Immune System II Flashcards
Describe four ways in which the immune system may misfire?
Changes to proteins (cancer cells)
Detection of receptors being faulty
Microbial molecular mimicry
Exposure of normally hidden proteins (cornea)
Name five risk factors for developing autoimmunity?
Smoking Genetics Increased no of infections Gender Diet
How do antibodies retain maximal diversity of immune detection?
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
Describe the three immune checkpoints within the periphery preventing autoimmunity?
- Anergy - Ag recognition without co-stimulation or CTLA-B7 interaction
- Activation induced cell death - FAS-FAS.L (apoptosis)
- Cytokine regulation - cytokine mediated inhibition of proliferation and effector action of cells
Describe ‘autoimmunity’?
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
Describe ‘autoimmune disease’?
- Activation of auto-receptive T and B cells and amplification of Ab response
- Increased or novel exposure of Self-Ag
Name four conditions where auto-antibodies are interfering with receptor function?
TSH - Grave’s disease
Ach - Myasthenia gravis
Insulin receptor - DM
Intrinsic factor - Pernicious anaemia
Describe ‘Hashimoto’s thyroiditis’?
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
Define ‘allergy’?
A type 1 hypersensitivity reaction which is IgE mediated
Describe the pathophysiology behind an allergic reaction?
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
Name the receptor on the mast cells that allow for coating with IgE?
FC Epsilon (high affinity for IgE)
Describe the actions of histamine?
- Bronchoconstriction and increased mucous secretion
- Vasodilation and increased vascular permeability
- Increased peristalisis
- Increased nerve stimulation (f.o.i.d)
Name the four main function of antibodies?
- Opsinisation and phagocytosis
- Cytotoxicity
- Immune complex formation
- Mediate inflammation
Describe the pathophysiology behind good pasture’s disease (Anti-GBM)?
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
A1 haemolytic anaemia is caused by autoimmune antibodies against which Ag?
RBC surface Ag
A1 thrombocytopaenic puerpura is caused by autoimmune antibodies against which Ag?
Platlet intergin
Goodpasture’s disease is caused by autoimmune antibodies against which Ag?
Glomerular basement membrane Ag
Pemphigus vulgaris (skin blisters) is caused by autoimmune antibodies against which Ag?
Epidermal cadherin
Acute rheumatic fever is caused by autoimmune antibodies against which Ag?
Streptococcal cell wall Ag cross-reacts cardiac muscle cell walls
Describe immune complex mediated autoimmune disease?
Type 3 hypersensitivity - XS immune complexes are deposited on the walls of blood vessels causing inflammation and vascullitis
Name 5 immune complex mediated autoimmune conditions and name their corresponding Ag?
- Mixed essential cryoglobinaemia (Ig) - Systemic
- SLE - nuclear Ag - glomerulonephritits
- Serum sickness - foreign proteins (drugs)
- Polyarteritis nodosa - Hep.B Ag
- Post-strep glomerulonephritis - Streptococcal Ag
Describe the management of anaphylaxis?
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
Describe the investigations that would be carried out in the acute phase of an anaphylatic reaction?
Mast cell tryptase = major protein released by mast cell as they degranulate - surge = 1-2 hours after degranulation
