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MICR > L5 Adaptive Immume Reksponse > Flashcards

L5 Adaptive Immume Reksponse Flashcards

1
Q

Helper T lymphocytes (CD4)

A

secrete cytokines that stimulate different mechanisms of immunity and inflammation.

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2
Q

Cytotoxic T lymphocytes (CD8)

A

kill any type of host cells (including nonphagocytic cells) that harbor infectious microbes, such as viruses in the cytoplasm

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3
Q

The class I MHC pathway converts proteins in the_____ into peptides that bind to MHC-I molecules for recognition by _____cells

A

cytosol
CD8 + cytotoxic T

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4
Q
A
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5
Q

The class II MHC pathway converts protein antigens that are_____ into vesicles of antigen-presenting cells into peptides that bind to MHC-II molecules for recognition by ____ cells

A

endocytosed
CD4 + helper T

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6
Q

T-cells will travel from where to develop the thymus

A

Bone marrow

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7
Q

Mature T-cells will leave the thymus to travel to the secondary ____

A

lymphoid tissues

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8
Q

Cell lineage of a T-cell

A

▪ T-cell precursors travel from the bone marrow to
develop in the thymus
▪ Mature T cells leave the thymus and travel to
secondary lymphoid tissues

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9
Q

T cells can be distinguished from other lymphocytes like B cells as the maturation and differentiation of T cells occurs where.

A

in the thymus

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10
Q

T cells are different from other lymphocytes as these have what on their surface

A

a T-cell receptor on the surface, which is absent in other lymphocytes.

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11
Q

Positive selection [T-cell]

A

In the positive selection, the CD4+ cells interact well with class MHC molecules, whereas the CD8+ cells interact well with class II MHC molecules.

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12
Q

What happens to T-cells that don’t. recognise MHC molecules

A

They don’t receive
survival signals and die by programmed cell death

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13
Q

Negative selection [T-cell]

A
  • process where all T cells are screened to check for strong recognition of self-antigens.
  • eliminates developing lymphocytes whose antigen receptors bind strongly to self antigens present in the lymphoid organs.
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14
Q

What happens to T-cells that react strongly to Self-antigens?

A

The cells that interact too strongly with the self-antigens receive an apoptotic signal resulting in cell death.

Avoiding that self-reactive T cells escape
to the periphery

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15
Q

True or False: every T-cell has a different T-cell receptor

A

True

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16
Q

What is self-tolerance

A

When the immune system can identify and won’t react to self-antigens.

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17
Q

Central tolerance Vs Peripheral tolerance

A

C:
* During lymphocyte development development (in thymus or bone marrow for T/B cells)
* Immune cells that bind to self antigen eliminated
* modifies number of naive lymphocytes circulating the periphery
P:
* After lymphocytes mature and go to lymph nodes
* prevent autoreactive immune cells from causing damage in the periphery
*

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18
Q

Immunologic tolerance

A

lack of response to antigens induced by exposure of lymphocytes to these antigens

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19
Q

What is the underlying cause of autoimmune disease?

A

Failure of self-tolerance

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20
Q

The principal mechanisms of central tolerance in T-cells

A
  • Immature T-cell death (neg selection)
  • Generation of CD4+ regulatory T-cells
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21
Q

When does peripheral tolerance lead to functional inactivation (anergy)/death/ suppression?

A

when the self-reactive lymphocytes are suppressed by regulatory T cells

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22
Q

Name the 2 types of TCR

A

αβ TCRs and γδ TCRs

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23
Q

What are the names of the antigen-recognising domains of receptors

A

Variable regions (V)
Constant regions (C)

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24
Q

Antigen receptor chains are associated with invariant membrane proteins whose function is to deliver intracellular signals following antigen recognition

A

Just a fact to learn

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25
Q

Invariant membrane proteins function

A

Deliver intracellular signals after antigen recognition

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26
Q

True or False: Each clone expresses the same TCR specificity

A

False
Each clone expresses a single TCR specificity

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27
Q

CD3 complex structure

A

Heterodimer with an alpha (α) and beta (β) polypeptide chain with each polypeptide containing a constant and a variable region.

