35. Cell-mediated immunity Flashcards

(64 cards)

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
FUNCTION of PERFORIN secreted by CD8 CYTOTOXIC T-cells to eliminate pathogen-infected cells
form PORES in MEMBRANE of virus-infected target cell
26
FUNCTION of GRANZYMES secreted by CD8 CYTOTOXIC T-cells to eliminate pathogen-infected cells
cause APOPTOSIS - activate CASPASES
27
FUNCTION of GRANULYSIN secreted by CD8 CYTOTOXIC T-cells to eliminate pathogen-infected cells
- contributes to APOPTOSIS - has ANTI-MICROBIAL activity - stop virus reproducing in cell
28
what do CD8 CYTOTOXIC T-Cells also SECRETE
CYTOKINES to ATTRACT MACROPHAGES (eat up viral particles from apoptosis - Degraded cells rapidly removed by macrophages)
29
CD4 HELPER T cells work largely by secreting..
CYTOKINES -COMMUMICATE with other IMMUNE CELLS and ACTIVATE OTHER EFFECTOR CELLS to eliminate the pathogens by appropriate immune responses
30
CD4 HELPER T-Cells secrete DIFFERENT CYTOKINES by different..
Th SUBSETS defined by the different cytokines they produce
31
once ACTIVATED, CD4+ HELPER T-cells....
DIFFERENTIATE into DIFFERENT SUBSETS - secreting DIFFERENT CYTOKINES
32
CD4+ SUBSETS (4)
- TH1, - TH2, - TH17, - T REG (t-regulator cell)
33
how do we get DIFFERENTIATION into DIFFERENT SUBSETS of CD4
- DIFFERENT CYTOKINES activate DIFFERENT COMBINATIONS of TRANSCRIPTION FACTORS - Expression of DIFFERENT GENES - DIFFERENTIATION of NAIVE CD4+ into different subsets TH1, TH2, TH17, Treg
34
Why is there such DIVERSE TYPES (SUBSETS) of HELPER T cells needed by our immune system?
Our body comes across MANY TYPES of PATHOGENS & infections * Different target sites * Different target cells Specialised responses for each pathogen/target site required`
35
what do TH1 HELPER T cells respond to
Intracellular Infection - VIRUS
36
what is secreted by antigen-presenting cell to stimulate differentiation of TH1
IL-12
37
what does TH1 helper T secrete
IL-2 IFN-GAMMA (interferon gamma)
38
what does IL-2 secreted by TH1 HELPER T cells do
promote GROWTH & DIFFERENTIATION of other T CELLS
39
what does IFN-GAMMA secreted by TH1 HELPER T cells do (2)
- ACTIVATES of MACROPHAGES & enhanced PHAGOCYTOSIS - UPREGULATES MHC EXPRESSION (more easily recognised by T-cells)
40
TH1 HELPER T cells stimulate production of...
ANTIBODIES (by secreting cytokines)
41
what do TH2 HELPER T cells respond to
PARASITIC infections
42
how do TH2 HELPER T cells KILL PARASITES
Stimulates B cells (class switch) for IgE antibody production Activates MAST CELLS and EOSINOPHILS to release TOXIC MOLECULES to kill parasites
43
TH2 HELPER T cells INDUCE PRODUCTION of..
MUCUS in INTESTINES (Stop parasites penetrating through gut wall)
44
TH2 HELPER T cells SECRETE
IL-4 IL-5 IL-13
45
TH2 HELPER T cells differentiation from naive CD4 is activated by APC cells releasing
IL-4
46
what do TH-17 HELPER T cells respond to
infection by Extracellular BACTERIA or FUNGI
47
how do TH-17 HELPER T cells KILL infections by BACTERIA/FUNGI
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
what does APC release to stimulate DIFFERENTIATION of Naive CD4 into TH17 SUBSET
IL-6 TGF-GAMMA
49
what does TH-17 HELPER T cell release
IL-17 IL-22
50
what is the role of T REG HELPER T cells
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
what does the role of Treg HELPER CELLS PREVENT by TOLERANCE
AUTO-IMMUNITY
52
what do T-REG HELPER T cells SECRETE to suppress T cell responses
IL-10 TGF-BETA
53
Recently recognised T cell subset : Follicular helper T cells (Tfh)
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
which CD4 HELPER SUBSET responds to PARASITES
TH2 help IgE antibody production eosinophil and mast cell activation
55
which CD4 HELPER SUBSET responds to EXTRACELLULAR BACTERIA & FUNGI
TH-17 produce antimicrobial peptides & cytokines & recruit neutrophils (by IL-8)
56
which CD4 HELPER SUBSET responds to VIRUSES
TH-1 macrophage activation
57
which CD4 HELPER SUBSET produces IL-17, IL-22
TH-17
58
which CD4 HELPER SUBSET produces IL-2, IFN-GAMMA
TH-1
59
which CD4 HELPER SUBSET produces IL-4, IL-5, IL-13
TH-2
60
which CD4 HELPER SUBSET produces IL-10, TGF-BETA
T REG
61
which CD4 HELPER SUBSET prevents auto-immunity
T-REG
62
which CD4 HELPER SUBSET IS stimulated by IL-12
TH-1
63
which CD4 HELPER SUBSET IS stimulated by IL-6 & TGF-BETA
TH-17
64
which CD4 HELPER SUBSET IS stimulated by IL-4
TH-2