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Trinity Term 1 > Immunology II > Flashcards

Immunology II Flashcards

1
Q

Describe some features of adaptive immune systems

A
  • immense Diversity
  • alterations in repertoire
  • memory
  • TCR and BCR (jawed vertebrates)
  • VLR (jawless fish)
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2
Q

Describe the immense diversity of adaptive immune systems

A

– alteration of genomic sequence
- “Anticipatory Repertoires”

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3
Q

Describe repertoire alterations in adaptive immunity

A

cell proliferation and clonal distribution of receptors according to circumstance

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4
Q

Describe adaptive immune receptors

A
  • antibodies
  • T cell receptors
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5
Q

Describe antibodies

A
  • duplicated heterodimer (heavy and light chains
  • two forms
  • secreted by B cells
  • membrane bound (B cell receptor)
  • recognise diverse products (e.g. protein or carbohydrate)
  • epitopes can be linear or conformational
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6
Q

Describe T cell receptors (TCR)

A
  • always membrane-bound heterodimer
  • TCRab and TCRgd
  • TCRab recognise linear peptide in context of a
    presentation complex called MHC
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7
Q

MHC

A

major histocompatibility complex

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8
Q

Adaptive immunity stimuli

A
  • antigen or immunogen
  • epitope
  • antigenic or immunogenic molecules
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9
Q

Describe antigens and immunogens

A

a molecule seen by the adaptive immune syste

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10
Q

Describe epitopes

A

the specific part of the antigen involved in recognition

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11
Q

Describe antigenic or immunogenic molecules

A

molecule capable of stimulating a specific adaptive response

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12
Q

Describe anticipatory repertoire generation

A
  • rearrangement with junctional modification
  • four chains, two heterodimeric pairs
  • TCRab and TCRgd
  • conserved organisation of TCR loci (multiple V regions, [D], J and C regions)
  • up to 10^15 different TCRVb rearrangements in humans
  • we only express ~108 different TCR at any time
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13
Q

Describe T cell receptor rearrangement

A
  • TCRalpha or TCRgamma with TCRbeta and TCRdelta D
    region inserts between the V-J junction
  • nucleotide modification
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14
Q

D region

A

Diversity region

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15
Q

CDR3 region

A

complementary determining region 3

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16
Q

The RAG complex

A
  • initiates rearrangement
  • Recombination Activation Gene
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17
Q

RSS=

A

Recombination signal sequence

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18
Q

Describe the action of the RAG Complex

A
  • RAG1/2 binds RSS
  • synapsis of RAG complices
  • cleavage of RSSs
  • Ku70:Ku80 binds 5’-phorphorylated DNA ends at signal and coding joints
  • DNA-PK:Artemis opens hairpin
  • TdT processes DNA ends and adds N-nucleotides
  • stands are paired
  • exonuclease removes unpaired nucleotides
  • gaps filled by DNA synthesis
  • DNA ligase IV:XRCC4 ligates DNA ends
  • forms coding joint
  • creates junctional diversity
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19
Q

TdT

A

terminal deoxynucleotidyl transferase

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20
Q

What is the importance of extreme diversity in the adaptive immune response?

A

avoidance of self-reactivity

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21
Q

Describe the avoidance of self-reactivity

A
  • clonal distribution of the receptor
  • selective removal of self-reactive cells
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22
Q

The rarity of successful cells means that success depends upon:

A

– self-renewal andrapid replication in the face of challenge
- evolution of the lymphocyte (T cell and B cell)
- specialised selective sites (e.g. Thymus for T cells)

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23
Q

Describe thymic T cell development

A
  • an ordered process
  • TCRbeta, gamma and delta at DN3 Allelic exclusion at DN4
  • RAG on in late DN2
  • RAG off in DN4
  • RAG on in early DP
  • RAG off in SP
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24
Q

DN

A

double negative

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25
Q

Describe memory in T cells

A
  • thymic selection
  • response
  • memory
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26
Q

Describe antibodies (imunoglobulins) as functional molecules

A

multiple antigen binding sites

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27
Q

Describe the Antibody Classes

A

have different numbers of units in the mature structure

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28
Q

List some antibodies

A
  • IgG/IgE
  • IgM
  • IgA
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29
Q

Describe soluble antibody morphology

A
  • two effective domains
  • antigen binding Fab fragment (two in each unit)
  • Fc region recruits other molecules (complement), or is bound by cells expressing the Fc-receptor
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30
Q

Describe the mechanisms of antibody activity

A
  • block function (bind to important molecules on the pathogen)
  • agglutinate (stick pathogens together)
  • activate Complement
  • opsonise (Fc recognised by receptors on cells)
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31
Q

Describe the main T cell types

A
  • TCRalphabeta and TCRgammadelta
  • TCRalphabeta divided into two subsets based upon co-receptor expression, type of MHC presenting the peptide and cytokine production
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32
Q

Describe CD4+ cells

A
  • restricted to MHC class II
  • TH1, TH2, TH3, TH17 and T-reg cells
33
Q

TH

A

T helper

34
Q

Describe CD8+ cells

A
  • restricted to MHC class I
  • TC1 and TC2 cells
35
Q

TC

A

T cytotoxic

36
Q

CD=

A
  • Cluster of Differentiation
  • A term for cell surface molecules
37
Q

Describe the relationship between TH and TC cells

A

distinct and overlapping functions

38
Q

Describe CD4 cells

A
  • help B cells make antibody (Th2 via IL4)
  • help macrophages become activated (Th1 via IFNg)
39
Q

What drives Th0 cell proliferation?

