Skin Immunology/Biochemistry – Skin Immunology Flashcards
List some of the factors which contribute to skin as an immunological system
•Structure:
–Eg. keratin layer (stratum corneum), stratification
•Cell types:
–Immune system cells and keratinocytes
•Cytokines, chemokines, eicosanoids, antimicrobial peptides:
–Chemical signals/molecules that influence cell behaviour or help target pathogens
•Genetics:
Define what an antigen is
Antigen (Ag) = Usually a protein/peptide or polysaccharide that elicits an immune response (antibody generator)
Which is typically the first immune response, innate or adaptive immune response ?
Innate - it is non-specific where as adaptive is from memory and specific
Briefly what is the keratin layer and what is it made up of?
Tough, lipid rich, physical barrier
Formed by terminal differentiation of keratinocytes to corneocytes.
Important structural proteins in the keratin layer and epidermis include:
- –Filaggrin/Involucrin/keratin
What is the immune functions of keratinocytes found in the epidermis ?
Sense pathogens via cell surface receptors and help mediate an immune response.
- Keratinocytes can be activated by UV (sunlight) and sensitizers (eg. allergic contact dermatitis)
Produce antimicrobial peptides (AMPs) that can directly kill pathogens:
AMPs have been found at high levels in skin of patients with psoriasis
Produce cytokines and chemokines:
Recruit and regulate cells of the adaptive and innate immune system (eg. in psoriasis)
What are the immune functions of langerhans cells in the epidermis ?
They are Antigen presenting cells (APC), characterized by the Birbeck granule.
- They act as sentinels in the epidermis.
- They process lipid Ag and microbial fragments and present them to effector T cells.
- They help to activate T cells.
What type of cell are langerhans cells ?
Dendritic cells that intersperse with keratinocytes in the epidermis.
Where are T cells found in the skin ?
CD8+ and CD4+ T cells are found in both the dermis and epidermis
- Mainly CD8+ T cells are found in the epidermis
- CD4 + and CD8+ T cells are found in the dermis
- Other subsets of T cells (eg. Natural Killer (NK) cells) are also found
What are the CD4+ TH cells associated with inflammation and give the specific inflammatory skin condition they are associated with
- TH1 associated with psoriasis
- TH2 associated with actopic dermatitis
- TH17 associated with both psoriasis and actopic dermatitis
Where are T cells produced and sensitised ?
Produced in bone marrow and sensitised in the thymus
What does Ag recognition and T cell activation involve?
It involves interaction with the T cell receptor (TCR) and the Major Histocompatibility Complex (MHC).
- Class I MHC molecules can only be recognised by CD8+
- Class II MHC molecules can only be recognised by CD4+
What are the functions of CD4+ helper cells ?
CD4+ Helper T cells:
•TH1: Activate macrophages to destroy microorganisms
This is achieved by the release of chemical mediators, or signalling molecules including substances such as interleukins and interferons. These mediators can influence the signals produced by other cell types that could enhance or diminish their activity, or they could be chemotactic signals that would attract neutrophils and other innate system cells to migrate to the affected area.
IL2, IFNg - these help do this
•TH2: Help B cells to make Ab
IL4, IL5, IL6 - these help do this
What are the functions of CD8+ cytotoxic cells ?
- Can kill infected cells directly
- Important protection against viruses and cancer
What are some of the dendritic cells found in the dermis ?
- Dermal DC: involved in Ag presenting and secreting cyto/chemokines
- Plasmacytoid DC (pDC): produce IFNα. Found in diseased skin
What is the function of the dendritic cells found in the dermis ?
- Transmit information to T (&B) cells
- Secrete cyto/chemokines during the inflammatory (immune) response which are chemical signals that modulate the immune response and recruit/activate different cell types to the locus
List some of the other cells found in the dermis (other than dendritic cells and T cells already mentioned)
- Macrophages
- Neutrophils
- Mast cells
What are neutrophils ?
They are leukocytes which are attracted to tissue by chemokines
Describe the action of mast cells and what type of reactions they are involved in
- Effectors of IgE-mediated immune response (allergy)
- Binding of IgE causes activation of the mast cell & release of inflammatory mediators
- Also activated by physical trauma/certain drugs/micro-organisms
Provide an overview for the functions of MHC
MHC region occurs on chromosome 6
Class I MHC:
- Found on almost all cells
- Present Ag to cytotoxic T cells
- Present endogenous (having an internal cause or origin) Ag
Class II MHC:
- Found on APC (B cells, macrophages)
- Present to TH cells
- Present exogenous (having an external cause or origin.) Ag
Give some examples of skin diseases associated with inappropriate Immune Response/Inflammation
- Psoriasis
- Atopic dermatitis
- Bullous pemphigoid
- Contact dermatitis
- Morphea/Systemic sclerosis
- Urticaria
- Systemic lupus erythematosus
- Skin infections
- Skin tumours
What can cause people to develop psoriasis?
Triggered by environmental factors in genetically susceptible individuals:
Triggering factors for the onset/exacerbation range from:
- Infection e.g. bacterial pharyngitis, HIV etc
- mild trauma of the skin know as Koebner phenomenon where skin lesions appear on lines of trauma
- Physchological stress
- Ingestion of medications such as β-blockers or lithium
What is the hallmark sign of psoriatic skin lesions?
Inflammation
Describe the immunopathogenesis of psoriasis
KC under stress:
- release factors that stimulate pDC to produce IFNα
- release IL-1β/IL-6 and TNF
Chemical signals activate DC, which migrate to skin draining lymph node to present to and activate T cells
- TH1 & TH17
T cells are attracted to the dermis by chemokines and secrete IL-17A/17F/22
- Stimulates KC proliferation, AMP release and neutrophil-attracting chemokines
CD8+ cells also contribute to pathogenesis.
Dermal fibroblasts become involved, which release KC and epidermal growth factors.
Who is the development of atopic eczema the most common in ?
Children
Describe the immunopathogenesis of atopic eczema
Defective skin barrier function due to:
- Mutations in fillagrin gene associated with severe/early onset disease.
- ↓AMP in skin
T cells (TH2), DC, KC, macrophages and mast cells are involved/found in the lesions (probably attracted by stressed KC)
The defective skin barrier allows access/sensitisation to allergen and promotes colonisation by micro-organisms.
What are the two main different types of immunodeficiency ?
Primary (Genetic) - Inherited defect, Specific or Non-specific
Secondary (Acquired) - due to e.g. AIDS, Malignancy, Aging, Diabetes, renal malfunction, burns, alcoholic cirrhosis,malnutrition
Define what autoimmunity is and give some examples of causes of it
Autoimmunity is the system of immune responses of an organism against its own healthy cells and tissues.
Causes e.g. Lymphocyte abnormalities, Intercell communication, Genetic predisposition etc
Read over the summary for this lecture
The skin immune surveillance system is important. It protects against infection and skin tumour development.
Multiple cell types are involved in immune surveillance and immune response in the skin:
- Immune system cells
- Skin tissue cells and structures
Chemical cross-talk and interaction between these amplify and modulate the immune response.
Immunodeficiency results from an inadequate immune response. Autoimmunity and hypersensitivity from an inappropriate/excessive immune response, resulting in the inflammatory reaction.
Use this link for a immunology video
http://www.nature.com/ni/multimedia/skin/index.html
