Antigen recognition T cells Flashcards

1
Q

What is the role of T cells in the immune response?

A

Designed to fight intracellular microbes

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2
Q

How do B cells recognise antigens?

A

B cells recognise antigens directly

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3
Q

How do T cells recognise antigens?

A

T cells do not recognise antigens directly
-They recognise antigens presented by APCs

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4
Q

What do T cells recognise in terms of cell bound Ags and foreign Ags?

A

→ T cells recognise cell-bound Ags (peptides)
→ peptides from foreign Ags only when bound to MHC

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5
Q

How do antigen presenting cells process antigens to be recognised by T cells?

A

APCs process antigens into peptides (for αβ T cells)
peptides bind to MHC molecules
peptide:MHC complexes are presented on the APC surface
→ activation of T cells specific for antigenic peptide

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6
Q

What are examples of professional APCs?

A
  1. Dendritic cells
  2. Macrophages
  3. B cells
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7
Q

What are dendritic cells capable of presenting to?

A

the only APCs capable to present to naïve T cells

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8
Q

What do macrophages present to?

A

present to previously activated effector T cells

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9
Q

What do B cells present to?

A

present to previously activated effector T cells

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10
Q

What do CD8+ T cells recognise?

A

CD8+ T cells recognise Ag displayed by nucleated cells (not
just APC but also cells that are not APCs)

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11
Q

Where are dendritic cells found?

A

Skin, mucosa and tissue

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12
Q

What do dendritic cells capture?

A

Capture microbes

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13
Q

What do dendritic cells transport?

A

transport microbes from
tissues (e.g. epithelia) to
draining lymph nodes

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14
Q

What are dendritic cells critical in the initiation of?

A

Critical in the initiation (priming) of T cell responses

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15
Q

How do dendritic cells signal for naive T cell activation?

A
  1. Signal 1 is antigen recognition of MHC peptide with TCR
  2. Signal 2 is the co-stimulation of CD80/CD86 with CD28
  3. Signal 3 is cytokines
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16
Q

What happens in signal 1 of naive T cell activation by dendritic cells?

A
  1. Recognition of Ag(peptide:MCH complex) on APC
    -This alone is not sufficient to induce T cell activation
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17
Q

What happens in signal 2 of naive T cell activation by dendritic cells?

A

binding of co-stimulatory molecules (B7 family, e.g.
CD80/CD86) on APC by co-stimulatory receptor (CD28) on
T cell

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18
Q

What does signal 2 of naive T cell activation by dendritic signal together with signal 1 do?

A

together with signal 1 → activation of naïve T cells

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19
Q

What increases the expression of costimulatory molecules and of MHC?

A

APCs exposed to infection increase the expression of co-
stimulatory molecules (B7) and of MHC

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20
Q

What does signal 3 regulate and what are examples?

A

regulate activated T cells differentiation into different
effector T cells
-IL-12 from APC–> Th1 differentiation
-IL-4 from APC –> Th2 differentiation

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21
Q

What does signal 3 ensure the generation of?

A

ensure the right effector T cell is generated
-Effector T cell most suited to respond to the trigger

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22
Q

What are the steps involved in the killing of microbes by macrophages?

A
  • phagocytose microbes (e.g. Mycobacteria tuberculosis)
  • Ag presentation to effector CD4+ T cells (Th1)
  • activation of Th1 cells
  • Th1 cells activate macrophage to kill ingested microbes
23
Q

What are the steps involved in B cell activation?

A

-Internalise protein Ags
-Present peptides to effector CD4+ T cells(Th2)
-Activation of Th2 cells
-Th2 cells provide help signals to B cells that:
–Regulate class switch(e.g. IFN-γ and IgG; IL-4 and IGE)
–Affinity maturation (Abs with higher affinity for Ag)

24
Q

What can all nucleated cells present?

A

All nucleated cells can present peptides derived from proteins
from antigens present in the cytosol to CD8+ T cells

25
Q

What can all nucleated cells be infected by?

A

all nucleated cells can get infected by viruses

26
Q

What are the 2 things that CD8+ T cells are specialised to do?

A
  • recognise viral antigens and mutated proteins
  • eliminate cells infected by viruses/malignant cells
27
Q

Where else can CD8+ T cells recognise antigens?

A

CD8+ T cells can also recognise Ag from phagocytosed microbes if these Ag
escape from the phagosome into the cytosol

28
Q

How do T cells recognise antigens?

A

T cells recognise antigens via their T cell receptor (TCR)

29
Q

What is the most common t cell receptor type?

A

2 chains:
-alpha and beta chains

30
Q

What are the 2 chains in gamma delta T cells?

A

-Gamma chain
-Delta chain

31
Q

What domain does each chain in T cell receptors have?

A

Each chain has:
-1 Variable domain
-1 Constant domain

32
Q

What are antigen binding sites formed by?

