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IMM2011 > ADAPTIVE IMMUNITY > Flashcards

ADAPTIVE IMMUNITY Flashcards

1
Q

What is the key cell that bridges the innate and adaptive immune responses?

A
  • Dendritic Cell
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2
Q

What do APCs stand for?

A
  • (Professional) Antigen Presenting cells (Dendritic cell most important)
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3
Q

What are dendritic cells found in the epidermis called? -

A
  • Langerhans cells
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4
Q

After antigen capture, where does the dendritic cell go?

A
  • To draining lymph node where it processes and presents antigen
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5
Q

Which chemokine receptor to dendritic cells express once they are activated?

A
  • CCR7 chemokine receptor
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6
Q

Which two chemokine ligands does CCR7 on dendritic cells bind to?

A
  • CCL19 and CCL20
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7
Q

What are CL19 and CCL20 expressed by and which region of the lymph node?

A
  • Expressed by lymphatic vessels in T cell region
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8
Q

Are naive T cells in blood also attracted to same region in lymph node?

A
  • YES!

- Because T cells in blood also express CCR7

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9
Q

Do T cells need 2 signals to activate?

A

YES

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10
Q

What is the first signal that happens with the dendritic cell and TCR to partially activate it?

A
  • TCR binding to MHC + Peptide ()processed antigen)
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11
Q

What is the second signal needed to activate T cells?

A
  • Costimulation
  • Receptor-ligand binding
  • Capture and processing of antigen drives the second signal
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12
Q

What does the second costimulation signal prevent?

A
  • Co-stimulation prevents overactivation of T cells
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13
Q

What is the key cell that bridges the innate and adaptive immune response?

A
  • D.C
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14
Q

Does a virally infected cell have MHC-I expressed?

A
  • It still has SOME but MHC expression is down regulated (by pathogens)
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15
Q

How do B cells recognise antigens?

A
  • Through a BCR(can recognise the whole antigen and phagocytose)
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16
Q

How do T cells recognise antigens?

A
  • Presentation by MHC complex molecules
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17
Q

How many signals do T cells need to be activated? -

A

2 signals

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18
Q

Is the TCR membrane bound?

A
  • YES!

- Formation occurs in thymus

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19
Q

Are T cells tested when made?

A
  • YES!
  • To make sure they are functional (to pass positive selection)
  • Negative selection- T cell actively killed
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20
Q

What is a good TCR?

A
  • One that can recognise our own molecules
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21
Q

What are MHC molecules?

A
  • Membrane bound proteins that display peptide antigens to T cells so that T cell can recognise and repsond to that antigen
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22
Q

How do class I and II MHC molecules differ?

A
  • In the type of cells they INTERACT WITH
  • The types of cells they’re FOUND ON
  • Method that the peptide is loaded into peptide binding cleft (MHC processing pathway)
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23
Q

What are the two types of chains that MHC class I has?

A
  • alpha chain (3)

- Non-MHC Beta-2 microglobulin (beta M) chain

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24
Q

What forms the peptide binding cleft (groove) of MHC class I ?

A
  • Alhpa 1 domain

- Alpha 2 domain

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25
Q

What is the general binding arrangement of the peptide binding in MHC?

A
  • floor of cleft binds peptides and walls make contact with TCR
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26
Q

What does the alpha 3 domain do on MHC class I?

A
  • Binds CD8 T cell coreceptor
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27
Q

How many transmembrane chains does MHC class I have?

A

-1 transmembrane chain

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28
Q

How many chains does MHC class II have?-

A
  • Polymorphic alpha chain

- Polymorphic Beta chain

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29
Q

What forms the binding cleft for MHC class II?

A
  • Alpha 1 and Beta 1 domains
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30
Q

Which domain of MHC class II binds the CD4 T cell coreceptor?

A
  • The non polymorphic Beta 2 domain
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31
Q

Can each molecule of MHC bind different peptides?

A
  • YES!

- But only one peptide can bind at a time

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32
Q

When are MHC molecules stable?

A

-Only when peptides are bound (also need stability because T cells need time to interact with peptide)

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33
Q

Why must cells present MHC class I on the surface as a self peptide if not infected?

A
  • Otherwise MHC not stable or NK cell will come and kill it
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34
Q

What type of T cells is the MHC class I pathway for?

A
  • For antigens tin cytosol e.g viruses

- When IFN-gamma (pro-inflammation) present

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35
Q

Which cell does MHC class I act on and what is the length of peptide binding?