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28
Q

All T-cells contain which cell marker CD_

A

CD3

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29
Q

How can T-cells be found within WBC

A

Via CD3 cell markers

30
Q

APCs provide additional signals required for T cell
activation

A

Fact

31
Q

First signal that APCs provide for T-cell activation

A

– presentation of the antigen by an APC (CD4 and CD8 co-receptors on T cells stabilise interaction of TCR and MHC/peptide)

32
Q

2nd signal that APCs provide for T-cell activation

A

Dendritic cell presents B7 (CD80/CD83) to T cells (CD28 receptor)

33
Q

3rd signal that APCs provide for T-cell activation

A

Release of cytokines by APC and T cells themselves (IL-2), driving T cell proliferation, survival and differentiation

34
Q

DC pathway simple

A
  1. Antigen captured by DC
  2. Activation of DC
  3. Migration of DC
  4. Maturation of migrating DC
  5. Mature DC presents antigen to naive T-cell
35
Q

What is enough for a Naive T-cell [simpleish]

A
  1. Naive T-cell
  2. Need TCR
  3. Signal CD28
  4. More cytokines Il2 and Il12 differentiate to helper T-cells
36
Q

APCs for T-cell activation you need to look at slide 10 on L5

A

look at it

37
Q

Adhesion molecules for T-cell activation

A

LFA-1 and ICAM-1

38
Q

What provide additional signals required for T cell activation?

A

APCs

39
Q

Several proteins that are homologous to B7 or CD28 function to stimulate or inhibit ____?

A

immune responses

40
Q

What two molecules are needed to activate naive T-cells

A

B7 and CD28

41
Q

What inhibits B7-CD28 interaction and how

A

CTLA-4 blocks and removes B7 molecules from the surface of APCs, reducing costimulation by CD28 and preventing the activation of T cells

42
Q

After T-cells act they express what on the surface to increase preferential binding to B7 and suppress activation of T-cells

A

CTLA-4

43
Q

Which molecules will inhibit kinase dependent activating signals from CD28 and the TCR complex?

A

PD-1 is expressed on T cells after antigen stimulation, and acts by inhibiting kinase dependent activating signals from CD28 and the TCR complex

44
Q

What is an example for application for blocking T-cell activation

A

Therapeutic application in cancer immunotherapy (checkpoint blockade, immune checkpoint inhibitors)

45
Q

IL12 differentiate into what

A

Helper T-cell 1

46
Q

IL4 differentiates into

A

Helper T-cell 2

47
Q

T lymphocytes activated by
antigen and costimulation begin to what

A

proliferate

48
Q

When are memory cells formed and how long do they last?

A

During primary adaptive immune response and can persist for extended periods in the absence of the og antigen.
▪ Memory T cells undergo metabolic reprogramming to
survive long-term
▪ More sensitive to restimulation by antigen than naïve T cells
▪ Memory T cells proliferate more rapidly and robustly compared to their naive precursors

49
Q

Memory cells

A

▪ Formed during primary adaptive immune response
▪ Memory T cells undergo metabolic reprogramming to survive long-term
▪ More sensitive to restimulation by antigen than naïve T cells
▪ Memory T cells proliferate more rapidly and robustly compared to their naive precursors

50
Q

T-helper 1 cells function

A

Further activate macrophages (boost them)

51
Q

T-helper 2 cells funtion

A

Respond to helminth infection (parasites in gut) will secrete more
1. mucus
2. Peristalsis
3. Contractility

52
Q

T-helper 17 function

A

In mucosal sites to fight antifungal infections and activate phagocytosis of yeast (and extracellular bacteria)

53
Q

T follicular helper cells (T-FH)

A

Affects all microbes

54
Q

T-reg

A

Regulates activated T-cells

55
Q

Th0 and IL4 pathway to helper cell

A

T-H0
↓
IL4
↓
T-H2
↓ activate
IL-4, IL-5, IL-13 (6 as well) (cytokynes)
↓
Activates B-cell

56
Q

TH0 and Il-12 and INF-gamma to Helper

A

TH0
↓
TH1
↓ activate
IL-2 and INF-gamma
↓
Activates CD8 and macrophages

57
Q

Cytokines that are produced by DCs during immune synapsis and trigger the differentiation of naïve T cells (Th0)

A

IL-4
IL-12
IL-any number

58
Q

Th17 cells develop in response to [what] and induces [what]?

