Hypersensitive Immunity

Question 1

hypersensitivity=

4 types of hypersensitivity:
type I- involves?
-antibody involved?
-involves what cell?
-1/3 eg's 

type II- involves?

• antibody involved?
• involves what cell/ pathway? -> activated by?
• 1/2 eg’s

type III- involves

• antibody involved?
• involves what cell/ pathway? -> activated by?
• 1/2 eg’s

type IV- involves?

• macrophage activation -> cell type? -> eg.
• ….. activation -> Th2 -> eg.
• cytoxicity -> 2eg’s

Answer 1

over-reaction to harmless molecules leading to immune response and tissue damage from inflammation

Type I -> soluble antigen
IgE
Mast cells
asthma, eczema, allergic rhinitis

Type II -> cell associated
IgG
Macrophages and compliment -> antibody activated
drug allergies, chronic urticaria

Type III -> soluble antigen
IgG
compliment and macrophages
serum sickness, arthus reaction

Type IV- T cell mediated

• macrophage activation -> Th1 -> eg. allergic contact dermatitis
• Eosinophilic activation -> Th2 -> eg. chronic asthma
• Cytotoxity -> eg’s graft rejection and allergic contact dermatitis to poison ivy

Question 2

Allergens 
I- eg for each
I
I
C

IgE normal function?
why would an allergen kick off an immune response?

Answer 2

Ingested- pollen, dust mite feaces
Injected- insect sting, drugs
Inhaled- peanut
Contact- nickel, poison ivy

IgE- kills multicellular parasites too large to phagocytose

why?
some allergen have similar molecular composition as parasites so can be mistakenly identified as dangerous

Question 3

Breakdown of Type I mechanism:
first exposure -> key word!
1)
2)
3)

second exposure 
4) 
5) 
6)    
7)

Answer 3

first exposure -> SENSITISATION

1) allergen picked up by APC
2) taken to lymph node, presented to T cell -> Th2 via IL-4 and IL-13 activates B cell -> IgE produced
3) IgE from plasma cells binds to Mast cells via the Fc£RI receptor and they circulate

second exposure
4) allergen presents again
5) binds to IgE on mast cells circulating
6) cross-linking of multiple IgE on mast cell greatly inc. signalling inside mast cell
7) huge overproduction of granule contents and enzymes (histamine) leading to hypersensitivity as well as other pro-inflam mediators: leukotrienes, cytokines, PGD2
also IgE can bind to eosinophils, platelets, lymphocytes, macrophages.

Question 4

Normal IgE function

why are _____ difficult to kill? (2)

Answer 4

Kills multi-cellular parasites too large to phagocytose

pathogens have similar molecular structures to us
therefore are more difficult to identify and kill -> less anti-genetic

Question 5

again the 4 ways an allergen can enter the body but the reactions they cause

Answer 5

• ingested eg. smth muscle contraction, antigen enters blood stream, anaphylaxis
• subcutaneous eg. local release of histamine, oedema
• inhaled eg. upper = inc. mucous + irritation and lower = contraction of smooth muscle and mucous inc.
• intravenous -> systemic anaphylactic shock

Question 6

Asthma
what type of sensitivity?

immediate phase:
what cells react?
cytokines involved (4) and what they do (in pairs)
2 other mediators involved and what they do

late phase
recruitment of (3) leading to….
what happens with smooth muscle?
overall leads to…

Answer 6

Type 1 hypersensitivity as immune system becomes hypersensitive to non-specific triggers

Immediate Phase:
mast cells (inc. in blood vessel permeability)
Cytokines:
IL-4 and IL-13 -> Th2
IL-3 and IL-5 -> Eosinophilic
leukotrienes -> smth muscle contraction, inc. vascular permeability
Histasmines -> smth muscle contraction, inc. mucous

Late phase:
synthesised mediators
eosinophils and more Th2 cells as well as monocytes

smth muscle THICKENS and Bronchospasm, oedema, airway obsruction.
chronic inflam and tissue remodelling

inc. Th2 and eosinophilic recruitment, collagen fibres, enzymes degrade tissue ad OVERALL AIRWAY DAMAGE

Question 7

Hygienic Hypothesis
what is it and what cells involved?
How does environment impact? 4/5

Atopy def.->
Abnormalities found on chromosome 5 if you are atopic (3/5)

Answer 7

Hygienic Hypothesis

• inc. allergy where parasite infection have been eliminated
• IgE ad Eosinophils are still present but are triggered by harmless antigens which have similar antigens to that of parasites eg. peanuts similar to that if a helminth

environment: developing countries
- low use of antibiotics
- rural and livestock
- more exposure to helminths
- poor sanitation
- larger family

Atopic-> a genetic predisposition to allergies, inc./ polymorphs of IgE and/or Eosinophils

chromsome 5

• inc. of MHC II presentation
• inc. IL-4R
• inc. IL-4
• inc. TCR
• inc. Fc£RI

Question 8

Type II
antibody involved?
initiated in 2 ways

Type III
what does it invove? and they form…
5 steps of the mechanism:

Answer 8

Type II
- IgG binds to cell surface -> destruction
Intrinsic - antibody + antigen that we make (more autoimmune)
Extrinsic - immune activated from allergen from outside

Type III
Pre-formed antibodies recognise and clump forming complexes
mechanism:
1) Antibpdy developed
2) Antigen + antibody ->complex formed
3) +ve charged complex attracted to -ve basement membrane
4) deposit complexes detected by compliment -> vasodilation
5) phagocytes attempt to engulf an dinduce inflam.+ neutrophils

Question 9

Type IV-> mediated by?

Delayed Type
antigen from?
it causes
Eg. TB test, 3 mechanism steps

Contact type
antigen from?
it causes
4 step mechanism

Answer 9

T cell mediated

Delayed Type
antgens: proteins eg. myobacterium or insect
causes: contact dermititis, local swelling
TB Test
1) antigen injected subcutaneously + taken up + APC
2) naive T cells acknowledge APC -> Th with CD4+ activated as they recognise antigen-> cytokines IL-2
3) recruitment of phagocytes, pro-inflams. O2 radicals

Contact Type
antigen: haptens such as poison ivy pr small nickel
causes: local epidermal reaction
mechanism:
1) activation of CD4+ and/or CD8+ by haptens highly reactive small mols)
2) reactive mol binds to hapten to endogneous protein which is recognised and uptaken
3) proteins recognised by Th1 cell-> IFNy and pro-inflams + keratinocytes
4) cytokines + keratinocytes activate macrophages -> further inflam. odema, exudate

Question 10

Transplant Rejection 3 types
name (think time), type, what happens = eg only one

what alloantigens?
linked to transplant
indirect
direct

Answer 10

1) Hyperacute, type II, preformed antibodies eg. blood group mismatch
2) Acute, Type IV, T cell mediated (months, weeks
3) Chronic IV, T cell mediated (months, years)

alloantigens -> antigens which differ between members of the same species, even of MHC is matched there will still be alloantigens which can be detected and kick off immune response
direct- donor APC migrate to lymph node + stimulate
indirect- recipient APC travels to lymph node + stim.