L8 - K Okkenhaug - T cells

Question 1

what does the T cell receptor bind / response to?

Answer 1

fragmented antigenic peptides bound to MHC molecules.

Question 2

describe a class 1 CD8 cytotoxic T cell

Answer 2

CD8 cytotoxic

Question 3

describe a class 2 helper T cell

Answer 3

Question 4

how are TCRs and antibodys closely related?

what structure do they share in commen?

Answer 4

The TCR is closely related to a single antibody Fab fragment

Question 5

how is TCR variability generated?

Answer 5

VDJ recombination - much like antibodies

Question 6

describe TCRs peptide structure?

Answer 6

two polypeptide chains each containing a constant and a variable region.

Question 7

4 differences between TCR and antibodies

Answer 7

TCR is:

• monovalent
• membrane bound - no secreted counterpart
• no somatic hypermutation
• solely used for antigen recognition
  
  • not linked to effector function

Question 8

where do T cells mature

Answer 8

thymus

Question 9

do you understand how VDJ recombination works?

Answer 9

Question 10

____ is the most variable region in TCR and is focused on the VDJ junctions.

Answer 10

CDR3 is the most variable region in TCR and is focused on the VDJ junctions.

Question 11

CDR3s role in the TCR is

Answer 11

CDR3 makes the major contact with peptide present in the MHC groove.

Question 12

Only abou X% of

double-positive (CD4+ /CD8+) thymocytes survive selection.

Answer 12

Only about 1-2% of

double-positive (CD4+ /CD8+) thymocytes survive selection.

Question 13

in T cell selection, whats the purpose of negative selection?

Answer 13

Negative selection helps prevent autoimmunity by deleting autoreactive cells.

Question 14

in T cell selection, whats the purpose of Positive selection?

Answer 14

Positive selection ensures that peripheral T cells will be useful since cells that cannot recognise self MHC cannot become activated.

Question 15

CD8+ T cells are selected for by MHC X molecules. CD4+ T cells are selected for by MHC X molecules

Answer 15

CD8+ T cells are selected for by MHC I molecules. CD4+ T cells are selected for by MHC II molecules

Question 16

Pictuer to help understanding of T cell selection

Answer 16

Question 17

is positive selection unique to T cells

Answer 17

yes

Question 18

T cell undergo positive and negative selection in the ____

Answer 18

T cell undergo positive and negative selection in the thymus

Question 19

where does positive selection take place?

Answer 19

cortical epithelium in thymus

Question 20

explain positive selection in the cortical epithelium in the thymus for t cells

Answer 20

Newly rearranged T-cell receptors are tested against self peptide/MHC complexes expressed on cortical epithelial cells.

TCRs with a “moderate affinity” for self MHC/peptide receive a positive signal to continue maturation.

Lack of interaction results in death by neglect.

Expression of CD4 and CD8 co-receptors is altered to match MHC restriction.

Cells that survive will be CD4+ single positive if selected against MHC class II/peptide or CD8+ single positive if selected against MHC class I/peptide.

Question 21

thymus organisation picture

where does negative selection occur

Answer 21

thymus medulla

Question 22

where do mature t cells travel to after the thymus

Answer 22

secondary lymph tissue

Question 23

describe negative selection

Answer 23

• potentially autoreactive thymocytes expressive TCRs with high affinity for MHC/self peptides

are eliminated from the repertoire by programmed cell death (apoptosis).

• Negative selection can not eliminate T cells with receptors recognising MHC/peptide combinations that are not expressed in the thymus. These are dealt with by mechanisms that operate in the periphery.

Question 24

why are macrophages important in the thymus

Answer 24

Macrophages are important for removing thymocytes that fail to mature.

Question 25

regarding T cell stimulation - what is teh 2 hit hypothesis

Answer 25

signal 1 is delivered by TCR engagement and co-stimulatory molecules deliver signal 2. CD40L on the T cell interacts with CD40 which activates the APC.

Question 26

is the second corstimulation for the activation of a T cell imporntat?

Answer 26

yep - Without CD28 costimulation, the T cells can become unresponsive to further exposure to the same antigen.

Question 27

describe how APCs present to T cells

Answer 27

Infection in the periphery is initially sensed by mechanisms of innate immunity. DCs, potent antigen presenting cells that reside in most tissues, take up antigen in the infected tissues and are activated by TLRs and CD40 receptors. They increase MHC class II synthesis and begin to express co-stimulatory molecules (B7.1 and B7.2) at the cell surface. Together with their antigen cargo they migrate to draining lymph nodes where they remain and present antigen to circulating T cell.

Question 28

Naïve T cells enter the lymphoid organs from the blood through/....

Answer 28

Naïve T cells enter the lymphoid organs from the blood through specialised endothelial cells (high endothelial venules)

Question 29

Binding of MHC II:peptide complexes by the TCR and CD28 by B7 induces the naïve T cell to....

Answer 29

Binding of MHC II:peptide complexes by the TCR and CD28 by B7 induces the naïve T cell to **proliferate** and **differentiate** into an expanded population of armed **effector T helper cells.**

Question 30

how do T helper Cells activate B cells?

Answer 30

B cell must bind antigen via its specific surface Ig and internalise it The endocytosed antigen is then processed and presented on the surface as MHC class II/peptide complexes The peptide MHC complex expressed by B cell is the same as that originally presented by the DC and can be recognised by the activated helper T cell The B cell-T cell interaction requires CD28 and CD40L on the T cell to bind B7 and CD40 on the B cell. Cross-linking of CD40 on the B cell (B cell activation signal 2) promotes B cell proliferation, provides B cell survival signals and promotes immunoglobulin class switching. Interaction between B cell and T cell co-stimulatory molecules (CD28/B7 and CD40L/CD40) is essential and leads to their mutual activation (B-T cell co- operation). long card

Question 31

describe the binding of activated B cells to follicular dendritic cells

Answer 31

The third cell-cell interaction involved is the binding of activated B cells to follicular dendritic cells. FDCs are specialised stromal cells that hold intact, i.e. unprocessed, antigen on their surface in the form of long-lived immune complexes. They are only present in B cell follicles and enable the activated B cell to form germinal centres.

