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Fitz 9th > 11 - Cellular Components of the Cutaneous Immune System > Flashcards

11 - Cellular Components of the Cutaneous Immune System Flashcards

1
Q

The innate immune system can adapt to repeated challenges

Provides protection against reinfection in a T- and B-cell-independent manner

A

Trained immunity

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2
Q

Primary cells of the adaptive immune system

A

T and B cells

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3
Q

Key players of the innate immune system

A

Dendritic cells and macrophages

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4
Q

Cellular components of the immune system in healthy skin: epidermal layer

A

Langerhans cells

Resident memory T cells, primarily CD8+

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5
Q

Cellular components of the immune system in healthy skin: upper dermis

A

CD4+ T cells

Gamma delta T cells

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6
Q

Cellular components of the immune system in healthy skin: in proximity to the dermal-epidermal junction

A

Innate lymphoid cells

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7
Q

Cellular components of the immune system in healthy skin: in proximity to dermal blood vessels

A

Mast cells

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8
Q

Cellular components of the immune system in healthy skin: dermis

A

Dermal dendritic cells

Macrophages

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9
Q

Both have innate and adaptive immune functions

A

Interstitial lymphoid cells

Innate-like T cells

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10
Q

Innate vs adaptive response: rapid response

A

Innate response

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11
Q

Innate vs adaptive response: pattern recognition receptors - germ-line encoded

A

Innate response

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12
Q

Innate vs adaptive response: recognition - initially low affinity receptors

A

Adaptive response

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13
Q

Innate vs adaptive response: Gene rearrangement and clonal expansion

A

Adaptive response

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14
Q

Innate vs adaptive response: direct response for host defense - phagocytosis, antimicrobial activity

A

Innate response

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15
Q

Innate vs adaptive response: response - T and B cells with receptors encoded by fully rearranged genes

A

Adaptive response

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16
Q

Innate vs adaptive response: memory

A

Adaptive response

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17
Q

Progenitor T cells mature in the

A

Thymus

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18
Q

Key lineages of T cells

A

Alpha beta

Gamma delta

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19
Q

T cells that have completed their primary development in the thymus, and have not encountered their specific antigen

A

Naive T cells

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20
Q

Once a naive T cell meets its specific antigen, it is able to develop into

A

Effector T cell

Central memory T cell

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21
Q 
Recognize peptide antigens in the binding pocket of MHC class I molecules
Differentiate into cytotoxic effector T cells
A

Naive CD8+ T cells

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22
Q 
Recognize peptide antigens in the binding pocket of MHC class II molecules
Differentiates into Th1, Th2, Th17, T follicular helper and T regulatory cells
A

Naive CD4+ T cells

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23
Q

Characterized by the production of the cytokines IL-2, IFN-gamma, and TNF-alpha and expression of the T-box transcription factor T-bet

A

T helper 1 cells

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24
Q

Main mediators of cell-mediated immunity

A

T helper 1 cells

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25
Q

Characterized by the production of IL-4, IL-5, and IL-13

A

T helper 2 cells

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26
Q

Facilitate humoral (antibody) responses and inhibit some cell-mediated immune responses

A

T helper 2 cells

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27
Q

Critical for inducing the Th2 program

A

Zinc-finger transcription factor GATA-3

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28
Q

Produces IL-9; coproduces TNF-alpha
Promotes upregulation of IFN-gamma, IL-13, and IL-17
Found primarily among the skin homing (cutaneous leukocyte antigen positive) T-cell population and are present in healthy human skin

A

T helper 9 cells

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29
Q

Characterized by the production of the cytokines IL-17A, IL-17F, IL-21, IL-22, and recently IL-26
Involved in antigen responses against extracellular pathogens including both bacteria and fungi

A

T helper 17 cells

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30
Q

Th17 cells depend on _____ for their survival and expansion

A

IL-23

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31
Q

Th17 cells are regulated by

A

Transcription factor RORyt

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32
Q

Key players in the pathogenesis of psoriasis

A

T helper 17 cells

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33
Q

Key role in maintaining tolerance to self-antigents

A

T regulatory cells

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34
Q

Loss of _____ happens in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, and X-linked) syndrome

A

T regulatory cells

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35
Q

Characterized by the expression of the transcription factor FOXP3

A

T regulatory cells

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36
Q

Genetic cause of IPEX syndrome

A

FOXP3

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37
Q

Primarily found in B-cell areas of lymph nodes, spleen, and Payer patches
Trigger the formation and maintenance of germinal centers in lymph nodes and spleen through the expression of CD40 ligand and the secretion of IL-21 and IL-4

A

T follicular helper cells

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38
Q

To gain entry into the skin, T cells need to express the right surface molecules and receptors. This includes the _____, and expression of specific chemokine receptors including _____

A

Cutaneous lymphocyte antigen

CCR4, CCR10

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39
Q

An inducible carbohydrate modification of P-selecting glycoprotein ligand-1 (PSGL-1), a known surface glycoprotein that is expressed constitutively on all human peripheral blood T-cells
Able to bind E-selectin which is highly expressed on skin endothelial cells

A

Cutaneous lymphocyte antigen

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40
Q

Binds to the chemokines CCL17 and CCL22

Present on essentially all skin-homing cells

A

CCR4

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41
Q

Binds to the chemokine CCL27

Only present on a subset of skin-homing T cells

A

CCR10

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42
Q

Healthy human skin contains about _____ as many T cells as are present in the entire blood volume, or about _____

A

Twice

20 billion

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43
Q

Of skin-tropic (CLA+) memory T cells, _____% are located in human skin under non-inflamed conditions

A

98%

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44
Q

Y/N: T cells that reside in noninflammed human skin are insufficient to create an inflammatory pathology in the absence of recirculating lymphocytes

A

No - sufficient

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45
Q

Nonrecirculating memory T cells that are found in epithelial barrier tissues, including the GI tract, lung, skin, and productive tract

A

Tissue resident memory T cells

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46
Q

Tissue resident memory cells have been suggested to exist as 2 phenotypically and functionally distinct populations. Both of these populations express _____ and are distinguished by the expression of _____

A

Tissue resident memory T cell marker CD69

Surface marker CD103

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47
Q 
Type of tissue resident memory T cells:
Enriched in the epidermis
Predominantly CD8+
Tendency for increased effector cytokine production
More limited proliferative capacity
A

CD69+CD103+ tissue resident memory T cells

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48
Q

Type of tissue resident memory T cells:
More frequently encountered in the dermis
Have slightly lower but still potent effector functions when compared with recirculating T cells

A

CD69+CD103- tissue resident memory T cells

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49
Q

Coexpress both the skin homing receptor CLA and CCR4 and the central memory markers CCR7/L-selectin (CD62L)
Variable expression of L-selectin

A

Recirculating memory T cells

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50
Q

Type of recirculating memory T cells:

L-selectin negative

A

Migratory memory T cells

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51
Q

Type of recirculating memory T cells:
L-selectin positive
Higher sensitivity to antigenic stimulation
Less dependent on costimulation compared to naive T cells

A

Central memory T cells

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52
Q

Central memory T cells produce mainly

A

IL-2

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53
Q

After central memory T cell proliferation, they differentiate into

A

Effector T cells

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54
Q

Characterized by rapid effector function
Capable of producing large amounts of effector cytokines including IFN-gamma, IL-4, and IL-17, as well as perforin in the case of CD8+ T cells

A

Effector T cells

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55
Q

As these cells do not migrate or recirculate, inflammatory lesions caused by these cells tend to be sharply demarcated, with abrupt cut-off from normal skin, a classic feature of skin lesions in diseases such as psoriasis

A

Tissue resident memory T cells

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56
Q

As these cells are already on-site, they can respond to repeated antigen challenges extremely rapidly, often within hours of exposure - such as that seen in fixed drug eruptions

A

Tissue resident memory T cells

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57
Q

The biology of the tissue resident memory T cells can help explain differences between types of cutaneous lymphomas, such as mycosis fungoides which is being mediated by _____, and Sezary syndrome which is being mediated by ______

A

Tissue resident memory T cells

Recirculating central memory T cells

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58
Q

_____ memory T cell-mediated inflammatory diseases tend to worsen over time, with an increasingly rapid onset of inflammation and increasing severity of inflammation with each exposure

A

Tissue resident

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59
Q

Characterized by antibody production

A

B cells

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60
Q

B cells emigrate from the

A

Bone marrow

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61
Q

B-cell activation usually requires help from

A

T follicular helper cells

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62
Q

Activated B cells differentiate into

A

Memory B cells or

Antibody-secreting plasma cells

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63
Q

Induces immunoglobulin A responses

A

TGF-beta

64
Q

B cells have been observed in

A 
Chronic inflammatory skin conditions such as:
Cutaneous leishmaniasis
Diffuse cutaneous sclerosis
Cutaneous lupus
Atopic dermatitis
65
Q

