Hypersensitivity reactions, skin, eczema Flashcards
where does the immune system fuck up
transplants
autoimmunity
allergy
why can the immune system fuck up transplants
memory, specificity and discrimination underlie transplant rejection
if match not perfect, T cells react to alloantigen presenting cells with non self HLA so host T cells attack graft- rejection
what goes wrong in autoimmunity
immune system fails to discriminate between self and non self, misrecognise self as dangerous
what is autoimmune disease
it may be x specific or non specific
autoimmune disease is a specific response to self antigen, resulting in pathophysiology (3/4 sufferers women)
may be organ specific- antigen confined to specific organ
organ non specific- antigen is widespread eg systemic lupus
generally can’t eradicate all so chronic inflammation leads to damage
what are 3 formats of autoimmune disease
autoantibody to self antigen-
sees antibody mediated damage, blocking of cunction and stimulation
activating cell mediated response
immune complex deposition-
antigen- antobody complexes dumped in highly vascular tissues, activates complement, causes tissue damage
can autoimmunity be transferred to fetus
if make autoantibodies will be passed to fetus in transplacental transfer
newborn will have symptoms h/e they dont produce the antibodues so remove them with plasmapheresis to remove mat antibodies and then cured
what is hypersensitivity caused by? (brief)
immune system misrecognising things (eg pollen, food proteins) as dangerous/ pathogenic, mounts immune response to get rid of
causes tissue damage in process
memory- must now always avoid substance
specificity- will respond to tiny amounts
allergy vs intolerance
allergy is a specific immune response to innocuous antigen resulting in pathology
allergy requires mg or micrograms vs intolerance requires grams to manifest
type 1 hypersensitivity reaction is classified as
IgE mediator
soluble antigen
mast cell and eosinophils are effectors
includes allergy, allergic rhinitis, asthma, atopic dermatitis
type 2 hypersensitivity reaction is classified as
IgG mediator
cell/ matrix antigen (cell bound drug)
complement and FcR+ cells are effectors
cytotoxic reaction mediated by IgG/IgM
type 3 hypersensitivity reaction is classfied as
IgG mediator
soluble antigen
complement and phagocytes are effectors
eg serum sickness
mediated by immune complexes
type 4 hypersensitivity reaction is classified as
T cells mediate
soluble antigen
macrophages effectors
eg contact dermatitis
type 1 vs type 4 hypersensitivity reaction
type 1 is immediate hypersensitivity
type 4 is 24-72 hrs after challenge
all allergic/ hypersensitivity reactions develop in 2 stages
induction/ sensitisation
- first exposure primes indiv
elicitation
- subsequnt exposure to allergen, sensitised indiv shows clinical manifestations
how do type 2 hypersensitivity reactions develop and occur
IgG antibodies vs cell/ matric assoc allergens, causing lysis or phagocytosis
some drug allergies are type 2
sensitisation phase:
drug binds to a cell
antibody is produced vs the cell-bound drug bc seen as foreign
elicitation phase:
antibodies bind to cell-bound drug
complement is recruited
antibody coated drug is ingested by phagocytes
cytokines are released, trigger inflammatory response eg skin rash
how do type 3 hypersensitivity reactions develop and occur
immune complexes of IgG antibodies with soluble antigen (immune complex= multiple antibody-antigen complexs in one)
immune complexes are deposited in small blood vessels
complement and phagocytes engage
causes inflammation, fever, vascultitis, arthritis etc
eg lupus, serum sickness
what is a type 4 hypersensitivity reaction, when does it present and how do you test for it. treatment?
reaction presents 48hrs after a challenge to sensitised indiv.
