Immunology Flashcards
how is the keratin layer formed?
through terminal differentiation of keratinocytes to corneocytes
name some important structural proteins in the keratin layer & epidermis
filaggrin
involucrin
keratin
name some features of the keratin layer
tough
lipid rich
physical barrier
what do keratinocytes do in the epidermis?
sense pathogens via cell surface receptors and help mediate an immune response
what can keratinocytes be activated in the epidermis?
UV light
sensitzers e.g. allergic contact dermatitis
what do keratinocytes produce in response to pathogens?
antimicrobial peptides (AMPs)
cytokines
chemokines
what are Langerhans cells?
a type of dendritic cell that intersperse with keratinocytes in the epidermis
what are Langerhans cells characterised by?
the birbeck granule
what do Langerhans cells do?
process lipid Ag & microbial fragments & present them to effector T cells to activate them
what type of T cells are found in the skin?
mainly CD8+ in the epidermis
CD4+ & CD8+ in the dermis
subsets (NK cells) are also found
which CD4+ Th cells are associate with inflammation?
Th1 - psoriasis
Th2 - atopic dermatitis
Th17 - atopic dermatitis & psoraisis
where are T cells produced?
bone marrow
where are T cells sensitised?
thymus
how are Ags recognised and T cells activated?
using the T cell receptor (TCr) & major histocompatibility complex (MHC)
enhanced by co-recptors
what do Th1 cells do?
activate macrophges to destroy macrophages using IL2 & IFN gamma
when are Th1 cells especially useful?
against viral invaders
what do Th2 cells to?
help B cells to make Ab using IL4, IL5 & IL6
when are Th2 cells especially useful?
against parasitic invaders
when are CD8+ cells useful?
important in the protection against viruses & cancer
which types of dendritic cell are found in the dermis?
dermal dendritic cell & plasmacytoid dendritic cell
what do dermal DCs do?
involved in Ag presenting & secreting cytokines & chemokines
what do plasmacytoid DCs do?
produce IFN alpha
when are plasmacytoid DCs found in the skin?
they are low or absent in normal skin but found in relatively high numbers in diseased skin
what is psoriasis?
an over-reaction of the immune response presenting as chronic inflammation, specifically a non-late phase wound response
describe the immunopathogeneis of psorasis
keratinocytes under stress release factors that stimulate pDC to produce IFN alpha, interleukins& TNF which activate DC which migrate to lymph nodes to present to & activate Th cells
T cells then attracted to dermis by cheekiness & secrete interleukins
what is the key factor in atopic eczema?
impairment of the skin barrier function due to mutations in the filaggrin gene and decreased AMP in skin
how does impairment of the skin barrier function cause atopic eczema?
allows access/sensitisation to allergen & promotes colonisation by micro-organisms
what does filaggrin do in normal skin?
normally found in granules in granular layer where it breaks down & binds water helping the skin to retain water, naturally moisturising the skin
which interleukin is clinically relevant in eczema?
IL4
what happens in vitiligo?
melanocytes are attacked by T lymphocytes
what happens in SLE?
auto-antibodies are produced by B lymphocytes
when are Type II hypersensitivity mechanisms important?
in autoimmunity & transplantation
mediated by IgG & IgM
when are type III hypersensitivity mechanisms important?
in certain drug reactions
mediated by IgG & IgM
when are type i hypersensitivity mechanisms important?
in allergies
mediated by IgE
when are type IV hypersensitivity mechanisms important?
in contact allergies & tuberculin reaction
mediated by Th1 cells
which factors affect skin immune response in organ transplant?
immunosuppression - after 10 years most probable cause of death is skin cancer as its more like to metastasis due to lack of active immune surveillance
which factors affect skin immune response to UV light?
immunosuppression & structure
which factors affect skin immune response in ageing?
changes in skin structure
decreased ability to detect maligned cells
decreased ability to detect Ag
decreased ability to distinguish self cells from non-self
what 2 types of drug reactions are there?
immunologically mediated reactions & non-immunologically mediated reactions
what types of immunologically mediated drug reactions are there?
