Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

2 - Immunology > Generation of Diversity in the T-Cell Repitoire > Flashcards

Generation of Diversity in the T-Cell Repitoire Flashcards

1
Q

T and B cells recognise what differently?

A

antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what does antigen processing generate?

A

antigenic peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

where can antigen processing take place?

A

lysosomes, and there is also a non-lysosomal mechanism of antigen processing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

when can the TCR bind to antigenic peptides?

A

only when the peptides are in complex with MHC molecules on APC’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how many types of MHC are there?

A

2 types of MHC (I and II)

-they interact with CD8 or CD4 T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is an antigen?

A

any molecule that can bind specifically to an antibody

antibodies are normally immunogenic - will initiate an immune response in the host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is an epitope?

A

a small portion of an antigen (could be a small peptide), it is a target for TCR’s and antibodies

adaptive immune reactions occur to specific epitopes as opposed to the entire antigen itself

immune reactions occur to specific epitopes and infection can induce polyclonal T or B cell response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how do B cells and T cells differ in the way they recognise antigens?

A

T cells cannot recognise native antigens – they must be processed into peptides and presented on surface of APC’s by MHC molecules

B cells will recognise and process native antigens, and undergo clonal expansion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

B cell clonal expansion?

A

B cells proliferate and make multiple clones of the same cell, which all produce the same antibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

if an APC is fixed what is the consequence?

A

it will not induce cell activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what do uptake mechanisms do?

A

the direct the antigen into intracellular vesicles for exogenous antigen processing

examples are:

  • phagocytosis
  • pinocytosis
  • membrane Ig medicated uptake
  • complement receptor mediated uptake
  • Fc receptor mediated phagocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which immune cells recognise and process antigen?

A

APC’s!!!!

monocytes
macrophages (terminally differentiated monocytes)
dendritic cells
B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

macrophages vs dendritic cells?

A

both rare in peripheral blood - enriched in mucosal tissues

highly phagocytic cells – induce strong T-cell responses and inflammation. Important for protection against Mycobacterium tuberculosis

Macrophages better-equipped to kill pathogens (higher NO production)

DCs better at migrating to lymph nodes (via CCR7) and presenting antigen to T- cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how are dendritic cells specialised for their function?

A

these cells have has multiple dendrites - extensions of the cell membrane which increase the cell surface interaction with the environment

these cells are enriched in mucosal tissues because these are exposed to the environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

B-cells

A

Highly abundant in blood and mucosal tissues

Receptor-mediated internalisation of antigens, as opposed to phagocytosis

Primary function is making antibodies, but still very good at antigen presentation

Possibly main inducer of T-cell immune response to pathogens, such as Neisseria meningitidis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Endogenous antigen processing - the steps

LHS slide 17

A

UPTAKE
Antigens/pathogens already present in cell cytoplasm

DEGRADATION
Antigens undergo proteolytic degradation in cytoplasm

ANTIGEN-MHC COMPLEX FORMATION
Peptide antigens transported to ER, enter via TAP and loaded onto MHC class I molecules

PRESENTATION
Transport and expression of antigen-MHC complexes on the surface of cells for recognition by CD8 T cells

eliminated by death by cytotoxic T cells

17
Q

why do we need endogenous antigen processing - isn’t exogenous processing sufficient

A

Macrophages have well-developed lysosomal systems

They are specialised for motility, phagocytosis and the introduction of particles to the lysosomal system

Most cell types do not have lysosomal systems developed as well as macrophages

Viruses can infect most cell types

A non-lysosomal mechanism to process antigens for presentation to T cells is required

18
Q

Non-lysosomal antigen processing requires what?

A

protein synthesis

19
Q

antigens from inactive viruses and infectious viruses - how are they processed?

A

ANTIGENS FROM INACTIVE VIRUSES ARE PROCESSED VIA THE EXOGENOUS PATHWAY

ANTIGENS FROM INFECTIOUS VIRUSES ARE PROCESSED VIA THE ENDOGENOUS PATHWAY

20
Q

Exogenous antigen processing? (RHS slide 17)

A

antigens are endocytosed into the cell, in the endosome they are broken down into peptides

loaded onto MHC class II molecules, recognised by CD4 T cells

eliminated by antibodies and phagocyte activation by T helper cells

21
Q

comparison of MHC class I and II?

