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IMMUNOLOGY (foundation B) > 35. Cell-mediated immunity > Flashcards

35. Cell-mediated immunity Flashcards

1
Q

pathway of how T CELLS are formed (5 steps)

A

1.HAEMATOPOEITIC STEM CELLS in BONE MARROW

  1. DIFFERENTIATE into LYMPHOID PROGENITORS
  2. become PRO-T CELLS which MIGRATE TO THYMUS
  3. known as THYMOCYTES in thymus
  4. MATURE to become T CELLS
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2
Q

how do thymocytes MATURE to become T CELLS
- creating DIVERSITY within ANTIGEN BINDING REGIONS of T cell RECEPTORS

A

REARRANGE T cell ANTIGEN RECEPTOR GENES RANDOMLY to form unique antigen binding pocket

REARRANGE V (variable) D (diversity) and J (joining) GENE SEGMENTS RANDOMLY
for both ALPHA and BETA CHAINS

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3
Q

what is EDUCATION of T CELLS

A

many REACT STRONGLY with SELF ANTIGENS and are DELETED

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4
Q

all RECEPTOR proteins on any ONE LYMPHOCYTE (clone) have

A

the SAME EPITOPE SPECIFICITY

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5
Q

majority of T CELLS express a … T CELL ANTIGEN RECEPTOR

A

ALPHA BETA T cell antigen receptor

(alpha and beta chains)

  • CD4+
  • CD8+
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6
Q

approx 5% of T cells express which T-cell Receptor

A

gamma-delta

(very low number, unclear function)

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7
Q

T CELLS REQUIRE

A

ANTIGEN PRESENTATION on MHC molecules on antigen-presenting cells or virus-infected cells

  • cannot recognise free antigens
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8
Q

CD8+ T CELLS recognise

A

ENDOGENOUS antigens (inside cell)

presented on MHC CLASS I

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9
Q

CD4+ T CELLS recognise

A

EXOGENOUS antigens (captures from outside cell)

presented on MHC CLASS II

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10
Q

T cells develop as Thymocytes in the Thymus and interact with…

A

STROMAL CELLS

which ACTIVATES them
- gives rise to ALPHA BETA T cells

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11
Q

what is CD3

A

common cell surface MARKER found on ALL T-Cells

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12
Q

what is an Immature DOUBLE-NEGATIVE THYMOCYTE

A

LACKS EXPRESSION of CD4 & CD8 RECEPTORS

subdivided into expression of CD44, CD25

DN4: EXPRESS BOTH CD44, CD25
DN3: EXPRESS CD25, LACK CD44

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13
Q

what is an Immature DOUBLE-POSITIVE THYMOCYTE

A

EXPRESS CD4 & CD8 RECEPTORS

rearrange t cell receptor alpha chain loci
migrate to thymus - mature

downregulation of either CD4 or CD8

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14
Q

what happens to T-Cells that REACT too STRONGLY to SELF-ANTIGENS or MHC

A

undergo APOPTOSIS
- DELETION

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15
Q

what on the T cell forms a COMPLEX to recognised the presented ANTIGEN

A

T-cell RECEPTOR
CD8/CD4
CD3

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16
Q

how do T and B CELL RECEPTORS have VARIABLE REGION - UNIQUE antigen-binding pocket

A

by VDJ RECOMBINATIONS

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17
Q

SIMILARITIES between T and B CELL RECEPTORS

A

-CONSTANT and VARIABLE regions
- 2 DIFFERENT CHAINS

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18
Q

DIFFERENCES between T and B CELL RECEPTORS

A

B CELL:
Recognise free antigen
Receptor SECRETED (antibodies)

T CELL:
Recognise MHC-bound peptides
Not secreted

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19
Q

what happens when T-CELLS ENCOUNTER specific presented ANTIGEN in lymphoid tissue

A

becomes ACTIVATED

undergoes PROLIFERATION : CLONAL EXPANSION

& DIFFERENTIATION into
EFFECTOR CELLS and MEMORY CELLS

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20
Q

T cell pathway
development - maturation - activation - action

A
  1. T-cell precursors migrate from bone marrow to thymus and REARRANGE its T-cell receptor genes
    - VDJ Rearrangement
  2. SELECTION - immature T-cells that recognise self-antigens too strongly are REMOVED.
    only thymocytes with LOW AFFINITY to self-antigens/MHC MATURE
  3. Mature T-cells exit thymus and encounter foreign ANTIGEN in lymphoid organs - ACTIVATED
  4. PROLIFERATION and DIFFERENTIATION to eliminate infection (as either CD4+ or CD8+)
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21
Q

