Immunology & biochemistry Flashcards
What factors contribute to the skins immune role?
Structure (a thick keratin layer which sheds regularly), presence of immune cells, cytokines, chemokines & antimicrobial peptides
Skin is a front-line barrier against pathogens. T/F
True
Define autoimmunity, hypersensitivity & immunodeficiency
Autoimmunity - immune response to host tissues
Hypersensitivity - overactive immune response
Immunodeficiency - underactive immune response
The keratin layer is also known as what?
Stratum corneum
What are some important structural proteins in the epidermis?
Filaggrin, keratin and involucrin
What is the role of keratinocytes in the immune response?
Cell surface receptors detect pathogens –> produce AMPs (antimicrobial peptides) to directly kill pathogens –> produce cytokines & chemokines which signal other immune cells
What can keratinocytes be inappropriately activated by?
UV light and various chemicals (once sensitised)
Langerhan’s cells and macrophages are the main skin immune cells. T/F
False - Langerhan’s cells are by far the most common immune cells in the skin
What is the function of Langerhan’s cells?
Present antigens (microbial fragments) to effector T cells & so helps in their activation
How are T cells distributed throughout the skin?
CD4 T cells are mainly found in the dermis
CD8 T cells are mainly found in the epidermis (but also present in the dermis in smaller numbers)
Natural killer cells are also present throughout the skin
Which types of CD4 T cells are involved in psoriasis and atopic dermatitis?
Th1 - psoriasis
Th2 - atopic dermatitis
Th17 - psoriasis & atopic dermatitis
Where are T cells produced and sensitised respectively?
Produced in bone marrow and modified in the thymus
Which two receptors are required to activate a T cell?
T cell receptor (TCR) and Major histocompatability complex (MHC)
What do Th1 & Th2 cells do?
Th1 - activate macrophages (IL2 & IFN gamma)
Th2 - enhance ability of B cells (IL4,5,6)
CD8 cells can kill cells directly and are important in protecting against cancer and bacteria. T/F
False - they protect mainly against cancer and viruses
Name and explain the function of the types of dendritic cell found in the dermis
Dermal dendritic cell - antigen presenting & releases chemo/cytokines
Plasmacytoid dendritic cell - produces interferon alpha & is ONLY found is diseased skin
What immune cells are found in the dermis?
Dendritic cells T cells Neutrophils Mast cells Macrophages
What are the preformed inflammatory mediators of mast cells?
Histamine, tryptase, chymase, TNF
Describe the differences between MHC class I & II
Class I - found on almost all cells & presents endogenous antigen to CD8 cells
Class II - found on antigen presenting cells (B cells & macrophages) & presents exogenous antigen to CD4 cells
Why is MHC particularly important?
Involved in transplant rejection & autoimmunity
Which drugs are associated with the development of psoriasis?
Beta-blockers
Describe the immunopathology of psoriasis
Keratinocytes under stress produce IL & TNF as well as other factors which stimulate Plasmacytoid dendritic cells to produce interferon alpha –> dendritic cells migrate to lymph nodes and activate T cells –> chemokines draw the activated T cells to the dermis where they produce interleukins which stimulate keratinocyte production, AMP release & neutrophil migration. End result mimics a non-healing late stage of injury
(NOTE - CD8 cells & fibroblasts also play a role)
Describe the immunopathology of atopic eczema
Skin barrier breaks down –> invaded by microbes –> cytokines secreted by keratinocytes attract immune cells –> constantly broken down barrier allows microbes to colonise and the body to become sensitised to allergens
What gene defect contributes to atopic eczema? How does this affect the disease?
A defect in the filaggrin gene. Causes severe and early onset eczema
In skin affected by atopic eczema there will be reduced anti microbial peptide. T/F
True
Name three autoimmune conditions involving the skin
Psoriasis, vitiligo & systemic lupus erythematosus
List some secondary (acquired) immunodeficiencies
AIDS, malignancy, aging, diabetes, alcoholic cirrhosis, malnutrition, etc
What is IgE mediated immune reaction also called?
Type 1 hypersensitivity reaction
Type 1 hypersensitivity reactions are fast. T/F
True - IgE binds to mast cell receptors and, upon exposure, cross-linking occurs causing the mass degranulation of mast cells
What is an Arthus reaction and what type of hypersensitivity is it associated with?
A reaction slower than type 1 and faster than type 4 hypersensitivity. Associated with type 3 hypersensitivity
What are type 2 hypersensitivity reactions and why are they relevant?
Antibody mediated reactions which recognise and react to foreign material in the body. They are important for blood transfusions and organ transplantation
What are type 3 hypersensitivity reactions?
Immune complexes which accumulate in tissues and create an immune response (granulomas)
What cell type are type 4 hypersensitivity reactions mediated by?
T helper 1 cells