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Immunology > Assignment 7 > Flashcards

Assignment 7 Flashcards

1
Q

what is a germinal center

A

sites within secondary lymphoid organs where mature B lymphocytes proliferate, differentiate, mutate their antibodies (through somatic hypermutation), and switch the class of their antibodies (for example from IgM to IgG) during a normal immune response to an infection.

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2
Q

where does B cell activation take place in a primary immune response?

A

secondary lymphoid tissue

  • Antigen entry affects site of immune response
    - Blood: spleen
    - Mucosal tissue: MALT (resp. GI, etc.)
    - Lymph: lymph node
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3
Q

where does B cells predominate in secondary lymphoid tissue?

A

follicles

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4
Q

where do T cells predominate in secondary lymphoid tissue

A

regions surrounding follicles

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5
Q

where does naive B cell activation initiation begin in the secondary lymphoid tissue

A

outer areas of follicles - so T cells can help out

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6
Q

what occurs during antigen recognition and processing (should already be familiar with)

A
  • Cross linking of BCR by antigen
  • Endocytosis into endosome & fusion of lysosomes w/ endosome
  • Formation of chimeric vescicle (endosome w/ antigenic peptides & MHC class II)
    occurring in
  • Formation of MHC class II-antigen peptide complex & translocation to B cell surface
    interfollicular
  • Presented to TCR of activated CD4+ TH cell (Th2)
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7
Q

what adhesion molecules stabilize the T cell/B cell conjugate? (role of the CD4+ T cell)

A

ICAM-1/LFA1

LFA-3/CD2

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8
Q

what costimulatory molecules of B cells also act on the Tcell/B cell conjugate? (role of the CD4+ T cell)

A

B7/CD28

CD40/CD40 Ligand

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9
Q

when is clonal expansion of B cells detectable

A

within 24 hours of immunization

-following burst of proliferation, activated B cells and T cells migrate to primary follicles where enhanced proliferation of B cells leads to the formation of germinal centers (hall mark of secondary follicles)

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10
Q

define clonal expansion

A

an immunological response in which lymphocytes stimulated by antigen proliferate and amplify the population of relevant cells.

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11
Q

what areas are associated with clonal expansion, isotype switching, affinity maturation, differentiation to plasma and differentiation to memory B cells ?

A

germinal centers

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12
Q

What is the role of CD40/CD40 ligand interaction?

A

delivers an essential signal for T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation.

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13
Q

what happens if CD40/CD40 ligand is disrupted?

A

steps in the differentiation pathway are prevented

results in hyper IgM => because of no isotype switching

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14
Q

what do secreted antibodies lack (from plasma cells) compared to expressed antibody surface receptors (B cells)?

A
  • carboxy terminal cytoplasmic sequences

- transmembrane domain required for anchorage to plasma membrane

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15
Q

when does differentiation of plasma cell stage occur and what it the event marked by

A

4 days after immunization

marked by secretion of IgM antibodies. Later, B cells undergo isotype switching and then B cell differentiation to the plasma cell stages is characterized by the secreted antibody isotype to which class switching occurred.

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16
Q

what antibody is NOT secreted?

A

IgD

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17
Q

define isotype switching

A

process by which cells expressing IgM and IgD are modified at the genomic level such that they produce antibodies of different isotypes (IgA, IgE, IgG)

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18
Q

what gene region/part of the antibody is modified during isotype switching?

A

the heavy chain constant region

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19
Q

what is switch recombination?

A

same as isotype switching?

occurs at unique switch regions, located between each gene encoding a constant segment of heavy chains

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20
Q

where does isotype switching/switch recombination occur and when?

A

germinal centers

1 week after initial B cell activation by T dependent antigen

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21
Q

what makes isotype switching irreversible? explain?

A

the segment of DNA that is downstream (3’) of the variable region, but upstream (5’) of the “new” switch region is deleted form the genome

22
Q

what decides the selection of one heavy chain constant region over another during switch recombination?

A
  • signal generated during B/Tcell conjugation

- T cell derived cytokines present in microenvironment

23
Q

disruption of the IL-4 gene in mice does what

A

inhibits switch recombination to IgE

24
Q

define affinity maturation/somatic mutation?

A

process that leads to the gradual accumulation, with time after immunization, of higher affinity antibodies for the immunizing antigen

25
Q

production of an antibody with increased affinity for the immunizing antigen occurs randomly as a result of _______ which gives rise to point mutations

A

somatic mutation

*point mutations - occur in “VDJ” regions of both light and heavy chain

26
Q

where does somatic mutation/affinity maturation occur and when

A

germinal center

7-10 days following B cell activation

27
Q

where does differentiation of activated B cells to memory B cells occur and when

A

germinal centers

1 weeks after antigenic challenge with a T dependent antigen

28
Q

why do memory B cells usually express high affinity immunoglobulin and isotypes other than IgM?

