ross hypersensitivity 2 and III

Question 1

what two things can hypersensitivity reactions react to?

Answer 1

Hyperreactive response to innocuous environmental antigens or to self.

Question 2

What two cell types mediate hypersensitivity reactions?

Answer 2

B and T cells.

Question 3

briefly, what are the drivers of each types of hypersensitivity?

Answer 3

type 1: IgE

type2: atibody mediated

type 3: immune complex-mediated

type 4: Only T cell mediated.

Question 4

How to think evolutionarily about the IgE response?

Answer 4

Can’t use neutralising Ab/ phagocytosis or TLRs to detect and rid genetically similar parasites to us.
Have to use general toxicity ‘natural chemotherapy’

Question 5

Process of IgE mediated pathogenesis?

Answer 5

B cells in BM produce IgE aginst environmental antibody, that will bind the surface of mast cells (via FcR).

Crosslink of the IgE ab on mast cells by environmental antigen causes mast cell degranulation and trpsin, histamine and protease release (+ recruitment of e.g. eosinophils)

Question 6

what complications arise with systemic mast cell degranulation in a short space of time?

Answer 6

bronchoconstriction, and vasodilation and anaphylactic shock.

Question 7

what is a mechanism for type IV responses involving lipid-soluble antigens like metal ions and lipids from poison oak?

Answer 7

lipid soluble antigens which cross the surface of molecules and cause protein haptenation, resulting in the presentation of neoantigen that stimulates pathogenic CD8+ t cells responses and activates macrophages.

Question 8

Why might type 1 diabetes not be considered a type IV hypersensitivity?

Answer 8

Because although destruction mediated by CD8+s, no haptenation like you see in definitive type IV hypersensitivity.

Question 9

What mechanisms cause damage in type II hypersensitivity?

Answer 9

antibodies bind to cell surface host proteins and are directly responsible for the destruction of cells due to complement activation and lysis, or via Fc and effector binding mechanisms.

Question 10

What disease are associated with type II hypersensitivity?

Answer 10

autoimmune hameolytic anaemia
myasthenia gravis
Goodpasture’s syndrome
graves disease

Question 11

What cells are destroyed in autoimmune haemolytic anemia and what hypersensitivity?

Answer 11

RBCs are destroyed (others can be blood cells that can be targeted).

type II hypersenstivity.

Question 12

What two forms can autoimmune haemolytic anemia be down to and what are symptoms?

Answer 12

could be due to primary (idiopathic) or secondary e.g. due to lymphoma (particularly IgM) or drugs.

symptoms are fatigue, anemia and breathlessness and dark urine.

Question 13

warm and cold autoantibodies can be seen in type II autoimmune haemolytic anemia, what happens to cold autoantibodies?

Answer 13

will bind RBC only when under 37C and will precipitate as well.

Question 14

What kind of lymphoma and monoclonal B cell most associated with AHA?

How does penicillin cause AHA?

Answer 14

IgM monoclonal Lymphoma

penicillin causes haptenation and a neoantigen.

Question 15

As well as cell damage, what are autoantibodies doing myasthenia gravis?

Answer 15

Causing physiological dysfunction of muscles.

Question 16

3 forms and severities of myasthenia gravis?

Answer 16

ocular,
generalised: face, neck, extremities and fatigue.
severe- affects intercostal muscles.

Question 17

when might you see neonatal myasthenia gravis?

Answer 17

mother with it passes IgG on to child.

Question 18

What kind of autoantibodies against ACHR in mother would make neonatal myesthneia gravis more sever, and what can it also cause in foetus?

Answer 18

Autoantibodies against foetal ACHR (y chain), which are present in adults but outnumbered by adult ACHRs.

Can prevent baby from kicking which is important for joint separation,
Fused joints seen: arthhrogyropsis.

Question 19

What subclasses of Ab are ACHR autoantibodies typically?

Answer 19

IgG1 and IgG3.

Question 20

What are three mechanisms of Ab-mediated pathology in myasthenia gravis?

Answer 20

complement activation and endplate damage, cross-linking of ACHR increasing its internalization.
binding and blocking of ACH binding.

Question 21

Why might you get improved symptoms with myasthenia gravis after sleep?

Answer 21

During sleep no muscle activity or Ach release, therefore more AchR will be free to bind initially.

Question 22

Why does lambon eaton syndrome get better throughout the day?

Answer 22

Ab blocking Ca2+ channels, but over day Ca2+ gradient can increase to level where easier to overcome threshold for NT release.

Question 23

how to detect physiological autoantiboides against ACHR?

Answer 23

radioactivley labelled bungarotoxin added to AHCR.
Then add patient serum and an anti human IgG Fc antibody for complex formation and pellet formation.

Look at the amount of ACHR radioactivity compared to amount of ACHR receptor complexes.

Question 24

What is the target of autoantibodies (type II) in goodpastures syndrome? What presentations do they cause?

Answer 24

type IV collagen which is found particularly in the glomerular of kidneys and on alveoli in the lungs.

Present with respiratory issues (haemoptysis-coughing up blood) and kidney failure.

Question 25

what does autoantibody levels correlate with type II hypersensitivity?

Answer 25

Correlates with severity of disease.

Question 26

What treatment might you use for goodpastures syndrome?

Answer 26

plsamaphoresis, followed by immunosuppression.

Question 27

What case of acute type II (goodpastures) hypersensistivity might you use chemotherapy agents?

Answer 27

If MGUS (precursor to myeloma) producing very high levels of autoantibody.

Question 28

What is the antibody against in Graves disease and what kind of hypersensitivity is this?

Answer 28

autoantibodies against the TSH receptor on the thryoid gland.

Question 29

normal TSH axis?

Answer 29

pituitary gland produces TSH that binds TSHR on thyroid. Leading to T4 release that breaks down into active T3.
T4 and T3 send negative feedback to pituitary gland.

Question 30

What levels of TSH, T4 and T3 might you see in Grave’s disease and why?

Answer 30

Very high levels of T4 and T3 due to constiuitive stimulation of TSHR by autoantibody.

But large negative feedback means very very low TSH levels are present.

Question 31

What symptoms of Graves disease are there?

what gender is it more common in?

Answer 31

hyperthyroidsim, wide eyes (due to changes in lipid metabolism around eye sockets), excessive sweating.

more common in females

Question 32

How to detect functional TSHR Ab?

Answer 32

With competition ELISA.
Ab known to bind stimulating site on TSHR.
Add patient serum which if functional will compete for this binding site, signal from known Ab will be less.

Or monoclonal antibody against binding epitope on TSHR autoantibody.

Question 33

How does type III differ from type II?

Answer 33

type II they are bound.

type III binds factors that are soluble- normally this can result in complement activation or clearance of toxin etc.

Question 34

Why does autoab: antigen ratio matter in type III?

Answer 34

higher ab: antigen ratio, then large immune complexes formed which can be cleared.

If antigen in excess, then only small complexes formed which aren’t cleared and can’t activate complement.
They then can deposit on tissue surface and build up to form complexes that activate complement.

Question 35

What tissues are often affected in type III hypersensitivity?

Answer 35

vasculitis.