Plasma cells can be found in

A

Certain inflammatory conditions such as:
Syphilis
Leprosy

66
Q

Have been found to have an anti-inflammatory effect

Named B-regulatory cells or Bregs

A

IL-10 producing B cells

67
Q

Nonrecirculating lymphocyte populations
Span the continuum between the innate and adaptive immune system and share a number of features pertaining to their tissue-resident functions

A

Unconventional and innate-like T cells

Innate lymphoid cells

68
Q

Defined by 3 main features:
Absence of recombinant activating gene (RAG)-dependent rearranged antigen receptors
Lack of myeloid and dendritic cell phenotypical markers (negative lineage markers)
Lymphoid morphology

A

Innate lymphoid cells

69
Q

Express the IL-7 receptor alpha chain CD127

A

Innate lymphoid cells

70
Q

Innate lymphoid cells require _____ for their development

A

IL-17

71
Q

Innate lymphoid cells can be subdivided into

A

Innate lymphoid cell 1
Innate lymphoid cell 2
Innate lymphoid cell 3

72
Q

Innate lymphoid cell type:

Similar to Th1 cells, generate IFN-gamma and TNF-alpha, have no cytotoxic molecules, and are dependent on T-bet

A

ILC1

73
Q

Innate lymphoid cell type:
Express and produce Th2 cytokines, including IL-4, IL-5, and IL-13, and have a high expression of the GATA-3 transcription factor

A

ILC2

74
Q

Innate lymphoid cell type:
Expressing variable levels of the transcription factors ROR gamma t, aryl-hydrocarbon receptor, and T-bet, and release variable amounts of IFN-gamma, IL-22, and IL-17

A

ILC3

75
Q

Innate lymphoid cells exhibit a close spatial relationship to

A

T lymphocytes

76
Q

Innate lymphoid cells exhibit a close spatial relationship to

A

T lymphocytes

77
Q

Express T-cell receptors of limited diversity, which recognize antigens in the context of nonclassical MHC-like molecules, or independent of MHC-related presenting molecules altogether
Expand the repertoire of antigens recognized by T cells

A

Unconventional or innate-like T cells

78
Q

Y/N: Unconventional T cells respond more slowly compared with their conventional counterparts

A

No - more quickly

79
Q

Lymphocytes belonging to this group: unconventional and innate-like T cells

A

Invariant natural killer T cells
Mucosal-associated invariant T cells
Gamma delta T cells

80
Q 
Structurally related to MHC class I genes
Unlike MHC class I molecules: non-polymorphic
A

Cluster of differentiation 1 (CD1) gene family

81
Q

CD1 molecules: The _____ molecules are more closely homologous to one another than to _____

A

CD1a, b, and c

CD1d

82
Q

CD1 molecules: The _____ isoforms are present on the surface of Langerhans cells, whereas _____ are expressed on dermal dendritic cells

A

CD1a and c

CD1a, b, and c

83
Q

Epidermal dendritic cells that mediate innate immune responses in skin, with phagocytic and antimicrobial function as well as a key role in antigen presentation to T cells

A

Langerhans cells

84
Q

Characterized by their high expression of CD1a and unique expression of langerin (CD207)

A

Langerhans cells

85
Q

Required for Birbeck granule formation

A

Langerin

86
Q

Secrete Th1 cytokines; cytolytic against infected targets as in case of myobacterial infections; trigger antimicrobial activity
Express perforin, granzyme B, and the antimicrobial protein granulysin

A

CD1-restricted T cells

87
Q

Cooperates with granulysin in killing intracellular bacteria

A

Granzyme B

88
Q

The expression of _____, as has been shown in leprosy, correlates with containment of infection, and is approximately 6-fold more frequent in tuberculous leprosy than lepromatous leprosy skin lesions

A

Granulysin

89
Q

Subset of T cells that express an invariant T-cell receptor, paired with TCR beta of limited diversity
Recognize glycolipid antigens presented by the MHC class-I like molecule CD1d

A

Invariant natural killer cells

90
Q

Invariant natural killer cells are dependent on _____ for their development

A

Transcriptional factor PLZF

91
Q

Five major distinct invariant natural killer cell subsets express and mirror _____ subsets in cytokine prouduction

A

T helper cell
iNKT1 - Th1
iNKT2 - Th2
iNKT17 - Th17

92
Q

Subset of T cells that express a semi-variant T cell receptor combining a unique TCR alpha chain
Evolutionarily conserved and have a capacity for rapid effector function

A

Mucosal-associated invariant T cells

93
Q

Activated by bacterial riboflavin biosynthesis intermediates that are presented by the MCH class-I like molecule MR1

