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Immunology 7070 > Lecture 4 > Flashcards

Lecture 4 Flashcards

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1
Q

What is cell mediated immunity and why do we need it?

A

System of recognition of cell-surface antigen is needed to deal with intracellular microbes = t cells for adaptive immunity.

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2
Q

Which cell type causes more collateral damage in the adaptive immune system?

A

T cells

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3
Q

How quickly can T cells kill?

A

One CD8+ T cell can kill 1 infected cell per hour

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4
Q

Why is B cell immunity better than T cell immunity?

A

One cell can produce 1000s of Abs per second, can hypermutate to mutating pathogen, causes less collatoral damage.

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5
Q

Why is T cell immunity less optimal than B cell immunity?

A

They cannot replicate in their entirety as quickly as B cells can produce Abs, they need massive clonal expansion which takes time, each clone is fixed and cannot mutate as the pathogen does, and can cause inflammatory diseases and collateral damage.

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6
Q

What is T cell memory?

A

Having more quantity of Ag specific cells circulating which can respond to the pathogen again if recognized another time.

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7
Q

What are the 5 steps of T cell immunity?

A 
Antigen recognition
Activation
Clonal expansion
Differentiation
Effector functions
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8
Q

Briefly describe the peptides recognized by T cells.

A

They are 7-9 amino acids long
Linear peptide portion
MHC displayed in the pocket of MHC molecule

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9
Q

What regions of the MHC complex do T cells interact with?

A

They all bind to non-polymorphic regions of the MHC complex
CD4+ T cells interact with MHC II
CD8+ T cells interact with MHC I

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10
Q

Where does MHC II get its peptides?

A

From endocytic pathways, i.e. the phagocytosis of microbes

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11
Q

Where does MHC I get its peptides?

A

From the cytosol of the host’s own cell, the reason it can detect and eliminate viruses - cytotoxic.

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12
Q

How does the TcR signal to the T cell?

A

Technically, the cytoplamic tail of the TcR can’t!

The CD4/CD3 complex does the signalling (in CD4+)

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13
Q

What signals are used for Signal transductions in T cells?

A

CD4, CD3, and CD28

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14
Q

What does CD28 bind?

A

B7-1/B7-2

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15
Q

What does CTLA-4 interact with? Why?

A

B7-1/B7-2 on APCs

Negative regulation of signal transduction.

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16
Q

What molecules on a T cell are for adhesion?

To what do they bind?

A

LFA-1 and VLA-4

ICAM-1 and VCAM-1

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17
Q

What are the major types of APCs?

A

Macrophages, Dendritic cells, and B cells

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18
Q

What do APCs influence during T cell activation?

A

Quantity and quality

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19
Q

Where are T cells activated and how?

A

T cells scan APCs (several per minute) in the lymph node

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20
Q

What is the function of the chemokines produced by activated PACs?

A

They promote T cell migration and adhesion to increase scanning of their cell surface.

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21
Q

What is the purpose of integrins?

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A

They cause the T cell to adhere to molecules and get a firm grip on the signaling cell/APC

22
Q

What happens when integrins are activated?

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A

Integrins flip up to cluster near the TcR/MHC and increase hold of APC.

23
Q

What is the outcome of a T cell recognition of an APC?

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A

An immune synapse structure.

24
Q

What is an immune synapse also known as?