Question 32

FDC are only present in........... and enable the activated B cell to form ......

Answer 32

They are only present in B cell follicles and enable the activated B cell to form germinal centres.

Question 33

what are Thymus independent antigens

Answer 33

antigens which dont require T cells help to activate a naïve B cell

Question 34

what are thymus independant antigens? (structurally composed of)

Answer 34

typically microbial products composed of repetitive elements (polysaccharides and lipopolysaccharides) which cross-link membrane Ig and induce B cell proliferation.

Question 35

are there many subsets of CD4 T helper cell?

Answer 35

yep

Question 36

CD8 T cells become?

Answer 36

cytotoxic T cells

Question 37

give some examples of T helper cell subsets

Answer 37

T_H1 T_H2 T_H17 T_FH T_regs

Question 38

describe TH1 cells

Answer 38

produce cytokines that support inflammation and cell mediated responses. Their signature transcription factor is **T-BET.** They activate mainly macrophages, NK cells and CTLs and are important in dealing with intracellular pathogens (e.g. mycobacteria).

Question 39

Describe TH2 cells

Answer 39

TH2 helper cells activate immune responses that assist in the elimination of parasitic infections. The TH2 signature transcription factor is **GATA3**.

Question 40

describe TH17 cells

Answer 40

involved in defence against extracellular bacteria and fungi defined by the transcription factor RORγT

Question 41

describe Follicular helper T cells (TFH)

Answer 41

essential promoting antibody responses defined by the transcription factor **BCL-6**

Question 42

describe Tregs

Answer 42

Tregs supress the activity of other T cells defined by the transcription factor **FOXP3**.

Question 43

give factors which favour TH1 polarisation

Answer 43

Abundant antigen and high affinity TCR interactions favour TH1 responses

Question 44

give factors which favour TH2 polarisation

Answer 44

low peptide abundance or with weak affinity for TCR favour TH2 responses.

Question 45

These early decisions are crucial as the TH1/TH2 bias becomes .....

Answer 45

These early decisions are crucial as the TH1/TH2 bias becomes **self-reinforcing.**

Question 46

CD8+ T cell are MHC-X restricted ....

Answer 46

CD8+ T cell are MHC-I restricted killer T cells

Question 47

CD4+ T cells are MHC-X restricted _____ T cells

Answer 47

CD4+ T cells are MHC-II restricted helper T cells

Question 48

T cells require ____ costimulation to be fully activated

Answer 48

T cells require CD28 costimulation to be fully activated

Question 49

CD4+ T cell subsets include: ....

Answer 49

CD4+ T cell subsets include: Th1, Th2, Th17, TFH, Treg

Question 50

TH1 cells secrete ...

Answer 50

TH1 cells secrete IFN-γ

Question 51

describe what the TH1 cell pathway does?

Answer 51

increases inflammation to defend against intracellular bacterial, viral and protozoan infections

Question 52

describe what the TH2 pathway does?

Answer 52

The TH2 pathway promotes production of pathogen-specific IgE antibodies that work with basophils, mast cells and eosinophils to control parasite infections. It corresponds to what was traditionally called humoral immunity, in which antibodies dominate. The response promotes tissue repair rather than inflammation

Question 53

what do TH2 cells secrete

Answer 53

TH2 cells secrete IL-4, IL-5 and IL-13

Question 54

fate specifying cytoines and cytokines secreted

Answer 54

Question 55

how do Treg cells modulate T cell differentiation

Answer 55

During inflammation in the presence of IL- 6 Tregs continue to produce TGF-β maintains homeostasis by inhibiting TH1 and TH2 cell differentiation IL-6 can drive TH17 commitment TGF-β prevents TH1 and TH2 cells from producing IL-4 or IFN-gamma that would otherwise inhibit the TH17 response.

Question 56

IFN-γ produced by TH1 cells ,.....

Answer 56

IFN-γ produced by TH1 cells blocks both TH2 and TH17 cell differentiation

Question 57

L-4 (TH2) blocks

Answer 57

L-4 blocks both TH1 and TH17 cell commitment.

Question 58

Pictrue summary

Answer 58

Question 59

T or F ## Footnote ILC1, ILC2, and ILC3 innate lymphocytes show parallels with TH1, TH2 and TH17 helper cells respectively

Answer 59

T

Question 60

ILCs act _____ their corresponding T- helper counterparts

Answer 60

ILCs act before their corresponding T- helper counterparts

Question 61

ILCs and their T cell counterparts share the same ........... .... ...... and often produce the same ....

Answer 61

ILCs and their T cell counterparts share the same signature transcription factors and often produce the same effector cytokines

Question 62

ILC1 and TH1 cells help control infections with....

Answer 62

ILC1 and TH1 cells help control infections with intracellular bacteria or viruses (IFN-γ).

Question 63

ILC2 and TH2 cells help deal with ...

Answer 63

ILC2 and TH2 cells help deal with parasite and helminth infections (IL-5 and IL-13).

Question 64

ILC3 and TH17 cells deal with....

Answer 64

ILC3 and TH17 cells deal with extracellular bacteria and fungi (IL-17 and IL-22).

Question 65

summary picture of ILCs

Answer 65

Question 66

another summary picture

Answer 66

Question 67

fat

Answer 67

Mamba