FUNCTIONS of CD8 T-CELLS

A
  • Detect and eliminate VIRUS-INFECTED CELLS before they can shed virus particles to infect other cells
  • Recognise and kill “altered-self” cells e.g. TUMOUR CELLS
  • Produce CYTOTOXIC MOLECULES that trigger APOPTOSIS
  • RELEASE CYTOKINES (attract macrophages)
  • Recognise foreign peptides bound to MHC CLASS I proteins
  • Clonal expansion and differentiation into activated cells and memory cells
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22
Q

how do CD8 T CELLS DESTROY TUMOURS

A

INDUCE APOPTOSIS

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23
Q

presenting ANTIGEN on MHC CLASS 1 to Naïve CD8 T CELLS causes

A

CLONAL EXPANSION & DIFFERENTIATION into
ACTIVATED CYTOTOXIC T CELLS
& MEMORY CYTOTOXIC T CELLS

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24
Q

CD8 CYTOTOXIC T-cells ELIMINATE pathogen-infected cells by releasing

A

CYTOLYTIC GRANULE CONTENTS:

  • PERFORIN
  • GRANZYMES
  • GRANULYSIN
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25
Q

FUNCTION of PERFORIN secreted by CD8 CYTOTOXIC T-cells to eliminate pathogen-infected cells

A

form PORES in MEMBRANE
of virus-infected target cell

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26
Q

FUNCTION of GRANZYMES secreted by CD8 CYTOTOXIC T-cells to eliminate pathogen-infected cells

A

cause APOPTOSIS
- activate CASPASES

27
Q

FUNCTION of GRANULYSIN secreted by CD8 CYTOTOXIC T-cells to eliminate pathogen-infected cells

A
  • contributes to APOPTOSIS
  • has ANTI-MICROBIAL activity - stop virus reproducing in cell
28
Q

what do CD8 CYTOTOXIC T-Cells also SECRETE

A

CYTOKINES
to ATTRACT MACROPHAGES

(eat up viral particles from apoptosis
- Degraded cells rapidly removed by macrophages)

29
Q

CD4 HELPER T cells work largely by secreting..

A

CYTOKINES

-COMMUMICATE with other IMMUNE CELLS
and
ACTIVATE OTHER EFFECTOR CELLS to eliminate the pathogens by appropriate immune responses

30
Q

CD4 HELPER T-Cells secrete DIFFERENT CYTOKINES by different..

A

Th SUBSETS

defined by the different cytokines they produce

31
Q

once ACTIVATED, CD4+ HELPER T-cells….

A

DIFFERENTIATE into DIFFERENT SUBSETS
- secreting DIFFERENT CYTOKINES

32
Q

CD4+ SUBSETS (4)

A
  • TH1,
  • TH2,
  • TH17,
  • T REG (t-regulator cell)
33
Q

how do we get DIFFERENTIATION into DIFFERENT SUBSETS of CD4

A
  • DIFFERENT CYTOKINES activate DIFFERENT COMBINATIONS of TRANSCRIPTION FACTORS
  • Expression of DIFFERENT GENES
  • DIFFERENTIATION of NAIVE CD4+ into different subsets TH1, TH2, TH17, Treg
34
Q

Why is there such DIVERSE TYPES (SUBSETS) of HELPER T cells needed by our immune system?