A

Mucosal-associated invariant T cells

94
Q

As mammals do not synthesize riboflavin, but instead rely on certain bacteria and yeast, _____ provide a means to control certain commensal bacteria and assess and control for either overgrowth or infection by these organisms

A

Mucosal-associated invariant T cells

95
Q

Characterized by the expression of the gamma delta T cell receptor, and in contrast to the strict MHC restriction of alpha beta T-cells, several modes of antigen-recognization have been described
Have an ability to self-renew in tissues independently of circulating precursors

A

Gamma delta T cells

96
Q

While representing the majority of lymphocytes in mouse skin, _____ only represent a small fraction (1% to 2%) of resident T cells in human skin

A

Gamma delta T cells

97
Q

Large granular lymphocytes

Characterized by being CD16+ CD56+ CD94+ CD161+ but negative for the T-cell markers CD3

A

Natural killer cells

98
Q

Have a role in surveying the body, looking for altered cells, either transformed or infected with viruses or parasites

A

Natural killer cells

99
Q

Main function is to process antigen material and present it on the cell surface and activate T cells

A

Dendritic cells

100
Q

3 cutaneous dendritic cell populations in healthy skin

A

Epidermal Langerhans cells
Resident dermal conventional dendritic cells
Plasmacytoid dendritic cells

101
Q

Previously called myeloid dendritic cells

A

Conventional dendritic cells

102
Q

Permits the presentation of exogenous antigens, which are normally presented by MHC class II molecules, to be presented by MHC class I molecules

A

Cross-presentation

103
Q

Important for immune defenses against many viruses and in elimination of autoreactive CD8+ T cells

A

Cross-presentation pathways

104
Q

The inflammatory dendritic cells in psoriasis produce TNF-alpha
and have inducible nitric oxide synthetase (iNOS) and have been termed

A

Tip-DCs

105
Q

Unique population of resident cutaneous dendritic cells, initially described by their morphology, which is similar to plasma cells

A

Plasmacytoid dendritic cells

106
Q

Sentinels in early defences against viral infection, particularly given their expression of TLR 7 and TLR9, and intracellular nucleic sensor such as RIG-1, that functions as a pattern recognition receptor for certain single stranded RNA viruses
Produce large amounts of type 1 interferons

A

Plasmacytoid dendritic cells

107
Q

Y/N: In contrast to conventional dendritic cells, plasmacytoid dendritic cells express more MCH class II and co-stimulatory molecules on their surface, and the process antigens more efficiently

A 
No - express less MCH class II and co-stimulatory molecules
process antigens less efficiently
108
Q

Langerhans cells account for _____% of cells in the epidermis

A

2-4

109
Q

Langerhans cells require the cytokines _____, both derived from keratinoytes, for their development and epidermal residence

A

IL-34

TGF-beta

110
Q

Essential component of innate immunity and play a central role in inflammation

A

Macrophages

111
Q

Also known as classically activated macrophages
Activated primarily by IFN-gamma
Produce pro-inflammatory cytokines such as IL-1beta, TNF-alpha, IL-12, and IL-18

A

M1 macrophages

112
Q

Phagocytize large numbers of pathogens and kill intracellular bacteria
Vitamin D is required for the adaptive immune responses to overcome the ability of intracellular pathogens to avoid this killing

A

M1 macrophages

113
Q

Also known as alternatively activating macrophages

Activated primarily by stimuli such as IL-4, IL-10, TGF-beta, and IL-13

A

M2 macrophages

114
Q

Central role in response to parasites, tissue remodeling, and allergic diseases, and may have a role in resolution of skin inflammation

A

M2 macrophages

115
Q

Central role in response to parasites, tissue remodeling, and allergic diseases, and may have a role in resolution of skin inflammation

A

M2 macrophages

116
Q

Usually most abundant at epithelial sites, such as the skin and mucosal tissue, where they are ideally situated to act as a first line of defense

A

Mast cells

117
Q

Key factors influencing the maturation of mast cells, including _____, which binds to the c-kit receptor (CD117), and IL-3

A

Stem cell factor, also known as KIT ligand

118
Q

Y/N: Mast cells are long-lived cells that can survive in tissues for months to years

A

Yes

119
Q

Best known cause of mast cell activation is when

A

Antigens crosslink IgE bound to receptors for igE

120
Q

Mast cells can also bind _____ antibodies

A

IgG

121
Q

Y/N: A relatively low level of allergen is sufficient to trigger degranulation of mast cells

