1.1.1 Type II Hypersensitivity Reactions

Question 1

What is the most common primary immunodeficiency?

Answer 1

Di George Syndrome
Deletion of part of chromosome 22q11.2

Question 2

What is the main cause of immunodeficiency in the UK?

Answer 2

Malnutrition

Question 3

What effects can the immune system have on the body in an autoimmune reaction?

Answer 3

Organ specific
Non-organ specific

Question 4

What are some examples of organ specific autoimmune diseases?

Answer 4

Goodpasture’s syndrome
Haemolytic anaemia
Myasthenia gravis
Grave’s disease

Question 5

What are some examples of non-organ specific disease?

Answer 5

Systemic lupus erythematosus
Rheumatoid arthritis

Question 6

Define hypersensitivity

Answer 6

Antigen specific immune responses that are either inappropriate or excessive and result in harm to the host

Question 7

What are the types of triggers for hypersensitivity reactions?

Answer 7

Exogenous antigens
Intrinsic antigens

Question 8

Give 3 examples of exogenous antigens causing hypersensitivity reactions

Answer 8

• Non-infectious substances (innocuous, allergens)
• Infectious microbes
• Drugs (e.g. penicillin)

Question 9

Give 2 examples of intrinsic antigens causing hypersensitivity reactions

Answer 9

• Infectious microbes (mimicry)
• Self antigens (auto-immunity)

Question 10

What are the 4 types of hypersensitivity reactions?

Answer 10

• Type I- or immediate Allergy, environmental non-infectious antigens
• Type II- or antibody mediated
• Type III- or immune Complexes mediated
• Type IV- or cell mediated (Delayed), environmental infectious agents and self antigens

Question 11

What antibody drives Type I reactions?

Answer 11

IgE mediated (Allergy)

Question 12

What antibody drives type II and III reactions and how are they different?

Answer 12

IgG and IgM

Type II- antibodies against tissue bound antigens

Type III- antibodies against soluble antigens

Question 13

What antibody drives type IV reactions?

Answer 13

Not antibody driven, cell mediated therefore T cells and macrophages mostly

Question 14

What are the two phases of hypersensitivity reactions?

Answer 14

Sensitisation phase - First encounter with antigen, activation of APCs and memory effector cells

Clinically silent phase, asymptomatic

Effector phase -Pathologic reaction upon re-exposure to same antigen and activation of memory cells

Question 15

Features of Type II hypersensitivity

Answer 15

• Develops 5-12 hours after re-encounter with infection
• Involves IgG (chronic infection) or IgM (acute infection) antibodies
• Targets cell bound antigens
• Induces different outcomes

Question 16

What are the targets of type II hypersensitivity?

Answer 16

Exogenous
-Blood group antigens
-Rhesus D antigens

Endogenous
-Self antigens

Question 17

What are the different induced outcomes of type II hypersensitivity reactions?

Answer 17

Tissue / cell damage
Physiological change in function

Question 18

What immune mechanisms are involved in type II hypersensitivity reactions causing tissue/ cell damage?

Answer 18

Complement activation
-Cell lysis
-Neutrophil recruitment/ activation (C3a/ C5a)
-Opsonisation (C3b)

Antibody-dependent cell cytotoxicity
-NK cells- part of innate immunity

Question 19

How do natural killer cells work?

Answer 19

NK cells have receptors for IgG, NK cell binds and releases its granules

Question 20

What are two clinical examples of type II hypersensitivity reactions causing tissue damage? -complement activation

Answer 20

• Haemolytic disease of the newborn, -Rhesus D antigen
• Transfusion reactions, ABO system (mainly due to human error)

Question 21

What are three clinical examples of type II hypersensitivity reactions causing tissue damage? -Antibody-dependent cell cytotoxicity

Answer 21

• Autoimmune haemolytic anaemia, RBC
• Immune thrombocytopenic purpura, Platelet
• Goodpasture’s syndrome, collagen in the basement membrane of the lung and glomerulus of the kidney

Question 22

Give an example of a hypersensitivity type II reaction driven by IgM

Answer 22

Haemolytic transfusion reaction (ATR)
-Medical emergency (carry out ABC approach)
-Caused mainly by human error e.g. mislabled specimen

Question 23

What is the immune mechanism behind haemolytic transfusion reaction?

Answer 23

• Incompatibility in the ABO antigens on RBCs
• Donor RBC lysis induced by type II hypersensitivity involving recipients IGM

Question 24

What is the clinical outcome of haemolytic transfusion reaction?

Answer 24

Shock
Respiratory distress
Kidney failure
Death

Question 25

What blood type can donate to all other blood types and what blood type is the universal plasma donor?

Answer 25

O- for whole blood AB- for plasma

Question 26

What is the pathophysiology of haemolytic disease of the newborn?

Answer 26

1. Rhesus positive father 2. Rhesus negative mother carrying rhesus positive foetus 3. During delivery rhesus positive antigens from foetus enter maternal circulation 4. Mother then produces anti-Rh +ve antibodies 5. If the woman becomes pregnant with another Rh +ve foetus, anti-Rh antibodies will cross the placenta and destroy foetal RBCs First encounter no effects as sensitisation occurs only affects the second baby **Anti-Rh antibodies cross the placenta as they are IgG**

Question 27

What complications arise as a result of haemolytic disease of the newborn?

Answer 27

* **Hydrops fetalis**- (fluid accumulation) liver failure, resulting in reduced albumin production, fluid moves into interstitium * **Liver/splenomegaly** * **Severe hyperbilirubinaemia** * **Kernicterus**- brain damage due to bilirubin accumulation in brain

Question 28

What is given to prevent anti-Rh antibodies forming, preventing the sensitisation phase?

Answer 28

**RhoGAM** Rh0(D) immune globulin * Give within 72 hours of giving birth * 0.1% of mothers are not protected- too much blood enters maternal circulation?

Question 29

How can we treat high antibody titres with Rh positive foetus?

Answer 29

Treat with plasmapheresis- removal of plasma which is replaced removing the anti-Rh antibodies High dose of IV immunoglobulin Intrauterine transfusions to ensure adequate blood supply to foetus through **umbilical vein** (not artery don't make that mistake again)

Question 30

How can haemolytic disease of newborn be diagnosed before birth?

Answer 30

-Check mother and fathers Rh antigens -Check if mother and father had a child previously **- Indirect Coombs Test-antiglobulin test, used to check for anti-Rh antibodies** -Doppler scan of foetus to check for anaemia -Foetal blood sample from umbilical vein for bilirubin

Question 31

What physiological changes are caused by type II hypersensitivity reactions?

Answer 31

* **Receptor stimulation**,eg Graves disease, TSH receptor is the antigen that the antibody binds to * **Receptor blockade**,eg Myasthenia gravis antigen is AChR * **Protein blockade**, eg Pernicious anaemia, antigen is intrinsic factor in gastric parietal cells

Question 32

What are the therapeutic approaches of type II hypersensitivity reactions?

Answer 32

**Tissue/cell damage:** -Corticosteroids - anti-inflammatory -Plasmapheresis - remove circulating antibodies and inflammatory mediators -Splenectomy - removal of opsonised material -IV immunoglobulin - blocks Fc receptor **Physiological change:** -Correct metabolism - antithyroid drugs in Graves -Replacement therapy eg Pyridostigmine (Ach esterase inhibitor) in Myasthenia gravis,Vit B12 (IM) in pernicious anaemia