A

class I expressed on all nucleated cells, class II expressed on APCs and activated T-cells

class I binds short peptides, class II binds long peptides

class I presents to CD8 T cells, II presents to CD4 T cells

class I presents antigens from the cytosol, class II presents antigens from phagosomes and endosomes

22
Q

The T-cell receptor:

  • what does it bind to?
  • how does it exist?
A

T cell receptor binds to peptide MHC complexes, cannot recognise peptide alone

Exists in a TCR complex with accessory molecules such as CD3

23
Q

T cell receptor and B cell receptor - similarities and differences

A

Similarities to B cell receptor/antibody:

Belongs to Ig superfamily
Fab-like fragment (peptide binding site for antibody)
Large diversity
Single specificity

Differences to B cell receptor/antibody:

Lower affinity
Cannot be released (remains on cell surface)
No Fc fragment, so no cellular functions
Single binding site rather than 2 
B cell receptor/Ab: 5 classes
T cell receptor: 2 classes
24
Q

Mechanisms which generate B-cell and T cell receptor diversity?

A

before antigen stimulation: somatic recombination

after antigen stimulation (BCR only): somatic hypermutation

25
Q

when does T cell receptor gene rearrangement occur?

A

takes place during T-cell development in thymus

26
Q

Three signal model of T-cell activation?

A
  1. Peptide-MHC (pMHC)
    - main signal delivered from the APC by a peptide-MHC complex to the TCR
  2. Co-stimulation
    - delivered from the APC by germline-encoded accessory receptors, eg. CD80 and CD86
  3. Cytokines
    - formed of cytokines secreted by the APC to determine the T-cell phenotype

IL-12 promotes TH1 cells
IL-4 promotes TH2 cells
IL-23 promotes TH17 cells

TH1 and TH2 produce cytokines that activate other cells

Signals 1 + 2 alone will activate a naïve T-cell, but Signal 3 is also important for a strong response and also determining T-cell phenotype

needs to be a direct physical attraction between APC and TCR

27
Q

The immunological synapse

A

Complex interaction of many molecules – but simplistically Signals 1 and 2 are central, and surrounding integrins and accessory molecules help to stabilise the interaction

28
Q

do CD4+ and CD8+ cells secrete cytokines?

A

Most cd4+ cells secrete cytokines to help the immune process, but cells that express cd8 are cytotoxic T cells which kill pathogens directly

29
Q

Negative regulators of antigen presentation

A

2 important regulatory molecules on T cells which dampen the immune response

  1. CTLA4 (Cytotoxic T-Lymphocyte-Associated Protein 4)
    - blocks TCR activation via SHP-2, which dephosphorylates TCR signalling molecules
  2. PD-L1 (Programmed Death-Ligand 1) are crucial for dampening the T-cell response
    - competes with CD28 for APC ‘attention’
30
Q

why is negative regulation needed?

A

because an overly-vigorous immune response is harmful to the host

31
Q

what is positive and negative selection?

A

removal of defected T cells - T-cells arise from the thymus (‘school’ for T-cells). T-cells are exposed to self-antigens and tested for reactivity.

T-cells that can’t bind self antigen-MHC are deleted → POSITIVE SELECTION
These T-cells are useless because they won’t protect against pathogens

T-cells that bind self antigen-MHC too strongly are also
deleted → NEGATIVE SELECTION
These T-cells are dangerous because they are too self- reactive

32
Q

how is excessive T cell activation down regulated?

A

T regulatory cells which express FOXP3

secrete anti- inflammatory cytokines:

  • Interleukin-10
  • TGF-β
33
Q

2 types of T cells?

A

helper (Th) or cytotoxic (Tc)

34
Q

Pathogens impeding antigen presentation - examples?

A

Mycobacterium tuberculosis

  • Blocks MHC Class II expression
  • Up-regulates PD-L1 on APCs to shut down T-cell activation

Neisseria meningitidis
-Blocks DC activation

Neisseria gonorrhoeae
-Expresses Opa protein, which binds to T-cells and induces tyrosine phosphatases that ‘switch off’ key molecules involved in TCR signalling

HIV
-Up-regulates PD-L1 on T-cells, which antagonises TCR signalling

HSV
-Produce protein which inhibits TAP, prevents viral peptide transfer to ER

Adenovirus
Produce protein which binds MHC class I molecule, prevents it from leaving ER

2 - Immunology (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions