10 - The Immunological Structure of the Skin

Question 1

Innate vs adaptive immunity: rapid onset

Answer 1

Innate

Question 2

Innate vs adaptive immunity: capacity to discriminate between danger and nondanger only, instead of distinguishing between individual antigenic specificities

Answer 2

Innate

Question 3

Innate vs adaptive immunity: lack of memory

Answer 3

Innate

Question 4

Innate vs adaptive immunity: needs 10-14 days to develop

Answer 4

Adaptive

Question 5

Innate vs adaptive immunity: peptide specificity

Answer 5

Adaptive

Question 6

_____ dendritic cells can fulfill both innate and adaptive immune functions

Answer 6

Plasmacytoid DCs

Inflammatory DCs

Question 7

Innate vs adaptive immunity:
Resident cells (nonleukocytic) - keratinocytes, fibroblasts, sebocytes, endothelial cells, nerve cells

Answer 7

Innate

Question 8

Innate vs adaptive immunity:

Granulocytes - neutrophils, eosinophils, basophils

Answer 8

Innate

Question 9

Innate vs adaptive immunity:

Macrophages

Answer 9

Innate

Question 10

Innate vs adaptive immunity:

Mast cells

Answer 10

Innate

Question 11

Innate vs adaptive immunity:

Innate lymphoid cells - cytotoxic ILCs (natural killer cells), helper ILC (ILC1), ILC2, ILC3

Answer 11

Innate

Question 12

Innate vs adaptive immunity:

Dendritic cells - inflammatory DC, plasmacytoid DC

Answer 12

Innate

Question 13

Innate vs adaptive immunity:

Dendritic cells - Langerhans cells, CD141+ DC, dermal DC, inflammatory DC, plasmacytoid CD

Answer 13

Adaptive

Question 14

Innate vs adaptive immunity:

T lymphocytes - naive T cells, memory T cells

Answer 14

Adaptive

Question 15

Innate vs adaptive immunity: memory

Answer 15

Adaptive

Question 16

React in an enhanced fashion to a repeated antigenic challenge

Answer 16

Memory

Question 17

Leukocytes and nonleukocytes involved in innate immunity are equipped with _____
Either surface-bound and/or cytoplasmic receptors

Answer 17

Pattern recognition receptors

Question 18

First responders after most forms of skin injury

Answer 18

Neutrophils

Question 19

Main effector function of neutrophils is to eliminate microbes by

Answer 19

1. Phagocytosis

2. Using neutrophil extracellular traps which enable them to kill extracellular pathogens

Question 20

Much less efficient phagocytes than neutrophils

Releases preformed cationic proteins that are toxic to several parasites

Answer 20

Eosinophils

Question 21

Contain histamine-filled granules
Rich source of cytokines such as IL-4 and IL-13
Resemble mast cells and play an important role in allergic tissue inflammation

Answer 21

Basophils

Question 22

Mast cells contain preformed mediators (_____) and molecules synthesized upon activation (_____)

Answer 22

Histamine, serotonin

TNF, IL-3, IL-4, IL-13

Question 23

Important activation mechanisms of mast cells

Answer 23

1. Interaction of complement cleavage products C3a and C5a with their respective receptors
2. Fc-mediated binding of immunoglobulin E

Question 24

Innate lymphocytes include

Answer 24

Cytotoxic (natural killer cells)

Helper innate lymphoid cells

Question 25

Recognition and killing of virally infected and neoplastic cells Secretion of interferon-gamma

Answer 25

Natural killer cells

Question 26

Helper innate lymphoid cells can be subdivided into

Answer 26

ILC1 ILC2 ILC3

Question 27

Next to polymorphonuclear neutrophils, _____ are heavily involved in the elimination of invading microbes

Answer 27

Macrophages | Mononuclear phagocytes

Question 28

Play a major role in antiviral defense by the massive production of type 1 interferons (IFN-alpha, IFN-beta) upon activation of TLR7 and TLR9

Answer 28

Plasmacytoid dendritic cells

Question 29

Production of TNF and inducible nitric oxide synthase | Priming of Th cell responses

Answer 29

Inflammatory dendritic cells

Question 30

Artificial TLR7 ligand _____ provides a strong activation signal for plasmacytoid dendritic cells

Answer 30

Imiquimod

Question 31

Normal human skin contains 3 distinct populations of antigen-presenting dendritic cells

Answer 31

Epidermal Langerhans cells Dermal dendritic cells CD141+ dendritic cells

Question 32

Express CD1a | Contain endocytic organells called Birbeck granules

Answer 32

Langerhans cells

Question 33

Major constituent of Birbeck granules

Answer 33

C-type lectin langerin/CD207

Question 34

Express CD1c Display the mannose receptor as well as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

