells lack CD3:TCR complex and is not MHC restricted

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25
Can responses be thymus-independent in the secondary response?
No
26
Overstimulation of superantigens can lead to the overproduction of which cytokines?
IL1 and TNF
27
What are the characteristics of the antigens that are present with Thymus indepedent B cell Response?
TI-1 antigen- Gram negative bacterial cell wall lipopolysaccharide (LPS) interacts via Ig receptor and TLRs; mitogenic TI-2 antigen- Highly repetitive molecules, like bacterial capsular polysaccharide, flagelin
28
Natural T regulatory cells originate in the \_\_\_\_\_\_\_\_\_\_. Is regulation antigen-specific?
Thymus; Yes because of the need for the TCR
29
Role of Induced T Regs
preventing the immune system from attacking the body's cells and tissues. Inhibit the development of autoimmune diseases by maintaining self tolerance Inflammatory Bowel Disease Allergic Encephalitis Autoimmune Diabetes (Type I) Arthritis
30
What is the function of Signal 2? What effect does this have? What happens if this signal doesn't happen?
Signal 2 increases the half life of the IL-2 mRNA and stabilizes it This allows for increased IL-2 production (100-fold) Secretion of IL-2 induces proliferation and differentiation into memory cells and effector cells In the absence of costimulatory signal 2, T cell receptor engagement results in T cell inactivity or Clonal Anergy.
31
Antiviral cytokines
IFNa, IFNb
32
Induced Tregs are _________ induced and ___________ mediated.
Inflammation; IL-10 and TGFBeta
33
Which proteins are a part of the B Cell Co Receptor Complex?
CD19 CR2 TAPA-1
34
Because of their immuno-modulatory role, cytokines and/or their receptors have been investigated for potential therapeutic use in :
Inflammation Cancer Allergy Infectious Disease Organ Transplantation
35
What are the roles of the alpha, beta, and gamma chains of IL-2?
Alpha: only expressed in activated T cells βγ-chains can induce signal transduction The trio chain is needed for high affinity binding
36
Characterstics of Cytokines
Pleiotropy Redundancy Synergy Anatagonism
37
38
What are the effector T cells? Which cytokines does each secrete? What are their functions?
short-lived cells with special functions: CD4 helper T cells : * CD4TH1 - IL-2, IFNγ, TNFβ * responsible for cell-mediated functions * Delayed hypersensitivity and Cytotoxic T cell activity * CD4TH2 - IL-4, IL-5, IL-6, IL-10 * responsible for B cell activation * CD4 CD25 T regulatory cell (Treg) * regulates T cell responses * CD4 Th17 * (inflammatory cell; involved in fungal and extracellular bacterial infections; also associated with chronic autoimmune disorders) * CD8 cytotoxic T cell
39
Cytokine- Induced Signal Transduction
1. Cytokine binds to the receptor on cell membrane 2. Dimerization of the receptor 3. Phosphorylation of JAK 4. Phosphorylation and dimerization of STATS 5. Translocation of STAT to the nucleus where transcription of target genes occurs.
40
What are ways that cytokines can play roles in theraputic use?
Place an antibody against the cytokine receptor Create an analog that binds in the place of the cytokine, thus preventing it from binding Attach a toxin. Allow the cytokine to bind and the toxin will destroy the target cell
41
Macrophage activating cytokines
IFNy
42
Hematopoietin (Class I) – dimers or trimers with conserved \_\_\_\_\_\_\_\_\_\_\_\_in their extracellular domains and a conserved \_\_\_\_\_\_\_\_\_\_\_\_sequence.
cysteines; Trp-Ser-X-Trp-Ser
43
B Cell Activating Cytokines
IL-4 IL-5 IL-6 IL-21
44
Ig- α tail is _______ aa in length Ig- β tail is ________ aa
61 48
45
B7 has 2 isoforms, \_\_\_\_\_\_\_\_\_\_and\_\_\_\_\_\_\_\_\_; they are constitutively expressed on \_\_\_\_\_\_\_\_\_\_\_and induced on activated ____________ and \_\_\_\_\_\_\_\_
