1
Q
What is the key cell that bridges the innate and adaptive immune responses?
A
- Dendritic Cell
2
Q
What do APCs stand for?
A
- (Professional) Antigen Presenting cells (Dendritic cell most important)
3
Q
What are dendritic cells found in the epidermis called? -
A
- Langerhans cells
4
Q
After antigen capture, where does the dendritic cell go?
A
- To draining lymph node where it processes and presents antigen
5
Q
Which chemokine receptor to dendritic cells express once they are activated?
A
- CCR7 chemokine receptor
6
Q
Which two chemokine ligands does CCR7 on dendritic cells bind to?
A
- CCL19 and CCL20
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
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
9
Q
Do T cells need 2 signals to activate?
A
YES
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)
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
12
Q
What does the second costimulation signal prevent?
A
- Co-stimulation prevents overactivation of T cells
13
Q
What is the key cell that bridges the innate and adaptive immune response?
A
- D.C
14
Q
Does a virally infected cell have MHC-I expressed?
A
- It still has SOME but MHC expression is down regulated (by pathogens)
15
Q
How do B cells recognise antigens?
A
- Through a BCR(can recognise the whole antigen and phagocytose)
16
Q
How do T cells recognise antigens?
A
- Presentation by MHC complex molecules
17
Q
How many signals do T cells need to be activated? -
A
2 signals
18
Q
Is the TCR membrane bound?
A
- YES!
- Formation occurs in thymus
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
20
Q
What is a good TCR?
A
- One that can recognise our own molecules
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
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)
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
24
Q
What forms the peptide binding cleft (groove) of MHC class I ?
A
- Alhpa 1 domain
- Alpha 2 domain
25
What is the general binding arrangement of the peptide binding in MHC?
- floor of cleft binds peptides and walls make contact with TCR
26
What does the alpha 3 domain do on MHC class I?
- Binds CD8 T cell coreceptor
27
How many transmembrane chains does MHC class I have?
-1 transmembrane chain
28
How many chains does MHC class II have?-
- Polymorphic alpha chain
| - Polymorphic Beta chain
29
What forms the binding cleft for MHC class II?
- Alpha 1 and Beta 1 domains
30
Which domain of MHC class II binds the CD4 T cell coreceptor?
- The non polymorphic Beta 2 domain
31
Can each molecule of MHC bind different peptides?
- YES!
| - But only one peptide can bind at a time
32
When are MHC molecules stable?
-Only when peptides are bound (also need stability because T cells need time to interact with peptide)
33
Why must cells present MHC class I on the surface as a self peptide if not infected?
- Otherwise MHC not stable or NK cell will come and kill it
34
What type of T cells is the MHC class I pathway for?
- For antigens tin cytosol e.g viruses
| - When IFN-gamma (pro-inflammation) present
35
Which cell does MHC class I act on and what is the length of peptide binding?
- Acts on CD8 T cells
| - Length of peptide binding is short (8-11aa) - more closed in cleft
36
Which cell odes MHC class II act on and what is the length of peptide binding?
- Acts on CD4 Helper T cells
| - Length of peptide binding is long (large) -10-30 aa in length (more open binding cleft)
37
What is the site of peptide binding in class I MHC?
- ER
38
What is the site of binding of peptide in class II MHC?
- Late endosome/lysosomes
39
Which cells are MHC class I found on?
- ALL nucleated cells
40
Which cells are MHC class II found on ?
- Professional antigen presenting cells (APCs) like DCs Macrophages and B cells
41
What is the purpose of cross presentation?
- To activate naive T cells so it can perform effector functions
42
What is the process of cross presentation?
- 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
Can only DCs provide this signal 2?
- YES!
44
What is Wherer are peptides found for the mHC clas I I processing pathway?
- OUTSIDE of cell
45
What is the function of Ii in MHC class II processing pathway ?
Invariant chain that binds in MHC II peptide groove (chain and CLIP)
46
What is the function of HLADM in the MHC processing pathway?
- Removes CLIP and allows other peptides to bind
47
What are the steps in DC capture (cross presentation process)?
- 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
Why does cross presentation happen?
- Because naive T cells must have 2 SIGNALS to be activated and only certain DCs can provide the 2 signals
49
Is the MHC I binding cleft more closed or open than the mHC class II binding cleft?
- More closed--> shorter peptides
50
Is the MHC class II binding cleft more or less open than MHC class I?
- More open than MHC class I--> longer peptides
51
How many anchor points may there be in a binding groove that can bind the peptide?
