Recognition Of Extracellular Pathogens Flashcards
Recap outline features of external pathogen response
- Macrophage (binding to PAMP)
- Complement
- Antibodies
Outline 4 types of pattern recognition receptors (PRRs) receptors on macrophages
- Mannose receptor (mannose different in configuration to out mannose)
- Lipopolysaccharide receptor (found in bacterial cell walls)
- Glucan receptor
- Scavenger receptor
- Toll- like receptor can be on cell surface or intracellular- TLR 3 intracellularly recognises double stranded RNA whereas TLR9 recognises unmethylated RNA
Explain extracellular recognition of pathogen B cells and following processes
1) Bacterial surface protein on surface of microbe
2) Recognised by a B cell, hence it secretes antibodies that recognise this bacterial protein
Therefore the bacterial protein is now an antigen which the antibody can specifically recognise
Define antibody
Antibody- released secreted form of the B cell receptor (act as antigen recognition proteins)
Define immunoglobulin
Immunoglobulin- globular protein of the immune system- used when talking about these proteins generally
How does antibody interact with microbe
Arms of the antibody: 2 antigen combining sites (identical)
- Small: Can interact with 5-6 amino acids on the surface of bacterial protein
- Called the antigenic determinant/ epitope: precise part of the antigen making a physical interaction with antigen combining site
SPECIFIC INTERREACTION: antigen binding sites specific for binding that epitope
Explain the different types of epitope interaction with antigen combining site
- Specific reactions resulting in a high affinity
- Cross reaction- as relatively complementary antigen and ACS so moderate affinity
- No specificity as antigen not bind to ACS- negligible affinity
Why is a high affinity reaction between the epitope/ antigenic determinant and ACS important
- As only bound by non-covalent interactions
Therefore has to be completely complementary to get sufficient SA of epitope in contact with antigen combining site
How might extracellular pathogen interact with B cell- outline steps and outcome of interaction
1) 1 B cell- contains surface immunoglobulins (thousands of identical antigen combining sites so are specific to same epitope). Additional transmembrane component keeps anchored in plasma membrane.
2) Interaction between epitope of antigen and antigen combining site activates the B cell
3) This leads to proliferation- making many copies of itself
4) Some of these copies undergo further differentiation and maturation to make plasma cells
5) Plasma cell makes secreted immunoglobulin with same antigen combining site as the surface immunoglobulin
- Mechanism ensures we create correct antibodies for the pathogen we are presented with.
What are clones and explain a process a clone goes through when binding to the antigen
B cells have small families- within a clone all cells have same antigen combining site
1) Upon first infection of microbe we have Clonal selection- antigen selects the antigen combing site on B cell that combines it most closely (highest interaction) and most antigens bind to this clone.
2) Activated B cell undergoes proliferation: Clonal expansion (clone B may undergo some proliferation but does not have the highest specificity to epitope so not as many produced as clone C)
3) Some revert to a resting state- carry with them memory of having being activated by that antigen. Memory lymphocytes more quickly activated than original naïve lymphocytes.
- Bigger and faster response upon reinfection (adaptive immunity)
Explain concept of vaccines
- Vaccine- inactivated version of toxin
- Same antigenic structure of original toxin
- Moderate antibody response
Generates memory B lymphocytes- important for bigger and faster response upon reinfection
Explain immunoglobulin structure
- Y shaped protein
- 4 polypeptide chains- 2 heavy, 2 light- mirror images so 2 light/heavy chains same polypeptides hence 2 antigen combining sites identical
- immunoglobulin domains : Series of globular regions along chains
○ Consists of 2 layers of b-pleated sheet at slight angles to each other forming B-barrel structure
○ We have heavy and light chain domains
○ VH, VL- Variable domains- different B cells have differences in amino acid sequence in these domains- have different antigen combining sites to recognise different epitopes
○ CL/CH = constant domains, constant in structure in immunoglobulins made by different B cells
○ B cell has capacity to make 9 different constant domains in the heavy chain- gives rise to different classes (5) and isotypes (9) in immunoglobulins
○ 9 different genes coding for different domains - Halfway down the heavy chain we have the hinge region- flexibility were there are no domains present
○ Above hinge: Fab region- fragment antigen binding
○ Below hinge: Fc region- Stem region - Disulphide bonds between:
○ Light chains covalently bound to heavy chain
Heavy chains bound to each other in hinge region
Explain how surface immunoglobulins become mobile antibodies- what is this process called
1) Naïve B cell expressing surface immunoglobulins in IgM form
2) B cell activated so any newly formed immunoglobulin now using new domains NOT change in any existing domains on B cell
3) Those with old IgM domains eventually degrade
4) B cell matures to form plasma cell
5) Gene encoding for the binding region to plasma membrane turned off so now secreted antibodies with new class of IgG
REM IgM (mini)–> IgG (giant)
Why do we use class switching
Different classes of antibodies have different biological functions in terms of their defence against infection
Outline Structure of antibodies with different constant regions?
- IgG1/IgG2/ IgG4: Appear visibly same yet at amino acid sequence level different within constant domains of heavy chains as coded for by different genes
- IgG3: Different as long rigid neck between Fab and Fc regions
- All IgG more closely related to each other than IgD (as gene coding for them more similar
- IgD: significant differences within heavy chin of IgD and IgG
- IgE: instead of 3 now 4 constant domains within heavy chain (and amino acid sequence differences)
○ ALL immunoglobulin monomers - IgA dimer: Protein called joining chain (J chain) can bind 2 antibodies together creating dimer- 4 antigen combining sites
○ Dimer found in mucosal secretions
○ Monomer found in blood - IgM found in pentamer form- 5 monomer units held together by J chain- antibody with 10 identical antigen combining sites
○ Useful if we have an pathogen with 10 identical epitopes on its surface which this antibody can bind to
PENTAMER/DIMER formed In cytoplasm of the plasma cell before released
