1. Immunity & Hypersensitivity MATT VREUGDE – M.VREUGDE@WARWICK.AC.UKM.VREUGDE@WARWICK.AC.UK SAMMY CASE – S.CASE@WARWICK.AC.UKS.CASE@WARWICK.AC.UK

2. Learning Outcomes List the components of the innate immune system List the components of the adaptive immune system Describe the normal functioning of the innate immune system Describe the normal functioning of the adaptive immune system Explain the interaction of key cell types in the recognition of self & non-self as part of immune function  Relate the process of acute inflammation to the development and presentation of hypersensitivity  Describe how immune mechanisms can cause or worsen disease with reference to hypersensitivity and anaphylaxis  Explain the underlying mechanism of allergy  Outline the mechanism of action and target of the classes of drugs used to treat hypersensitivity reactions  Outline the range of allergic conditions, their investigations and management

3. The immune system InnateAdaptive Primary line of defenceSecondary line of defence Immediate responseDelayed response Recognises certain threats Recognises all threats No antigen presentation Antigen presentation No clonal selectionClonal selection No immunological memory Immunological Memory

4. Cells

5. Lymphocytes

6. Antibodies and the complement cascade

7. MHC Complexes & Antigen Presentation

8. Cell mediated vs humoral mediated immunity B Cells & Antibodies T Cells and antigen presenting cells

9. Cell Mediated Immunity Tc + Cell +Ag Tc Th 1 Ts Tc m Ag = antigen Tc = undifferentiated T cytotoxic cell Ts = T suppressor cell Th 1 = T helper cell Tc + = activated T cytotoxic cell Tc m = T cytotoxic memory cell

10. Humoral Mediated Immunity Ag Ts B Bp Ab Th 2 APC Bm

11. Immunological Memory

12. Hypersensitivity Hypersensitivity = an inappropriate & excessive immunological reaction to an (external) antigen Allergy = local reaction (eg. mucous membranes, skin, lungs) Anaphylaxis = systemic reaction (including shock & death) Allergen = antigen that induces a hypersensitivity reaction (Autoimmunity = an inappropriate & excessive immunological reaction to a self-antigen / auto-antigen) Due to dysfunctional control of the immune system (& tolerance)

13. Classes of hypersensitivity (LEARN!) TypeNameMediatorsExamples IImmediate or IgE-MediatedIgE + mast cells Allergies (most) Anaphylaxis Asthma Atopy IIAntibody-DependentIgM / IgG Autoimmune haemolytic anaemia Goodpasture’s syndrome Myasthenia gravis Graves’ disease IIIImmune ComplexIC Serum Sickness Extrinsic allergic alveolitis (EAA) Rheumatoid arthritis (RA) Systemic lupus erythematosus ( SLE ) IVDelayed or Cell-MediatedT lymphocytes Allergic contact dermatitis Chronic transplant rejection Multiple sclerosis (MS) Tuberculin skin test (TST)

14. Clinical Features & Symptoms  Type I Airway & eye mucous membranes → pruritus & sneezing, rhinorrhoea & lacrimation Skin → pruritus & urticaria Oral & intestinal mucous membranes → pruritus & angioedema Systemic exposure → anaphylaxis = local swelling, flushed, faint, dyspnoea, peri-oral paraesthesia, throat/chest tightness, wheeze, pale, sweaty, hypotensive, collapse, unconscious, death  Type IV Slowly developing, localised immune reactions e.g. contact dermatitis Can be fulminant and life-threatening e.g. organ rejection

15. Investigations To prove Type 1 (immediate/IgE-mediated) hypersensitivity → measure blood markers such as tryptase, IgE, eosinophil count To identify exact allergen (whether causing Type 1 or IV reaction) → skin patch testing (works for full range of allergens) : Apply solutions of appropriate test allergens, plus negative & positive controls (saline & histamine) to the skin & review at 7 days Positive result = lesion >3mm larger than negative control

16. Treatment Avoidance :pollen, house dust mites & animals, insects, food & drugs metals (eg. nickel) & chemicals (eg. latex) Anti-histamines : topical (eg. eye drops) or systemic (eg. tablets) Steroids : topical (eg. nasal spray) or systemic (eg. tablets) De-sensitisation :also called “allergen immunotherapy” relies on creating tolerance to allergens by exposure to gradually increasing doses delivered sublingually or subcutaneously small risk of anaphylaxis during therapy requires weekly/monthly treatment for ~3 years

17. Emergency Treatment A irway – B reathing – C irculation Lie patient down High-flow oxygen IV fluids Adrenaline (epinephrine) 500 mcg IM (0.5 ml of 1mg/ml) IV chlorphenamine (anti-histamine) IV hydrocortisone (steroid) Nebulised salbutamol (bronchodilator) Repeat adrenaline IM if no improvement after 5 minutes