A

Yes

122
Q

Mast cells granules are filled with preformed compounds such as

A

Histamine

Serotonin

123
Q

Can also produce a large number of cytokine following activation, including TNF-alpha, IL-3, IL-4, IL-5, and IL-6, as well as lipid mediators such as leukotrienes, prostaglandins, and platelet-activating factor

A

Mast cells

124
Q

Given the presence of cytokines such as IL-4, mast cell responses are more directed toward Th_____ responses

A

2

125
Q

Classified as granulocytes

A

Basophils
Neutrophils
Eosinophils

126
Q

Most abundant leukocytes in the blood accounting for about 45% to 70% of the peripheral blood leukocytes

A

Neutrophils

127
Q

Neutrophils are short-lived with a life span somewhere between

A

5 and 90 hours

128
Q

Generation of neutrophils is controlled by

A

Granulocyte colony-stimulating factor

129
Q

Hallmark cell of acute inflammation

A

Neutrophil

130
Q

Y/N: On a per-cell basis, neutrophils make fewer
molecules of a given cytokine than macrophages or lymphocytes, but neutrophils often outnumber other leukocytes at inflammatory sites by several orders of magnitude

A

Yes

131
Q

Neutrophil recruitment can be amplified exponentially in a phase termed

A

Neutrophil swarming

132
Q

Neutrophil granules:
Include proteins such as lactoferrin, lipocalin, and cathelicidin (LL37) along with several metalloproteinases
Have an important role in facilitating neutrophil recruitment and tissue breakdown

A

Peroxidase-negative

133
Q

Neutrophil granules:

Next granules to be emptied usually occurring as the concentration of chemoattractants increases

A

Peroxidase-positive

134
Q

Iron-containing enzyme that colors pus green

A

Myeloperoxidase

135
Q

The _____ released by neutrophils have been shown to cleave the IL-36 cytokines into their more active forms

A

Serine proteases

136
Q

Neutrophil _____ has been shown to cleave the IL-36 receptor antagonist into its highly active antagonistic form

A

Elastase

137
Q

Rapid release of reactive oxygen species driven by the NADPH oxidase
Used by neutrophils to degrade bacteria and particles that have been ingested

A

Respiratory burst

138
Q

Neutrophils undergo a unique form of cell death in which the nuclear chromatin is released into the extracellular space and forms a matrix known as

A

Neutrophil extracellular traps

139
Q

Neutrophil extracellular trap formation requires the generation of ROS, and patients with _____, apart from having defective respiratory burst, also have reduced NET formation

A

Chronic granulomatous disease

140
Q

Neutrophil activation can lead to substantial tissue damage, evident from disorders such as

A

Pyoderma gangrenosum

141
Q

Neutrophils can leave sites of inflammation in a process termed

A

Neutrophil reverse migration

142
Q

Eosinophils have the capacity to be stained by (acidophilic/basophilic) dyes

A

Acidophilic

143
Q

Eosinophils are readily recruited into tissues in response to appropriate stimuli such as

A

IL-5

Eotaxin chemokines CCL11 (eotaxin-1), CCL13, and CCL26 (eotaxin-3)

144
Q

Eosinophils account for somewhere between _____% of peripheral blood leukocytes

A

0 and 5

145
Q

The granules in eosinophils contain 4 major proteins

A

Eosinophilic peroxidase
Major basic protein
Ribonucleases eosinophilic cationic protein
Eosinophil-derived neurotoxin

146
Q

When eosinophils are in tissues, they are usually found in proximity to

A

Mast cells

147
Q

Least common type of granulocyte

A

Basophil

148
Q

Basophils account for less than _____% of peripheral blood leukocytes

A

1

149
Q

Basophils were for a long time thought to be a redundant variant of _____ in the blood

A

Mast cells

150
Q

In contrast to mast cells, which mature in _____, basophils complete their maturation in _____

A

Tissues

Bone marrow

151
Q

Basophils have a life span of _____, in contrast to _____ for mast cells

A

Several days

Weeks to years

152
Q

Y/N: Basophils retain the ability to proliferate unlike mast cells

A

No - Do not retain

153
Q

Basophils are an important source of _____ cytokines, and secrete large quantities of _____, suggesting that basophils may be involved in mediating allergic diseases and immunity against parasites

A

Th2-type

IL-4

154
Q

Most abundant cell type in skin and form the epidermis

A

Keratinocytes

155
Q

(High/Low) pH of the skin inhibits growth of bacteria

A

Low

156
Q

Another term used for keratinocytes because of the production of antimicrobial peptides, cytokines, and chemokines

A

Cytokinocyte

Fitz 9th (108 decks)

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