10 - The Immunological Structure of the Skin Flashcards
Innate vs adaptive immunity: rapid onset
Innate
Innate vs adaptive immunity: capacity to discriminate between danger and nondanger only, instead of distinguishing between individual antigenic specificities
Innate
Innate vs adaptive immunity: lack of memory
Innate
Innate vs adaptive immunity: needs 10-14 days to develop
Adaptive
Innate vs adaptive immunity: peptide specificity
Adaptive
_____ dendritic cells can fulfill both innate and adaptive immune functions
Plasmacytoid DCs
Inflammatory DCs
Innate vs adaptive immunity: Resident cells (nonleukocytic) - keratinocytes, fibroblasts, sebocytes, endothelial cells, nerve cells
Innate
Innate vs adaptive immunity:
Granulocytes - neutrophils, eosinophils, basophils
Innate
Innate vs adaptive immunity:
Macrophages
Innate
Innate vs adaptive immunity:
Mast cells
Innate
Innate vs adaptive immunity:
Innate lymphoid cells - cytotoxic ILCs (natural killer cells), helper ILC (ILC1), ILC2, ILC3
Innate
Innate vs adaptive immunity:
Dendritic cells - inflammatory DC, plasmacytoid DC
Innate
Innate vs adaptive immunity:
Dendritic cells - Langerhans cells, CD141+ DC, dermal DC, inflammatory DC, plasmacytoid CD
Adaptive
Innate vs adaptive immunity:
T lymphocytes - naive T cells, memory T cells
Adaptive
Innate vs adaptive immunity: memory
Adaptive
React in an enhanced fashion to a repeated antigenic challenge
Memory
Leukocytes and nonleukocytes involved in innate immunity are equipped with _____
Either surface-bound and/or cytoplasmic receptors
Pattern recognition receptors
First responders after most forms of skin injury
Neutrophils
Main effector function of neutrophils is to eliminate microbes by
- Phagocytosis
2. Using neutrophil extracellular traps which enable them to kill extracellular pathogens
Much less efficient phagocytes than neutrophils
Releases preformed cationic proteins that are toxic to several parasites
Eosinophils
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
Basophils
Mast cells contain preformed mediators (_____) and molecules synthesized upon activation (_____)
Histamine, serotonin
TNF, IL-3, IL-4, IL-13
Important activation mechanisms of mast cells
- Interaction of complement cleavage products C3a and C5a with their respective receptors
- Fc-mediated binding of immunoglobulin E
Innate lymphocytes include
Cytotoxic (natural killer cells)
Helper innate lymphoid cells
Recognition and killing of virally infected and neoplastic cells
Secretion of interferon-gamma
Natural killer cells
Helper innate lymphoid cells can be subdivided into
ILC1
ILC2
ILC3
Next to polymorphonuclear neutrophils, _____ are heavily involved in the elimination of invading microbes
Macrophages
Mononuclear phagocytes
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
Plasmacytoid dendritic cells
Production of TNF and inducible nitric oxide synthase
Priming of Th cell responses
Inflammatory dendritic cells
Artificial TLR7 ligand _____ provides a strong activation signal for plasmacytoid dendritic cells
Imiquimod
Normal human skin contains 3 distinct populations of antigen-presenting dendritic cells
Epidermal Langerhans cells
Dermal dendritic cells
CD141+ dendritic cells
Express CD1a
Contain endocytic organells called Birbeck granules
Langerhans cells
Major constituent of Birbeck granules
C-type lectin langerin/CD207
Express CD1c
Display the mannose receptor as well as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin
Dermal dendritic cells
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
CD141
The 3 different types of “resident” skin DCs exhibit the characteristic features of bone marrow-derived DCs
- Migration (from the skin to the draining lymph nodes during primary immune responses)
- Induction of helper or cytotoxic antigen-specific immune responses in naive resting T cells
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
Cross presentation
Langerhans cells display phenotypic features that favor and facilitate the activation of
Regulatory T cells (Tregs)
Largest, and probably the most important, lymphocyte population within normal human skin
T lymphocytes
Y/N: T lymphocytes in the skin exceed that of the T-cell population in the peripheral blood
Yes
Most skin T cells are localized in the
Dermis
Only 10% in the epidermis
Dermal T cells are mainly _____
Epidermal T cells preferentially display the _____ phenotype
CD4+
CD8+
T cells in the skin express the (memory/naive) rather than the (memory/naive) phenotype
Memory (CD45RO+)
Naive (CD45RA+)
Memory T cells are generally subdivided into
Central (Tcm) memory T cells
Effector (Tem) memory T cells
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
Central memory T cells
Effector memory T cells can be subdivided into
Recirculating memory T cells
Tissue-resident memory T (Trm) cells
Constantly recirculate between nonlymphoid tissues and lymphatic organs
CD62L-/CCR7+
Recirculating memory T cells
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
Tissue-resident memory T cells
Maintenance of cellular and tissue homeostasis requires
- Prevention of exaggerated responses to innocuous substances
- Occurrence of host-defense reactions at a subclinical level
AMP with baseline production by keratinocytes
Antimicrobial effects is mainly directed against E. coli
S100 calcium-binding protein A7 (S100A7) or
Psoriasin
First passenger cells invading the skin or amplifying in skin are usually cells of the _____ response
Innate
Plasmacytoid denditic cells are usually detected on the _____ of the individual lesions
Active margins
Innate lymphoid cells of psoriatic lesions belong in their majority to the _____ subset
ILC3
Inflammatory skin diseases are characterized by a prominent, often predominating, lymphocytic infiltrate consisting mostly of
T lymphocytes
B cells tend to avoid the skin with few notable exceptions such as
Cutaneous Leishmania infection
T-cell pattern: Lichen planus ACD Tuberculoid leprosy Cutaneous leishmaniasis
Th1
T-cell pattern: AD Acute GVHD Lepromatous leprosy Diffuse leishmaniasis
Th2/Th22
T-cell pattern:
Chronic lichenoid GVHD
Th1/Th17
T-cell pattern:
Acne vulgaris
Psoriasis
Th17
T-cell pattern:
ACD
TEN
Cytotoxic T cells
Y/N: The cancer-destructive capacity of immune cells becomes weaker and weaker the longer the (primary) tumor persists
Yes
Studies in human skin cancers are urgently needed to determine the anticancer potential of _____ cells, and thus, their possible relevance for cancer immunotherapy
Th9
Presence of high number of intratumoral and peritumoral _____ heralds a bad prognosis
Granulocytes Plasmacytoid dendritic cells Myeloid-derived suppressor cells M2 macrophages Production of IL-4, IL-10, IL-13 and TGF-beta
Large numbers of _____ are associated with a longer disease-free survival
CD3+ T cells
Memory T cells of both the CD4 and the CD8 type