Skin Immunology (Mainly Revision) Flashcards
Describe how keratinocytes in the epidermis help with the immune response
• 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)
Describe how langerhan’s cells help with the immune response
• A type of dendritic cell that intersperse with keratinocytes in the epidermis.
• The main skin resident immune cell.
• 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.
Mainly ___1____ cells are found in the epidermis. Whereas _____2_____ cells are found in the dermis.
1) CD8+ T
2) CD4 + and CD8+ T
What type of T cell is associated with allergy/ atopy?
TH2
Describe the difference between CD4 and CD8 T cells
CD4 are helper T cells. CD8 are cytotoxic T cells so they kill infected cells.
Describe the difference between class 1 and 2 MHC molecules
Class 1 is found on all nucleated cells and presents to CD8 cells. Class 2 is found only on professional antigen presenting cells and presents to CD4.
Describe type 1 hypersensitivity
Allergy- IgE mediated
Allergic response is driven by allergen binding to IgE coated mast cells. it can only occur after initial sensitisation. When IgE binds there is mast cell degranulation and release of histamine etc.
Describe type 2 hypersensitivity
Antibodies are generated to self antigen. Autoimmune disease.
Describe type 3 hypersensitivity
Immune complexes are deposited activating complement and inflammatory cells. e.g. hypersensitivity pneumonitis.
Describe type 4 hypersensitivity
Delayed reaction. T cell mediated e.g. sarcoidosis and TB.
In response to injury or infectious agent what do mast cells release? What does this result in?
Inflammatory mediators such as histamine. Inflammatory response is generated and neutrophils move into the wounded tissue by trans endothelial migration.
How do tissue resident macrophages, mast cells and newly recruited neutrophils recognise extracellular pathogens? What does this result in?
By PAMPs (pathogen associated molecular pattern- these are LPS that normal cells don’t have). Recognition of PAMPs results in activation and killing through various mechanisms.
Describe how dendritic cells form a link between the innate and adaptive immune system
Dendritic cells take up debris from pathogen containing PAMPs or antigen via phagocytosis. They then process display this material on MHC molecules. These activated dendritic cells leave the tissue and migrate to the lymph nodes where they can show the peptides to specific T and B cells which will then be activated.
When are NK cells activated?
NK cells are activated by intracellular pathogens through absence of MHC-1 surface expression on pathogens.
If there is a mixture of intracellular and extracellular pathogens what happens?
NK cells produce pro-inflammatory cytokine interferon gamma which acts on macrophages to turn them into superkillers. Interferon gamma also activated dendritic cells which then produce IL-12. IL-12 in turn activates more NK cells.
NOTE MACROPHAGES DO NOT PRODUCE INTERFERON GAMMA.
Explain what interferon gamma favours T cell differentiation to
Favours TH1 cell differentiation this makes sense as these helper cells go to infected tissue and interferon gamma will be being produced due to presence of intracellular pathogens which you need good t cell response for.
What 2 signals do B cells need to become activated?
Antigen and T helper cell signal
What do B cells do?
Produce specific antibodies that circulate through out the body helping to kill and eliminate pathogens.
Explain what class switching is
Cytokines produced by T cells induces class switching (of antibodies) therefore depending on the cytokine environment (which will be influenced by the type of pathogen) you get different Ig classes.
Describe restoration to homeostasis
Some B and T cells become memory cells allowing quicker response to reinfection, these reside in the bone marrow. Macrophages switch behaviour and return to sweeping up dead cells. They also secrete anti-inflammatory cytokines to promote tissue repair and healing. Pro-inflammatory mediators, cytokines and acute phase proteins have a short half life.
The immune response has a systemic effect on the liver what happens?
Activation of acute phase proteins which migrate into infected tissue. Also get activation of the complement system by mannose-lectin pathway and alternate pathway.
What does CRP do?
CRP (C reactive protein) this protein primes certain bacteria for destruction by the complement system. It also has a prognostic role as can levels of it can give an indication of severity and duration of inflammation.
Describe the complement system
This is a family of approximately 30 proteins that are produced in liver. They circulate in the blood and constitute 10% of serum proteins. The complement system, when activated, creates a cascade of chemical reactions that promotes opsonization, chemotaxis, and agglutination, and produces the MAC.
Describe the MAC
The last five proteins in the complement cascade self-associate to form a membrane attack complex (MAC). MACS inserts themselves into pathogen membranes allowing extracellular salts and water to enter, causing the microbe to swell and burst. (OSMOTIC LYSIS)
