Immune1&2 - Hypersensitivity Reactions

Question 1

4 general features of hypersensitivity reactions

Definition
Types of Antigens
Sensitization Phase
Effector Phase

Answer 1

1.) Definition - inappropriate/excessive antigen-specific immune response that result in harm to the host

2. ) Types of Antigens - exogenous or intrinsic (from host)
   - exogenous: microbes, drugs, allergic substances
   - intrinsic: self antigens, microbes (mimic host antigens)
3. ) Sensitization Phase - first encounter w/ antigen which activates APCs and memory effector cells
4. ) Effector Phase - pathological reaction upon antigen re-exposure which activates memory cells of adaptive immunity

Question 2

4 types of hypersensitivity reactions

Type I
Type II
Type III
Type IV

Answer 2

1. ) Type I - IgE mediated, immediate (Allergy)
   - antigens are allergens which can be environmental or non-infections antigens (proteins)
2. ) Type II - antiBody mediated, organ specific, 5-12 hrs
   - IgG/IgM antibodies bind to cell-bound antigens
   - causes direct tissue damage or physiological change
3. ) Type III - immune Complexes (ICs) mediated
   - IgG/IgM antibodies bind to soluble antigens (systemic)
   - causes tissue damage by deposition of immune complexes in host tissues
4. ) Type IV - cell mediated (Delayed, 24-72hrs)
   - involves lymphocytes and macrophages

Question 3

6 features of allergic reactions (type I hypersensitivity)

Types of Allergens/Exposure x3
Common Allergic Diseases x5
Mechanism x2
Mast Cells
Manifestations of Mast Cell Activation x3
Treatments x6

Answer 3

1. ) Types of Allergens/Exposure
   - seasonal: tree/grass pollen
   - perennial: dust mites, animal dander, fungal spores
   - accidental: food, chemicals, medicines, insect venom
2. ) Common Allergic Diseases
   - asthma, allergic rhinits (hay fever), food allergy
   - acute urticaria, systemic anaphylaxis
3. ) Mechanism - Th2, IgE, mast cells
   - 1st exposure: Th2 response (rather than Th1)
   - 2nd exposure: IgE cross-linking –> mast cell activation
4. ) Mast Cells - degranulation when activated
   - location: mucosal and epithelial tissues
   - mediators: e.g tryptase, histamine, leukotrienes, platelet-activating factor
5. ) Manifestations of Mast Cell Activation
   - urticaria (epidermis), angio-oedema (deep dermis)
   - anaphylaxis (systemic)
6. ) Treatments
   - allergen desensitization, anti-IgE mab, corticosteroids
   - anti-histamines, leukotriene receptor antagonists
   - IM adrenaline for anaphylaxis (delays biphasic reaction)

Question 4

3 ways type II hypersensitivity reactions cause damage

Complement Activation
NK Cells
Physiological Change

Answer 4

1. ) Complement Activation - tissue/cell damage
   - rhesus D antigen: haemolytic disease of the newborn
   - ABO antigens: transfusion reactions
2. ) NK Cells - tissue/cell damage
   - antibody-dependent cell cytotoxicity, examples:
   - autoimmune haemolytic anaemia
   - immune thrombocytopenia purpura (ITP)
   - anti-GBM disease (Goodpasture’s)
3. ) Physiological Change - changes in receptors
   - stimulation: Grave’s disease
   - blockade: myasthenia gravis

Question 5

5 features of haemolytic disease of the newborn (HDN)

Rhesus Blood Groups
Sensitization Phase
Effector Phase
Treatment
Clinical Features x2

Answer 5

1. ) Rhesus Blood Groups - D antigen is most important
   - Rh+ = D antigens present, Rh- = D antigens absent
   - D antibodies are produced when Rh- mothers are exposed to D antigens during pregnancy
2. ) Sensitization Phase - pregnancy w/ 1st Rh+ fetus
   - occurs if Rh antigens from the fetus enters the mother’s circulation during delivery/miscarriage etc.
   - mother produces anti-Rh+ antibodies (IgG)
3. ) Effector Phase - pregnancy w/ 2nd Rh+ fetus
   - anti-Rh+ antibodies cross the placenta in T3, damaging the fetal RBCs causing haemolytic anemia in newborn
4. ) Treatment - RhoGAM (antibodies for Rh antigens)
   - binds to Rh antigens in the newborn, so the mother doesn’t become sensitized (not exposed to Rh antigens)
   - it is given to unsensitized Rh- women within 3 days after miscarriage or delivery of an Rh+ fetus
5. ) Clinical Features
   - ↑bilirubin leads to jaundice
   - bilirubin can enter the the brain to cause kernicterus which can cause permanent neurological damage

