Immune System II

Question 1

Describe four ways in which the immune system may misfire?

Answer 1

Changes to proteins (cancer cells)
Detection of receptors being faulty
Microbial molecular mimicry
Exposure of normally hidden proteins (cornea)

Question 2

Name five risk factors for developing autoimmunity?

Answer 2

Smoking
Genetics
Increased no of infections
Gender
Diet

Question 3

How do antibodies retain maximal diversity of immune detection?

Answer 3

Antibody specificities are generated randomly through recombination of variable/hyper-variable regions = lots of different alleles of the Ig gene
Negative selection prevents high affinity self-Ag recognition

Question 4

Describe the three immune checkpoints within the periphery preventing autoimmunity?

Answer 4

1. Anergy - Ag recognition without co-stimulation or CTLA-B7 interaction
2. Activation induced cell death - FAS-FAS.L (apoptosis)
3. Cytokine regulation - cytokine mediated inhibition of proliferation and effector action of cells

Question 5

Describe ‘autoimmunity’?

Answer 5

Auto-reactive B-cells and T-cells are found in normally healthy individuals however various central and peripheral mechanisms are in place to maintain tolerance to self

Question 6

Describe ‘autoimmune disease’?

Answer 6

1. Activation of auto-receptive T and B cells and amplification of Ab response
2. Increased or novel exposure of Self-Ag

Question 7

Name four conditions where auto-antibodies are interfering with receptor function?

Answer 7

TSH - Grave’s disease
Ach - Myasthenia gravis
Insulin receptor - DM
Intrinsic factor - Pernicious anaemia

Question 8

Describe ‘Hashimoto’s thyroiditis’?

Answer 8

Self-Ag from thyroid picked up by APC and activates T-cells = antibody production and damage to thyroid cells - gland eventually destroyed = hypothyroidism however this comes on with spikes of hyperthyroidism

Question 9

Define ‘allergy’?

Answer 9

A type 1 hypersensitivity reaction which is IgE mediated

Question 10

Describe the pathophysiology behind an allergic reaction?

Answer 10

B-cell internalises the allergen and migrate to LN finding cognate T-cell - activated B-cell proliferates and differentiates to IgE producing plasma cell
Mast cells coat themselves with IgE antibodies produced. Once the allergen is re-encountered they bind to these IgE and cause mast cells to de-granulate releasing immune modulators

Question 11

Name the receptor on the mast cells that allow for coating with IgE?

Answer 11

FC Epsilon (high affinity for IgE)

Question 12

Describe the actions of histamine?

Answer 12

1. Bronchoconstriction and increased mucous secretion
2. Vasodilation and increased vascular permeability
3. Increased peristalisis
4. Increased nerve stimulation (f.o.i.d)

Question 13

Name the four main function of antibodies?

Answer 13

1. Opsinisation and phagocytosis
2. Cytotoxicity
3. Immune complex formation
4. Mediate inflammation

Question 14

Describe the pathophysiology behind good pasture’s disease (Anti-GBM)?

Answer 14

Anti-GBM antibodies bing to capillary basement membanes they attract and activate WCC (neutrophils) this causes the WCC to attack vessel walls and cause inflammation = glomerulonephritis and pulmonary haemorrhage

Question 15

A1 haemolytic anaemia is caused by autoimmune antibodies against which Ag?

Answer 15

RBC surface Ag

Question 16

A1 thrombocytopaenic puerpura is caused by autoimmune antibodies against which Ag?

Answer 16

Platlet intergin

Question 17

Goodpasture’s disease is caused by autoimmune antibodies against which Ag?

Answer 17

Glomerular basement membrane Ag

Question 18

Pemphigus vulgaris (skin blisters) is caused by autoimmune antibodies against which Ag?

Answer 18

Epidermal cadherin

Question 19

Acute rheumatic fever is caused by autoimmune antibodies against which Ag?

Answer 19

Streptococcal cell wall Ag cross-reacts cardiac muscle cell walls

Question 20

Describe immune complex mediated autoimmune disease?

Answer 20

Type 3 hypersensitivity - XS immune complexes are deposited on the walls of blood vessels causing inflammation and vascullitis

Question 21

Name 5 immune complex mediated autoimmune conditions and name their corresponding Ag?

Answer 21

1. Mixed essential cryoglobinaemia (Ig) - Systemic
2. SLE - nuclear Ag - glomerulonephritits
3. Serum sickness - foreign proteins (drugs)
4. Polyarteritis nodosa - Hep.B Ag
5. Post-strep glomerulonephritis - Streptococcal Ag

Question 22

Describe the management of anaphylaxis?

Answer 22

ABCDE
Cyanosis = late and worrying sign 
Circulation = lie pt flat and raise legs
- IM adrenelin 0.5ml of 1 in 1000
- Fluid bolus
- Cholphanamine IM 10mg
- Hydrocortisone 100mg IV

Question 23

Describe the investigations that would be carried out in the acute phase of an anaphylatic reaction?

Answer 23

Mast cell tryptase = major protein released by mast cell as they degranulate - surge = 1-2 hours after degranulation