A

extracellular bacterial and fungal infections and induce inflammatory reactions that destroy these organisms

59
Q

Regulatory T cells main function

A

Regulatory T cells main function is to suppress immune response

60
Q

CD4+ helper T cells – Th1

A
  • DCs produce INF-gamma & IL-12 which TH0 differentiates to TH1.
  • Th1, acting through CD40 ligand and IFN- γ , increase the ability of macrophages to kill phagocytosed
    microbes
61
Q

T cells mediate protection against Mycobacterium tuberculosis

A

▪ IFN-γ is produced by Th1 cells,
▪ IFN-Y contribute to the recruitment of monocytes and granulocytes and activate the antimicrobial activity of macrophages - phagosome maturation, production of reactive nitrogen intermediates and antigen presentation
▪ T cells participate in granuloma formation, the pathologic hallmark of tuberculosis

62
Q

HiV on TB

A

CD4 T cells deficiency (e.g., HIV+) dramatically increases susceptibility to both primary and reactivation tuberculosis

63
Q

CD4+ Helper T cells – Th2

A

▪ DCs produce IL-4 = Th0 → Th2 cells
▪ Th2, secrete IL-4, IL-5 and IL-13, to stimulate antibody responses and defend
against helminth parasites
▪ Th2 cytokines inhibit activation of classical macrophages (microbicidal and proinflammatory), and stimulate alternative pathway of macrophage activation - important in tissue repair and fibrosis

64
Q

Th2 cells are involved in allergic reactions to environmental antigens . What do repeat exposure to allergens trigger?

A

Triggers mast cell and eosinophil activation

65
Q

CD4+ Helper T cells – Th2 picture look at it

A

SLIDE 21 on L5

66
Q

CD8+ T cells

A
  • Activated upon binding to non-self antigen presented by DC in the context of MHC-I
  • CD8 + T lymphocytes recognise peptides on infected cells and tumor cells expressed in MHC-I molecules
  • Cytotoxic T lymphocytes (CTL) uses perforin and granzymes to destroy infected cells
  • look at slide
67
Q

Cytotoxic T cells effector functions

A

▪ Perforin disrupts integrity of target cell plasma membrane and endosomal membranes - facilitates the delivery of granzymes into cytosol
▪ Granzymes activate enzymes caspases that are present in cytosol of target cells and whose major function = induce apoptosis

68
Q

Cooperation between CD4+ and CD8+ T cells

A

▪ In a macrophage infected by an intracellular bacterium, some bacteria are sequestered in vesicles (phagosomes), and others may escape into the cytosol
▪ CD4 + T cells recognise antigens derived from vesicular microbes and activate macrophages to kill microbes in vesicles
▪ CD8 + T cells recognise antigens derived from cytosolic bacteria and are needed to kill infected cell -> eliminating reservoir of infection.

69
Q

IL-4 pathway simple - hel,inth parasites

A

IL-4 produced by DCs lead to the differentiation of naïve CD4+ T cells into Th2 cells. Th2, acting through IL-4, IL-5 and IL-13, stimulate antibody responses and defend against helminth parasites

70
Q

INF-γ and IL-12 pathway to kill microbes

A

INF-γ and IL-12 produced by DCs lead to the differentiation of naïve CD4+ T cells into Th1 cells. Th1 cells increase the ability of macrophages to kill phagocytosed microbes via CD40 ligand and IFN- γ

71
Q

After the antigen is eliminated, contraction occurs (homeostasis/ equilibrium). However, some T cells differentiate into memory T cells, which are long-lived cells with an enhanced ability to react against the antigen

A

Read and understand

72
Q

CD4 + helper T cells express molecules that recruit and activate other leukocytes to phagocytose and destroy microbe. CD4+ T cells include ???

A

Th1, Th2, Th17 and T-regs

MICR (18 decks)

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