Hypersensitivity Type 2 Flashcards
What is type 2 hypersensitivity also referred to as?
Cytotoxic hypersensitivity
Involve tissue-specific antibody mediated destruction of healthy cells
Can also be systemic destruction, but this is usually type 3 hypersensitivity
What is central tolerance?
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
What are the primary lymphoid organs?
Where immune cells are developed
Thymus for T cells
Bone marrow for B cells
What is an autoimmune disease?
When a healthy self reactive cell attacks another healthy self cell
What is the problem in type 2 hypersensitivity?
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
What are the 2 types of antigens implicated in type 2 hypersensitivity?
Intrinsic - normally made by the host
Extrinsic - antigen from infection or medication that attaches to host cell
Type 2 hypersensitivity pathway
- 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
When do antigen-antibody complexes occur?
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)
What is cytotoxic mechanism 1?
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)
What is the complement system?
A family of small proteins that work in an enzymatic cascade to fight of bacterial infections
What is the definition of chemotaxis?
The movement of an organism or cell along a chemical gradient either towards or away from the cell releasing the chemical
Examples of damage that can occur as a result of a type 2 hypersensitivity reaction
- Haemolytic anemia
- Thrombocytopenia
- Neutropenia
What is Goodpastures Syndrome?
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
What is cytotoxic mechanism 2?
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)
What is Coomb’s Test (direct)?
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
What is Coomb’s Test (indirect)?
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
What is cytotoxic mechanism 3?
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
What is cytotoxic mechanism 4?
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
What is the non-cytotoxic mechanism? Give examples
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
