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IP > Activation of B and T cells by Antigen > Flashcards

Activation of B and T cells by Antigen Flashcards

1
Q

Priming in T cells?

A
  • when a naive T cell encounters its specific antigen and is stimulated to differentiate into an effector T cell
  • first step in any adaptive immune response
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2
Q

is the adaptive immune response initiated at the site of infection?

A

no, helper T cells and naive cells come into contact with pathogen and then T cells differentiate into effector cells in secondary lymph tissue

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3
Q

Where does activation of helper T cells generally occur?

A

-secondary lymph tissue

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4
Q

Where does activation of helper T cells occur for antigens in the skin and other peripheral tissues?

A

regional lymph nodes

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5
Q

Where does activation of helper T cells occur for antigens that are blood borne?

A

spleen

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6
Q

Where does activation of helper T cells occur for antigens in the respiratory mucosa?

A

tonsils and bronchial associated lymph tissue

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7
Q

Where does activation of helper T cells occur for antigens in the gastrointestinal system?

A
  • peyers patch
  • GALT
  • appendix
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8
Q

How does the antigen get to secondary lymphoid tissue?

A

dendritic cells and macrophages:

  • act as sentinels for infection in tissue
  • upon infection, both cells uptake pathogens
  • can process and present antigen
  • macrophages have a range of function
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9
Q

What is the function of dendritic cells?

A

trigger T cell responses

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10
Q

Difference in dendritic cells vs macrophages?

A

Dendritic:

  • migratory
  • carry antigen load from site of infection to nearest secondary lymph tissue

Macrophage:

  • resident in tissues, do not migrate
  • macrophages resident in lymph tissue can process and present antigen that is carried passively in lymph form infected tissue
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11
Q

Dendritic cells reach their locations because activation induces expression of what?

A

CCR7, the receptor for chemokine CCL21

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12
Q

Once dendritic cells enter lymph nodes, where do they settle?

A

T cell areas -in the center

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13
Q

What is the anatomy of an immune response (general process)?

A
  • naive T cells brought to lymph nodes via the blood
  • they bind to endothelial cells in thin walled high endothelial venues (HEV)
  • squeeze through vessel wall
  • enter cortical region of lymph node
  • pass through tissue, examine antigen presenting cells (dendritic and macrophages)
  • if they see antigen, they active, proliferate, and differentiate into effector cells
  • if they don’t see antigen, they recirculate out from efferent lymph
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14
Q

What is the detailed process about how lymphocytes leave the blood stream and enter secondary lymph tissue?

A
  1. circulating lymphocyte enters the HEV
  2. L-selectin binds with CD34 and GlyCam-1 on the endothelium which allows rolling interaction
  3. LFA-1 is activated by chemokines (CCL21 binds to chemokine receptor CCR7)
  4. activated LFA-1 binds to ICAM-1 and ICAM-2 (Ig superfamily)
  5. diapedesis- lymphocyte leaves blood and enters lymph node
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15
Q

What enhances the homing of T cells to draining lymph nodes?

A

sites of acute inflammation:

  • egress via efferent lymphatics transiently reduced
  • due to cytosine produced as part of the innate immune response (IFNs)
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16
Q

Once inside the lymph tissue, what are the initial adhesive interactions between T cell and dendritic cell?

A
  1. T cells initially bind dendritic cell though low affinity LFA1: ICAM1 interactions
  2. subsequent binding of T cell receptors (TCR) to MHC class 2 in CD4+ cells, signals LFA1
  3. conformational change in LFA1 increases affinity and prolongs cell to cell contact
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17
Q

What is the first signal that antigen presenting cells deliver to naive T cells?

A
  1. engagement of the TCR
  2. signals activation of helper T cells
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18
Q

How does the engagement of TCR induce activation of T cells? process?

