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IMMUNOLOGY VDMP817 > lecture 5 > Flashcards

lecture 5 Flashcards

1
Q

number of combinational diversity possible

A

10^6
VDJ combinations, less than junctional

heavy chain has a lot more V gene segments
light chain has no D gene segments

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2
Q

number of junctional diversity possible

A

10^11

VDJ a lot more than combinatinoal because of the N and P nucleotides
can really respond to any attack

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3
Q

antibody heavy chain isotype switchin

A

only happens in B cells
will keep the arms but switch the tail - each tail comes with own unique function

will change messengers produced depending on secretions from B cell -> helper T cell

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4
Q

activation induced cystidine deaminase

A

AID
converts IgM to IgG, IgE, IgA antibodies

involved in high rate of CDR mutation
improves affinity of BCR:
1. b cells w strongest affinity to an antigen receive greater survival signals
2. those differentiate to become plasma cells and generate memory!

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5
Q

pathway from B cell to messengers/antibodies

A

B cell -> IgM

  • > helper T cell (CD40L, cytokines) -> IFNgamma -> IgG
  • > IL4 -> IgE
  • > cytokines produced in mucosal tissues (TGFbeta, BAFF) -> IgA
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6
Q

B1 B cells cycle

A

come from fetal liver as primary lymphoid organ

FLHSC -> pro B -> pre B -> immature B -> B1 B cell w IgM and CD5

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7
Q

B2 B cells cycle

A

come from bone marrow as primary lymphoid organ
BM HSC -> pro -> pre -> immature -> a. SPLEEN -> transtional B2 (igM) -> a. follicular B2 bcell w IgM and IgD (most common) b. marginal zone B2 Bcell w Igm and CD21/CR2
b. immature B straight to B cell follicles -> follicular B2 (conventional)

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8
Q

B1 Bcell details

A
  1. develop from fetal liver HCS
  2. large # of B1 found as self renewing population in peritoneum and mucosal sites - continue secreting IgMs (antibodies)
  3. B1 develop earlier during ontogeny than conventional (b2) and express a relatively limited repertoire of V genes and far less junctional diversity than conventional (B2) cells - decreased recognizing ability and are always present
  4. B1 and marginal zone B cells (B2) spontaneously secrete igm antibodies (natural antibodies) that often react to microbil polysacharides and lipids (PAMPS) - t cell independent responses
  5. B1 provide source of rapid antibody production against microbes in particular sites (peritoneum)
  6. at mucosal sites B1 may differentiate into half Iga secreting in lamina propria (IgA microbe biome in gut will stimulate the igM to igA)
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9
Q

T cell independent responses

A

no generation of memory

B1 cells and marginal zone cells responding to PAMPS

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10
Q

marginal zone B2 cell

A
  1. located primarily in vicinity of marginal zone in spleen
  2. limited diversity, ability to respond to polysaccharide/phospholipid antigens to create natural antibodies (IgM)
  3. express igM and CD21 surface markers, respond very rapidly to blood borne microbes and differentiate into short lived igM secreting plasma cells (which is good becasue the spleen filters all blood borne pathogens which allows Bcells to make new antibodies)
  4. dont need t cell help (like B1 does) but do appreciate it
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11
Q

b2 bcells details

A
  1. develop in bone marrow HCS
  2. conventional B cells found in follicle of lymph nodes and spleen
  3. require dual activation via BCR and T cell interaction
  4. activation occurs w/in germinal centers of lymph nodes and spleen
  5. affinity maturation - the more it binds to antigen the more efficient the claws come to bind antigen for antibodies
  6. generate large number of plasma cells and memory B cells (B2 memory follicular) - long term protection
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12
Q

affinity maturation of B2 follicular B cells

A

naive B cell from bone marrow -> clonal expansion (army!) -> somatic hypermutation (uber recongnition) -> improved affinity (claw shortens so closer to B cell) -> selection (only B cells that bind remain) -> class switching -> differentiation

into plasma cells, or memory B cells
have help from follicular DC and follicular helper T cells

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13
Q

B10 details

A

immune regulation

  1. develop from B1 or B2 after specific stimulation
  2. T cell independent or dependent
  3. characterized by presence and secretion of IL10!
  4. similar to regulatory T cells (Tregs): Bregs modulate immune response to limite inflammation
  5. lack of b10 b cells lead to increase in inflammation and some diseases - rheumatoid arthritis
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14
Q

B cell activation and signaling

A

immunogens
requires cross linking of multiple BCRs or recquires protein antigens to attract T cell help
only macromolecules are capable of stimulating B cells to initiate antibody responses
epitope (antigenic determinant): portion of macromolecule that an antibody binds (can see 2D epitope)

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15
Q

immunogens

A

B10 activators/signalers
molecules that stimulate an immune response
ex: sugars, lipids, complex carbohydrates, phospholipids, nucleic acids, and proteins

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16
Q

Bcell activation and signaling results

A 
transcription factors (through CD79 signal transducing components)
proliferation
differentiation
cytokine secretion
antibody secretion

inflammation/immune system help!

