MCB Lecture 48 Cooperative Immune Response Flashcards Preview

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Flashcards in MCB Lecture 48 Cooperative Immune Response Deck (36)
0

Describe (and point out the differences) between antigen processing for MHC I and MHC II

MHC I: endogenous protein (synthesised inside the cell, may be viral DNA)
1. MHC I synthesised in ER, protein degraded into peptide by proteosome and delivered via vesicle to ER
2. Peptide binds to the cleft
3. MHC I - pep exported to surface in a vesicle

MHC II: exogenous protein
1. Protein endocytosed, and degraded into peptides by phagolysosome
2. MHCII synthesised in ER
3. Invariant chain binds in the cleft to prevent peptide binding there
4. MHC II loaded into vesicle, which fuses with phagolysosome.
5. Peptide loaded into MHC II cleft, invariant chain displaced
6. Transported to the surface via a vesicle

1

What are the two different types of T lymphocyte?

T cytotoxic, CD8+
T helper, CD4+

2

Compare the different proteins found on T lymphocytes

CD8, binds to conserved alpha-3 of MHC I
Cd4, binds to conserved beta-2 of MHC II

3

Differentiate between the type of MHC that both types of lymphocyte interact with

CD8+: MHC I
CD4+: MHC II

4

What is the function of CD8+?

Bind to and kill cells that have been infected by a pathogen, or neoplasticism cells

5

What is the function of CD4+?

Help B cells and macrophages
Moderate immune response

6

Briefly describe the process of activation of lymphocytes

Naïve lymphocyte -> Effector cell

7

What is a dendritic cell?

It is a professional antigen presenting cell

8

What is the normal function of an APC?
How does it do this?

It samples the environment via:
Macro-pinocytosis
Mannose-R
FcR

The protein it takes in via this sampling is degraded and presented in MHC II

9

How are APCs activated?

1. PAMP binds to PRR (Licensing)
2. Endocytosis of pathogen

10

Describe the steps involved in APC and T lymphocyte interaction

1. APC undergoes licensing and expression of invader peptide in MHC
2. APC moves to the lymph node via lymphatics
3. Once in lymphatics, the peptide expressed in the MHC is recognised by TCR on T lymphocytes, activating them

11

Outline the post-Licensing maturation events of an APC

Increased MHC I and MHC II expression
Stop sampling
Migration to lymphoid tissue
Expression of co-stimulatory and adhesion molecules
Secretion of cytokines

12

What is licensing?

This is when an APC becomes active after binding a PAMP of an invading pathogen

13

What is signal one?

This is the binding of T lymphocyte and APC, via the TCR and MHC

14

What is signal 2?

APC cost insulate T cells, causing them to proliferate

15

What is signal 3?

This is release of cytokines onto T lymphocytes, causing them to differentiate

16

Outline the specific steps in APC - CD4+ interaction

1. Adhesion: ICAM-1 + LFA-1
2. Signal 1: MHC II-pep + TCR (CD4+)
3. Signal 2: costimulation CD80, CD86 + CD28 --> proliferation
4. Expression of CD40L by CD4+
5. Autocrine signalling by CD4+: IL-2 and IL-2R
6. Signal 3: cytokines released by APC stimulate CD4+ --> differentiation

17

How do APCs and CD4+ adhere to each other?

ICAM-1 and LFA-1

18

How do CD4+ perform autocrine signalling?

IL-2 and IL-2R

19

What causes the expression of CD40L on a CD4+?
What is the function of this molecule?

Co stimulation, interaction between APC and CD4+

This ligand then binds to CD40 on B cells, bringing about isotype switching

20

What is a super antigen?
What is the outcome when these occur?

This is an antigen that does not need to be specific for the alpha and beta parts of a TCR, instead, can bind directly to the MHC and TCR.

This results in a huge decrease in specificity, and up to 20% of T cells being activated at once
This huge immune response can have damaging effects on the body

21

Describe the outcome of cytokines signalling to CD4+ (Signal 3)

Differentiation of T helper cells:
Eg. Th1: activate macrophages
Th2: activate mast cells and eosinophils
Tfh: aid B cell activation and proliferation
Th17: recruit neutrophils
Treg: regulation of "self-responses"

22

Describe how Cd4+ and B cells interact

1. B cells are clonally selected by their complimentary antigen when in the lymph node
2. Receptor mediated endocytosis of this antigen
3. Presentation of peptide on MHC II
4. T cell TCR binds to this antigen on MHC II
5. Interaction between CD40 and CD40L --> isotype switching
6. Cd4+ releases cytokines IL-4 and IL-5

23

How does a CD4+ recognise the B cell that it is going to 'help'?

The B cell is presenting the antigen peptide in its MHC II with its BCR

24

What does 'help' from CD4+ result in for B cells?

Isotype switching
Proliferation
Increased antibody affinity
Antibody secretion
Memory

25

Outline how CD4+ help macrophages

1. CD4+ becomes activated in the lymph node
2. CD4+ returns to the infected tissue
3. Here, it releases IFN-gamma
4. IFN-gamma stimulates macrophages to undergo increased phagocytosis

26

Describe how CD8+ becomes activated

1. Licensed APC moves to lymph node
2. Co stimulatory molecules help CD8+ and APC interact
3. MHC I - pep + TCR
4. Activation and Proliferation of T cell

27

Once CD8+ is activated, what happens?

1. Returns to the infected tissue
2. TCR recognises epithelial cells presenting that antigen on their MHC I (eg. Virus inside has taken over the machinery and is making peptide)
3. CTL releases granules: perforin and granzymes released
Perforin: puts holes in the epithelial cells -> lysis
Granzymes: induce apoptosis of the infected cells
4. Fas and Fas-L interact --> induction of apoptosis

28

Which molecules does Cd8+ release that kills cells? How does this happen?

Perforin --> lysis
Granzymes --> induction of apoptosis

29

What is the function of Fas and FasL?
Where are these located?

Fas and Fas-L are on the membrane of epithelial cells and CD8+
It causes apoptosis of the infected cell

30

List all the ways that a phagocyte can kill the bacterium once it is in the cell

1. Acidic environment (pH 3-4)
2. Competition: lactoferrin binds to the iron in the bacteria so it can't function
3. Enzymes: hydrolytic enzymes break down the structures
4. Antimicrobial Peptides: cationic peptides, defensins
5. Reactive oxygen species: superoxide, hydrogen peroxide
6. Toxic nitrogen intermediates: Nitric oxide, NO

31

Describe how mycobacterium tuberculosis avoids intracellular killing

1. Mycobacterium tuberculosis is taken up by alveolar macrophages
2. Produces NH4 once in the phagosome to maintain pH around 6-7 (neutral)
3. Inhibits the fusion of lysosomes with the phagosome by mycobacterium lipids in the cell wall
4. Contains enzymes that neutralise reactive oxygen species

Now, it can survive and replicate

32

What does IL-2 autocrine signalling bring about?

Proliferation of the CD4+

33

Super antigens do not require ... , unlike normal antigen

Processing

34

Once pathogens bind to the BCR bound to a B cell, what happens?

Receptor mediated endocytosis.
The pathogen is taken in, broken down and the antigen is presented on MHC II

35

How does a T helper cell interact with (bringing about activation) a macrophage back in the infected tissue?

The macrophage is displaying the antigen on its MHC II, which the T cell recognises with its TCR.
CD4+ releases IFN-gamma

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