A
  1. V regions of TCR engage the MHC 2 complex containing the peptide
  2. CD4 interacts with MHC 2
  3. intracellular signaling by CD3 which activates protein kinase C and GTP binding proteins
  4. activation of Helper T cells
  5. changes in gene expression in cytokines, growth factors, cytokine receptors, and other activation proteins
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19
Q

What is the 2nd signal that antigen presenting cells deliver to naive T cells (now activated)?

A

co stimulation CD28 and B7-1/B7-2 interaction

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20
Q

Why is the 2nd signal important? what interacts? what happens in the absence of this interaction?

A
  • ligation of just TCR is insufficient for activation -survival
  • B7-1 (CD80) and B7-2 (CD86) interact with CD28 -costimulatory
  • in its absence, leads to inactivation of T cell, anergy, tolerance
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21
Q

What is used as a costimulatory blockade?

A

CTLA-4-Ig associates with B7 (cannot associate CD28)

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22
Q

What makes the IL-2 receptor have high affinity for IL-2?

A

activation induced expression of CD25 (IL-2Ra)

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23
Q

Functions of IL-2?

A
  • stimulates survival, proliferation, and differentiation of T lymphocytes (autocrine growth factor)
  • maintains functional regulatory T cells and thus controls immune responses
24
Q

What is the most important protein involved in CD4+ effector function?

A

CD40L

-binds to CD40 on macrophages, dendritic cells and B cells to secrete cytokines that differentiate and proliferate T cells (Th1, Th2, Th17)

25
Q

What does the activation of CD40 do for B cells? macrophages?

A

B- promotes proliferation, antibody secretion, class switching (humoral)

macro- activation, killing of phagocytksed microbes (cell mediated)

26
Q

Th1? Th2? Th17?

A

1, 17-inflammation

2- humoral

27
Q

What is signal 3 in T cells?

A
  • differentiation
  • cytokines drive this step
28
Q

What cytokines cause differentiation of CD4+ cells into TH17?

A

TGF-beta

IL-6

29
Q

What cytokines cause differentiation of CD4+ cells into TH1?

A

IL-12

IFN-gamma

30
Q

What cytokines cause differentiation of CD4+ cells into TH2?

A

IL-4

31
Q

What cytokines do TH1 cells produce? functions?

A

IFN-gamma:

  • macrophage activation
  • IgG production
  • intracellular microbes- host defense
  • autoimmune disease
  • tissue damage associated with chronic inflammation
32
Q

What cytokines do TH2 cells produce? functions?

A

IL-4, IL-5, IL-13

  • mast cell, eosinophil activation
  • IgE production
  • helminthic parasites- host defense
  • allergies
33
Q

What cytokines do TH17 cells produce? functions?

A

IL-17, IL-22

  • neutrophilic, monocytic inflammation
  • extracellular bacteria, fungi- host defense
  • autoimmune inflammatory diseases
34
Q

What is the role of B cells in the immune response?

A

Production of antibodies:

-clearance of organisms present in extracellular space like free virus that replicate inside cells and bacteria

Not toxic by themselves:

  • neutralization
  • opsonization (phagocytosis), promotes complement
  • targets for complement mediated destruction
35
Q

Primary response vs secondary response in antibodies?

A

primary:

  • peak response smaller, slower
  • usually IgM
  • lower affinity
  • induced by immunogens

secondary:

  • larger peak, faster
  • increases in IgG
  • higher affinity
  • unduced by protein antigens
36
Q

What type of antigens do B cells see? how do they recognize them?

A
  • see linear or conformational
  • recognized by surface immunoglobulin
37
Q

How does surface immunoglobulin in B cells recognize antigens?

A

Induces intracellular signal events:

  • BCR
  • Tyrosine kinase
  • complement receptor
  • Toll like receptor
38
Q

How are soluble (native) antigen delivered to B cells? small and large?

A
  • small antigens delivered to B cells in follicles through afferent lymphatics and via conduits
  • large are delivered by sub scapular sinus macrophages or by dendritic cells in the medulla
39
Q

What are follicular dendritic cells?

A
  • no show MHC class 2
  • B cells encounter antigens here
40
Q

What cell responses does antigen induced cross linking of the B cell antigen receptor cause?