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17
Q

CR2 role in B cell activation

A

aids in binding to C3d (complement proteins that tagged for opsonization) and holds microbe to B cell for more improved activation
drawn in through signals of Ig’s and CR2 complex

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18
Q

TLR role in B cell activation

A

B1 or marginal zone (B2) cells

TLR is PAMP recognizer of microbe that signals different TLRs that will lead to specific responses to specific microbe

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19
Q

TLR2/1

A

gram + PAMP

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20
Q

TLR2/6

A

zymosan PAMP

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21
Q

TLR3

A

dsRNA PAMP

22
Q

TLR4

A

gram - PAMP

23
Q

TLR5

A

flagellin PAMP

24
Q

TLR7

A

ssRNA PAMP

25
Q

TLR8

A

ssRNA PAMP

26
Q

TLR9

A

CpG DNA

27
Q

Tcell dependent B cell activation

A

follicular MZ Bcells (B2) that need T cell help
helper tcell activation of bcells
needed for costimuating follicular b cells and sometimes MZ Bcells

two BCRs recognize antigen and internalize it then MHC2 presents peptides (epitope) to T cell
CD40 is required for B - T interaction
cytokines released and attracts
RESULT:
-enhanced proliferation
-differntiation
-cytokine secretion
-antibody secretio
-affinity maturation
-isotype switching
-memory
-plasma cells produced
28
Q

Tcell independent Bcell activation

A

bacterial cell walls have multiple identical linear nonprotein epitopes:

  • ex: haemophilus influenzae polysaccharide (Gram - LPS)
  • bind to BCR (same 2) leading to B cell activation
  • immediate activation is short lived response w only IgM produced!

TI -1 antigen
TI -2 antigen

29
Q

TI - 1 antigen

A

mitogen/TLR agonist

30
Q

T1 -2 antigen

A

repeating motif of encapsulated bacteria

31
Q

secondary antibody response

A

each subsequent challenge creates more and more memory cells - exposure after primary antibody response (plasma cells, memory b cell and antibodies secreted)

32
Q

plasma cells are

A

antibody factories which express few surface markers

33
Q

anti RBC antibodies

A

complement mediated RBC lysis (IMHA)

34
Q

anti platelet antibodies

A

thrombocytopenia

35
Q

anti penicillin antibodies

A

anemia, shock, allergic reaction

36
Q

rheumatoid arthritis

A

rheumatoid factor build up, immune complexes

37
Q

SLE (lupus)

A

systemic inflammation affecting one or multiple organs

38
Q

antinuclear antibodies

A

lupus or lupus like symptoms

39
Q

lymphoma

A

uncontrolled expansion of B cells or T cells

40
Q

leukemia

A

uncontrolled expansion of immature B cells or T cells

41
Q

cancer transformation

A

bovine leukemia virus (B cell)

42
Q

multiple B cell subsets…

A

exist and have unique activation and signaling pathways

T cell independent
T cell dependent

43
Q

VDJ re arrangement of BCR

A

generates extensive diversity to recognize pathogens

heavy has VDJ junctional and combinaitonal
light doesnt have D

44
Q

only follicular B cell responses generate

A

long lived plasma and memory cells

45
Q

MZ B cells act as

A

early sentinels for blood borne pathogens

46
Q

B1 act as

A

innate effector cells, producing antibody for protection prior to encounter with antigen

47
Q

B10 play a

A

regulatory antiinflammation role via production of IL10

48
Q

b cell activation occurs through the

A

BCR BCR, BCR CR2complex, or BCRTLR ligation

49
Q

t cell independent B cell responses occur via

A

recognition of some antigens conserved patterns (repetitive motifs)

50
Q

tolerance protects the body from

A

self-reactive B cells

51
Q

clinical responses to antibody mediated diseases

A

lots of examples and really dangerous bc mess up immune system and inflammation

IMMUNOLOGY VDMP817 (22 decks)

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