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MSI Unit II > MCM 2-9 Innate Lymphocytes > Flashcards

MCM 2-9 Innate Lymphocytes Flashcards

1
Q

A patient presents with a common cold. Respiratory epithelial cells begin producing interferon. Which is least likely to be an outcome of the activation of the interferon response?

a. Decreased viral replication within the cell
b. A virus specific, cell mediated immune response
c. Upregulation of NK cell ligands on the infected cell
d. Activation of NK cells
e. Interferon binding to nearby uninfected epithelial cells

A

B

A virus specific cell mediated immune response is least likely

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2
Q

Type I interferon. Source? Acts on?

A

Type 1 interferon is IFN-Alpha and IFN-Beta

Excreted from virally infected cells

Autocrine action (within the cell to decrease syntehsis) as well as paracrine (neighboring cells) acting on NK cells, activating them to kill.

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3
Q

innate vs adaptive

A

innate - inborn, ready to go, nonspecific, no recombination (mucus, tight junctions, macrophages, neutrophils)

adaptive - tailored to specific antigen, delayed primary response, antigen specific, must ramp up, some recombination necessary

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4
Q

General Innate and Adaptive Bifurkation at the hematopoietic stem cell

A

Innate - differentiates into common myeloid progenitor which gives rise to innate immune cells

in adaptive - differentiates into common lymphoid progenitor which gives rise to adaptive immune cells

However, there is a class of INNATE that are derived from the common lymphoid progenitor that ussually gives rise to ADAPTIVE immune cells

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5
Q

Natural Killer Cells

A

are ready to go, do not need priming or proliferation. They can recognize and kill a target cell without priming or sensitization

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6
Q

NK Cells express what cell markers

A

CD56 (adhesion molecule) and CD16 (an Fc receptor)

-also have cytoplasmic granules to kill target cells

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7
Q

NK cells do not express

A

CD3, they are CD3-

despite being lymphoid, do not express a BCR or TCR

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8
Q

where do NK cells mature?

A

unlike T-cells, NK cells mature in the bone marrow, there is no thymic stage. they are ready to go right out of the bone marrow

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9
Q

What do NK cells do?

A
  1. fight viral infection
  2. kill tumor cells
  3. support placentation (during pregnancy)
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10
Q

describe how an NK cell finds an infected cell?

A

a virally infected cell excretes type-1 interferon (alpha or beta), which stimulates the NK to divide, and seek out the infected cells to kill.

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11
Q

NK cells and the kinetics of infection response

A
  1. subject infected
  2. IFN-1 and other inflammatory mediators released
  3. NK cells quickly begin killing
  4. much later in response. T-cells begin killing

NK cells are thought to stave off the viral infection until T-cells are ramped up and able to eradicate the infection. NK cells will level out the viral titer. More pronounced in primary infection when T-cells take a few days to activate.

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12
Q

Crosstalk between NK cells and macrophages

A

NK cells secrete IFN-Gamma (type 2 interferon) to stimulate macrophages, makes macrophage better able to take up antigen and kill

Activated macrophages secrete IL-12

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13
Q

Interferon types 1 and 2

A

Type 1 - alpha and beta, released by infected cells, stimulates NK cells to activate, divide, and kill

type 2 - interferon gamma - secreted by NK cells to stimulate macrophages, makes them better able to take up antigen and kill

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14
Q

how do NK cells recognize target cells without a TCR?

A

they have a spectrum of receptors that are either inhibitory or stimulatory. the balance of these receptors determines if the NK cell will kill or not. by default, inhibitory NK signal dominates (protective)

-these receptors are germline encoded, no recombination like B or C receptor

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15
Q

difference between NK receptors and TCR/BCRs?

A

NK are germline encoded, no recombination like in BCR or TCR

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16
Q

what are the main ligands for the different NK receptors?

A

most ligands are MHC1 and HLA class molecules

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17
Q

MHC(HLA) Class I types, diversity, and functions

A

MHC1a - presents antigen to CD8+ cells
A,B,C with 2 alleles each (one per parent)
highly polymorphic in binding pocket. SNPS in this region allow to hold certain peptide better than others

MHC1b - (other functions)
E,F,G, sometimes Mic-a and Mic-b
E has lowest polymorphism

18
Q

most important inhibitory receptor and activating receptor for NK cells?