A
  • Acts on CD8 T cells

- Length of peptide binding is short (8-11aa) - more closed in cleft

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36
Q

Which cell odes MHC class II act on and what is the length of peptide binding?

A
  • Acts on CD4 Helper T cells

- Length of peptide binding is long (large) -10-30 aa in length (more open binding cleft)

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37
Q

What is the site of peptide binding in class I MHC?

A
  • ER
38
Q

What is the site of binding of peptide in class II MHC?

A
  • Late endosome/lysosomes
39
Q

Which cells are MHC class I found on?

A
  • ALL nucleated cells
40
Q

Which cells are MHC class II found on ?

A
  • Professional antigen presenting cells (APCs) like DCs Macrophages and B cells
41
Q

What is the purpose of cross presentation?

A
  • To activate naive T cells so it can perform effector functions
42
Q

What is the process of cross presentation?

A
  • Cell is infected, DC phagocytoses it, antigens mpve from phagolysosome–> cytosol–> go through same MHC class I process
  • CD8 T cell is ‘seeing’ the antigen to be activated and gets signal 2 (costimulator)
  • CD8 T cells can then kill infected cells WITHOUT signal 2 from DCs
43
Q

Can only DCs provide this signal 2?

A
  • YES!
44
Q

What is Wherer are peptides found for the mHC clas I I processing pathway?

A
  • OUTSIDE of cell
45
Q

What is the function of Ii in MHC class II processing pathway ?

A

Invariant chain that binds in MHC II peptide groove (chain and CLIP)

46
Q

What is the function of HLADM in the MHC processing pathway?

A
  • Removes CLIP and allows other peptides to bind
47
Q

What are the steps in DC capture (cross presentation process)?

A
  • Whole virally infected cell or phagocytosed parts of virus present in body–> phagocytosed pathogen–> moves antigens into cytosol–> goes through MHC class I presenting process–> Presents MHC I + viral antigen on surface + COSTIMULATORY MOLECULE
  • NAIVE T CELL (CD8) ACTIVATED
  • Casn go and kill any cell expressing same MHC peptide complex–> can then kill ANY abnormal body cell infected with virus
48
Q

Why does cross presentation happen?

A
  • Because naive T cells must have 2 SIGNALS to be activated and only certain DCs can provide the 2 signals
49
Q

Is the MHC I binding cleft more closed or open than the mHC class II binding cleft?

A
  • More closed–> shorter peptides
50
Q

Is the MHC class II binding cleft more or less open than MHC class I?

A
  • More open than MHC class I–> longer peptides
51
Q

How many anchor points may there be in a binding groove that can bind the peptide?

A
  • 1 or 2
52
Q

What is meant by MHC is polymorphic?

A
  • FOr each gene, there are MANY different alleles
53
Q

What is meant by MHC being polygenic?

A
  • Presence of several different related genes with similar functions
54
Q

What is meant when MHC is co dominantly expressed?

A
  • Every MHC gene that you have IS EXPRESSED
55
Q

Which chains does the MHC class I gene contain?

A
  • alpha chain (1 mhc gene)

- invariant beta microglobulin chain (non MHC gene)

56
Q

How many MHC class I genes does our genome have?

A
  • 6 (3 from father, 3 from mother)
57
Q

How many genes is MHC class II encoded by?

A
  • TWO MHC genes
    1. Alpha chain
    2. Beta chain
58
Q

How many genes does our genome have?

A
  • 6 or more genes
59
Q

What is a haplotype?

A
  • Group of alleles on one chromosome
60
Q

What is Mhc known as in humans?

A
  • HLA (Human Leukocyte Antigen)
61
Q

What is MHC known as in mice?

A
  • H-2
62
Q

In humans, what are the MHC I genes known as?

A
  • HLAA, HLAB HLAC

- 3 different MHC class I alpha genes

63
Q

What do the 3 different MHC class I alpha genes encode for?

A
  • Three different MHC class I alpha chains
64
Q

In humans, what are MHC II genes known as?

A

-HLA-DR
-HLA-DP
HLA-DQ
-3 different MHC II genes for alphachain
- 3 different MHC II genes for Beta chain

65
Q

Where is the variation in the MHC gene?

A
  • Peptide binding cleft (lots of variation)
66
Q

How did multiple MHC genes arise?

