Immunity & Hypersensitivity

MATT VREUGDE – M.VREUGDE@WARWICK.AC.UK

SAMMY CASE – S.CASE@WARWICK.AC.UK

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

The immune system

Innate Adaptive

Primary line of defence

Secondary line of defence

Immediate response Delayed response

Recognises certain threats

Recognises all threats

No antigen presentation

Antigen presentation

No clonal selection Clonal selection

No immunological memory

Immunological Memory

Cells

Lymphocytes

Antibodies and the complement cascade

MHC Complexes & Antigen Presentation

Cell mediated vs humoral mediated immunity

B Cells & Antibodies

T Cells and antigen presenting cells

Cell Mediated Immunity

Tc+

Cell+Ag

Tc Th1

Ts

Tcm

Ag = antigen

Tc = undifferentiated T cytotoxic cell

Ts = T suppressor cell

Th1 = T helper cell

Tc+ = activated T cytotoxic cell

Tcm = T cytotoxic memory cell

Humoral Mediated Immunity

Ag Ts

B

Bp

Ab Th2

APC

Bm

Ag = antigen APC = antigen presenting cell Ts = T suppressor cellTh2 = T helper cellB = undifferentiated B cellBp = B plasma cellsBm = B memory cellsAb = antibody

Immunological Memory

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)

Classes of hypersensitivity (LEARN!)

Type Name Mediators Examples

I Immediate or IgE-Mediated IgE + mast cells

Allergies (most)Anaphylaxis

AsthmaAtopy

II Antibody-Dependent IgM / IgG

Autoimmune haemolytic anaemia Goodpasture’s syndrome

Myasthenia gravisGraves’ disease

III Immune Complex IC

Serum SicknessExtrinsic allergic alveolitis (EAA)

Rheumatoid arthritis (RA)Systemic lupus erythematosus (SLE)

IV Delayed or Cell-Mediated T lymphocytes

Allergic contact dermatitisChronic transplant rejection

Multiple sclerosis (MS)Tuberculin skin test (TST)

Clinical Features & Symptoms

Type IAirway & eye mucous membranes → pruritus & sneezing, rhinorrhoea & lacrimationSkin → pruritus & urticariaOral & intestinal mucous membranes → pruritus & angioedemaSystemic exposure → anaphylaxis = local swelling, flushed, faint, dyspnoea, peri-oral paraesthesia, throat/chest tightness, wheeze, pale, sweaty, hypotensive, collapse, unconscious, death

Type IVSlowly developing, localised immune reactions e.g. contact dermatitisCan be fulminant and life-threatening e.g. organ rejection

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

Treatment

Avoidance : pollen, house dust mites & animals,insects, food & drugsmetals (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 allergensby exposure to gradually increasing dosesdelivered sublingually or subcutaneouslysmall risk of anaphylaxis during therapyrequires weekly/monthly treatment for ~3 years

Emergency Treatment

Airway – Breathing – Circulation

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