Week 2: B and T cell Mediated Immunity Flashcards
What is an immunoglobulin?
They function as the B lymphocyte receptor for antigen
Soluble recognition molecules secreted by B lymphocytes
High capacity for recognizing fine molecular detail
What are important functions of Immunoglobulins?
Directly kill or neutralize microbes
Help target phagocytes to microbes
Regulation of Immune responses (indirectly)
clearance of antigens and termination of immune response
What happens if antibodies recognize host proteins or host cells (immunopathologies)?
They mediate allergic responses
Cause immune complex diseases
Mediate autoimmune cell destruction
What are the 5 main classes(isotypes) of antibody?
IgA, IgD, IgE, IgG, IgM
How do classes of antibody differ?
They differ in valency and function
What are the 4 subclasses of IgG?
IgG1, IgG2, IgG3, IgG4,
Decreasing order of abundance in serum ie) IgG1 > IgG2
What are the 2 subclasses of IgA?
IgA1> IgGA2
What are polymorphic variants of IgG and IgA antibodies referred to as?
allotypes
An allotype would be a good way of distinguishing between antibodies in different individuals.
How can subclasses of IgG antibodies differ?
They can have same valency but different function.
What are domains in antibodies?
Within the light and heavy chains of the antibodies, there are structural regions of the molecule with a particular function
What is an antigen?
Any molecule that can be recognized by an antibody and doesn’t need to be immunogenic
What is an epitope?
The portion of the antigen which is recognised specifically at a molecular level by the antigen binding site
What is the antigen binding site described as being due to involvement of both light and heavy chains?
combinatorial
Affinity
The ability of one binding site to interact with each ligand
Avidity
The combined ability/ strength of having multiple binding sites to a specific epitope
What is the purpose of the constant chain?
They are important for determining the function of the antibody.
Basic structure of antibody
What are the further nomenclature in antibodies?
Fab = Fragment antigen binding - the 4 domains of the terminal part of the heavy chain and the light chain
Fc- Fragment crystalizable - termnial portions of the heavy chain -binding site for receptors on other cells
VL - variable light
CL - Control light
cy1 = constant gamma 1 , etc
What does the hinge in antibodies help with?
Flexibility
How are antibodies of infinitely different specificities created?
Antibody molecule is encoded by multiple gene segments
1) Germ line diversity of genes
2) Combinatorial diversity
3) Junctional Diversity
What is somatic recombination?
It is the rearrangement of DNA where gene segments can be put together in different ways to generate proteins with different structures using the processes of combinatorial diversity and junctional diversity.
What chromosome is the genes for heavy and light chains found on?
Heavy - Ch14
Kappa Light - Ch2
Lambda Light - Ch22
What is somatic hypermutation?
When the B cells increase their affinity of antibodies over time of an immune response by affinity maturation using the enzyme AID,
Basic principle of somatic recombination?
The unwanted DNA is excised out of the gene and the desired genes are “glued together”
Each B cell undergoes this during maturation independently of all other B cells.
Recombination only occurs once in the life of a B cell so each B cell has specificity
What happens if you have enzyme defects that are responsible for somatic recombination?
You cannot recombine your antibody molecules and B cell maturation cannot be completed an therefore have primary immunodifficiemcy diseases
Stages of Clonal selection of b cells
Proliferation and diversification of Progeny cells (specificity)
Antigen binds to specific B cell
Proliferation and Differentiation of B cell (amplification)
Somatic Hypermutation acts after
How does somatic hypermutation work?
It introduces random changes into the antibody binding site
Activation induced cytidine deaminase (AID) directs replacement mutations
Sequences in the antibody binding site accumulates point mutations
Mutations can increase, decrease or not change Ab affinity
Selection mechanism for higher affinity clones is called affinity maturation
Where does somatic hypermutation take place?
Germinal centres in lymphoid tissue
Light zone = site for selection of high-affinity clones
Dark Zone = site for somatic hypermutation
Recognise that different classes and subclasses of immunogloblins have different functions
Isotype switching (class switching recombination) allows for what
change of function but specificity stays the same that was developed during antibody maturation
IgA and IgM have increased valency through …..
multi-merisation
*valency changes but same specificity
What is the structure of IgM and its valency?
pentameric structure and valency of 10
Structure of IgA and valency?
Dimeric structure and valency of 4
multimeric IgM has increased capacity to interact with….
complement
A multimeric IgM means that a C1q molecule can cross link all of its components on the same antibody molecule and become activated whereas with a non multimeric antibody only some of the C1q molecule components can cross link and becomes less activated so a multimeric IgM increases the efficiency of activation of complement and increased avidity for actual surface.
Ig Isotypes have differential tissue distribution
Revise complement with classical and alternative pathway
Where do T cells come from?
Derived from bone marrow derived hematopoietic stems cells that migrate to thymus
98% of t cells die in thymus by positive and negative selection
only T cells with TCR able to recognise foreign peptides bound by MHC escape to periphery
Structural similarity between t cell and b cell receptors
How do T cells recognise antigens differently to B cells?
B cells use Ab to recognize conformational epitopes or tertiary structure. Conformational epitopes can be made up from discontinuous stretches of AAs.
T cells use TCR to recognize linear epitopes enzymatically digested out of antigens (“antigen processing”).
What are MHC molecules?
Major Histocompatibility complex molecules are very specialized peptide transporters that transfer pepides/antigen pieces from the phagosome to the cell surface so T cell receptors can bind to them.
Structure of class 1 and 2
class 1
Made of single heavy chain with 3 domains bound to accessory protein called Beta 2 microgloblin
class 2
Made up of 2 polypeptide chain each with 2 domains with each chain being alpha and beta
What is the effect of MHC molecules being highly polymorphic peptide transporters?
Shape of transporter is different in everyone so picks up slightly different peptides but should be able to pick up some peptides from antigen that is digested
Difference between MHC class 1 and class 2 molecules?
