Hypersensitivity Type 2

Question 1

What is type 2 hypersensitivity also referred to as?

Answer 1

Cytotoxic hypersensitivity
Involve tissue-specific antibody mediated destruction of healthy cells
Can also be systemic destruction, but this is usually type 3 hypersensitivity

Question 2

What is central tolerance?

Answer 2

Developing immune cells that are self-reactive get destroyed or inactivated
Immune cells that aren’t self-reactive survive
Occurs in the primary lymphoid organs

Question 3

What are the primary lymphoid organs?

Answer 3

Where immune cells are developed
Thymus for T cells
Bone marrow for B cells

Question 4

What is an autoimmune disease?

Answer 4

When a healthy self reactive cell attacks another healthy self cell

Question 5

What is the problem in type 2 hypersensitivity?

Answer 5

Self reactive B cells become activated and produce IgM (sometimes), or IgG (usually) (with the help of CD4 positive T helper cells), which bind to antigens on self cells

Question 6

What are the 2 types of antigens implicated in type 2 hypersensitivity?

Answer 6

Intrinsic - normally made by the host
Extrinsic - antigen from infection or medication that attaches to host cell

Question 7

Type 2 hypersensitivity pathway

Answer 7

• An extrinsic antigen (ie penicillen) can bind to a host cell (ie red blood cell)
• IgG antibody (penicillen specific) binds to antigen > antibody-antigen complex
• Antibody activates complement proteins, which act to kill the red blood cell

Question 8

When do antigen-antibody complexes occur?

Answer 8

When an antibody binds to an antigen
Can occur in a normal infection - ie the antibody binds to the antigen attached to the bacteria
Can occur when the antibody is loacted on a host cell (this is problematic - occurs in type 2 hypersensitivity)

Question 9

What is cytotoxic mechanism 1?

Answer 9

Activation of the complement system:
- C1 binds to the Fc region of the antibody
- C1 engages C2-C3 (some need to be activated by being cleaved or chopped by an enzyme)
- These cleaved fragments (C3a, C4a, C5a) act as chemotactic factors (attract neutrophils)
- Neutrophils degranulate and release enzymes (peroxidase, myeloperoxidase, proteinase 3) which generate oxygen radicals that are highly cytotoxic to cells (can cause tissue damage)

Question 10

What is the complement system?

Answer 10

A family of small proteins that work in an enzymatic cascade to fight of bacterial infections

Question 11

What is the definition of chemotaxis?

Answer 11

The movement of an organism or cell along a chemical gradient either towards or away from the cell releasing the chemical

Question 12

Examples of damage that can occur as a result of a type 2 hypersensitivity reaction

Answer 12

• Haemolytic anemia
• Thrombocytopenia
• Neutropenia

Question 13

What is Goodpastures Syndrome?

Answer 13

Antibodies bind to intrinsic antigens:
Bind to collagen of basement membranes in the glomeruli (kidney) and alveoli (lungs)
These cells are then destroyed through the hypersensitivity type 2 pathway

Question 14

What is cytotoxic mechanism 2?

Answer 14

The cytokines were recruited in mechanism 1
C5b, C6, C7, C8, and C9 come together to form a membrane attack complex (MAC)
MAC inserts itself into the cell membrane, creating a channel that allows fluid to rush in due to the osmotic difference
This leads to cell lysis (the cell bursts)

Question 15

What is Coomb’s Test (direct)?

Answer 15

Can diagnose autoimmune haemolytic anemia
Red blood cells are separated from the plasma, and mixed with Coomb’s reagent (anti-human globulin - an antibody against human antibodies)
If blood cells agglutinate (clump together) they probably had antibodies on their surface

Question 16

What is Coomb’s Test (indirect)?

Answer 16

Usually done to test for bloodgroup incompatibility
Done to test if the antibodies are present before being exposed to the antigen (ie if you had a mismatched blood transfusion, or second pregnancy with mismatched Rh factor)
Patient’s serum is mixed with lab RBCs with no antigens on their surface, and then mixed with Coomb’s reagent
If the cells agglutinate, this suggests antibodies or complement in the serm

Question 17

What is cytotoxic mechanism 3?

Answer 17

Occurs if IgG antibodies coat a blood cell bound by C3b (complement particle)
This means the cell has been opsonised (targeted for phagocytosis)
The cell moves to the spleen where it encounters a phagocyte
Phagocyte binds to the Fc region of the antibody, or the C3b
Phagocyte engulfs and destroys cell

Question 18

What is cytotoxic mechanism 4?

Answer 18

Antibody-dependent cell-mediated cytotoxcity (ADCC)
The antigen-antibody complex gets recognised by NK cells
NK cell recognises Fc tail of antibody and releases toxic granules (containing perforins - create pores/holes in the cell)
Pores allow entry of granzymes and granulysin which cause ‘quiet’ cell death without surrounding inflammation

Question 19

What is the non-cytotoxic mechanism? Give examples

Answer 19

Antibody-mediated cellular disfunction
Antibody disrupts function
The antibody binds to the antigen and gets in the way of ligands

Example: Myasthenia Gravis
Antibodies for AchRs block the ACh binding sites in muscles > muscles don’t get stimulated > muscles weaken over time

Example: Graves Disease
Antibodies target receptors that stimulate thyroid hormone production
They activate receptors > produce excess thyroid hormone > hyperthyroidism