Adaptive immunity 1

Question 1

2 components of the adaptive immune system

Answer 1

humoral immunity
= B-cell mediated immunity + antibodies

cell mediated immunity
= T-cells and TCRs

Question 2

what are the features of adaptive immunity?

Answer 2

not activated until there’s an antigenic challenge

high specificity
- selected immune cells proliferate

memory cells

Question 3

basic life of a B cell

Answer 3

mature B-cell expresses membrane-bound antibody

when foreign antigen binds to this immunoglobulin
-> stimulates B-cell to proliferate
= gives rise to plasma cells + memory cells

Question 4

where are B cells produced?

each B cell expresses a different..?

Answer 4

bone marrow

antibody on their surface

Question 5

antibody effector functions

Answer 5

neutralisation

mark for phagocytosis

activates complement system

Question 6

what do antibody’s neutralise?

how?

Answer 6

antigens
toxins

by binding to them
-> so they cannot bind to their targets

Question 7

5 classes of antibody

why is the most common in blood + lymph?

Answer 7

IgA
IgD
IgE
IgG
IgM

IgG

Question 8

what is the difference between the 5 classes of antibody?

Answer 8

differ in their constant regions

-> have different properties as they’re normally bound by different cellular receptors

Question 9

why would a B cell switch to a different Ig isotope?

Answer 9

different isotopes have different types of heavy chain

• > different effector functions
• > can interact with different types of receptor

Question 10

describe the general antibody structure

Answer 10

2 heavy and 2 light chains
covalently attached to one another via disulphide bonds

N termini of the chains contain antigen binding sites
= variable regions

hinge region
- flexible

Question 11

what are the heavy and light chains of an Ig made up of generally?

how long are these domains?

Answer 11

similar structural domains

100-110 amino acids

Question 12

describe an immunoglobulin fold

Answer 12

C-region is composed of 7 B strands
V-region has 9 strands

each form 2 beta sheets that fold over to form a sandwich, held together by hydrophobic interactions\

hyper variable regions are on the outside at 1 end of the molecule

Question 13

what are CDRs?

what is their role?

Answer 13

complimentary determining regions
= hypervariable regions

• make up the antigen binding site
• determine antigen binding specificity

Question 14

what are the framework regions?

Answer 14

the remainder of the VH and VL excluding CDR

Question 15

what are is an epitope?

what are the different types?

Answer 15

the part of an antigen which an antibody binds to

linear epitope
- linear sequence of amino acids unaffected by denaturation

discontinuous epitope

Question 16

define:
antigencity

immunogenicity

Answer 16

the ability to combine with antibodies

the ability to induce a humoral/cell mediated immune response

Question 17

factors that contribute to immunogenicity

Answer 17

foreignness

molecular size
- larger = more immunogenic

chemical composition + heterogeneity
- e.g. proteins are more immunogenic than a carbohydrate

Question 18

what are adjuvants?

Answer 18

substances used in combination with an antigen

that produce a more robust immune response than the antigen alone

Question 19

4 adjuvants

Answer 19

antigen persistance is prolonged

co-stimulatory signals are enhanced

local inflammation increased

non-specific proliferation of lymphocytes is increased

Question 20

what is the no. of different antibodies that can be produced?

what is most antibody diversity generated by?

Answer 20

virtually limitless

gene rearrangements

Question 21

what needs to happen for immunoglobulin genes to be expressed?

why is this?

Answer 21

individual gene segments need to be rearranged
-> to assemble a functional gene

Ig genes cannot be expressed in germline configuration

Question 22

how many light and heavy loci are there?

what are these divided up to?

Answer 22

2 light (lambda and kappa)
1 heavy 

gene segments
- named V, J and C (+ D in heavy)

Question 23

what rearrangement music occur for a light chain to give a functional gene?

what about for a functional heavy chain?

Answer 23

via recombination:

V segment randomly joins to a J segment

DJ need to join to V

Question 24

describe the VDJ recombination

Answer 24

germline DNA
-> somatic recombination

= DJ joined DNA

-> somatic recombination
= VDJ-joined rearranged DNA

Question 25

in which CDR is there most variation?

Answer 25

CDR3 (HV3) | formed by the junction of V and J in the light chains

Question 26

how are RSS's involved in these segments recombining?

Answer 26

RSS's (recombination signal sequences) that flank the 3' of V segment both sides of D and 5' of J segments recombination can only occur between RSS's of different types - ensures correct order of joining

Question 27

what are the 2 types of RSS?

Answer 27

Nonamer Spacer 12 Heptamer Nonamer Spacer 23 Heptamer

Question 28

which genes encode a protein complex involved in recombination in B and T cells? what else is involved?

Answer 28

RAG 1 and 2 = recombination activating gene enzymes e.g. VDJ recombinase for repairing ds breaks etc

Question 29

how is additional antibody diversity created?

Answer 29

P-nucleotides introduced by part of recombination reaction that generates short palindromic sequences at cut ends of DNA strands N-nucleotides added at random to cut 3' end by TdT (terminal deoxynucleotidyl transferase)

Question 30

describe the segment recombination process

Answer 30

RAG complex binds + cleaves RSSs -> hairpins form at ends of D + J segments hairpins are cleaved -> palindromic P-nucelotides TdT adds N-nucleotides randomly strands pair up unpaired nts removed by exonuclease -> gaps filled by DNA synthesis

Question 31

what is the consequence of random nucleotide insertion on protein?

Answer 31

if you don't have multiple of 3 -> frame shift -> no immunoglobulin fold = unproductive rearrangement could introduce a stop codon

Question 32

when a B cell undergoes its initial rearrangement, which transcripts are produced? how are antibody isotypes made?

Answer 32

only IgMew and IgDelta - via alternative splicing of primary transcript ``` via 'class switching' - occurs in an active immune response when B cells are proliferating ```

Question 33

what else does alternative splicing give rise to?

Answer 33

membrane-bound or secreted forms of immunoglobulin

Question 34

what do membrane-bound Igs complexed with other proteins form?

Answer 34

functional B cell receptors

Question 35

how do B-cells have single antigen specificity?

Answer 35

Ig gene rearrangement is tightly regulated -> only 1 H and 1 L chain are expressed (allelic exclusion) B cells that don't produce functional immunoglobulin are eliminated from the population

Question 36

how does binding specificity diversify after encountering an antigen? how does affinity maturation affect this?

Answer 36

somatic hypermutation in the V-regions of H and L chains = generates additional diversity only those cells expressing high affinity immunoglobulin survive - most mutations will be deleterious