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A

Super molecular activation comples - SMAC

25
What are the parts of the SMAC?
Central and peripheral (c and p) SMACs.
26
What is co-stimulation of the T cell?
A necessary second signal that is required for the T cell activation that is delivered by the APC to the T cell
27
What is the B7 family?
A major co-stimulatory family of receptors
28
Briefly describe B7-1 and B7-2 and their function.
Formerly known as CD80 and CD86 Expressed limited to activated immune cels Binds CD28 on T cells required for "go" signal Also inhibits CTLA-4
29
Why would a medication want to block CTLA-4 binding?
By blocking CTLA-4 the T cells are not able to be shut off and this increases T cell activation to act upon tumours.
30
What happens when Ag recognition happens without co-stimulation?
T cells will not respond and will become anergic and be deleted via apoptosis.
31
When do APCs express the costimulatory molecules?
If they have been activated by TLRs, NLRs, RLRs, etc. previously.
32
How does an APC know whether is has encountered an Ag activated T cell?
T cells activate APC site via CD40L (CD154) CD40L (CD154) is rapidly and transiently expressed fter T cell activation by Ag CD40L interacts with CD40 constitutively expressed on APCs Interaction provides further cell contact dependant signal that sustains/amplifies both APC and T cell activation. CD40L expression is highly controlled and expressed only on activated T cell
33
Give a brief summary of CD40:CD40L interactions.
Sends activating signals to APC from activated T cell. | Tells APC to express more CD80/CD86 (B7-1/B7-2) thereby increasing the potential to activate more T cells.
34
What does T cell activation by Ag induce?
A new gene transcriptional program.
35
What does ITAM stand for?
immunoreceptor tyrosine-based activation motif
36
What transcription factors does ZAP-70 activation eventually turn on?
NFAT, FNkB, and AP-1
37
What does the activation of ZAP-70 lead to?
The phosphorylation of scaffold proteins (LAT and SLP76) which leads to the activation of PLCgamma.
38
What is the function of PLCgamma?
Activates calcium responses.
39
What does NFAT stand for?
Nuclear factor of activated T cells
40
What activates the transcription factor NF-AT?
Elevated intracellular calcium.
41
Which IL plays a critical role in T cell clonal expansion?
IL-2
42
What is the receptor for IL-2?
IL-2R alpha | aka CD25 - marker for regulatory T cells
43
How do the co-stimulatory receptors enhance activation of some signaling pathways?
B7.1 and B7.2 can engage a number of different things in activated T cells. Engagement of CD28 induces PI3K Phosphorylated CD28 activates Grb2 recruitment Proline residues in CD28 bind and activate Lck or Itk
44
How do the co-stimulatory receptors enhance activation of some signaling pathways?
B7.1 and B7.2 can engage a number of different things in activated T cells. Engagement of CD28 induces PI3K Phosphorylated CD28 activates Grb2 recruitment Proline residues in CD28 bind and activate Lck or Itk
45
What does IL-4 do to B cells?
It is a potent activating factor which causes B cells to produce IgE for mast cell degranulation (which releases histamines) and neutralizing IgG antibodies (IgG4 in humans).
46
What is the major importance of CD40L and cytokines in tandem? In T cells? In B cells?
In T cells they are able to activate the macrophage and allow the killing of phagocytosed microbes. In B cells they are able to activate Ag specific B cells which allow them to secrete antibodies and neutralize/eliminate the antigen
47
What are some of the available factors that influence T cell functional specialization?
``` Tissue environment Which tissue Which APC type Inflammatory milieu Cytokines Cell:cell interactions ```
48
What is the distinct function of Th1 cells?
IFNgamma sectetion Host defense against intracellular microbes Inflammation
49
What is the distinct function of Th2 cells?
Secretion of IL-4, 5, and 13 Host defense against helminths Allergic reactions
50
What is the distinct function of Th17 cells?
IL-17 secretion Host defense against some bacteria Inflammatory disorders
51
Describe in brief how Th1 cells are activated and what happens afterwards.
Microbes activate the APC APC activates naive CD4+ T cell which proliferates Th1 cells produce IFNgamma IFNgamma in macrophages enhances killing/activation IFNgamma in B cells allows complement binding and opsonizing antibodies to bind to microbes allowing easier phagocytosis by macrophages.
52
Describe in brief how Th2 cells are activated and what happens afterwards.
Microbes or protein Ag activate the APC Naive CD4+ T cells are activated by APC = proliferation Th2 cells produce IL4 and 5 IL-4 activates B cells to produce Neutralizing IgG and IgE (mast cell degranulation/allergies) IL-5 activates eosinophils to attack helminths/parasites

Immunology 7070 (15 decks)

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