Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology > Lecture - 9 - T cell Immunity (2 lectures together - 1 powerpoint) > Flashcards

Lecture - 9 - T cell Immunity (2 lectures together - 1 powerpoint) Flashcards

1
Q

The following describes which type of cell:

  1. Utilize a primitive MHC type system that recognizes LIPID RICH ANTIGENS
  2. Especially important at
    - respiratory
    - gut
    - urethra
    - skin & endometrium
  3. Produce IL-1 and IL- 6, and IL-17
A

T - gamma delta cells!!

  • precursor to alpha beta during evolution of immune system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Are T gamma delta cells act as cells in innate or adaptive immune system?

A

INNATE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

____ are necessary for optimal functioning of BOTH Cell Mediated Immunity (CMI) and Humoral (B cell immunity)

A

T cells!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What ar the 8 cardinal rules of T cells?

A
  1. T cells are the orchestrators of immune responses
  2. T Cells are necessary for optimal functioning of both cell mediated immunity and B cell immunity
  3. T cell responses are regulated by specific cytokines and T regulator cells (Tr)
  4. Antibodies recognize 3D conformations of antigens, T cells recognize peptides in the context of MHC.
  5. Antigens presented in MHC-I are recognized by CD8 T cells
  6. If an antigen is processed & presented by MHC-II by an APC to a naive CD4 T cell, one of 4 responses can occur:Th1, Th2, Th17 or T reg.
  7. Commitment to a subset depends upon host genetics, type of infection and which type of TLR and cytokine profile dominates the early phase of T cell activation
  8. Each subset has specific functions and is associated with with specific cytokine profiles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Antibodies recognize _______, T cells recognize _____ in the context of what?

A
  1. 3D conformations of antigens

2. peptide fragments in the context of MHC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Antigen processed and presented by MHC - II involves what type of cells?

A

APCs!!

Macrophages and DC’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the 4 responses that can occur if antigen is processed & presented by MHC-II by an APC to a naive CD4 T cell?

A

Th1

Th2

Th17

Treg

T-FH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the roles of the following

  1. Th1
  2. Th2
  3. Th17
  4. Treg
  5. T-FH

Commitment to these responses by the Th0 cell (once an antigen has been presented by Class II MHC to CD4 cell)
depends on what??

A
  1. Th1
    - amplifies CMI by activating MACROPHAGES
    - promotes cytotoxic responses by CD8
  2. Th2
    - Antibody Production
  3. Th17
    - Chronic Inflammation
  4. Treg
    - modulates/suppresses Immune response
  5. T-FH
    - promote optimal high affinity antibody production in germinal center of lymph node

Commitment depends on WHICH TLR IS ACTIVATED and which CYTOKINE profile becomes dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the cytokines and the transcription factors for the following responses:

  1. Th1
  2. Th2
  3. Th17
  4. Treg
  5. T-FH
A
  1. Th1
    - IL 12
    TF: T-Bet
  2. Th2
    IL - 4
    TF: GATA - 3
  3. Th17
    IL - 23
    TF: ROR
  4. Treg
    TGF - Beta
    TF: FOXP3
  5. T-FH
    IL - 6
    TF: BCL6
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the structure of cytokines?

What do they exhibit?

A
  1. Two chain peptides encoded by SEPARATE Genes

2. Pleotropism/redundancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the great communicators of the immune system?

What uses them to regulate the intensity of an immune response?

A
  1. CYTOKINES
  2. Macrophages and DC’s

Most cell/cytokine systems have agonist/antagonist (yin/yang) dynamics

Cytokine actions can vary and are dependent upon the state of the target cell

Abnormal cytokine responses are associated with serious clinical diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

TMMI or T cell Mediated Macrophage Immunity is used for what type of response?

What is always the trigger for TMMi?

Complex antigen phagocytes by a DC will be presented by what?

The recognition and uptake of a living pathogen or complex antigen by a DC triggers conversion of what?

A

Infections by organisms that require phagocytosis & INTRACELLULAR killing
- Th1 response!!

  1. Trigger = TLR on a DC
  2. MHC - Class II!
  3. Immature DC to a mature DC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do mature DC’s do ( once the cell has recognized and uptake the pathogen)?

What do they do to the antigen?

What 2 things do they up regulate?

Where do they migrate?

