Humoral Immunity Flashcards
What is the definition of immunoglobulins
• Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies
What is general functions of immunoglobulins, Ag binding and effector
• Ag binding
– Can result in protection
– Valency
• Effector functions
– Fixation of complement
– Binding to various cells
what is the basic immunoglobulins structure
• Immunoglobulins - heterogeneous
• Myeloma proteins - homogeneous immunoglobulins
What is antigen
Antigen - “anything that can be bound by an antibody“ or
that can elicit an immune response (immunogen). Eg: simple chemicals, sugars, small peptides to complex protein complexes such as viruses.
what is haptens ?
Small antigens (haptens) are not immunogenic – they need to be coupled to a carrier to elicit an IR.
Antibodies interact specifically small parts of antigen molecules. These are known as antigenic determinants or epitopes.
what is isotypes, allotypes and idiotypes
• ISOTYPES - antigenic determinants characterizing classes & subclasses of heavy chains, types and subtypes of light chains.
• Allotypes - antigenic determinants specified by allelic forms of the Ig genes -slight differences in the amino acid sequences of heavy or light chains
light chain allotypes – Km (Inv) heavy chain - Gm
• Idiotypes - unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity – specific antibody molecules have the exact same hypervariable regions
What is the immunoglobulins structure
• Heavy & Light Chains
• Disulfide bonds – Inter-chain – Intra-chain
• Variable & Constant Regions
– VL & CL
– VH & CH
• Hinge Region
• Domains – VL & CL
– VH & CH1 - CH3 (or CH4)
• Oligosaccharides( carbo on CH2)
what is the immunogobulin fragments
Ag binding
Complement binding ite
Placenta transfer
binding to fe receptor
immunoglobulins fragments, Fab and Fc
• Fab
– Ag binding
– Valence = 1
– Specificty determined by VH and VL
• Fc
– Effector functions
• F(ab’)2
Human Immunoglobulins Classes ,5
• IgG - Gamma heavy chains
• IgM - Mu heavy chains
• IgA - Alpha heavy chains
• IgD - Delta heavy chains
• IgE - Epsilon heavy chains
Human Immunoglobulin Subclasses (Heavy Chain)
• IgG Subclasses
– IgG1 - Gamma 1 heavy chains
– IgG2 - Gamma 2 heavy chains
– IgG3 - Gamma 3 heavy chains
– IgG4 - Gamma 4 heavy chains
• IgA subclasses
– IgA1 - Alpha 1 heavy chains
– IgA2 - Alpha 2 heavy chains
Human Immunoglobulin (Light Chain)
• Kappa
• Lambda
Subtypes
• Lambda 1
• Lambda 2
• Lambda 3
• Lambda 4
Structure of IgG
• Structure - 7S Monomer
• Properties
– Major serum Ig
– Major Ig in extravascular spaces
– Placental transfer – No Ag binding required ( IgG2)
– Fixes complement (IgG4)
– Binds to Fc receptors (IgG2, IgG4)
• Phagocytes – opsonization, K cells - AD
Structure of IgM
• Structure
– Pentamer (19S)
– Extra domain (CH4)
– J chain(tgh tgh)
• Properties
– 3rd highest serum Ig
– First Ig made by fetus and B cells
– Fixes complement
– Agglutinating Ig
– Binds to Fc receptors
– B cell surface Ig
Structure of IgA
• Structure
– Serum - monomer – Secretions (sIgA)
• Dimer (11S)
• J chain
• Secretory
component
• Properties
– 2nd highest serum Ig
– Major secretory Ig (Mucosal or
Local Immunity) Tears, saliva, gastric & pulmonary secretions
– Does not fix complement
– Binds to Fc receptors on some cells
Structure IgD
• Structure
– Monomer
– Tail piece
• Properties
– 4th highest serum Ig
– B cell surface Ig
– Does not bind complement
Structure IgE
• Structure
- Monomer
– Extra domain (CH4)
• Properties
– Least common serum Ig – Binds to basophils
& mast cells
– Allergic reactions
– Parasitic infections (Helminths)
• Binds to Fc receptor on eosinophils – Does not fix complement
Effector function of antibodies
• Neutralisation. block biological activity of their target molecule e.g a toxin binding to it’s receptor
• Opsonisation. interact with special receptors on various cells, - macrophages, neutrophils, basophils & mast cells allow them to “recognise” & respond to the antigen b
• Complement Activation. cause direct lysis by complement recruitment also enhances phagocytosis
What is B cell Antigen Receptor (BcR)7
BCRs enable the cell to bind to & be activated by and respond to an epitope on molecules of a soluble antigen. The response ends with descendants of the B cell secreting vast numbers of a soluble form of its receptors. These are antibodies.
What is B cell Antigen Receptor (BcR)
• Are integral membrane proteins
• Are present in thousands of identical copies exposed at
the cell surface.
• Are made before the cell ever encounters an antigen
• Are encoded by genes assembled by the recombination of
segments of DNA
• Are very similar to TCRs
How antibodies are produced ?
• BCRs bind soluble antigens
• Bound antigen molecules are engulfed into B cell by
receptor- mediated endocytosis
• Antigen is digested into fragments
• Then displayed at cell surface nestled inside a class II histocompatibility molecule
• Helper T cells specific for this structure bind the B cell and secrete lymphokines
- stimulate the B cell to enter the cell cycle and develop into a clone of cells with identical BCRs
- switch from synthesizing their BCRs as integral membrane proteins to a soluble version
- differentiate into plasma cells to secrete these soluble BCRs, which we now call antibodies.
How clonal expansion process
The mature B-cells have antibody molecules on their surface. When a surface bound antibodies binds to the antigen for which it is specific, this stimulates that B-cell to divide (clonal expansion) and mature into a population of clonal plasma cells that produce large quantities of uniquely specific soluble antibodies.
Immunoglobulin Isotype switching
Reconfiguration of genes for IgM to IgA with same antigen binding specificity.
Switch sites combine,
intervening DNA is looped out and deleted.
IgA antibody gene containing VDJ genes and C-alpha gene is formed
CS occurs by - Class Switch Recombination (CSR) binding.
Mechanism of generation of diversity
• Ig Gene Rearrangements
Random joining of VDJ genes (in HC), VJ (LC) – around 107 possibilities
• Somatic hypermutations – Point mutations in VDJH & VJL
• Affinity maturation
• Antibody Function : Isotype switching, existence of Abs as membrane bound or secreted form