Question 6

4 features of the ABO system and haemolytic transfusion reactions

ABO Blood Groups
Type of Antibody
Donors and Receipients
Haemolytic Transfusion Reaction

Answer 6

1. ) ABO Blood Groups - antigens on RBCs
   - A has B antibodies whilst B has A antibodies
   - AB has no antibodies, O has A and B antibodies
2. ) Type of Antibody - usually all IgM
   - IgM cannot cross the placenta so mixture of antigens does not cause haemolytic disease in the newborn
   - IgG can be produced during a blood transfusion
3. ) Donors and Receipients
   - A receives A, B receives B, preventing RBC damage
   - AB can receive A or B since it has no antibodies
   - O can give to A or B since it has no antigens
4. ) Haemolytic Transfusion Reaction - life-threatening
   - cardiovascular shock/collapse, kidney failure

Question 7

4 features of myasthenia gravis

Pathophysiology
Symptoms x5
Infants
Treatments x2

Answer 7

1. ) Pathophysiology - abnormal antibodies (AChR-ab)
   - block ACh receptors, preventing ions from entering cells preventing depolarisation –> muscle weakness
2. ) Symptoms - muscle weakness
   - diplopia, ptosis
   - difficulty chewing, swallowing, and breathing
3. ) Infants - newborns temporarily exhibit symptoms
   - IgG antibodies pass onto infant
   - disease disappears as the antibodies are filtered out

4.) Treatment - pyridostigmine (AChEi) or plasmapheresis

Question 8

6 types of treatments for type II hypersensitivity reactions

Anti-Inflammatory Drugs
Splenectomy 
Intravenous Immunoglobulin (IVIG)
Plasmapheresis 
Correct Metabolism
Replacement Therapy

Answer 8

1. ) Anti-Inflammatory Drugs - ↓tissue/cell damage
   - reduces complement activation
2. ) Splenectomy - ↓tissue/cell damage
   - ↓opsonisation which reduces phagocytosis
3. ) Intravenous Immunoglobulin (IVIG)
   - used when antibodies are being attacked
4. ) Plasmapheresis - can be used in both mechanisms
   - used in conditions driven by primary antibodies:
   - anti-GBM, Graves’ disease, myasthenia gravis
   - can also be used to remove inflammatory mediators
   - short-term relief and allows healing of damaged tissue
5. ) Correct Metabolism - physiological change
   - e.g. anti-thyroid drugs in Graves’ disease
6. ) Replacement Therapy - physiological change
   - e.g. pyridostigmine (AChEi) in myasthenia gravis

Question 9

4 features of type III hypersensitivty

Immune Mechanism
Factors Affecting IC Pathogensis x3
Location of IC Depostion
Treatment x2

Answer 9

1. ) Immune Mechanism - intermediate ICs deposited in tissues, activating complements –> neutrophil damage
   - small ICs are cleared by macrophages
   - large ICs are cleared by opsonins and complements
2. ) Factors Affecting IC Pathogenesis
   - complex size: small and large ICs are easily cleared
   - host response: low affinity Abs, complement deficiency
   - local factors: haemodynamic and physiochemical
3. ) Location of IC Deposition - multi-system disease
   - common: joints, kidneys, small vessels, skin,
4. Treatment - anti-inflammatories and monoclonal ABs
   - e.g. NSAIDs, corticosteroids, azathioprine etc.
   - monoclonal ABs to APCs, lymphocytes, cytokine

Question 10

3 examples of type III hypersensitivity reactions

Answer 10

1. ) Rheumatoid Arthritis - self antigen (Fc portion of IgG)
   - have articular and extra-articular features
   - episodes of inflammation and remission
2. ) SLE - self antigen (double stranded DNA)
   - more prevelent in females (9:1 ratio)
   - can cause cardiac, respiratory, renal, joint, and neurological features, repeated miscarriages
3. ) Glomerulonephritis - infectious
   - sustained production of microbe –> IC formation
   - e.g. bacterial endocarditis, or Hep B infection

Question 11

5 examples of type IV hypersensitivty reactions

Answer 11

1. ) Contact Hypersensitivity - exogenous antigens
   - epidermal reaction to endogenous proteins
   - e.g. nickel (jewellery), poision ivy, organic chemicals
2. ) Granulomatous Hypersensitivity - exogenous antigen
   - occurs 21-48 days post-exposure
   - e.g. TB, leprosy, schistosomiasis, sarcoidosis
3. ) Type I Diabetes - endogenous antigen
   - destruction of pancreatic islet cells
4. ) Hashimoto’s Thyroiditis - endogenous antigen
   - destruction of the thyroid gland
5. ) Rheumatoid Arthritis - endogenous antigen
   - rheumatoid factor (Fc portion of IgG)