Autoimmunity &Hypersensitivity

Question 1

What is hypersensitivity

Answer 1

An over reactive immune response causing pathology

Question 2

What is the concentration of IgE in most peoples blood?

Answer 2

<60 IU/ml - very minute

Question 3

What is the concentration of IgE in atopic peoples blood?

Answer 3

> 450 IU/ml - very high

- Still relatively low compared to other antibodies

Question 4

What are mast cells derived from?

Answer 4

Basophil’s

Question 5

What receptors do mast cells have? What do they do?

Answer 5

Fcε (epsilon) receptors - Bind to the Fc region of IgE antibodies.

Question 6

How are mast cell activated?

Answer 6

Antigen binds and cross-links two IgE molecules on mast cells

Some drugs

C3a & C5a

Question 7

What are three functions of mast cells granules?

Answer 7

1. Chemoaattractants (neutrophils etc.)
2. Activators - vasodilation, complement, platelet.
3. Spasmogens - SM contraction and mucus secretion.

Question 8

What are some common causes of allergies?

Answer 8

1. Rhinitis (From breathing in)
   - house dust mites
   - animal dander
   - pollen
2. Insect stings
   - Proteins in venom
   - Anaphylaxis is common (as in blood)
3. Food allergies
   - Wheat, milk, peanuts
4. Small molecules (drugs)
   - Penicillin, morphine

Question 9

Common sites for allergies to occur

Answer 9

1. Respiratory tract - rhinitis, sinusitis, asthma
2. Skin - Urticaria
3. Gut - food allergies
4. Eyes - conjunctivitis

Question 10

Allergy treatment

Answer 10

Avoidance - often difficult

Anti-histamines - for mild forms

Sodium cromoglycate - Stabilizes mast cells

Corticosteroids - for chronic atopy (asthma)

Sympathomimetics - Adrenaline (epi-pen)

Question 11

Type 2 hypersensitivity

Answer 11

Antibodies against cell surface antigens (auto-immunity)

Question 12

Result of type 2 hypersensitivity rxn:

Answer 12

ADCC

Complement activation

Frustrated phagocytosis
- when cell can’t be phagocytosed (blood vessel endothelial cells) so releases contents which damages cell.

Question 13

Treatment given for Rh(D) negative mother who’s just given birth to Rh(D) positive baby.

Answer 13

Anti Rh antibodies to neutralize

Question 14

Type III hypersensitivity:

Answer 14

Immune complex formed against free antigens.

Question 15

When does type III rxn’s usually occur?

Answer 15

In chronic infections, when antibodies (IgM) are finally being produced by B cells but antigens are still present. Because they’re IgM, they form large immune complexes that lodge in small capillaries and activate complement/inflammation in them causing vasculitis and nephritis.

Question 16

Blood vessel effects of immune complexes in type III rxn’s:

Answer 16

Microthrombus formation after deposition of immune complex

Complement activation causing neutrophil chemotaxis causing vascular damage (frustrated phagocytosis)

Question 17

Type IV hypersensitivity reaction:

Answer 17

Mediated by CD4 T cells and takes about 24-48hrs.

Question 18

What is a classic example of Type IV rxn? What is it?

Answer 18

Mantoux test: (Delayed-type hypersensitivity) Used to test immunity for pathogens

e.g Intra-dermal injection of protein pathogen. Some CD4 memory cells recognize antigen and release cytokines to recruit other immune response. This takes a day or two as CD4 has to find antigen, become activated and recruit cells to the site.

Question 19

What is a hapten

Answer 19

Small molecules e.g. nickel which are conjugated with a protein. Usually nickel is to small to be recognized as an antigen but a hapten is.

Question 20

What type of antibodies are natural autoantibodies.

Answer 20

IgM - common but low concentrationas

Question 21

What anti bodies are found in elderly and SLE?

Answer 21

Anti-Nuclear antibodies

Question 22

How rare are autoimmune antibodies

Answer 22

Rare - they form later in life meaning there is a change in the immune system somewhere during life.

Question 23

Mechanisms of tolerance

Answer 23

Clonal deletion (central) during B and T cell ontogeny

Clonal regulation (peripheral) - If no co-stimulators present then anergy.

Clonal suppression - Treg control self reactivity

Ignorance - Where self reactive T cells and Ab’s antigens are hidden in immunologically privileged sites. e.g. ant. chamber of eye

Question 24

What are some organ specific auto-immune conditions?

Answer 24

Myasthenia Gravis - Ab’s against ACh receptors

Pernicious anaemia - Ab’s against B12/IF .

Idiopathic thrombocytopenic prpura - Ab’s against platelets

Question 25

What is a way auto-immunity can develop?

Answer 25

Molecular mimicry - Antibodies made against pathogens + HLA peptide from previous infections that happen to LOOK the same as self peptides and HLA receptors.

Don’t get it in all people with the same bacteria as HLA restrictions.