- 1 or 2
52
What is meant by MHC is polymorphic?
- FOr each gene, there are MANY different alleles
53
What is meant by MHC being polygenic?
- Presence of several different related genes with similar functions
54
What is meant when MHC is co dominantly expressed?
- Every MHC gene that you have IS EXPRESSED
55
Which chains does the MHC class I gene contain?
- alpha chain (1 mhc gene)
| - invariant beta microglobulin chain (non MHC gene)
56
How many MHC class I genes does our genome have?
- 6 (3 from father, 3 from mother)
57
How many genes is MHC class II encoded by?
- TWO MHC genes
1. Alpha chain
2. Beta chain
58
How many genes does our genome have?
- 6 or more genes
59
What is a haplotype?
- Group of alleles on one chromosome
60
What is Mhc known as in humans?
- HLA (Human Leukocyte Antigen)
61
What is MHC known as in mice?
- H-2
62
In humans, what are the MHC I genes known as?
- HLAA, HLAB HLAC
| - 3 different MHC class I alpha genes
63
What do the 3 different MHC class I alpha genes encode for?
- Three different MHC class I alpha chains
64
In humans, what are MHC II genes known as?
-HLA-DR
-HLA-DP
HLA-DQ
-3 different MHC II genes for alphachain
- 3 different MHC II genes for Beta chain
65
Where is the variation in the MHC gene?
- Peptide binding cleft (lots of variation)
66
How did multiple MHC genes arise?
Thought to be duplication
67
Are MHC polymorphisms ACTIVELY selected for (if so, what via)?
- YES!
- Via replacement--> point mutations (substitutions)
- Change in coding sequence
- These mutations will lead to MHC alleles
68
What are the two ways new alleles can occur?
- Point mutations
| - Gene conversion
69
What is MHC restriction?
- T cell must recognise SELF MHC molecule (AND PEPTIDE) to be able to recognise and respond to peptide
70
T cells that recognise self receive...
SURVIVAL SIGNAL
71
When does MHC restriction occur?
- When T cells are being formed in thymus (tested)
72
What are subunit vaccines?
- 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
What is the benefit and disadvantage of subunit vaccines?
- benefit: Safe for young, pregnant, elderly
| - disadvantage: not strong response so must get booster shots.
74
How are the subunit vaccines made?
- 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
What is an example of a subunit vaccine for disease?
- Acellular pertusis (whooping cough)
- but need repeated immunisations
- Hep B
76
Can MHC haplotypes influence sucdeptibility to certain disease?
- 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
In transplantation, what does the T cell see if rejection occurs?-
- It sees donor MHC: Peptide as self
| - And sees self MHC: Peptide as FOREIGN
78
Which proinflammatory cytokines are release upon DC interaction with microbe?
- Cytokines - TNF-alpha
| - IL-1
79
What are 3 functions of T cells?
1. Activation of phagocytes
2. Killing of infected cells
3. Help for B cells
80
Do naive T cells have effector functions?
- NO
81
Once a naive T cell recognises antigen in peripheri what happens to it?
- It proliferates and differentiates into effector T cells and memory cells
82
What are the steps for T cell activation in naive T cells?
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
Do all activated T cells go to effector organs/tissues?
- NO! Some effector T cells stay in the lymph nodes--> eradicate infected cells OR give signals to B cells (antibody production)
84
What do naive T cells do?
- Circulate through peripheral lymphoid organs to FIND ANTIGENS matching their receptor
85
Which receptors/coreceptors are required on T cells that recognise ligands on APCs to allow for T cell activation of responses?
- 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
What is the recognition of MHC-associated peptides by?
- TCR + CD4/Cd8 coreceptor
| - Both recognise complexes of peptide antigen and MHC molecules on APCs
87
Do the TCR alpha and beta chain BOTH take part in antigen recognition?
- YES!
88
What does the TCR recognise specifically?
- Displayed peptide and residues of MHC around peptide binding cleft `
89
Do the CD4/CD8 coreceptor recognise MHC at the same site to the peptide binding cleft?
- NO they recognise it at a site different to the peptide biding cleft
90
Which surface molecule does signal transduction by the TCR complex?
- CD3 (x3) + zeta chain
| - TCR alpha and beta chain can recognise antigens but NOT TRANSDUCE BIOCHEMICAL SIGNALS
91
Can TCR alhpa and beta chain transmit biochem signals?
- NO! Only CD3 + zeta chain can do that