Answer 34

Dermal dendritic cells

Question 35

Also known as BDCA-3 or thrombomodulin Express CD11c and DEC-205 Initially identified in the peripheral blood, but has been found to also constitute a very small cell population in the human dermis Take up extracellularly necrotic cells and viral nucleic acids

Answer 35

CD141

Question 36

The 3 different types of "resident" skin DCs exhibit the characteristic features of bone marrow-derived DCs

Answer 36

1. Migration (from the skin to the draining lymph nodes during primary immune responses) 2. Induction of helper or cytotoxic antigen-specific immune responses in naive resting T cells

Question 37

In the case of CD141+ DCs, the T-cell response is usually cytotoxic in nature and directed against antigenic moieties expressed by and taken up from surrounding symbionts and then channeled in the MHC class I presentation pathway

Answer 37

Cross presentation

Question 38

Langerhans cells display phenotypic features that favor and facilitate the activation of

Answer 38

Regulatory T cells (Tregs)

Question 39

Largest, and probably the most important, lymphocyte population within normal human skin

Answer 39

T lymphocytes

Question 40

Y/N: T lymphocytes in the skin exceed that of the T-cell population in the peripheral blood

Answer 40

Yes

Question 41

Most skin T cells are localized in the

Answer 41

Dermis | Only 10% in the epidermis

Question 42

Dermal T cells are mainly _____ | Epidermal T cells preferentially display the _____ phenotype

Answer 42

CD4+ | CD8+

Question 43

T cells in the skin express the (memory/naive) rather than the (memory/naive) phenotype

Answer 43

Memory (CD45RO+) | Naive (CD45RA+)

Question 44

Memory T cells are generally subdivided into

Answer 44

Central (Tcm) memory T cells | Effector (Tem) memory T cells

Question 45

Exhibit the CCR7+/CD62L+ phenotype Mainly found in secondary lymphoid organs such as lymph nodes and spleen Only sparsely scattered within normal human skin, but present in slightly larger numbers in chronic inflammatory and neoplastic skin diseases

Answer 45

Central memory T cells

Question 46

Effector memory T cells can be subdivided into

Answer 46

Recirculating memory T cells | Tissue-resident memory T (Trm) cells

Question 47

Constantly recirculate between nonlymphoid tissues and lymphatic organs CD62L-/CCR7+

Answer 47

Recirculating memory T cells

Question 48

Permanently reside in the skin Can provide an extremely rapid onsite protection upon exposure to previously encountered antigens Express CD69 and some of them (mostly CD8+ Trm cells) express the alpha E integrin CD103

Answer 48

Tissue-resident memory T cells

Question 49

Maintenance of cellular and tissue homeostasis requires

Answer 49

1. Prevention of exaggerated responses to innocuous substances 2. Occurrence of host-defense reactions at a subclinical level

Question 50

AMP with baseline production by keratinocytes | Antimicrobial effects is mainly directed against E. coli

Answer 50

S100 calcium-binding protein A7 (S100A7) or | Psoriasin

Question 51

First passenger cells invading the skin or amplifying in skin are usually cells of the _____ response

Answer 51

Innate

Question 52

Plasmacytoid denditic cells are usually detected on the _____ of the individual lesions

Answer 52

Active margins

Question 53

Innate lymphoid cells of psoriatic lesions belong in their majority to the _____ subset

Answer 53

ILC3

Question 54

Inflammatory skin diseases are characterized by a prominent, often predominating, lymphocytic infiltrate consisting mostly of

Answer 54

T lymphocytes

Question 55

B cells tend to avoid the skin with few notable exceptions such as

Answer 55

Cutaneous Leishmania infection

Question 56

``` T-cell pattern: Lichen planus ACD Tuberculoid leprosy Cutaneous leishmaniasis ```

Answer 56

Th1

Question 57

``` T-cell pattern: AD Acute GVHD Lepromatous leprosy Diffuse leishmaniasis ```

Answer 57

Th2/Th22

Question 58

T-cell pattern: | Chronic lichenoid GVHD

Answer 58

Th1/Th17

Question 59

T-cell pattern: Acne vulgaris Psoriasis

Answer 59

Th17

Question 60

T-cell pattern: ACD TEN

Answer 60

Cytotoxic T cells

Question 61

Y/N: The cancer-destructive capacity of immune cells becomes weaker and weaker the longer the (primary) tumor persists

Answer 61

Yes

Question 62

Studies in human skin cancers are urgently needed to determine the anticancer potential of _____ cells, and thus, their possible relevance for cancer immunotherapy

Answer 62

Th9

Question 63

Presence of high number of intratumoral and peritumoral _____ heralds a bad prognosis

Answer 63

``` Granulocytes Plasmacytoid dendritic cells Myeloid-derived suppressor cells M2 macrophages Production of IL-4, IL-10, IL-13 and TGF-beta ```

Question 64

Large numbers of _____ are associated with a longer disease-free survival

Answer 64

CD3+ T cells | Memory T cells of both the CD4 and the CD8 type