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Flashcards in 4. B cells Deck (35)
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1
Q

three basic principles of adaptive immunity

A
  1. diverse repertoire of receptors for antigens
  2. clonal expansion of the complementary type
  3. memory cells for faster secondary response
2
Q

TCR vs BCR

A

alpha/beta or gamma/delta vs heavy and light chain
membrane bound only vs membrane or free antibody
antigen presented peptide recognition vs whole molecule antigen recognition
BCRs can also be different isotypes

3
Q

what is initial generation of diversity

A

Gene rearrangement and heterodimer formation. Occurs in bone marrow for B cells or the thymus for t cells - naive cells.

4
Q

heterodimer formation

A

the mixing of alpha, beta, gamma and delta chains or heavy and light chains

5
Q

Fv region

A

variable region
two binding sites
determines antigen specificity

6
Q

Fc region

A
constant region
determines the class and function of antibody
7
Q

gene rearrangement

A

different combinations of variable, diversity and joining genetic regions form the complementarity determining regions

8
Q

which enzymes complete gene rearrangement

A

RAG1/2 (recombination activating genes)

9
Q

light chain gene rearrangements

A
VJ and C only
either kappa (two thirds) or lambda (one third)
10
Q

heavy chain gene rearrangements

A

VDJ and C

beta

11
Q

mathematics of gene rearrangement

A

61 HCV regions x 26 HCD regions x 6 HCJ regions x 40 LCV regions x 7 LCJ regions = 4.9x10^6 (but in reality there are more than 5 million)

12
Q

Junction region diversity

A

the region where the different segments join together creates more diversity
nucleotides can be accidentally removed or deliberately inserted by TdT (terminal deoxynucleatidyl transferases)

13
Q

TCR gene rearrangement

A

VDJ - beta, delta

VJ - alpha, gamma

14
Q

B cell development

A
  1. BCR
  2. whole antigen recognition
  3. differentiation into plasma cells that secrete antibodies
  4. antibody binding to antigen
15
Q

processes and locations of B cell development

A

gene rearrangement in bone marrow, clonal expansion in lymph nodes, hypermutation in dark zone of germinal centre, selection in light zone

16
Q

B cell activation by three types of antigen

A

T independent 1
T independent 2
T dependent

17
Q

receptors involved in b cell activation

A

BCR
PAMPs (innate)
co-stimulatory molecules
cytokines produced by Tfh cells

18
Q

T independent 1 antigens

A

polyclonal
non-specific
e.g. PRR

19
Q

T independent 2 antigens

A

alone produce IgM
large molecules with a repeating determinant
activates B cells by causing the BCRs to cluster
no memory cells produced
aided by cytokines released by dendritic cells to induce class switching

20
Q

T dependent antigens

A

B cell phagocytoses whole antigens and degrades them to be presented to T helper cells which activate the B cell
Forms memory cells

21
Q

B cell activation via T cells sends signals that include…

A

proliferation, differentiation, isotype switching, upregulation of surface molecules, development of germinal centre

22
Q

post-activation B cell development includes…

A
hypermutation and class switching
once antibody has met antigen
do not occur in T cell
take place in the germinal centre
need T helper cells
23
Q

enzyme involved in affinity maturation and class switching

A

AID (activation induced cytidine deaminase)

24
Q

affinity maturation principle

A

as B cells proliferate, their Ig genes mutate randomly. only the best ones with better binding and higher affinities are kept while the rest die by apoptosis

25
Q

affinity maturation process in germinal centre

A

Centroblasts hypermutate in dark zone, enter light zone as centrocytes after co-stimulation and activation by Tfh cells and cytokines, leave as memory or plasma cells.
lack Bcl2 meaning they can be apoptosed if not high affinity. only safe if antigen is presented to it from follicular dendritic cells

26
Q

hypermutation

A

deliberate mutation of Ig genes

27
Q

class switching

A

changing the Fc region to change the function

but the Fv region is still the same

28
Q

importance of antibodies

A

neutralises toxins and viruses
opsonisation to promote phagocytosis by macrophages
activates the complement cascade
agglutination of debris and viruses
antibody dependent cell mediated cytotoxicity through Fc regions

29
Q

which isotype can form dimers

A

IgA2

30
Q

which classes are more likely to be produced before and after switching and why

A

before: M and D - genes come first
after: G, A and E - genes come later on

31
Q

IgD

A

membrane bound

naive B cells

32
Q

IgM

A

default
pentamers - immune complexes but too large to cross into tissues or placenta
activate the complement cascade through classical pathway

33
Q

IgG

A
main antibody after switching
opsonisation
important in neonatal immunity - only antibody that can cross the placenta
targets for NK cells (ADCC)
4 subclasses
34
Q

IgA

A

mucosal
dimerises - protects from enzymatic breakdown but usually as monomer
2 subtypes

35
Q

IgE

A

parasites
mast cells - causes the mast cells to degranulate
low concentration but can increase in allergy (immediate hypersensitivity)