A
  • initial stimulus
  • IL-2 and IL4
40
Q

Describe TH1

A
  • active macrophage
  • IL-2 and IFNgamma
41
Q

Describe TH2

A
  • helper B cell
  • IL-4, Il-5, IL-6 and IL-10
42
Q

Describe TH3

A
  • helper B cell (IgA)
  • TGFbeta, IL-4, IL-10
43
Q

Describe TH17

A
  • neutrophil recruitment
  • IL17
44
Q

Describe T-regs

A
  • down-regulate T cell responses
  • IL-10
45
Q

Delineate the two antigen presentation pathways

A

MHC class I pathway
MHC class II pathway

46
Q

Describe the MHC class I pathway

A
  • samples the cytoplasm
  • endogenous
  • CD8+
47
Q

Describe the MHC class II pathway

A
  • samples the extracellular compartment
  • exogenous
  • CD4+
48
Q

Describe the mechanics of the MHC class I pathway

A
  • partly folded MHC class I alpha chains bind to calnexin until Beta2-microglobulin binds
  • MHC class I a:beta2m complex is released from calnexin, binds to a complex of chaperone proteins and binds to TAP
  • cytosolic proteins and DRiPs are degraded to peptide fragments by the proteasome
  • TAP delivers peptides to the ER
  • peptide binds the MHC class I molecule and completes its folding
  • MHC class I molecule is released from the TAP complex and exported to the cell membrane
49
Q

What are the chaperone proteins involved in MHC class I antigen presentation

A

calreticulin, Erp57

50
Q

How is TAP bound in the MHC class I antigen presentation pathway

A

tapesin

51
Q

DRiPs

A

defective ribosomal products

52
Q

Describe the mechanics of the MHC class II antigen presentation pathway

A
  • Ii forms a complex with MHC class II molecule, blocking the binding of peptides and misfolded proteins
  • Ii is cleaved in an acidified endosome, leaving a short peptide fragment, CLIP, still bound to the MHC class II molecule
  • endocytosed antigens are degraded to peptides in endoscopes, but the CLIP peptide blocks the binding of peptides to MHC class II molecules
  • HLA-DM binds to the MHC class II molecule, releasing CLIP and allowing other peptides to bind
  • the MHC class II molecule then travels to the cell surface
53
Q

Ii

A

invariant chain

54
Q

CD4+ T cells

A
  • restricted to peptides in MHC class II
  • only respond to some cell types and use soluble mediators to affect the local area
55
Q

CD8+ T cells

A
  • restricted to peptides in MHC class I
  • “recognise” any cytoplasmically infected cell
  • major cytotoxic function
56
Q

MHC class I is

A

constitutively expressed by most cells in the body

57
Q

MHC class II is

A

constitutively expressed on restricted set of cells (professional APCs)

58
Q

pAPCs

A

professional antigen presenting cells

59
Q

Describe pAPCs

A
  • constitutively express MHC class I and MHC class II
  • dendritic cells
  • macrophages
  • B cells
60
Q

Describe dendritic cells

A
  • the innate cell that drives the adaptive immune response
  • the only cell to stimulate naïve T cells
  • after presentation and activation of lymphocytes, they undergo apoptosis
61
Q

Describe macrophages

A

active scavengers, activity increased by interaction with CD4+ T cells

62
Q

Describe B cells

A

Interactions with CD4+ T cells needed for efficient maturation and antibody production

63
Q

Describe the immature dendritic cell

A
  • in most tissues
  • take up and processes antigens
64
Q

Describe the mature dendritic cells

A
  • do not take up microbes
  • migrate to the lymphoid organs
  • present antigens to naive T cells
65
Q

Describe dendritic cell maturation

A
  • pathogen uptake
  • PRR activation
  • MHC I + II high
  • TCR:MHC (signal 1)
  • costimulatory molecules such as CD80/86 (signal 2)
  • cytokine production (signal 3) to drive TH0 cell differentiation
66
Q

NK helps to create

A

active macrophage on exposure of TH1 to IFNgamma

67
Q

PMN mast cell helps to create

A

helper B cell on exposure to IL4 of TH2

68
Q

Describe immunology memory

A
  • population of specific cells is larger
  • easier to activate
  • migration patterns differ
69
Q

Why are memory cells easier to activate?

A
  • transcriptional profile
  • signalling status
  • surface molecules
  • earlier commitment to effector status
70
Q

Why do memory cell migration patterns differ?

A
  • less focussed on lymph nodes
  • migration through tissues
  • chemokine receptors
  • adhesion molecules
71
Q

How does a vaccine work?

A
  • antigens from the pathogen stimulate T and B cells and induce memory
72
Q

Describe the role of the adjuvant in vaccines

A
  • carrier
  • immunostimulatory components
  • stimulate PRRs
73
Q

Describe the types of vaccine

A
  • live vaccines
  • dead vaccines
  • vectored vaccines
74
Q

Describe live vaccines

A
  • attenuated pathogen
  • related pathogen
75
Q

Give examples of live vaccines

A
  • Sabin polio
  • Bacillus Calmette-Guerin vaccine - attenuated form of Mycobacterium bovis, to protect against M. bovis and M. tuberculosis
76
Q

Describe dead vaccines

A
  • need adjuvant
  • whole killed pathogen
  • sub-unit
77
Q

Describe vectored vaccines

A

Sub-unit delivery using a live carrier or DNA

78
Q

Give examples of dead vaccines

A
  • Salk polio
  • Influenza
  • tetanus toxoid

Trinity Term 1 (38 decks)

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