Recognition of Invaders Flashcards
Lymphocytes
B cells - act outside the cell T cells (CD4/CD8) - attack inside the cell
Antibodies (also known as Ig)
Cell surface, produced from B cells to bind foreign bodies and mediate effector functions
Structure of antibodies
Two Fab arms, which are variable and bind the antigen
Fc region, the constant domain
What are antigens vs antigenic epitopes?
Whole molecule antibodies recognise, usually large, >4KDa, can be proteins/carbs/lipids/DNA
Antigenic epitopes - bits that antibodies recognise, smaller regions e.g. spike proteins
Many epitopes on one antigen
Hypervariable region of antibodies?
Form the complementary determining region (CDR)
Types of epitopes?
Linear - amino acids in sequence recognised
Conformational - amino acids brought close together by protein folding
Affinity of antigen binding?
Weak, non-covalent bonds = must be close together for strong interactions
Affinity refers to just one binding site and its antigen, determined by how good the fit is
Avidity of binding?
Total strength of binding - increases with number of binding sites used
Cross-reactivity in antibodies?
Antibodies bind different epitopes with differing affinities i.e. one well, one less well
Useful in mutated states
Antibody production?
Need 10^11 in 5L of blood for specificity
Protective level = 10ng per ml, i.e. 5000kg!
Therefore only produced in large amounts after infection, and then kept in low levels for the rest of the time
Functions of Fc fragment?
Effector domain - neutralise, preventing bacterial adherence to epithelium
Opsonisation = phagocytosis
Complement activation
ADCC
What is the humoral immune response? What are the 4 mechanisms?
That mediated by antibodies Neutralisation (block pathogen binding sites, useful for viruses) Opsonisation (flagging for phagocytosis) Complement Activation ADCC (extracellular pathogens)
5 classes of antibodies?
IgG, IgM, IgD, IgA1, IgE
IgG?
Most abundant, IgG1-4
Diffuses into extravascular sites
Involved in all four functions, mostly neutralisation
IgG3 strongly involved in complement
IgM?
First one produced by B cells so found across epithelium, up to 10 binding sites
Used somewhat in neutralisation and opsonisation
Mainly involved in complement
IgD?
Rare
Don’t really know what it does
IgA?
Major Ig in mucosa and serum, subclasses 1 and 2
Mainly in mucosal associated lymphoid tissue (MALT)
Found as dimer in epithelium (when secretory), monomer when diffusing
Most involved in neutralisation
IgE?
Produced by mast cells so involved heavily in sensitising them
Worm infections/allergy
What form do the Igs exist in?
IgM and A - polymers, IgM pentameric and IgA dimeric due to cysteine residue in the constant J chain
T cell life cycle?
Originate in bone marrow (common lymphoid progenitor)
Mature in thymus
Migrate to lymphoid tissues
Thymus and aging?
Reduces in size with age - 30g newborns, 3g at 80
Therefore t cell populations decline over time
Types of t-cell?
CD4 - helper cells, Th
CD8 - cytotoxic, Tc/CTL
B cell antigen receptors?
Antibody structure - Fc regions of light and heavy chain, with CDR and signal transducing molecules (Igs) in membrane for signalling
T cell antigen receptors? (TCR)
Two chains, alpha and beta, bound by disulphide bonds with carbohydrate groups.
Top variable region, lower constant region
Va and Vb have hypervariable regins with different CDRs for antigen specificity
Also have signal transducing molecules - CD3
How do TCRs recognise antigens?
Antigen presented from antigen-presenting cells, via MHCs
MHCs?
MHC -1 : 3 alpha chain regions, a1-3, which binds to membrane
Non-covalently linked to a 2beta chain
1 transmembrane domain
Expressed by all cells
MHC-2 : 2 alpha, 2 beta - both chains have transmembrane domains
Less expressed - e.g. in macrophages, beta cells