What specific cytokines are unregulated?

A
  1. Can no longer phagocytose
  2. Processes the antigen to peptide fragments
  3. Upregulates MHC II
  4. Upregulates costimulatory factors (CD28 and CD40L)
  5. Migrates to Lymphoid tissue
  6. Upregulates production of IL-12 and IL-18
C28 = for microorganism
CD40L = for antigen (not technically a microorganism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

IL-12 and IL-18 are cytokines that are unregulated by what cells and when?

A

Unregulated when immature DC converted to Mature DC (once pathogen has been engulfed)

  • in TMMI!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What MHC class does TMMI recognize?

A

MHC Class II - CD4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What 2 cytokines initiate the commitment of Th0 to Th1?

How can this commitment be identified?

Antigen Activated Th1 cells in the presence of these 2 cytokines, up regulate what?

A

IL- 12 and IL-18

By induction of transcription factor T-Bet

Costimulatory factors!

  • CD28
  • CD40L

* required during T cell mediated reactions*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What cytokines does the Th1 (not dendritic cell) provide to propagate the TMMi response?

A

IL - 2 and INF - Gamma

  • committed lymphocyte is producing these (not the dendritic cells)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the Th1 initiation steps:

A

1.DC/MAC
pathogen binds to DC (TLR)

  1. TLR says that it is a pathogen
  2. organism is phagocytosed
  3. TLR tells the cell it needs a Th1
  4. Dendritic cell begins making IL-12
  5. DC has processed the pathogen and presenting part of the peptide as MHC-Class II
  6. The antigen is now presented to Th0 cells
    Th0 cell IN THE PRESENCE OF IL-12 = tells itself to commit to Th1
  7. upregulates IL-12 receptors and IL-12 binds to it
  8. Activates itself to Th1
  9. Upregulates MHC – II and the Costimulatory factors (CD40L and CD28)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

IFN - Gamma:

  1. Is produced by what 3 cells?
  2. Activates ______
  3. Signature cytokine for ____ helper reaction
  4. Upregulator of _____
  5. Suppressor of ____ and ___ responses!!
A

1.

  • activated Th1 (CD4) cells
  • NK cells
  • activated CD8 cells
  1. Macrophages
  2. Th1
  3. MHC - Class II
  4. Th2 and Th17 responses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

IL- 12 activated Th1 cells produce ______.

What is its function?

A
  1. IL-21
  • growth factor (similar to it)
  • potent promoter of CD8 killing activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

IL - 21 in the absence of _____ is potent promoter of B cell growth and development.

A

IFN - Gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the critical growth cytokine produced by activated Th1 and CD8?

What cells are strongly dependent on it?

A

IL - 2

Tregs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

IL - 2 acts in _____ and ____ modes

A

Paracrine & Autocrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Genetic defects in assembly of IL -2 or IL - 2R can result in sever immune deficiency diseases?

A

IL- 2R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When IFN - gamma is dominant, it down regulates what 2 helper responses?

A

Th2 and Th17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the purpose of Th1 reactions?

A

provide antigen specific and efficient way to recruit highly activated macrophages to infection site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

True or False:

A large number of Th1 cells recruit a small number of macrophages

A

FALSE

A small number of Th1 cells recruit a LARGE number of macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the end result of TMMI once the macrophage has been activated?

A

Tetrad of pro-inflammatory cytokines

IL - 1
IL -6
IL - 8
TNF - ALPHA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the 4 pro-inflammatory cytokines?

A

IL - 1
IL -6
IL - 8
TNF - ALPHA

30
Q

What cytokine is released in response to STRESS?

A

IL - 1

31
Q

IL -1 :

  1. Produced by _____ cell types
  2. Promotes _____ growth & emigration from the marrow
  3. Acts with ___ on CNS to cause fever, depression
  4. Neuroendocrine effects on _____ gland.

What is its antagonist?

What does it stimulate to increase Ag presentation?

A
  1. ALL cell types
  2. Neutrophil growth and emigration from bone marrow
  3. IL- 6!!!!
  4. Adrenal gland

IL - 1Ra (antagonist)

Stimulates APC’s!

32
Q

What cytokine is redundant with IL - 1?

A

IL - 6

33
Q

IL - 6:

  1. Is the primary cause of _____ and other signs of infection
  2. Promotes responsiveness to _____
A
  1. FEVER

2. IL -2 accelerates antigen activation

34
Q

How is IL - 6 different from Il - 1?

