Describe the innate immune response
- Rapid
- Non-specific (generic anti-bacterial or anti-viral mechanisms)
- Most often fails to completely eliminate infection
Describe the adaptive immune response
- Delayed
- Highly specific
- Usually eliminates infection
- Memory - long term immunity, but specific to that particular pathogen
What is humoral immunity mediated by and how is this different do cellular immunity? What are they both regulated by?
- Humoral - mediated by B-lymphocytes
- Cellular - mediated by _CD8+ cytotoxic T-_lymphocytes
Both branches regulated by CD3+ helper T-lymphocytes
What is meant by humoral immunity?
- Humor = fluid
- Following an infection
- Plasma contains substances - antibody
- Neutralises specific infectious agent
- demonstrate in vitro
- or in vivo - adoptive immunotherapy
What is antibody - and what globulin band is it derived from?
- Protein - immunoglobulin
- Migrates in the gamma-globulin fraction on serum electrophoresis
- each antibody binds to a specific antigen on infectious agent
- but plasma contains many different antibodies
- note how diffuse the gamma-globulin band is
What is the general structure of antibody?
- Y shaped
- Tetrameric protein
- 2 identical heavy chains
- 2 identical light chains
- held together by non-covalent interaction by disulfide crosslinks between cysteine aa reisdues
- Constant region + variable region
- Two binding sites on 1 molecule
- Flexible hinge region
What is “light chain restriction”?
- Kappa (K) + lambda (λ)
- But any B-cell will only make one type
- Any Ig molecule will contain EITHER kappa or lambda, never both
- This is called light chain restriction
Each antibody chain has a variable and constant region, what do these both do?
- Variable - AA sequence varies from one Ig to another, binds antigen
- Constant - for effector functions eg. activating complement, binding to phagocytes
What kind of protein is antibody?
Glycoprotein - carbohydrate added in the golgi
What are 3 ways of antibody fighting an infection?
- By coating and neutralising a pathogen
- Eg. if a virus is coated with antibody then it cannot bind to its receptors on cell surface
- By activating complement
- which can then blow holes in a bacterial cell membrane
- By opsinization
- phagocytes have Fc receptors on their cell membrane
- bind to pathogens coated with Ab + phagocytose them
So, how does an antibody actually bind to an antigen?
- Non-covalent interactions
- Eg. electrostatic, hydrophobic, van der Waals, hydrogen bonds
- Depends on antibody binding site being exactly complementary, sterically + chemically, with a site on the surface of the antigen
What is an epitope?
The binding site on the antigen for one specific antibody
How does the body design a specific antibody to bind a specific antigen?
- It can’t
- Body generates over 100 million diff B-cells each making random Ig
- Each B-cell only makes 1 specific Ig
- These naive B-cells sit around in lymph nodes doing not v much
- During infection a small # of B-cells will by chance be making an Ig that binds to one of the foreign antigens
- These B-cells are activated + begin to multiply - “clonal selection”
What is the pathway of lymphocyte development in the bone marow?
Describe B-cell activation
- functional Ig first expressed as IgM on cell surface (sIgM)
- acts as a “B-cell receptor”
- IgM associated w other tyrosine kinases
- binding of antigen to sIgM activates tyrosine kinases + their signal transduction pathways
- also co-stimulation by T-cells
- activated B-cell secretes soluble IgM
- differentiate into memory B-cells
What do memory B-cells do?
- allow a very rapid response to a second exposure
- immediate production of IgG rather than IgM
What is meant by natural immune responses being “polyclonal”? Explain this
- More than 1 clone of B-cells is generated
- More than 1 antibody synthesised
- This is bc:
- multiple antigens on organism
- multiple epitopes on each antigen
- more than 1 antibody may recognise the same epitope
What is ‘class switching’?
Once a B-cell starts making an antibody which binds to a specific antigen…
- it can switch to make antibodies with the same antigen binding site
- but different constant regions
- to carry out different functions in different parts of the body
What are the different classes of Ig?
- IgG (4 subtypes)
- IgM
- IgA (2 subtypes)
- IgD
- IgE
All differ slightly in heavy chain constant region amino acid sequence, have different functions
Describe IgM
- First class of Ig made by B-cells in primary response
- First made as membrane-bound protein on B-cell surface
- Activates B-cell by signal transduction
- Later made in secreted form
- Activates complement + acts as opsonin
What kind of infection will presence of specific IgM antibodies to an antigen indicate?
A current primary infection
On the other hand, presence of IgG antibodies may be due to past exposure to antigen
What is IgM structure (membrane-bound + secreted)?
- membrane-bound IgM is formed of a single Ig tetramer
- secreted - igM five molecules of basic Ig tetramer, polymerise to form a pentamer
What is IgG?
- major class of Ig in circulation
- V good at activating complement system
- Good as opsonin
- Formed of a single Ig tetramer
What is IgA?
- Most abundant class in external secretions
- Milk, sweat, tears, gut secretions
- Protects mucosal surfaces
- Does not activate complement
- Does bind Fc receptors triggering phagocytosis + inflammatory rxns