A
  • production of proteins that promote survival and proliferation
  • expression of costimulators and cytokine receptors that promote interactions with helper T cells
  • responsiveness to helper T cells
  • migration of cells toward T cells as a result of expression of CCR7
41
Q

What is the sequence of events in humoral immune response?

A
  1. recognition of antigens by B cells and CD4+ T cells
  2. activated lymphocytes migrate toward one another and interact, resulting in B cell proliferation and differentiation
  3. restimulation of B cells by helper T cells in extra follicular sites leads to early isotope switching and short lived plasma cell generation, activation of T cells by B cells results in the introduction of follicular helper T cells
  4. late events occur in germinal centers and include somatic mutation and the selection of high affinity cells (affinity maturation)
    - additional isotype switching
    - memory B cell generation
    - generation of long lived plasma cell
42
Q

Explain antigen presentation on B cells to helper T cells?

A
  1. antigen activates B cells
  2. induce expression of MHC class 2
  3. becomes plasma cell
  4. some antigen goes through receptor mediated endocytosis, is internalized and processed
  5. antigen fit into MHC class 2 peptide complex
  6. looking for activated CD4+ T cell
43
Q

How does the T cell interact with the B cell?

A

TCR and CD40L on the activated T cell interact with MHC class 2 and CD40 on on the B cell

44
Q

What is the interaction of CD40 and CD40L important for in B cells?

A

differentiation and class switching

45
Q

What does the dark zones contain in germinal centers of lymph? what happens here?

A
  • contain activated proliferating B cells
  • extensive isotype switching
  • somatic hypermutation of Ig V genes
  • migrate to light zones
46
Q

What are light zones rich in at germinal centers? what B cells are selected to survive?

A
  • rich in follicular dendritic cells (displaying antigen) and T FH cells
  • B cells with highest affinity Ig receptors are selected to survive
  • differentiate into antibody secreting cells and memory B cells
47
Q

What cells leave germinal centers? where do they go?

A
  • antibody secreting cells leave
  • reside in bone marrow as long lived cells
  • memory B cells enter recirculating lymphocyte pool
48
Q

Describe the overall process at germinal centers?

A
  1. B cells proliferate in dark zones
  2. move to light zones where B cells with high affinity for Ig are selected to survive, differentiate into antibody secreting cells or memory B cells
  3. leave lymph and go to bone marrow or are recirculated
49
Q

How do the helper T cells migrate to the germinal center to activate B cells?

A
  1. follicular helper T cells express CXCR5 (chemokine receptor)
  2. follicular dendritic cells are producing relevant chemokine (ICOS-L, ICOS) to bring it close to the germinal center
  3. enter B cell zone once activated by B cell
50
Q

lower number = ____ affinity.

A

greater

51
Q

somatic mutations in Ig V genes leads to what?

A

greater affinity to antigen

52
Q

T cell CD40L engages ____ on an ______.

A

CD40 on activated B cell

53
Q

If cytokines produced by interaction of B cell with T cell are IL-4, what class switching do we get?

A

IgE

IgG4

54
Q

If cytokines produced by interaction of B cell with T cell are IFN-gamma, what class switching do we get?

A

IgG subclasses (IgG1, IgG3)

55
Q

What are T independent antigens? how? what are often TI antigens?

A
  • some antigens stimulate B cells without T cells antigen has repeating subunits:
  • causes extensive BCR cross linking
  • pnuemococcal, salmonella antigen can directly stimulate B cell at high concentrations:
  • binds to B cell via surface marker distinct from surface Ig (ex. bacterial polyliposaccharide) polysaccharides are often TI antigens:
  • can be made T-dependent if conjugated to a protein
  • implications for vaccine, not ideal
56
Q

What do TI antigens cause? Because no T cell help, what doesn’t happen?

A
  • cause proliferation and IgM secretion in absence of T cell help
  • No T cell help:
  • no class switching
  • no memory

IP (29 decks)

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