A

IL - 6 has strong GROWTH and DIFFERENTIATION effects on B cells in the presence of other “B” cell cytokines

  • effects bone mineral metabolism (activates osteoclasts)
35
Q

What pro-inflammatory cytokine is involved in menopausal loss of bone marrow in women?

A

IL - 6

36
Q

What pro-inflammatory cytokine plays a central role in the immune system?

A

TNF - Alpha

37
Q

TNF - Alpha

  1. _____ activator
  2. Activator of _____homing and adhesion molecules
  3. Induces _____
  4. Upregulates _____
A
  1. Macrophage activator
  2. Endothelial
  3. Apoptosis
  4. MHC

Has systemic effects that range from flu-like symptoms to death (can kill you if unregulated)

The availability of anti-TNF biologicals provides a way to manipulate its effects clinically.

38
Q

What is the most potent stimulus for mobilizing and recruiting neutrophils to the site of infection?

It is actually a _____ but acts as a cytokine.

A

IL - 8

CHEMOKINE

39
Q

What produces IL - 8?

A

Macrophages, neutrophils, and endothelial cells (during intense inflammation)

40
Q

What is delayed hypersensitivity?

What can it be used to detect?

A

Archaic term for TMMI

  • DH or TMMI can be used to detect pas infections
    ex: tuberculosis
41
Q

TB skin testing proves what?

A

Why a TMMi is called DH

Patient with TB coughs on tired first year resident
first year resident inhales organism and it is subsequently phagocytized by a lung macrophage/dc which migrates to the hilum
TB antigens presented to T cells
TB specific CD4 Th1 cells migrate to site, activate macs that can now kill or suppress TB*

  • Many years later…..physician skin tested with dead TB antigens
    which are phagocytosed by mac/DC at site and presented to passing TB specific CD4
    CD4 recruit more macs which then form a papule over next 24-48
  • bump = ACTIVATED MACROPHAGES
42
Q

Lymphocyte Cytotoxic Immunity is Antigen specific.

True or False?

A

FALSE!

  • it is not antigen specific, TMMI is antigen specific!!!!
43
Q

Lymphocyte Cytotoxic Immunity relies on what cells?

  1. What do these cells lack?
  2. Do they require MHC?
  3. What INF do they produce?
A
  1. Lack CD3 or alpha beta or delta gamma chains
    - no Ag receptors
  2. Not MHC restricted
  3. Produce INF- Gamma
    - activate macrophages!
44
Q

How is NK cytotoxicity suppressed?

What happens in the absence of self-MHC?

A

Suppressed by killer cell inhibitory receptors (KIR) on surface that recognize NORMAL SELF - MHC Class I markers

  • In absence of self MHC - KIR will be turned off ONLY if the target cell has an NK activation receptor
45
Q

Why don’t NK cells attack RBCs?

What is the main purpose of Nk cells?

A

RBC’s lack the NK activating receptor!!!

(do not have an MHC, but in order for KIR to be completely off it also needs the NK activating receptor!!)
= smart evolution

  1. But time for CD8 cells to develop (antigen specific response)
46
Q

What can NK cells mediate?

How?

A

Antibody Dependent Cell Mediated Cytotoxiity (ADCC)

  • via Fc receptors
47
Q

Besides NK cells utilizing cytotoxic mechanisms similar to CD8 cells, what other cytotoxic response can they mediate?

What do they need for this response?

A

Antibody Dependent Cell Mediated Cytotoxicity (ADCC)

  • need Fc receptors
  • NK cells do not have antigen specific action, but can use the antibodies as “bombs”
  • cause apoptosis once the NK cell FC receptors cross link
48
Q

What is the purpose of the CD3+ CD8+ subset?

How does CD8 recognize the antigen ? (which MHC) What type of antigen is this (exogenous/endogenous)?

A

Highly specific defensive capacity that enables this lineage to DIRECTLY kill foreign, infected, or mutated cells by ANTIGEN SPECIFIC cytotoxic mechanisms

(NK cells are NOT antigen specific)

  1. Recognizes ENDOGENOUS antigen in MHC - I determinant
49
Q

What is preferably required for optimal activation of CD8 cells?

