Hypersensitivity

Question 1

What is Type 1 hypersensitivity?

Answer 1

Classic allergy, rapid immune response to allergen
Host has pre-existing IgE to allergen
Localised response- hives, blisters, nasal discharge (hay fever, asthma, allergic rhinitis)
Systematic- anaphylaxis

Question 2

Describe the Th2 response (Type 1)

Answer 2

Allergen presented on MHC2, activated T cell, differentiates to TH2, IL-4, IL-5 (eosinophil activation), IL-13- B cells produces IgE, epithelial cells produce mucus

Question 3

Describe the mast cell response (Type 1)

Answer 3

Allergen induces cross-linking in Fc epsilon Receptor 1, activation, degranulation releases histamine, serotonin and proteases, synthesises cytokines, prostaglandins and leukotrienes (mediators)
Inflammatory cell recruitment, vasodilation
Immediate muscle contraction, hypotension
Later- eosinophils. neutrophils, tissue destruction

Question 4

What are allergens?

Answer 4

Proteins, often proteases
Low does may favour IL-4 Th2 producing response
Low molecular weight and highly soluble- diffuse through mucus
Very stable- can survive in desiccated particle
Contains peptides that can bind MHC 2- T cell priming

Question 5

What is anaphylaxis?

Answer 5

Profound systematic response to allergens
Vasodilation due to histamines, hypotension (low bp) and oedema, bronchoconstriction (histamine, bradykinins)
Adrenaline (hypotension), Beta agonists (airways), IV fluids (Bp), corticosteroids (dampen inflammation)

Question 6

What are the genetic risk factors of autoimmunity?

Answer 6

Complex multigenic disorders
MG=HC- Major Histocompatibility Complex
Non MHC genes- NOD2 Crohns,

Question 7

What are the environmental factors of autoimmunity?

Answer 7

Endocrine factors- females more commonly affected than males- reduced in pregnancy

Question 8

What are factors initiating autoreactivity?

Answer 8

Infection- release of sequestered antigen, upregulation of costimulators on APCs
T cell bypass- tolerance bypassed by modification (neoantigen generated by binding of a pathogen to a self component), inflammation (immunostimulatory environment activates self-reactive T cells), molecular mimicry (antibodies or T cell generated in response to infection cross-react with self)

Question 9

What is molecular mimicry?

Answer 9

High concentration of microbial antigen similar to self detected by professional APC and cases Th cell activation/ maturation primed Th cells interact with target even without Costimulation, self auto antigen in low concentration affected

Question 10

What are autoantigens?

Answer 10

Antigens on target tissue

Question 11

What is type 2 hypersensitivity?

Answer 11

Antibody mediated- antibodies formed against altered component on host cells- IgG or IgM
Binds to own cells
Accelerates cell clearance by phagocytosis, ADCC, complement- mediated lysis

Question 12

Name examples of Type 2 hypersensitivity diseases

Answer 12

Haemolytic anaemia (Rhesus reaction)
Myasthenia Gravis
Graves disease

Question 13

Describe haemolytic anaemia

Answer 13

ABO blood groups- incompatibility leads to transfusion reaction, antigen on red blood cells and other tissue types, preformed antibody in naïve untransplanted, untransfused patient
Induced by natural exposure to similar antigens from gut microorganisms

Question 14

How does Rhesus reaction lead to haemolytic anaemia?

Answer 14

RhD- mother with RhD+ foetus blood transfusion into maternal circulation during childbirth, IgM cannot cross placenta, production of anti-RhD IgG postpartum
Subsequent pregnancy- IgG crosses placenta into foetal circulation- lysis of RBC

Question 15

What is Myasthenia Gravis?

Answer 15

Antibodies against acetyl choline receptors
Association with thymic abnormalities
Muscle weakness, shortness of breath, ptosis (drooping eyelids), diplopia (double vision), unstable gait

Question 16

What is Grave’s disease?

Answer 16

IgG antibodies against thyroid stimulating hormone receptors, no negative feedback so excess hormone
Stimulate thyroxin release
Nervousness, heat intolerance, bulging eyes, tremor, tachycardia, weight loss

Question 17

What is Type 3 hypersensitivity?

Answer 17

Immune complex mediated disease
Complexes arise from persistent infection or inhalation and long term exposure to proteins
Deposited in tissues with high blood filtration pressure

Question 18

What is serum sickness?

Answer 18

Transient immune complex mediated syndrome caused by injection of horse serum (passive immunisation)- snake bite

Question 19

What is systematic lupus erythematosus?

Answer 19

Failure of tolerance/ anti-DNA antibodies

• Genetic factors; MHC/non-MHC genes
• Immunologic; failure in self tolerance in T and B cells, nuclear DNA and RNA bind receptors, cytokines
• Environmental; exposure to UV light, female over male, drugs

Question 20

What are the clinical manifestations of systematic lupus erythematosus?

Answer 20

Immune complex deposition DNA-anti-DNA complexes

Vasculitis, glomerulonephritis, pericarditis, butterfly rash, arthritis, pleural effusions

Question 21

What is type 4 hypersensitivity?

Answer 21

Delayed type hypersensitivity, T cell mediated
Response 1-3 days after contact with antigen
Contact hypersensitivity/ granuloma formation (TB)

Question 22

What is the tuberculin reaction?

Answer 22

Exposure to tubercule bacilli, CD4+ T cell and macrophage accumulation with associated cytokine expression (IFNy and TNF)
Epithelioid macrophages surrounded by lymphocytes

Question 23

Summary Type 1 hypersensitivity

Answer 23

IgE mediated
Below 30 mins
Antigen induces cross-linking of IgE bound to mast cells with release of vasoactive mediators
Hay fever, eczema

Question 24

Summary Type 2 hypersensitivity

Answer 24

Antibody- mediated cytotoxic hypersensitivity
5-8 hours
Antibody directed to cell surface, antigen mediates destruction by ADCC or complement
Blood transfusion, Rhesus

Question 25

Summary Type 3 hypersensitivity

Answer 25

Immune-complex mediated
2-8 hours
Ag-IgG/M complexes induce mast cell degranulation vis Fcgr3
Arthurs reaction/ serum sickness

Question 26

Summary Type 4 hypersensitivity

Answer 26

Cell mediated
1-3 days
Th1 cells release cytokines that recruit and activate macrophages
Contact dermatitis, tubercular lesions