type 1 - anaphylactic
type 2 - cytotoxic reactions
type 3 - immune complex-mediated reactions
type 4 - cell mediated delayed hypersensitivity reactions
are immunologically mediated drug reactions does dependant?
no
what non-immunologically mediated drug reactions are there?
eczema drug induced alopecia phototoxicity skin erosion/atrophy from topical therapy psoraisis pigmentation
are non-immunologically mediated drug reactions does dependant?
can be
who do drug reactions present?
exanthematous/morbiliform/maculopapular urticarial papulosquamous/pustular/bullous pigmentation itch/pain photosensitivity
what are the risk factors for developing a drug eruption?
age - young adults > infants/elderly gender - females > males genetics concomitant disease immune status chemistry route does kinetics/half-life
what are exanthematous drug eruptions?
Most common type of drug eruption (90%).
Idiosyncratic, T-cell mediated delayed type hypersensitivity (Type IV) reaction,
describe some of the clinical features of an exanthematous drug eruption
usually mild & self-limiting
widespread symmetrically distributed rash sparing the mucous membranes
pruritus & mild fever is commone
what are the indicators of a potential severe reaction in exanthematous drug eruptions?
Involvement of mucous membrane and face. Facial oedema & erythema. Widespread confluent erythema. Fever (>38.5⁰C). Blisters, purpura, necrosis. Lymphadenopathy, arthalgia. Shortness of breath, wheezing.
name some drugs associated with exanthematous drug eruptions (at least 4)
Penicillins Sulphonamide antibiotics Erythromycin Streptomycin Allopurinol Anti-epileptics: carbamazepine NSAIDs Phenytoin Chloramphenicol
what is the mechanism of urticarial drug reactions?
IgE mediated hypersensitivty reaction after rechallenge with drug or direct release of inflammatory mediators from mast cells on first exposure
give 2 examples of pustular/bullous drug eruptions
acne
acute generalised exanthematous pustulosis (AGEP)
what do fixed drug eruptions look like?
well demarcated round/ovoid plaques
what do fixed drug eruptions feel like?
red & painful
where are fixed drug eruptions found?
hands, genitalia, lips & occasionally oral mucosa
how do fixed drug eruptions resolve?
with persistent pigmentation when the drug is stopped
can fixed drug eruptions re-occur?
yes, on the same site on re-exposure to the drug
how fixed drug eruptions present?
as eczematous lesions, papules, vesicles or urticaria
which drugs are associated with fixed drug eruptions?
tetracylcine, doxycycline, paracetamol, NSAIDs, carbamazepine
what do combined cutaneous and systemic symptoms include in severe cutaneous adverse reactions?
stevens-johnson sydrome
toxice epidermal necrolysis
drug reaction with eosinophilia & systemic symptoms
acute generalised exanthematous pustulosis
what is stevens-johnson syndrome (SJS)?
a form of toxic epidermal necrolysis, is a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis
what is toxic epidermal necrolysis (TEN)?
also known as Lyell’s syndrome, is a rare, life-threatening skin condition that is usually caused by a reaction to drugs
what is drug reaction with eosinophilia& systemic symptoms (DRESS)?
a severe idiosyncratic drug reaction with a long latency period
what is acute generalised exanthematous pustulosis (AGEP)?
a common cutaneous reaction pattern that is characterized by a sudden eruption that appears on average five days after the medication is started
what are the acute phytotoxic drug reactions?
skin toxicity
systemic toxicity
photodegradation
what are the chronic phytotoxic drug reactions?
pigmentation
photoageing
photocarcinogenesis
what are photooptic cutaneous drug reactions?
Non-immunological mediated skin reaction which will arise in any individual providing there is enough photo-reactive drug and the appropriate wavelength of light
what is the waveband usually associated with phototoxic cutaneous drug reactions?
UVA/Visible
what are the major patterns of cutaneous phototoxicity?
immediate prickling with delayed erythema & pigmentation
exaggerated sunburn
exponsed telangiectasia
delayed 3-5 days erythema & pigmentation
increased skin fragility