A

because memory B cell differentiation occurs within the same time frame as isotype switching and affinity maturation

29
Q

where do memory B cells hang out (2 places generally)

A

secondary lymphoid tissue

most join the pool of recirculating B cells that circulate from blood, lymph, and tissues that were the primary sites of previous antigen encounter.

30
Q

how do memory B cells enter lymph nodes

A

afferent lymphatics (no HEV) - why? because they have reduced expression of L-selectin which is the molecules that facilitates extravasation of naive B cells fro the blood to the lymph nodes at the HEVs

31
Q

what is the time memory B cells can survive without stimulation and are they in the cell cycle or not

A

survive for weeks or months without stimulation

not in cell cycle

32
Q

what is the major role of BLys (B cell stimulator/ BAFF B cell activating factor)?

A

role in B cell selection and survival

33
Q

what cells types produce BLys?

A

monocytes/macrophages
dendritic cells
some lymphocytes

34
Q

how can BLyS be expressed?

A
  • first as a cell surface protein

- released as soluble molecule

35
Q

what triggers the release of BLyS from monocytes/macrophages and dendritic cells?

A

cytokines or by crosslinking of FCgammaR by IgG (opsonin) => link between innate and adaptive immunity and B cell survival

36
Q

what receptors does BLyS bind to on peripheral B cells? which receptor has the highest affinity?

A

BR3, BCMA, TACI

BR3 - highest affinity

*each receptor = different cascade = each has different outcomes

but all 3 receptors play a key role in B cell differentiation in the bone marrow

37
Q

what does BR3 signaling do?

A

leads to B cell survival by preventing apoptosis

38
Q

when is BR3 upregulated?

A

following crosslinking of the B cell antigen receptor

39
Q

what happens when abnormal production of BLyS occurs?

A

alters immune tolerance by allowing the survival of autoreactive B cells = triggering autoimmune disorders

Rheumatoid arthritis (RA)
systemic lupus erythematosus (SLE)
MS

40
Q

what does down regulation of B cell activation require

A

colligation of Fcgamma R II B-IgG/antigen with membrane bound immunoglobulin/antigen = decreases BLyS receptor levels = negatively impacts effects of BLyS and B cell survival

41
Q

define negative signaling

A

inhibition of B cells following antigen induced activation

42
Q

what is the mechanism of negative signaling?

A

when secreted IgG crosslinks the membrane bound antibodies (same specificity) with the integral membrane receptor, FcgammaR (low affinity FcgammaR) => secreted immunoglobulin serves as a negative feedback regulator to inhibit further activation of the naive cells and subsequent secretion of antibodies

43
Q

what is the only ligand for BR3?

A

BLyS

44
Q

what ligands bind to TACI and BCMA

A

APRIL and BLyS - APRIL is higher affinity than BLyS

45
Q

where doe secondary immune responses occur?

A

outside of the secondary lymphoid tissue

46
Q

is secondary immune response faster or slower than primary immune response

A

much faster - the progeny is nearly one log greater than that generated in primary immune response

47
Q

what are characteristics of secondary immune responses?

A
  • shorter lag time
  • lead to a higher antibody titer
  • secretion of antibodies of the new isotype
  • can occur anywhere in the body!
48
Q

what are T independent antigens?

A

antigens that can induce naive B cell activation int he absence of cognate interaction with T cells

leads mainly to IgM production

49
Q

what are examples of T independent antigens?

A
  • lipopolysaccharide (LPS) - bacterial cell wall component = T-indep at low concentration (at high concentrations = mitogenic)
  • pneumococcal polysaccharide form Streptococcus pneumoniae
50
Q

The immune response to an antigen can be enhanced in the presence of ____

A

adjuvants => important for deliberate immunization like when administering vaccines - maybe causes slow release of antigen so antigen presentation to T cell is prolonged

-examples = alum precipitate, Freund’s complete adjuvant

51
Q

what are mitogens?

A

naturally occurring molecules that have the capacity to bind to and trigger proliferation of many clones of lymphocytes

B cell mitogens
-pokeweed
- LPS - at high concentration
T cell mitogens
-concanavalin A (Con A)
-phytohemagglutinin (PHA)
-pokeweed
52
Q

what are oligoclonal acitvators

A

superantigens (bacterial products) that act in a non-antigen specific nut non-polyclonal (oligoclonal) fashion on T cells

bind to regions of the T cell receptors called Vbeta

triggers the activation of all the clones that express any given Vbeta = will lead to the clonal expansion of many clones (oligoclonal) but not ALL clones

Immunology (12 decks)

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