4. B cells

Question 1

three basic principles of adaptive immunity

Answer 1

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

Question 2

TCR vs BCR

Answer 2

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

Question 3

what is initial generation of diversity

Answer 3

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

Question 4

heterodimer formation

Answer 4

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

Question 5

Fv region

Answer 5

variable region
two binding sites
determines antigen specificity

Question 6

Fc region

Answer 6

constant region
determines the class and function of antibody

Question 7

gene rearrangement

Answer 7

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

Question 8

which enzymes complete gene rearrangement

Answer 8

RAG1/2 (recombination activating genes)

Question 9

light chain gene rearrangements

Answer 9

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

Question 10

heavy chain gene rearrangements

Answer 10

VDJ and C

beta

Question 11

mathematics of gene rearrangement

Answer 11

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)

Question 12

Junction region diversity

Answer 12

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

Question 13

TCR gene rearrangement

Answer 13

VDJ - beta, delta

VJ - alpha, gamma

Question 14

B cell development

Answer 14

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

Question 15

processes and locations of B cell development

Answer 15

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

Question 16

B cell activation by three types of antigen

Answer 16

T independent 1
T independent 2
T dependent

Question 17

receptors involved in b cell activation

Answer 17

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

Question 18

T independent 1 antigens

Answer 18

polyclonal
non-specific
e.g. PRR

Question 19

T independent 2 antigens

Answer 19

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

Question 20

T dependent antigens

Answer 20

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

Question 21

B cell activation via T cells sends signals that include…

Answer 21

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

Question 22

post-activation B cell development includes…

Answer 22

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

Question 23

enzyme involved in affinity maturation and class switching

Answer 23

AID (activation induced cytidine deaminase)

Question 24

affinity maturation principle

Answer 24

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

Question 25

affinity maturation process in germinal centre

Answer 25

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

Question 26

hypermutation

Answer 26

deliberate mutation of Ig genes

Question 27

class switching

Answer 27

changing the Fc region to change the function | but the Fv region is still the same

Question 28

importance of antibodies

Answer 28

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

Question 29

which isotype can form dimers

Answer 29

IgA2

Question 30

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

Answer 30

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

Question 31

IgD

Answer 31

membrane bound | naive B cells

Question 32

IgM

Answer 32

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

Question 33

IgG

Answer 33

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

Question 34

IgA

Answer 34

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

Question 35

IgE

Answer 35

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