A

Thought to be duplication

67
Q

Are MHC polymorphisms ACTIVELY selected for (if so, what via)?

A
  • YES!
  • Via replacement–> point mutations (substitutions)
  • Change in coding sequence
  • These mutations will lead to MHC alleles
68
Q

What are the two ways new alleles can occur?

A
  • Point mutations

- Gene conversion

69
Q

What is MHC restriction?

A
  • T cell must recognise SELF MHC molecule (AND PEPTIDE) to be able to recognise and respond to peptide
70
Q

T cells that recognise self receive…

A

SURVIVAL SIGNAL

71
Q

When does MHC restriction occur?

A
  • When T cells are being formed in thymus (tested)
72
Q

What are subunit vaccines?

A
  • Only use specific peptides from virus

- Can take parts of virus and make into vaccine–> so you have protection from those parts and virus

73
Q

What is the benefit and disadvantage of subunit vaccines?

A
  • benefit: Safe for young, pregnant, elderly

- disadvantage: not strong response so must get booster shots.

74
Q

How are the subunit vaccines made?

A
  • Find the peptides that will fit into MOST people in the population’s MHC molecules
  • ‘Immunodominant peptide’ - the one that most people mount an immune response against
75
Q

What is an example of a subunit vaccine for disease?

A
  • Acellular pertusis (whooping cough)
  • but need repeated immunisations
  • Hep B
76
Q

Can MHC haplotypes influence sucdeptibility to certain disease?

A
  • YES!
  • can be a protective or a risk factor
  • protective risk factor–> can prevent some antigens from binding
  • Risk factor–> May display certain haplotypes better
77
Q

In transplantation, what does the T cell see if rejection occurs?-

A
  • It sees donor MHC: Peptide as self

- And sees self MHC: Peptide as FOREIGN

78
Q

Which proinflammatory cytokines are release upon DC interaction with microbe?

A
  • Cytokines - TNF-alpha

- IL-1

79
Q

What are 3 functions of T cells?

A
  1. Activation of phagocytes
  2. Killing of infected cells
  3. Help for B cells
80
Q

Do naive T cells have effector functions?

A
  • NO
81
Q

Once a naive T cell recognises antigen in peripheri what happens to it?

A
  • It proliferates and differentiates into effector T cells and memory cells
82
Q

What are the steps for T cell activation in naive T cells?

A

IN LYMPHOID TISSUE:
T cells produce cytokines (IL-2) AND express the IL-2 receptor (autocrine signalling)
- IL-2 binding causes T cell proliferation
IN PERIPHERAL TISSUES:
- Differentiation into effector T cells (CD4–> activates macrophages and CD8 –> kills infected target cells)

83
Q

Do all activated T cells go to effector organs/tissues?

A
  • NO! Some effector T cells stay in the lymph nodes–> eradicate infected cells OR give signals to B cells (antibody production)
84
Q

What do naive T cells do?

A
  • Circulate through peripheral lymphoid organs to FIND ANTIGENS matching their receptor
85
Q

Which receptors/coreceptors are required on T cells that recognise ligands on APCs to allow for T cell activation of responses?

A
  • TCR (recognise MHC on peptide antigens)
  • CD4/CD8 coreceptors on T cell (recognise MHC to allow TCR complex to deliver activating signals
  • Adhesion molecules –> strengthens binding of T cell-Antigen Presenting Cell
  • Costimulator molecule–> binding to costimulatory receptor on naive T cell
  • Cytokines
86
Q

What is the recognition of MHC-associated peptides by?

A
  • TCR + CD4/Cd8 coreceptor

- Both recognise complexes of peptide antigen and MHC molecules on APCs

87
Q

Do the TCR alpha and beta chain BOTH take part in antigen recognition?

A
  • YES!
88
Q

What does the TCR recognise specifically?

A
  • Displayed peptide and residues of MHC around peptide binding cleft `
89
Q

Do the CD4/CD8 coreceptor recognise MHC at the same site to the peptide binding cleft?

A
  • NO they recognise it at a site different to the peptide biding cleft
90
Q

Which surface molecule does signal transduction by the TCR complex?

A
  • CD3 (x3) + zeta chain

- TCR alpha and beta chain can recognise antigens but NOT TRANSDUCE BIOCHEMICAL SIGNALS

91
Q

Can TCR alhpa and beta chain transmit biochem signals?

A
  • NO! Only CD3 + zeta chain can do that

IMM2011 (7 decks)

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