A

CD94:NKG2A inhibitory, interacts with HLA-E which presents fragments from other MHC molecules. Many HLA-E receptors on surface ligated? inhibitory signal dominantes.

-Low HLA-E expression? NK cell sees this as an unhealthy cell, and prepares to kill it. Why? Viruses downregulate MHC1

CD16 - activating. it is an Fc receptor that recognizes IgG antibody. When it sees that there are antibodies on a target, the NK cell kills the target. “Antibody Dependant Cellular cytotoxicity” or ADCC

19
Q

describe NK cells

what does CD16 see?
what does cd94:nkg2a see?

how does it activate macrophages?

A

Large granular lymphocytes, CD56+ and CD16+

sees antibody
MHC1

IFN-gamma (type 2 interferon)

20
Q

gamma:Delta T-cells have a thymic phase T/F?

A

True, when lymphoid progenitors enter thymus they can become either an alpha:beta (cd4 or cd8) or gamma:Delta

21
Q

Alpha Beta T cell Vs Gamma Delta T cell

A

alpha beta - b chain rearranges first, lots of diversity, positive and negative selection to prevent autoimmunity. tend to move around bloodsteam and lymphatics

gamma delta - gamma and delta chains rearrange first, limited diversity, no selection (limited specificity excludes autoimmunity), tend to be in tissues and express CD3. They are IELS - interepithelial lymphocytes

22
Q

role of gamma delta T-cells in intestines?

A

GD t-cells hang out in intestial epithelia

cell becomes infected, gamma delta t-cell is there and responds to stress molecules, kills the cell via lytic granules.

gamma:delta secretes growth factors which then stimulate cell division/repair to fill the gap.

23
Q

what makes gamma:deta T-cells unique?

A

they are not MHC restricted and do not need to see peptide cradled in MHC, their receptor is more like an antibody. Can see a limited number of antigens like a B cell would.

can see small phosphoantigens (metabolism of stressed/infected cells)

can see lipid antigens presented in CD1

24
Q

CD1 molecules do what?

A

present lipid antigens to gamma:delta T-cells.

CD1’s generally present endogenous lipids at the cell surface. When infected, endogenous lipid is exchanged for a bacterial lipid and presented on surface.

25
Q

do gamma:Delta t-cells have a TCR?

roles?

A

yes, but gamma:delta not alpha:beta

they are cytotoxic to infected/stressed cells, but also contribute to tissue repair

26
Q

NK-T cells

what type of TCR? What diversity?

AKA?

A

express alpha:beta TCR with very low diversity (1 possible alpha, 3 possibly beta) - can only see a limited number of lipids

AKA invariant natural killer T cells

27
Q

NKT cells recognize..

A

lipids and glycolipids in CD1d

NKT, CD1d, NKT, CD1d, NKT, CD1d

28
Q

NKT cells would be beneficial against…

what do they excrete?

A

bacteria excreting lots of weird lipids - like mycobacteria

NKT cells excrete IFN-gamma and IL4

29
Q

NKT function is very similar to that of…

A

Helper T cells.

Th - recognize peptide in MHCII, are not directly cytotoxic, and are late cytokine production as effector mechanism

NKT recognize lipid in CD1d, not directly cytotoxic, and their effector mechanisms are EARLY cytokine production (excretes IFN-gamma similarly to TH1, and IL-4 similarly to TH2)

30
Q

A virus infected cell excretes ______ which induce what response?

A

IFN-alpha and beta (Type 1 Interferon)

  1. induce resistance to viral replication in all cells
  2. increase expression of ligands for receptors on NK cells
  3. Activate NK cells to kill virus-infected cells
31
Q 
A laboratory accident results in a research subject gaining superpowers while
losing all lymphoid progenitor cells. Which innate cell populations would be
affected?
I. neutrophils
II. NK cells
III. γδ T cells
IV. NKT cells
A. Choice I only
B. Choices I and II
C. Choices I, II, III and IV
D. Choices II, III, and IV
A

Answer is choice D.
This is a straightforward question that requires you to know that all of the
populations of innate lymphocytes studied derive from a lymphoid lineage.
Neutrophils come from a myeloid lineage.