A

Our body comes across MANY TYPES of PATHOGENS & infections
* Different target sites
* Different target cells

Specialised responses for each pathogen/target site required`

35
Q

what do TH1 HELPER T cells respond to

A

Intracellular Infection - VIRUS

36
Q

what is secreted by antigen-presenting cell to stimulate differentiation of TH1

A

IL-12

37
Q

what does TH1 helper T secrete

A

IL-2
IFN-GAMMA (interferon gamma)

38
Q

what does IL-2 secreted by TH1 HELPER T cells do

A

promote GROWTH & DIFFERENTIATION of other T CELLS

39
Q

what does IFN-GAMMA secreted by TH1 HELPER T cells do (2)

A
  • ACTIVATES of MACROPHAGES &
    enhanced PHAGOCYTOSIS
  • UPREGULATES MHC EXPRESSION
    (more easily recognised by T-cells)
40
Q

TH1 HELPER T cells stimulate production of…

A

ANTIBODIES
(by secreting cytokines)

41
Q

what do TH2 HELPER T cells respond to

A

PARASITIC infections

42
Q

how do TH2 HELPER T cells KILL PARASITES

A

Stimulates B cells (class switch) for IgE
antibody production

Activates MAST CELLS and EOSINOPHILS to release TOXIC MOLECULES to kill parasites

43
Q

TH2 HELPER T cells INDUCE PRODUCTION of..

A

MUCUS in INTESTINES
(Stop parasites penetrating through gut wall)

44
Q

TH2 HELPER T cells SECRETE

A

IL-4
IL-5
IL-13

45
Q

TH2 HELPER T cells differentiation from naive CD4 is activated by APC cells releasing

A

IL-4

46
Q

what do TH-17 HELPER T cells respond to

A

infection by Extracellular BACTERIA or FUNGI

47
Q

how do TH-17 HELPER T cells KILL infections by BACTERIA/FUNGI

A

IL-17 & IL-22 Stimulate ENDOTHELIAL CELLS,
FIBROBLASTS & MACROPHAGES
- to produce ANTIMICROBIAL PEPTIDES
& CYTOKINES (e.g. IL-6, IL-8, TNFa)

  • INDIRECTLY RECRUITS NEUTROPHILS to
    infection sites
    (IL-8 from other cells which IL-17 binds to as human neutrophils dont have receptors for IL17)
48
Q

what does APC release to stimulate DIFFERENTIATION of Naive CD4 into TH17 SUBSET

A

IL-6
TGF-GAMMA

49
Q

what does TH-17 HELPER T cell release

A

IL-17
IL-22

50
Q

what is the role of T REG HELPER T cells

A

come at END of infection to SWITCH EVERYTHING OFF
- TOLERANCE (resetting immune system)

BALANCE the PRO-INFLAMMATORY RESPONSE (by TH1,TH17, CD8)

SUPPRESS T cell RESPONSES & limit
inflammation

  • Potent SUPRESSION of MACROPHAGE
    function
  • Prevent auto-immunity
  • Induces generation of more Treg cells
51
Q

what does the role of Treg HELPER CELLS PREVENT by TOLERANCE

A

AUTO-IMMUNITY

52
Q

what do T-REG HELPER T cells SECRETE to suppress T cell responses

A

IL-10
TGF-BETA

53
Q

Recently recognised T cell subset : Follicular helper T cells (Tfh)

A

produce IL-21

critical for B cell differentiation & antibody-production

Reside in Germinal Centres (GC) of lymphoid tissues, closely associated with GC B cells

54
Q

which CD4 HELPER SUBSET responds to PARASITES

A

TH2

help IgE antibody production
eosinophil and mast cell activation

55
Q

which CD4 HELPER SUBSET responds to EXTRACELLULAR BACTERIA & FUNGI

A

TH-17

produce antimicrobial peptides & cytokines
& recruit neutrophils (by IL-8)

56
Q

which CD4 HELPER SUBSET responds to VIRUSES

A

TH-1

macrophage activation

57
Q

which CD4 HELPER SUBSET produces IL-17, IL-22

A

TH-17

58
Q

which CD4 HELPER SUBSET produces IL-2, IFN-GAMMA

A

TH-1

59
Q

which CD4 HELPER SUBSET produces IL-4, IL-5, IL-13

A

TH-2

60
Q

which CD4 HELPER SUBSET produces IL-10, TGF-BETA

A

T REG

61
Q

which CD4 HELPER SUBSET prevents auto-immunity

A

T-REG

62
Q

which CD4 HELPER SUBSET IS stimulated by IL-12

A

TH-1

63
Q

which CD4 HELPER SUBSET IS stimulated by IL-6 & TGF-BETA

A

TH-17

64
Q

which CD4 HELPER SUBSET IS stimulated by IL-4

A

TH-2

IMMUNOLOGY (foundation B) (7 decks)

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