Caroline Dalton

What does innate immunity include ? (proteins)

Compliment

Cytokines

What are the 6 beneficial molecules in plasma?

1. Clotting factors

2. Antibodies

3. Compliment proteins

4. Nutrients

5. Lysozymes

6. Transferrin

when does plasma leakage occur?

During inflammation

What allows plasma leakage occur?

Capillary permeability allows plasma to leak into tissues

Benefits of plasma leakage? (6)

1. Clots form localising the infection

2. Antibodies enter the tissue

3. Activation of complement pathways

4. Nutrients enter tissue

5. Lysozymes enter the tissue and degrade microbes

6. Transferrin enters to deprive microbes of iron

What is complement?

Biochemical cascade that helps antibodies to clear pathogens or mark them for destruction.

What is special about compliment (2)

1. Composed of 30 small plasma proteins

2. Can be activated independently of antibodies

Functions of complement (5)

1. recruits inflammatory cells

2. Chemotactically attracts phagocytes

3. opsonisation of pathogens

4. Disrupts plasma membrane of infected cells

5. Clearance of antigen-antibody complexes

what are the 3 complement pathways?

1. classic

2. Alternate

3. Mannose-binding lectin

What do all complement pathways produce?

C3 convertase

How is the classic complement pathway activated?

By antibodies

How is the alternative complement pathway activated?

Activated by pathogens

How is the mannose-binding lectin pathway activated?

by mannose-binding lectin binding to mannose on the surface of a pathogen

What do the complement pathways do? (3)

1. Promotes opsonisation

2. Promote inflammatory responses

3. Membrane Attack Complex

What does the alternative complement and mannose-binding lectin pathway do?

Same as the classical pathway

What antibodies types activate the compliment pathway?

IgG or IgM

What is the first 2 steps of the classical compliment pathway?

1. Antibody binds to the subunits

2. C1q, C1r, C1s subunits combine to form the enzyme C1

What does the C1 enzyme do (classic pathway) (2)

1. cleaves C4 into 2 subunits (C4a, C4b)

2. Cleaves C2 into subunits (C2a, C2b)

What does C4b and C2a do (2)?

1. Combine together and stick to the C1 enzyme complex

2. Functions as a C3 convertase

How many subunits does C4b2a (C3 convertase) cleave C3 into?

3 subunits

What does C3a do?

promotes inflammatory response

What does C3b do?

attaches antigens to phagocytes for opsonisation

What does C4b2a cleave apart from C3?

Cleaves C5 into 2 subunits

What is the most potent inflammatory compliment protein?

C5a

What does C5a do (4)?

1. causes mast cells to release vasodilators

2. Promotes extravasation of leukocytes

3. Causes neutrophils to release toxic O2 radicals for extracellular killing

4. Chemoattractant for phagocytes

What does C5b do?

becomes part of the membrane attack complex

What is the membrane attack complex?

Forms a channel in the cell membrane changing osmolarity causing cell lysis

What is the first step in the Alternate pathway?

C3b binds to pathogen creating C3 convertase.

What happens to C3 when it binds to the pathogen in the alternative pathway?

B and D factors become stable after binding and then bind to properdin protein.

What are the first 3 steps in the Mannose-binding lectin pathway?

1. mannose binding lectin (MBL) in serum binds to mannose on surface of pathogen

2. Protease binds to this complex

3. The complex cleaves C4 and C2 into subunits that form C3 convertase.

What is a cytokine?

Small molecules used to communicate between immune cells.

What kind of bonds form between ligands and receptors?

Non-covalent bonds

What does ligand-receptor binding cause?

1. A change in the receptor

2. A cascade of events

What is a multivalent receptor?

A receptor that has more than one ligand binding site.

What is a bivalent immunoglobulin?

Binds 2 identical antigens on the bacterial surface

How are IL-2 receptors expressed on lymphocytes (3)?

1. Antigens on pathogen bind to lymphocyte

2. Increase expression of third chain in cell-surface

3. Increase affinity of IL-2 receptor for IL-2, allowing it to bind.

What kind of pathway occurs after a ligand-receptor interaction?

Signal Transduction Pathway

What is a signal transduction pathways?

cascade of events leading to transcription factor binding and gene activation

What does the formation of a B-cell receptor complex result in?

Phosphorylation which activates downstream signalling

What do cytokines do? (2)

1. increase or decrease activity of enzymes

2. Change transcriptional activity

What are 4 cytokines?

1. IL-1 from macrophages

2. IL-2 from T-cells

3. Tumour necrosis factor

4. Interferons

What are cytokines?

All molecules that communicate between immune cells

What is a chemokine?

cytokines that mobilise immune cells

How do chemokines work?

Attract immune cells towards the area with the highest conc. of chemokines (chemoattractant)

What does pleiotrophic mean?

One cytokine can have different effects on different cells

How do cytokines have redundancy?

several cytokines have the same effect

What 3 methods of action can cytokines act in?

1. paracrine

2. autocrine

3. endocrine

What does synergise mean?

When cytokines work together to enhance each other's effects. (summation)

What does antagonise mean?

When cytokines inhibit each other.

Where do soluble receptors bind to cytokines?

in solution

How are receptors secreted?

1. proteolytic cleavage releases the receptor from the cell membrane

2. Splicing out the transmembrane-encoding sequence results in a secreted protein

What is the role of soluble receptors? (3)

1. antagonist

2. receptor down-regulation

3. ligand bind to receptor then delivered to other cell to illicit the same response.