What are the initial cytokine signals?

What produces these cytokines to promote a continuing CD8 response?

A
  1. Activation of CD4 helper cells (antigen specific) and NK cells, and/or memory cells
  2. IL-21, IL-2 and IFN - gamma
    * IL-21 w/ IFN -g**
  3. Antigen Activated CD4 cells continue to produce IL-21, IL-2, and IFN-Gamma to promote CD8 response
50
Q

For Th1, the inititating cytokine was IL-12 (IL-18), but what to CD8 cells need to become cytotoxic?

A

Activated NK cells (to recognize viral infected cells)

  • CD4 helper cells
  • memory cells
51
Q

What are the critical “co-stimulatory” cytokines.signals that activate CD 8 cells?

WHAT IS THE MOST IMPORTANT INFLUENCE ON THE DEVELOPMENT OF CTL? (Cytotoxic T cells?)

What is the potent proliferative stimulus to antigen activated CD8 cells?

A
  1. IFn - gamma and IL-2
  2. parallel development of CD4 T helper cells!
    - they produce IL-2 and IL-21 and IFN-Gamma
  3. IL-21
    - also enhances CD8 killing mechanisms
52
Q

Which of the following is antigen independent and which is antigen dependent?

  1. Nk cell
  2. CD8 Cytotoxic T cell
A
  1. ANTIGEN INDEPENDENT

2. Antigen dependent

53
Q

Once activated, do CD8 cells require further costimulatory signals?

What are they dependent on?

A

NO!

  • to maintain cytotoxicity does not require B7 etc
  • WHY? Sine more viral infected cells are SOMATIC
    (lung, gut, skin etc)

ONLY NEEDS IFN-GAMMA

  1. Dependent on VIRAL DISPLAY on targets
54
Q

Although an APC is not infected with viruses, they can RECOGNIZE viruses with ____ and phagocytose viral particles.

Sine they also display MHC Class II just like bacterial antigens, what is the only difference?

What is the advantage and disadvantage to this process?

A
  1. TLR
  2. APC exports some antigen into the CYTOSOL and loads them on to MHC Class I

Advantage: this maximizes CD 8 activation
Disadvantage: eventual APC death

55
Q

What happens if an activated CD8 no longer has a specific target & is not displaying viral antigens?

What is the ONLY WAY to turn off cytotoxicity?

A

ACTIVATE cell death by Fas/FasL

This deletes about 90% of the expanded CD8 population

The remaining ~10% become memory cells

  1. KILL ALL VIRAL ANTIGENS in order to turn off cytotoxicity (ex: mono - genetic defect that prevents cytotoxic T cells from being turned off)
56
Q

What Transcription factor is needed for Th2 response?

What cytokine?

When will this occur?
(3)

A
  1. GATA 3
  2. IL-4

Occur when
1. a Th1 TLR is NOT engaged and IL-12 is not produced

  1. There are TLRs that induce DCs to produce IL-4 instead of IL-12
  2. when B cells present antigen
    - efficient development of high affinity specific antibodies and memory cells
57
Q

A lot of IL-4 will skew the section from Th0 into _____

A

Th2

58
Q

What is different between the activation of a Th2 response and a Th1 response (besides cytokines Il-4 and IL-12 or IFN-gamma)?

What pivotal cells drive Th0 to Th2? (4)

A

Th2:
soluble antigens and EXTRACELLULAR PATHOGENS

Th1: INRACELLULAR antigen or intracellular infection

  1. DC cells and TLR under specific gene influence and antigens that produce IL-4
  2. PREVIOUSLY committed Th2 cells that are producing IL-4
  3. B cell presentation of antigen promotes IL-4 by Th0 cells
  4. Mast cells/basophils produce Il-4 and Il-13
59
Q

WHAT IS ABSOLUTELY NECESSARY for a Th2 reaction?

What is the major, but not sole. source of IL-4?

A

IL-4

  • initiates and commits Th0 to Th2
  • GROWTH HORMONE
  1. Th2 cell!
60
Q

What potent B cell stimulator is also produced by the Th2 cell?

This only occurs in the absence of what?