mediated by Th1 and T cytotoxic cells
test with Tuberculin (mantoux and heaf test), results in contact allergy
contact allergens may be manmade or natural. misidentified as virus/ bacteria, so cell mediated response
no treatment. identify allergens and avoid (prick test). treat symptoms with mid to high topical corticosteoids. if extensive then systemic steroids
how does a type 4 hypersensitivity reaction develop and occur
induction phase:
exposure to allergen
interacts with dendritic cells
which activate allergen-specific T cells
elicitation phase: dendritic cells present allergen activates Th1 and T cytotoxic cells Th1 cells release chemokines, cytotoxins, cytokines so macrophages produced cutaneous inflammation
type 1 hypersensitivity allergic reaction
involve IgE which recruits mast cells
types of response: acute, chronic or systemic anaphlyaxis
how do acute type 1 hypersensitivity reactions develop and occur
sensitisation:
IgE produced, distributed systemically, IgE binds to mast cells
elicitation phase:
allergen crosslinks the IgE on surface of mast cells
causes degranulation
so preformed mediators are released (prostaglandin, histamine etc)
symptoms depend where exposed
what is the chronic response in type 1 hypersensitivity reaction
molecules released from degranulation cause recruitment of eosinophils and Th2 cells to site
more inflamm mediators so more delayed response
what are the signature Th2 cytokines and what do they do
IL 4
IL 5
IL 10
IL 13
IgE production, mucin hypersecretion, activate and recruit eosinophils, activate and differentiate mast cells
what are the symptoms of type 1 hypersensitivity reaction general note and skin, airway, gut
same as if mast cell/ basophil trying to get rid of parasite
type of immune response depends on how much allergen, site of, amount and affinity of IgE
Skin- only local mast cells activated so local histamine, see wheals and flares. Confined to skin.
Airways- if small amount, mast cell activation confined to lungs. contstrict and incr vascular permeability
short term- oedema, SOB, wheezing
long term- airway remodelling by eosinophils, lungs sensitised to further stimuli (asthma)
Gut- local. contraction of smooth muscle, incr fluid,incr peristalsis. vomit and diarrhoea
symptoms of type 1 hypersensitivity in blood and systemic anaphylaxis
direct into blood
potentially life threatening
both mast cells and basophils triggered to release histamine and cytokines
anaphylaxis is caused by mismatch btwn O2 delivery from lungs and tissue needs. can result in cardiovascular failure 10-15 minutes
how may ingestion of allergen result in anaphylaxis
allergen can get into blood by other routes, eg mast cell degranulation makes vessels leaky so allergen can enter blood from gut
examples of type 1 hypersensitivity reactions
food allergy asthma rhinitis atopic eczema systemic anaphylaxis
if have a propensity for then called atopic
management of allergy
some childhood can be outgrown, but othw sensitisation is irreversible and lifelong
no cure, treat symptoms, avoid
teenagers more vulnerable as risky behav
peanut/ nut allergies can be v severe bc the proetin remains for so long so lots of exposure
how is a type 1 allergy diagnosed
detection of IgE- specific serum test, RAST, skin prick tests
provocation challenge-
food allergy: DBPCFC
rhinitis: nasal challenge
asthma: bronchial provocation test
how treat symptoms allergy
avoid exposure
anti-histamines
mast cell stabilising compounds
topical and systemic corticosteroids
anaphylaxis- adrenalin, epipen
how common is eczema
affects 1 in 5 children, though 90% grow out of it by age 10
genetics behind eczema
strong genetic component-
MZ CR 75%
DZ CR 25%
if no parents affected 1/10
if 1 parent 50%
if 2 parents 75%
6-20 genes associated with eczema
Filaggrin mutation v common
Filaggrin facilitates terminal differentiation of keratinocytes and so the formation of the skin barrier
have palmar hyperlinearity
filaggrin loss of function mutation (in 10% EU) means allergens better penetrate epidermis and interact with APCs this stimulates Th2 cells release IL 4 IgE release mast cell degranulation and inflammation
Th2 skewing and eczema
eczema skin has overexpression of TSLP cytokine, amplifies Th2 responses
overproduction of cytokines that promote Th2
so in total, eczema is caused by:
skin barrier defect (fillaggrin mutation)
antigen/ bacteria entry, interact with APCs
inflammatory cytokines
Th2 cells
more cytokines
IgE release
recruitment mast cells degranulation and eosinophils
inflammation
why won’t antihistamines work for eczema
Th2 is the main cell involved which goes on to trigger IgE and mast cell degranulation. Th2 is the root of the problem so antihistamines not helpful
treating eczema
best to restore skin barrier with emollients
topical corticosteroids
avoid excacerbation factors- allergens, smoke
what is ichthyosis vulgaris
dry, scaled skin (have filaggrin mutation)
what is the atopic march
atopic dermatitis then asthma then allergic rhinitis
70% pts with severe atopic dermatitis get asthma
childhood eczema one of biggest risk factors for eczema so lots research put into stopping atopic march
functions of skin
barrier to ext env protects- mech, chem, osmotic, thermal, UV, microbes vit D synthesis regulate body temp psychosexual communication major sensory organ
skin may be hirsute or glabrous- explain
hirsute skin- thin and hairy
glabrous- thick and hairless (palms, soles)
what is the epidermis and what cells is it composed of
most superficial layer of skin
largely formed by keratinocytes undergoing terminal maturation (increased keratin production and migration to external surface (cornification))
melanocytes- responsible melanin production and pigment formation (black people have more melanin not more melanocytes)
Langerhans cells- antigen presenting dendritic cells
Merkel cells- sensory mechanoreceptors
the epidermis consists of 4/5 layers, what are they and what cells are there/ whats goin on
stratum basale-
single row cuboidal keratinocytes and stem cells for supply (where mitosis occurs)
contains melanocytes and merkel cells
stratum spinosum-
squamous cell layer
cells heald together by spiny projections, tight intercellular junctions (desmosomes)
langerhans cells present
stratum granulosum
cells flattened and undergoing apoptosis
cells secrete lipids and waterproofing molecules
stratum lucidum*
only present in thick areas of skin
flattened, clear keratinocytes with lots of keratin
lose nuclei
stratum corneum
flattened, dead keratinocytes have lost all organelles, esentially packages of keratin
10-50 layers depending where
sloughed off continually, slows with age
process takes 30 days as young adult, 50 days as old
what are the layers of the epidermis
stratum basale stratum spinosum stratum granulosum strautum lucidum stratum corneum
what is the dermis and what are its cells
immediately deep to epidermis, is tightly connected via dermo-epidermal junction
composed of dense, irregular connective tissue, containing collagen and connective fibres
woven network of fibres has great tensile strength and so resists pulling stretching and has ability to stretch
cells:
fibroblasts: synthesis extracellular matrix (collagen and elastin)
mast cells
meissner corpuscles (touch nerve cells)
skin appendages (hair follicles, nails, sebacioous and oil glands)
has 2 layers
papillary layer of dermis
superficial dermal layer
of thin collagen and elastin fibres
SA increased by dermal papillae (nipples) small nipple shaped structures that project into undersurface of epidermis
capillary loops, some with meissner corpuscles
epidermal ridges are downward projections from epidermis, creates strong bond between layers in regions of high mechanical stress, increase SA for grip and more meissner corpuscles so better touch. fingerprints.
reticular region of dermis
thick collagen bundles, course elastic fibres. some fibroblasts.
net like structure resist stretching etc
has the hair follicles, sebaceous glands, sweat glands
hair follicles and sebaceous glands combine to form a pilosebacious unit. only found in hirsute skin. oil glands release secretions via holocrine mechanism, into hair shaft
sweat glands
-eccrine glands- major sweat glands, release clear, odourless substance, mostly sodium chloride. for thermoregulation
- apocrine glands- large sweat glands in axillary and genital regions, products broken down by cutaneous microbes into body odour
what is the hypodermis
subcutis/ subcutaneous layer
major store of adipose tissue, amouont varies on how much of a fattie you are
absorbs shock, heat insulation
blood vessels and nerves
