Skin immunology Flashcards
What is the immune function of keratinocytes?
Sense pathogens via cell surface receptors and help mediate an immune response
What can activate keratinocytes?
UV (sunlight) and sensitizers (allergic contact dermatitis)
What AMPs can the epidermis produce?
Defensins and cathelicidins
In what disease process are AMPs in high levels?
Psoriasis
What is the main immunce cell present in the epidermis?
Langerhans cells
What type of cell is a langerhans cell?
Dendritic cell that can intersperse with keratinocytes in the epidermis
How do langerhans cells act as immune cells?
They act as sentinels in the epidermis and process lipid antigens and microbial fragments and present them to effector T cells to activate them
They have birbeck granules
Where can T cells be found in the skin?
In high numbers in the epidermis and dermis
What type of T cell is found in the epidermis?
CD8+ cells
What type of T cell is found in the dermis?
CD4+ and CD8+ cells
What is Th1 associated with?
Psoariasis
What is TH2 associated with?
Atopic dermatitis
What is TH17 associated with?
Psoriasis and atopic dermatitis
Where are T cells produced?
Bone marrow and sensitised in the thymus
What does Th1 do?
Activates macrophages to destroy microorganisms and produces IL2 and IFN-gamma
What does TH2 do?
Helps B cells make antibodies
Producecs IL4, IL5 and IL^
What do CD8+ cells do?
Kill infected cells directly
Protect against viruses and cancer
What dendritic cells are found within the dermis?
Dermal dendiritc cell
Plasmacytoid dendritic cell
What is the function of dermal DC?
Involved in antigen presentation and secreting cytokines and chemokines
What is the function of plasmacytoid DC?
To produce IFN-alpha
Found in diseased skin
What immune cells are found in the dermis?
Macrophages, neutrophils, mast cells
What is the function of neutrophils?
Circulating leukocytes attracted to tissue by chemokines
What is the function of mast cells?
Tend to be found in barriers
Effectors of IgE mediated immune response (allergy)
Binding of IgE causes activation of the mast cell and release of inflammatory mediators
Where are MHC1 found?
On all cells
Present antigens to cytotoxic T cells
What is an endogenous Ag?
Endogenous antigens are generated within normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with MHC class I molecules.
Where are MHC2 found?
Found on antigen presenting cells (B cells and macrophages)
Present to Th cells
What is an exogenous Ag?
By endocytosis or phagocytosis, exogenous antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present the fragments to T helper cells (CD4+) by the use of class II histocompatibility molecules on their surface
What chromosome codes for MHC molecules?
Chromosome 6
What skin conditions are associated with an inappropriate immune response/ inflammation?
Psoriasis Atopic dermatitis Bullous pemphigoid Contact dermatitis Morphea Urticaria SLE Skin infections Skin tumours
What is the hallmark of psoriasis?
Inflammation
There is a non-ending accelerated phase 2 wound response
What skin appendages can psoriasis affect?
Nails and joints
What are the symptoms of psoriasis?
Erythema
Itchy plaques
Bleeding of lesions
Arthritis
What can cause the onset or exacerbation of psoriasis?
Bacterial pharyngitis (gram +ve) Mild trauma of skin (koebner phenomenom) HIV infection Stress B-blockers or lithium Genetic
What is the immunopathogenesis of psoriasis?
KC under stress releases factors to produce IFN-alpha
Chemical signals activate DC which migrate to skin draining lymph nodes to present to and activate T cells Th1 and Th17
T cells attracted to dermis by chemokiles where they secrete interleukins causing KC proliferation, AMP release and neurtrophil attracting chemokines
How can atopic eczema occur?
Mutations in filaggrin gene
Decrease in AMP in skin
T cells (Th2), DC, KC, macrophages and mast cells are involved
What skin conditions are autoimmune?
Psoriasis
Vitiligo
SLE - fault apoptosis causing lots of DNA to accumulate in the blood and therefore the body starts to form auto-antibodies to its own DNA
What is type 1 hypersensitivity?
Antibody mediated IgE
What is the pathogenesis of type 1 hypersensitivity?
Early exposure to allergen causes the production of IgE which binds to the IgE receptor on mast cell. Later exposure causes rapid crosslinking of the receptors, signal transduction and degranulation of the mast cell
What is type 2 hypersensitivity?
Antibody mediated: IgG and IgM
Important in autoimmunity and transplantation
What are some common disaeses via type 2 hypersensitivity?
Haemolytic disease of the newborn
Blood transfusion recipients
What is type 4 hypersensitvity?
Cell mediated: Th1
Delayed type hypersensitivity is based on T-cell mediated response
What are some examples of type 4 hypersensitivity reactions?
Tuberculin reaction
Contact allergy
Metals - nickel and chromate
What cell types are involved in skin immunity in the epidermis?
Keratinocytes
Langerhans
CD8+ T cells
Melanocytes
What cell types are involved in skin immunity in the dermis?
DC cells Macrophages CD4+ and CD8+ T cells NK cells Fibroblasts Lymph/ vasculature