What other cytokines do Th2 cells produce? (3) What specifically do these cytokines produce (2)

What cytokines SUPPRESS the development of a Th1 reaction?(3)

A
  1. IL-21
  2. INF - Gamma
  3. IL- 5, 6, and 10 (Il -4 initiates and IL-21)
    a) B cell differentiation
    b) isotype switching
  4. IL- 4
    IL- 10
    IL - 13
61
Q

What cytokine is an absolute requirement for an IgE response to parasites and other antigen specific IgE responses?

_____ cytokine produced by activated Th2 cells that down regulates cytotxic and inflammatory functions of M/M and DC

A

IL-4!

( and Il-13)

IL - 13: is a Th1 antagonist cytokine produced by activated Th2 cells that down regulates cytotoxic and inflammatory functions of M/M and DC

62
Q

What is the main function of the Th2 response?

What are some other functions?

A
  1. Enhance B cell function and antibody production
    - make pathogens more attractive to macs and poly’s
  • bind toxins
  • target mutant/viral infected cells for killing
63
Q

Describe the Th2 B cell response

A
  1. Virus binds B cell (antigen)
  2. brings it into the cell
  3. Represents it in MHC – II (NOT ANTIGEN)
  4. (Th1 uses CD28) but Th2 uses 40/40L  costimulatory signal
  5. Once this occurs, B cell commits because of the IL – 4 and the antigen
  6. Th0 becomes Th2
  7. Th2 begins producing IL – 4 (and IL -21)
  8. Drives B cell through growth & differentiation to plasma cell
  9. IL 5, 6, and 10 produced
  10. Driving cell from isotype switch from IgM to IgG to Plasma cell
    IgG binds antigen
64
Q

What are the antibodies made by the Th2 immune system used for? ( 4)

A
  1. make pathogens, viruses, more attractive to NK cells, macrophages, and neutrophils
  2. Recognize and mount immune responses to antigens
  3. Bind toxins for efficient elimination
  4. Target mutant and infected cells for killing
65
Q

What 3 things dictate the T helper response that is generated?

A
  1. type of infection
  2. the type of TLR activated
  3. the dominant cytokine(s) present

IL-12 activated Th1, IL-23 activated Th17 (coming up) and Il-4 activated Th2 are unique to each subset

-Interference in the balance between the generation of these subsets has implications on the manifestations of infectious, autoimmune and malignant diseases

66
Q

IL-12 activated __Th__, IL-23 activated _Th____ (coming up) and Il-4 activated __Th___ are unique to each subset

A

IL-12 activated Th1, IL-23 activated Th17 (coming up) and Il-4 activated Th2 are unique to each subset

67
Q

What is the signature cytokine of Th17 reactions? The transcription factor?

What type of stimulus is required to Trigger TLR to instruct DC to produce TGF- Beta, IL-6 and IL-23 for Th17 action?

What is the main function of Th17? What cytokine is necessary for this? What other cytokine has this function?

A
  1. IL-23
  2. ROR
  3. Bacteria and Fungi OUTSIDE of host cells
    - trigger Th17
  4. Potent recruiter of NEUTROPHILS via IL-17!!!

IL-8 also recruits (other one)

68
Q

How is the Th17 reaction inhibited?

A

If IL-4 or IFN - Gamma is the dominant cytokine

69
Q

The following describe with Th subset:

  1. Produce IL-17- an inflammatory cytokine
  2. Induced by DC production of IL-23
  3. Unique nuclear receptor is ROR
  4. Suppressed by either IL-4 or IFN-
  5. May have innate defense role
    Central role in autoimmune diseases
A

Th17

70
Q

What CD markers and Transcription Factors are required for the Th1 Treg subset?

Where are Tregs generated from?

A

CD3, CD25, and FoxP3 (Tf)

  1. THYMUS ( where the AIRE gene complex influences the auto antigen specificity)
  2. POST- THYMUS
    - peripheral lymphoid tissue
71
Q

What cytokine are Tregs dependent on for proliferation and survival? What strongly influences Tregs?

A
  1. IL-2

2. TGF - B

72
Q

What is the TF for T-FH cells?

What is it restricted to?

What do they promote

What CD marker identifies them?

which cytokines are upregulated by it?

A
  1. transcription factor- Bcl-6
  2. Restricted to B cell follicles in lymphoid tissue
  3. Promotes high affinity antigen specific B cell responses
  4. Can be identified by CD278 &
  5. upregulation of IL-6 and IL-21 receptors

Immunology (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions