5. Antibody mediated immunity Flashcards
How are Ig’s and T cell receptors highly variable recognition molecules?
Effector B cells (plasma cells) secrete soluble forms of immunoglobulins called antibodies
TCR’s are only expressed as cell-surface recognition molecules, never as soluble proteins
B cells recognise native proteins whereas T cells recognise degraded proteins bound by major histocompatibility complex (MHC) molecules
What are AB’s produced by?
Mature B - cells express membrane-bound immunoglobulin (Ig) of a single antigen specificity
- When a foreign antigen first binds to the immunoglobulin the B cell is first stimulated to proliferate
- Its progeny differentiate into plasma cells that secrete antibody of the same specificity as the membrane - bound immunoglobulin
How are B cells activated?
NaÏve B cells (like T cells) requires two signals:
- engagement of the B cell receptor
- help provided by T cells
Thymus dependant (TD) antigens - mostly proteins
In some cases, accessory signals can also be provided directly from microbial consitituents
- Thymus - independent (T1) antigens e.g. lipopolysaccharide (LPS)
What are the two signals required for B-cell activation by thymus - dependant antigens?
1st - signal binding of antigen to Ig 2nd - delivered by T helper cell that recognises degraded fragments of the antigen as peptides bound to MHC class II molecules on B-cell surface
What is B cell differentiation?
B cell recognised antigen in its natural state
T cells recognise processed antigen
T cell dependant Ab responses require activation of B helper cells by T cells that respond to the same antigens: linked recognition
Secretion on Interleukins (4,5 and 6) drives proliferation and differentiation of the B cells into antibody secreting plasma cells
- although it must be the same antigen the epitopes are not
How are the antibodies produced?
Specific memory is the hallmark of the adaptive immune response
- production of an antibody is a sign that an antigen is present - antigen triggers immune response
- IgM normally the first class of antibody to be released in response to a new challenge from an antigen
- IgG is produced after repeated challenge to the same antigen and is an indicator of previous antigenic challenge (normally quicker rate & greater amount produced)
What happens between the IgM and the IgG response?
Somatic mutation - mechanism for introducing mutation into V regions of activated B cells (antigen driven) - increase antibody affinity Class switching - main purpose is that each class displays a different biological function
Comparison of IgM and IgG
IgM - low affinity interaction - C' activated - Good agglutinator IgG - High affinity interaction - C' activator - good neutraliser - FcR mediated phagocytosis
How are high affinity antibodies produced?
Variable domain changes to induce a better fit
Constant domain changes to have a different function - isotype (class) switching
What is the importance of isotype (class) switching?
Ab’s are bi-functional proteins
In the course of the immune response the effector arm (class) of an antibody needs to change in order to mount a serious/different challenge to harmful pathogen
- neutrilisation
- opsonisation
- complement activation
- Fc receptor engagement
Isotype switching is T cell dependant, requiring both direct cell-cell contact and the production of cytokines
What do different cytokines induce?
Switching to different isotypes
- inhibit or induce the production of certain isotypes
- most of the inhibitory effect is probably the result of directed switching to a different isotype
How do interactions between T and B cells occur in specialised tissues?
- Mature B cells travel to the lymph node via the bloodstream and leave via the efferent lymph
- B cells that encounter antigen form primary foci from which proliferating cells migrate to the primary follicle, forming a secondary follicle with a germinal centre
What induces somatic hypermutation?
Germinal centre is a specialised micro-environment that allows B cells to differentiate into either antibody-secretory plasma cells or memory B cells and induces somatic hypermutation
What are T-dependant antigens?
For thymus independent, the second signal can be delivered by the antigen its self
Signal sufficient to induce proliferation and antibody secretion by B cells in the absence of specific T cell help because of the special property of some bacterial polysaccharides, polymeric proteins, or lipopolysaccharides (LPS)
Such reagents activate a large number of B cells and are often known as B - cell mitogens