B7-1; B7-2; dendritic cells; macrophages; B cells
46
What are the systemic reactions to superantigens?
Fever, widespread blood clotting, and eventually shock
47
48
Is IL-2 a dimer or trimer?
Trimer
49
In naive cells CD44 is \_\_\_\_\_\_\_\_\_\_\_\_, CD62L is __________ and CCR7 is \_\_\_\_\_\_\_\_\_\_\_\_\_. In effector cells CD44 is \_\_\_\_\_\_\_\_\_\_\_\_, CD62L is __________ and CCR7 is \_\_\_\_\_\_\_\_\_\_\_\_\_. In effector memory cells CD44 is \_\_\_\_\_\_\_\_\_\_\_\_, CD62L is __________ and CCR7 is \_\_\_\_\_\_\_\_\_\_\_\_\_. In central memory cells CD44 is \_\_\_\_\_\_\_\_\_\_\_\_, CD62L is __________ and CCR7 is \_\_\_\_\_\_\_\_\_\_\_\_\_.
Low, positive, positive Positive, low, negative Postitive, variable, negative Positive, positive, positive
50
What roles do CD28 and CTLA-4 play in relation to B7?
CD28 and CTLA-4 compete to bind to B7. C28 is expressed on both resting and active T cells. CTLA-4 is virtually undetectable on resting T cells but is expressed on active T cells. CTLA-4 has a higher binding affinity. C28 yields a positive signal and CTLA-4 yields a negative signal.
51
T- Cell activating Cytokines
IL-2 IL-4 IL-12 IFNy
52
T cell dependent B cell response (Sequence of Events)
Sequence of events: 1. Ag binding to BCR provides “Signal 1” to B cell. 2. Ag internalized; processed; antigenic peptides displayed on MHC for T cell recognition. 3. helper T cell recognizes ag:MHC complex via the TCR, which provides “Signal 1” to T cell. 4. B7 on B cell binding to CD28 on T cell provides “Signal 2” to T cell. 5. T cell activation leads to up-regulation of CD40L which bind to CD40 providing “Signal 2” to B cell. 6. Cytokine production by activated T cell also helps to activate B cell. 7. B cell proliferates and differentiates into antibody secreting B cell (plasma cell).
53
Tregs act antagonistically with the \_\_\_\_\_\_\_\_\_\_\_cells
Th17
54
What three forms can the IL-2 receptor exist in?
Monomeric (just alpha chain, no signaling) Intermediate (beta and gamma chains, signaling) High affinity (all three chains)
55
What is the characteristic of cells in central memory?
Cells stay in secondary sites for long periods of time
56
T cell - B cell collaboration
•Required for antibody response to complex antigens such as proteins, lipids • Requires direct, physical B-T interaction • Involves multiple cell surface receptors on T and B cells • Both B and T cell must recognize antigen (but not necessarily the same epitope). • Both B and T cells need signal 1 (through antigen receptor) and signal 2 (co-stimulation)
57
What is CVID?
a disorder that impairs the immune system. People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections, particularly in the lungs, sinuses, and ears. Low Ig levels, especially IgM, IgA, and IgG
58
All isotypes of the \_\_\_\_\_\_\_Ig have short cytoplasmic tails. What's the significance of this?
Monoclonal ## Footnote Tails are all too short to interact with tyrosine kinase to generate a signal Ig-α/Ig-β heterodimer acts as the signaling complex, while the mIg acts as the ligand binding molecule
59
Chemokine Family – have _________ transmembrane helices Includes receptors for \_\_\_\_\_\_, \_\_\_\_\_\_, and \_\_\_\_\_\_\_\_. Also the ______ and ________ receptors which are used by the HIV virus are included.
7; IL-8, MIP-1, and Rantes; CCR5 and CXCR4
60
Which cytokine makes IgE? IgA?
IL-4; IL-5
61
3.Tumor Necrosis Factor Family four extracellular domains; include receptors for\_\_\_\_\_\_\_\_,\_\_\_\_\_\_\_\_\_\_,\_\_\_\_\_\_\_\_\_, and \_\_\_\_\_\_\_\_\_
TNFα, TNFβ, CD40 and Fas

Molecules and Cells II (14 decks)

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