A

Formed by the variable domains of both chains

33
Q

What domains in immune cells are homologous?

A

V and C domains of TCR and BCR are homologous

34
Q

What does each variable domain contain?

A

each variable domain
contains 3 hypervariable regions

35
Q

How is T cell receptor diversity generated and what are the process called in variable region for the beta chain and alpha chain?

A

generated by re-arrangement of gene segments via a
process similar to immunoglobulin generation (VDJ
rearrangement for Vβ and VJ rearrangement for Vα)

36
Q

When are genes for T cell receptor chains rearranged?

A

genes for TCR chains are rearranged during T cell
development in the thymus

37
Q

What are the steps involved in the rearrangement of TCR genes?

A
  1. Germline DNA for both alpha and beta chains undergo recombination
  2. This rearranged DNA undergoes transcription, splicing and translation leading to formation of a protein(T cell receptor)
38
Q

What are the 2 types of major histocompatibility complexes?

A

MHC 1 and 2

39
Q

What T cells does the MHC I present its peptides to and what chains is the T cell composed of?

A

Presentation of peptides CD8+ T cells and is composed of alpha chain and beta2 microglobulin

40
Q

What T cell does the MHC II present its peptides to and what chains is that T cell composed of?

A

Presentation of peptides to CD4+ T CElls and is composed of alpha chain and beta chain

41
Q

What antigens do gamma delta T cells recognise?

A

γδ T cells recognise antigens that are not displayed by MHC I
and MHC II (are not MHC restricted)

42
Q

What cells express MHC I?

A

All nucleated cells

43
Q

What cells express MHC II?

A

antigen presenting cells: dendritic cells
macrophages

44
Q

What are human leukocyte antigens(HLA)?

A

Human leukocyte antigens (HLA) are genes in major histocompatibility complexes (MHC) that help code for proteins that differentiate between self and non-self.

45
Q

How does CD4/CD8 bind to MHC?

A

CD4/CD8 bind to MHC away from Ag peptide binding groove

46
Q

What does CD4/CD8 binding decrease the threshold of?

A

CD4/CD8 binding decreases the threshold for T cell activation:
T cells need to make contact with fewer peptide:MHC
complexes to get activated

47
Q

What are the steps involved in antigen processing and presentation to CD4+ T cells for extracellular Ags like bacteria?

A

Extracellular Ags (e.g. bacteria) taken up in cells,
processed and presented by MHC II to CD4+ T cells
1. Uptake of extracellular proteins into vesicular compartments of APC
2. Processing of internalized proteins in endosomal/lysosomal vesicles
3. Biosynthesis and transport of class II MHC molecules to endosomes
4. Association of processed peptides with class II MHC molecules in vesicles
5. Expression of peptide-MHC complexes on cell surface

48
Q

What are CD8+ T cells specialised to kill?

A

CD8+ T cells specialised to eliminate cells infected
by viruses and cancer cells

49
Q

What are the steps involved in antigen processing and presentation to CD8+ T cells?

A
  1. Production of proteins in the cytosol
  2. Proteolytic degradation of proteins
  3. Transport of peptides from cytosol to ER
  4. Assembly of peptide-class I complexes in ER
  5. Surface expression of peptide-class I complexes
50
Q

What are the steps involved in antigen processing and presentation to CD8+ T cells?

A
  1. Cytosolic Ag protein are broken down by proteasomes into peptides
  2. These peptides leave the ER and bind to MHC I
  3. MHC I is then translocated to golgi apparatus where it is processed and leaves in exocytic vesicle
  4. Exocytic vesicle fuses with membrane to present MHC I with peptide to CD8+ T cell to be recognised
51
Q

If both MHC I and MHC II are produced and
assembled in ER how come MHC II can’t load
peptides that derive from cytosolic pathogens
(viruses) and MHC I can’t load peptides that derive
from phagocytosed extracellular pathogens?

A

MHC II is associated with Ii (invariant chain) which blocks the groove of MHC II → prevents loading of peptides transported by
TAP from cytosol into ER

Peptides for MHC II are not transported to ER but are located in late endo- lysosomal vesicles; only MHC II reaches these
vesicles; MHC I is loaded with peptides in ER and then
transported directly to the cell surface

52
Q

What are the steps involved in antigen processing and presentation to CD4+ T cells?

A
  1. Extracellular Ag proteins enter cell in endosome
  2. These Ag proteins are broken down into peptides in endo-lysosome
  3. The invariant chain binds to MHC II and is transported to the golgi where it is further processed and is put into an exocytic vesicle
  4. This enters into a space alongside peptides
  5. HLA-DM is important in keeping class II molecules competent for antigenic peptide loading
  6. The T cell receptor is then presented on the surface for CD4+ T cell
53
Q
A