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Infection and immunity 2 > Adaptive immunity 1 > Flashcards

Adaptive immunity 1 Flashcards

1
Q

2 components of the adaptive immune system

A

humoral immunity
= B-cell mediated immunity + antibodies

cell mediated immunity
= T-cells and TCRs

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2
Q

what are the features of adaptive immunity?

A

not activated until there’s an antigenic challenge

high specificity
- selected immune cells proliferate

memory cells

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3
Q

basic life of a B cell

A

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

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4
Q

where are B cells produced?

each B cell expresses a different..?

A

bone marrow

antibody on their surface

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5
Q

antibody effector functions

A

neutralisation

mark for phagocytosis

activates complement system

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6
Q

what do antibody’s neutralise?

how?

A

antigens
toxins

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

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7
Q

5 classes of antibody

why is the most common in blood + lymph?

A 
IgA
IgD
IgE
IgG
IgM

IgG

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8
Q

what is the difference between the 5 classes of antibody?

A

differ in their constant regions

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

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9
Q

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

A

different isotopes have different types of heavy chain

  • > different effector functions
  • > can interact with different types of receptor
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10
Q

describe the general antibody structure

A

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

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11
Q

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

how long are these domains?

A

similar structural domains

100-110 amino acids

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12
Q

describe an immunoglobulin fold

A

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

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13
Q

what are CDRs?

what is their role?

A

complimentary determining regions
= hypervariable regions

  • make up the antigen binding site
  • determine antigen binding specificity
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14
Q

what are the framework regions?

A

the remainder of the VH and VL excluding CDR

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15
Q

what are is an epitope?

what are the different types?

A

the part of an antigen which an antibody binds to

linear epitope
- linear sequence of amino acids unaffected by denaturation

discontinuous epitope

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16
Q

define:
antigencity

immunogenicity

A

the ability to combine with antibodies

the ability to induce a humoral/cell mediated immune response

17
Q

factors that contribute to immunogenicity

A

foreignness

molecular size
- larger = more immunogenic

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

18
Q

what are adjuvants?

A

substances used in combination with an antigen

that produce a more robust immune response than the antigen alone

19
Q

4 adjuvants

A

antigen persistance is prolonged

co-stimulatory signals are enhanced

local inflammation increased

non-specific proliferation of lymphocytes is increased

20
Q

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

what is most antibody diversity generated by?

A

virtually limitless

gene rearrangements

21
Q

what needs to happen for immunoglobulin genes to be expressed?

why is this?

A

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

Ig genes cannot be expressed in germline configuration

22
Q

how many light and heavy loci are there?

what are these divided up to?

A 
2 light (lambda and kappa)
1 heavy

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

23
Q

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

what about for a functional heavy chain?

A

via recombination:

V segment randomly joins to a J segment

DJ need to join to V

24
Q

describe the VDJ recombination

A

germline DNA
-> somatic recombination

= DJ joined DNA

-> somatic recombination
= VDJ-joined rearranged DNA

25
Q

in which CDR is there most variation?

A

CDR3 (HV3)

formed by the junction of V and J in the light chains

26
Q

how are RSS’s involved in these segments recombining?

A

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

27
Q

what are the 2 types of RSS?

A

Nonamer
Spacer 12
Heptamer

Nonamer
Spacer 23
Heptamer

28
Q

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

what else is involved?

A

RAG 1 and 2
= recombination activating gene

enzymes e.g. VDJ recombinase
for repairing ds breaks etc

29
Q

how is additional antibody diversity created?

A

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)

30
Q

describe the segment recombination process

A

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

31
Q

what is the consequence of random nucleotide insertion on protein?

A

if you don’t have multiple of 3
-> frame shift

-> no immunoglobulin fold

= unproductive rearrangement

could introduce a stop codon

32
Q

when a B cell undergoes its initial rearrangement, which transcripts are produced?

how are antibody isotypes made?

A

only IgMew and IgDelta
- via alternative splicing of primary transcript

via 'class switching' 
- occurs in an active immune response when B cells are proliferating
33
Q

what else does alternative splicing give rise to?

A

membrane-bound or secreted forms of immunoglobulin

34
Q

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

A

functional B cell receptors

35
Q

how do B-cells have single antigen specificity?

A

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

36
Q

how does binding specificity diversify after encountering an antigen?

how does affinity maturation affect this?

A

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

Infection and immunity 2 (13 decks)

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