Hypersensitivity reactions, skin, eczema

Question 1

where does the immune system fuck up

Answer 1

transplants
autoimmunity
allergy

Question 2

why can the immune system fuck up transplants

Answer 2

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

Question 3

what goes wrong in autoimmunity

Answer 3

immune system fails to discriminate between self and non self, misrecognise self as dangerous

Question 4

what is autoimmune disease

it may be x specific or non specific

Answer 4

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

Question 5

what are 3 formats of autoimmune disease

Answer 5

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

Question 6

can autoimmunity be transferred to fetus

Answer 6

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

Question 7

what is hypersensitivity caused by? (brief)

Answer 7

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

Question 8

allergy vs intolerance

Answer 8

allergy is a specific immune response to innocuous antigen resulting in pathology

allergy requires mg or micrograms vs intolerance requires grams to manifest

Question 9

type 1 hypersensitivity reaction is classified as

Answer 9

IgE mediator
soluble antigen
mast cell and eosinophils are effectors
includes allergy, allergic rhinitis, asthma, atopic dermatitis

Question 10

type 2 hypersensitivity reaction is classified as

Answer 10

IgG mediator
cell/ matrix antigen (cell bound drug)
complement and FcR+ cells are effectors

cytotoxic reaction mediated by IgG/IgM

Question 11

type 3 hypersensitivity reaction is classfied as

Answer 11

IgG mediator
soluble antigen
complement and phagocytes are effectors
eg serum sickness

mediated by immune complexes

Question 12

type 4 hypersensitivity reaction is classified as

Answer 12

T cells mediate
soluble antigen
macrophages effectors
eg contact dermatitis

Question 13

type 1 vs type 4 hypersensitivity reaction

Answer 13

type 1 is immediate hypersensitivity

type 4 is 24-72 hrs after challenge

Question 14

all allergic/ hypersensitivity reactions develop in 2 stages

Answer 14

induction/ sensitisation
- first exposure primes indiv

elicitation
- subsequnt exposure to allergen, sensitised indiv shows clinical manifestations

Question 15

how do type 2 hypersensitivity reactions develop and occur

Answer 15

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

Question 16

how do type 3 hypersensitivity reactions develop and occur

Answer 16

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

Question 17

what is a type 4 hypersensitivity reaction, when does it present and how do you test for it. treatment?

Answer 17

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

Question 18

how does a type 4 hypersensitivity reaction develop and occur

Answer 18

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

Question 19

type 1 hypersensitivity allergic reaction

Answer 19

involve IgE which recruits mast cells

types of response: acute, chronic or systemic anaphlyaxis

Question 20

how do acute type 1 hypersensitivity reactions develop and occur

Answer 20

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

Question 21

what is the chronic response in type 1 hypersensitivity reaction

Answer 21

molecules released from degranulation cause recruitment of eosinophils and Th2 cells to site

more inflamm mediators so more delayed response

Question 22

what are the signature Th2 cytokines and what do they do

Answer 22

IL 4
IL 5
IL 10
IL 13

IgE production, mucin hypersecretion, activate and recruit eosinophils, activate and differentiate mast cells

Question 23

what are the symptoms of type 1 hypersensitivity reaction general note and skin, airway, gut

Answer 23

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

Question 24

symptoms of type 1 hypersensitivity in blood and systemic anaphylaxis

Answer 24

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

Question 25

how may ingestion of allergen result in anaphylaxis

Answer 25

allergen can get into blood by other routes, eg mast cell degranulation makes vessels leaky so allergen can enter blood from gut

Question 26

examples of type 1 hypersensitivity reactions

Answer 26

food allergy
asthma
rhinitis
atopic eczema
systemic anaphylaxis

if have a propensity for then called atopic

Question 27

management of allergy

Answer 27

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

Question 28

how is a type 1 allergy diagnosed

Answer 28

detection of IgE- specific serum test, RAST, skin prick tests

provocation challenge-
food allergy: DBPCFC
rhinitis: nasal challenge
asthma: bronchial provocation test

Question 29

how treat symptoms allergy

Answer 29

avoid exposure

anti-histamines
mast cell stabilising compounds
topical and systemic corticosteroids

anaphylaxis- adrenalin, epipen

Question 30

how common is eczema

Answer 30

affects 1 in 5 children, though 90% grow out of it by age 10

Question 31

genetics behind eczema

Answer 31

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

Question 32

Th2 skewing and eczema

Answer 32

eczema skin has overexpression of TSLP cytokine, amplifies Th2 responses
overproduction of cytokines that promote Th2

Question 33

so in total, eczema is caused by:

Answer 33

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

Question 34

why won’t antihistamines work for eczema

Answer 34

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

Question 35

treating eczema

Answer 35

best to restore skin barrier with emollients
topical corticosteroids
avoid excacerbation factors- allergens, smoke

Question 36

what is ichthyosis vulgaris

Answer 36

dry, scaled skin (have filaggrin mutation)

Question 37

what is the atopic march

Answer 37

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

Question 38

functions of skin

Answer 38

barrier to ext env
protects- mech, chem, osmotic, thermal, UV, microbes
vit D synthesis
regulate body temp
psychosexual communication
major sensory organ

Question 39

skin may be hirsute or glabrous- explain

Answer 39

hirsute skin- thin and hairy

glabrous- thick and hairless (palms, soles)

Question 40

what is the epidermis and what cells is it composed of

Answer 40

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

Question 41

the epidermis consists of 4/5 layers, what are they and what cells are there/ whats goin on

Answer 41

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

Question 42

what are the layers of the epidermis

Answer 42

stratum basale
stratum spinosum
stratum granulosum
strautum lucidum
stratum corneum

Question 43

what is the dermis and what are its cells

Answer 43

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

Question 44

papillary layer of dermis

Answer 44

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.

Question 45

reticular region of dermis

Answer 45

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

Question 46

what is the hypodermis

Answer 46

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