32
Q
  1. A young patient presents with recurrent viral infections. Laboratory findings
    note an absence of peripheral blood large granular lymphocytes and
    subsequent flow cytometry testing indicates the presence of normal numbers
    of CD3+ and CD19+ cells but a lack of CD56+ cells. Which answer choice
    indicates a possible mechanism for this immunodeficiency?
    A. Failure of the thymus to form
    B. Homozygous deletion of recombinase genes
    C. Inability to form reactive oxygen species
    D. Mutation of an essential transcription factor
A
  1. Answer is choice D.
    The question passage states that the patient lacks “large granular lymphocytes”
    and CD56+ cells in the peripheral blood, suggesting an absence of natural killer
    cells (NK cells). The answer choices test knowledge of NK cell chracteristics.

Choice A is incorrect because NK cells don’t undergo a thymic stage of
development, so we would expect that, even without a thymus, this patient would
have normal numbers of NK cells. Choice B is incorrect because NK cells don’t
undergo recombination to form receptors like B or T lymphocytes - their receptors
are innate. Choice C is incorrect because NK cells don’t rely on a respiratory
burst for their effector mechanism. Whenever you hear “reactive oxygen species”
in reference to immunity, think macrophages!

33
Q
  1. Following vaccination of a previously naïve subject with a live-attenuated
    virus, CD56-positive cells are observed at the inoculation site. Two days later,
    you isolate CD56+ cells from the tissue and find they can efficiently kill
    virally-infected cells in vitro. What is the MOST LIKELY mechanism for the
    RECOGNITION of infected cells by the CD56+ population?
    A. Recognition of viral peptides in MHC II by CD4 TCR
    B. Loss of HLA-E expression detected by CD94:NKG2A
    C. Antibody-dependent killing initiated by CD16
    D. TCR binding to viral lipids presented by CD1
    E. Induction of apoptosis by perforin and granzyme
A
  1. Answer is choice B.
    The subject has been vaccinated with a live virus, CD56-positive cells (NK cells)
    have been isolated and their killing is being studied in the laboratory. This is a
    tricky question…

Choice A is incorrect because it refers to helper T cells and this question is about
NK cells (which don’t have a TCR and don’t see peptide in MHC-II). Choice C is
wrong because the cells were isolated only two days after inoculation – too short
for an antibody response in a previously naïve subject. Choice D is incorrect
because NK cells don’t have a TCR – this answer choice hints at NKT cells,
which aren’t CD56 positive. Choice E is wrong because, although perforin and
granzymes are likely the MECHANISM of killing, the question asks about
RECOGNITION. I know, that one was a cheap shot.

34
Q

NK cells

A

lymphoid lineage but develope in bone marrow

large granular lymphocytes

CD16, CD56+, CD94+

respond to IFN-1 (alpha, gamma)

activates macrophages with IFN gamma

35
Q

gamma delta T cells

A

express a delta gamma TCR
develop in thymus with no + or - selection
low diversity in antigen spec
dont require MHC
can be cytoxic but also secrete growth factors
most are in tissues (IELs)

36
Q

NKT cells

A

not NK cells

see lipid antigens on CD1d

no cytotoxic, cytokines only

37
Q

Innate lymphocytes develop from a lymphoid lineage but

A

respond to challenge quickly
have limited anitgen repertoire
dont develop memory

(three things ussually associated with innate, myeloid lineage immunity)

38
Q

CD94:NKG2A

A

heterodimeric protein on NK cells

when target cell expression of HLA-E is low, fewer CD94:NKG2A receptors provide NK cell with inhibitory signals

several viruses cause cells to downregulate MHC-1 presentation to prevent alerting CD8 t-cells

39
Q

ADCC

A

antibody dependant cellular cytotoxicity - NK receptor CD16 recognizes IgG Fc region.

40
Q

which class of MHC have b2-microglobin?

A

MHCI

MSI Unit II (46 decks)

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