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Immunology Exam 1 > 5 - T cells and CMI > Flashcards

5 - T cells and CMI Flashcards

1
Q

What can Trichuris suis be used to treat?

A

Trichuris suisis is found in live ova of pig intestinal helminth and can be used to treat Crohn’s disease (ewwwwww)

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2
Q

What is the mechanism of therapy in Trichuris suis?

A

The mechanism of therapy might entail the shifting of the predominate TH1-mediated immune response that is involved in Crohn’s disease to a TH2-mediated response that eliminates the parasitic worm

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3
Q

What family are T lymphocytes a part of?

A

T lymphocytes are a subset of the lymphocyte family, which also includes B cells and NK cells

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4
Q

How large are T lymphocytes?

A

8 - 10 um in diameter

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5
Q

Can you distinguish between T cells and B cells?

A

No!

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6
Q

What is the difference between B cells and T cells?

A

Unlike B cells, T cells only recognize antigens when they are presented by an APC with MHC proteins - this is termed “MHC restriction”)

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7
Q

Describe the path of T lymphocyte maturation

A

Ontogeny

  • Prothymocytes from bone marrow migrate to the thymus (thymocytes)
  • Thymocytes then differentiate into mature T cells
  • Mature T cells from the thymus travel to peripheral lymphoid organs
  • Memory T cells reside in the bloodstream until directed to enter non-lymphoid tissues to elicit cell-mediated immune responses
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8
Q

Where do mature T cells reside?

A

Peripheral lymphoid organs

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9
Q

Where do memory T cells reside?

A

In the bloodstream (until they are needed for an immune response)

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10
Q

What are the three types of T lymphocytes?

A
  1. T helper lymphocytes
  2. Cytotoxic T lymphocytes
  3. Regulatory T lymphocytes
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11
Q

What are the different types of T helper lymphocytes (4)? What is their role?

A

Called the CD4+ subsets

  1. TH1 cells
    • Cell mediated immunity (IgG can be produced)
  2. TH2 cells
    • Humoral immunity (especially IgE)
  3. TH17
    • Enhances inflammation
  4. TFH
    • Promotes germinal center formation in lymphoid organs
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12
Q

What is the role of cytotoxic T lymphocytes?

A

Called either CTLs or CD8+ cells

  • Function to lyse virus-infected cells
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13
Q

What is the role of regulatory T lymphocytes?

A

Treg cells which downregulate immunity

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14
Q

What is a TCR?

A

T cell antigen receptor (TCR)

  • The TCR encompasses the proteins on the surface of T cells that allow them to recognize and respond to antigen
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15
Q

How many identical copies of a TCR would you find embedded on a T cell surface?

A

30,000

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16
Q

What type of genes are rearranged similar to how immunoglobulin genes are?

A

Genes encoding for the TCR

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17
Q

Is TCR responsible for MHC?

A

NO!

MHC restriction is a function of CD4+ and CD8

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18
Q

Describe the physical structure of a TCR

A

T cell antigen receptor structure

  • TCRs are found as a heterodimer of disulfide-linked alpha and beta chains
  • Each chain has constant and variable regions that are similar to antibodies
  • Different antigen specificities are generated by altering variable regions
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19
Q

Which of the two chains (alpha or beta) of a TCR is involved in binding antigen and MHC?

A

Trick question… BOTH

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20
Q

Is the cytoplasmic tail of a TCR long enough to act as a signal transducer?

A

No - it requires CD3

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21
Q

How do T cell antigen receptors (TCRs) differ from the immunoglobulin antigen receptors of B cells?

A
  • TCR has a single antigen binding site whereas B cell antigen receptors have two antigen binding sites
  • Unlike antibody, TCR is never secreted
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22
Q

CD3 (which is required for the cytoplasmic tails of T cell antigen receptors to be able to act as signal transducers) is composed if several invariant polypeptides… What are they?

A

Normal stoichiometry

  • 1 gamma chain
  • 1 delta chain
  • 2 epsilon chains
  • 2 zeta chains
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23
Q

What is the purpose of phosphorylation sites on the cytoplasmic tails of CD3 (part of TCRs)?

A

Signal transduction

24
Q

How do “co-stimulatory molecules” aid in the T cell response?

A

Co-stimulatory molecules

  • Help the T cell to become activated by triggering signal transduction
  • CD28 can then bind to B7
  • CD40 ligand (CD40L) can bind to CD40
  • B7 and CD40 are then expressed on all professional antigen presenting cells
25
Q

What is CD4? Where is it found?

A

CD4

  • A transmembrane glycoprotein consisting of a single polypeptide
  • Expressed on 65% of mature T lymphocytes
  • Most CD4-expressing lymphocytes are T-helper cells
  • They are present in small quantities on the surface of macrophages
26
Q

What is the function of CD4?

A

CD4 is an accessory protein

  • Functions as a cell adhesion molecule
  • Aids signal transduction
  • Restricts T cell responses to recognizing only class II MHC proteins (CD4 binds to invariant regions of class II MHC proteins)
27
Q

What is CD8? Where is it found?

A

CD8

  • An accessory protein
  • Composed of a homodimer or heterodimer
  • Most CD8-expressing lymphocytes are cytotoxic T lymphocytes
28
Q

What is the function of CD8?

A

CD8 function

  • Cell adhesion
  • Signal transduction
  • Restricts T cell responses to recognizing only class I MHC proteins (CD8 binds to invariant regions of class I MHC proteins)
29
Q

What four things occur during signal transduction?

A
  1. TCR binds to MHC-bound antigen
  2. Early activation events
  3. Gene transcription
  4. Mitosis
30
Q

During signal transduction, what happens when TCR binds to MHC-bound antigen?

A
  • Clustering of the TCRs with multiple MHC-peptide complexes
  • As few as 10 MHC-peptide complexes can trigger T cell activation
31
Q

During signal transduction, what happens during early activation?

A
  • Phosphoinositide pathway is activated, RAS is activated, and therefore the MAP kinase pathway is activated
  • Protein kinase C and other kinases phosphorylate transcription factors
32
Q

During signal transduction, what happens during gene transcription?

A
33
Q

During signal transduction, what happens during mitosis?

A
  • Expands antigen-specific clones to amplify an immune response
  • Mitosis is detected 48-72 hours after stimulation through the TCR
34
Q

What are the two subsets of T helper cells?

A

TH1 (T helper cell 1) and TH2 (T helper cell 2)

35
Q

What is similar about the two subsets of T helper cells (TH1 and TH2)? What is different?

A

Same:

  • Both TH1 and TH2 develop from the same antigen naïve CD4+ T cell precursors (called a Th0 cell)

Defferent:

  • TH1 and TH2 cells have very different immune functions
36
Q

What is the role of TH1 cells?

A

TH1 cells

  • Direct the immune response toward cell-mediated immunity
  • They do this my producing interferon-gamma (IFN-gamma)
  • Also by activating macrophages and CTLs
37
Q

What do TH1 cells develop from?

A

Development

  • TH1 cells develop from uncommitted naive T cells
  • This occurs when the naive T cells receive the proper cytokine signal
38
Q

The presence of ____________ signals uncommitted naive T cells to develop into TH1 cells instead of TH2 cells during conditions of inflammation

A

Answer = Interleukin-12 (IL-12)

  • This is produced under conditions of inflammation as caused by various bacteria, viruses and other pathogens
39
Q

What is present during inflammation that encourages the production of interleukin-12?

A

Macrophages

40
Q

What is achieved by activating macrophages?

A

Enhanced microbial killing

41
Q

What are two ways to stimulate the differentiation and development of cytotoxic T lymphocytes (CTLs)?

A
  1. CD4+ helper T cells produce cytokines - this stimulates CTL differentiation
  2. CD4+ helper T cells enhance the ability of APCs to stimulate CTL differentiation
42
Q

What is the role of TH2 cells?

A

TH2 cells…

  • Direct the immune response toward IgE production for anti-parasite defense
  • Particularly helminth (i.e. worm) infestations
  • They do so through the production of IL-4, IL-5 and IL-13
43
Q

How do TH2 cells develop?

A

TH2 development

  • TH2 cells develop from uncommitted naive T cells when exposed to interleukin-4 (IL-4)
  • IL-4 is thought to be produced by mast cells or antigen-activated T cells
44
Q

When will the immue response take the TH2 pathway instead of the TH1 pathway?

A

In the absence of inflammation - the immune response will default to the TH2 pathway when no inflammation in present

45
Q

Are TH1 and TH2 immune responses seen at the same time?

A

No, not usually

  • As a regulatory immune mechanism, there is an antagonistic effect of Th1 and Th2 cytokines, therefore Th1 cytokines inhibit Th2 responses and, conversely, Th2 cytokines inhibit Th1 responses
  • Therefore, an immune response usually is dominated by either a Th1 or Th2 response
  • Mixed responses can be seen under some circumstances
46
Q

What are TH17 cells?

A

Promotors of inflammation

  • They do this by producing IL-17 and IL-22
47
Q

How do TH17 celld develop?

A

TH17 cell development

  • Develop from uncommitted naive T cells when exposed to IL-1, IL-6 and transforming growth factor-beta (TGF-B)
48
Q

When are IL-1 and IL-6 produced? What do they do?

A

IL-1 and IL-6

  • Produced by dendritic cells during anti-microbial defense
  • They are considered to be inflammatory cytokines
  • They allow for TH17 cells to develop from naive T cells
49
Q

What is the source of TGF-B? (the other factor that allows for TH17 cell development)

A

Transforming growth factor-beta (TGF-B)

  • The source of TGF-B includes various cell types
  • There is no one specific source
50
Q

What is the role of IL-23?

A
  • IL-23 serves to stabilize TH17 (a T helper cells that promotes inflammation)
  • Also, IL-23 is produced by dendritic cells
51
Q

Recall the antagonistic effect of TH1 and TH2 cytokines… How are these regulated?

A

Antagonistic effect of TH1 and TH2 cytokines

  • IFN-gamma inhibits the TH2 response
  • IL-4 and IL-13 inhibit the TH1 response

Recall that the immune response is usually dominated by either a TH1 or a TH2 response

52
Q

What are the 3 main functions of a CTL? (cytotoxic T lymphocyte)

A

Cytotoxic T lymphocyte (CTL)

  1. Destroys intracellular microbes (viruses and some bacteria)
  2. Destroys some tumor cells
  3. Destroys transplanted tissues and organs
53
Q

Is CTL activation part of the TH1 or TH2 pathway?

A

CTL activation is part of cell-mediated immunity stimulated by the TH1 cells

54
Q

How do CTLs recognize endogenous peptides that are presented on class I MHCs?

A

Antigen recognition through the TCR and the binding of CD8

55
Q

The CTL killing process is a 5 step process… What are the 5 steps?

A
  1. Target cell binding and recognition of class I MHC and antigen
  2. CTL activation
    • CTL becomes activated due to the signal transduction cascade that occurs with TCR binding
  3. Delivery of the “lethal hit”
    • There are two different mechansims (next cards)
  4. Disengagement from the target cell in order to attack other target cells
  5. Death of the target cell
56
Q

There are two mechanisms for delivering the “lethal hit.” What is the primary/principle mechanism?

A

Principle mechanism

  • Perforin facilitates deliver of granzyme B to the target cell cytoplasm
  • Granzyme B activates the caspase pathway, which leads to target cell death through the mitochondrial pathway of apoptosis
57
Q

What is the secondary mechansim for CTL killing by “lethal hit”?

A

Secondary mechanism

  • First, the target cell’s Fas protein will bind to a Fas ligand expressed by the CTL
  • This activates the caspase pathway
  • Leads to apoptosis of the target cell

Immunology Exam 1 (8 decks)

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