adaptive immunity 1 Flashcards
How is an immunity developed?
what happens first? what does it stimulate? how do you recover? aftermath?
Most previously unseen infections progress through – Initial infection stimulating an immune response Innate & Adaptive (Acquired) – Recovery due to immune activity – Lasting acquired immunity Specific Often for life
Innate response
spped?
acts on?
The Innate Response to new infections is
FAST
acts on PRE DETERMINED NON SELF SIGNALS
SOMETIMES can be primed for intense re activation ( INNATE MEMORY
Adaptive response
speed?
key feature? (2)
The Adaptive Response to new infections is
SLOW
and SELECTS for SPECIFIC SIGNALS
and generates MEMORY
T and B cells
made where?
key feature?
Each T or B cell is made in the bone marrow with
a randomly assigned antigen binding specificity.
An individual has at any one time > 100,000,000
individual cells each with a different specificity
T and B cells can have the same specificity
T cell development
what migrates where?
what happens here?
Naïve (Double negative) T lymphocyte will migrate to thymus gland for processing where it will either become
CD8+ Cytotoxic T lymphocyte (CTL)
CD4+ Helper T lymphocyte (Th)
Destroyed if strongly recognise self antigens (Central tolerance)
B cell development
where? what does it express?
Naive B lymphocyte will develop and mature in Bone Marrow To express a single epitope antibody used as a receptor
ENDOGENOUS PATHWAY of T cell priming
what is infected? what happens to this cell? what is presented?
what recognises this? what happens and what is produced?
what happens to the infected cell? what happens to the activated cell? (2)
Antigen from virus will infect an antigen presenting cell. The viral proteins in the cytoplasm will be detected and processed. Viral antigens are presented with MHC Class I molecule on cell surface
ONLY CD8+ T cell recognises antigen, becomes cytoxic and begins to make cytokines (recognise MHC Class I)
THe infected cell is destroyed by the cytotoxic cell via chemicals. Also, CTL (same as CD8+) will proliferate making memory cells and CTL cells looking for cells with presented antigen hence specifity (and memory)
EXOGENOUS PATHWAY of T cell priming
what happens to antigen?c by what? what happens to the anitgen? presented with?
what recognises this and what does it release?
Antigen of a pathogen will be engulfed by a dendrtic cell or macrophage into a vesicle. The antigen will be processed into small peptides. Antigen is presented with MHC Class II molecule on cell surface and T - Helper cells (TH) recognises the presented antigen. TH (CD4+) cell becomes primed and release cytokines looking for a B cell
EXOGENOUS PATHWAY of B cell priming
B cell activation (T cell independent)
what kind of pathogen must it be?
what does activation lead to?
what is this pathway restircted to and what can it lead to?
Pathogen containing multiple identical antigen
epitopes eg. Lipopolysaccharide (LPS) able to strongly activate B cell (rare)
Activation initiates proliferation with some cells being
memory cells
Activated B cells convert to Plasma cells and begin making antibody
This pathway is restricted to specific antigens and is
not checked for tolerance CAN lead to problems
such as Toxic Shock Syndrome
EXOGENOUS PATHWAY of B cell priming
B cell activation (T cell dependent)
how does this avoid auto immunity?
what activates B cell? effect of this?
Antibody production required co stimulation with a Th cell that was already screened against self thus auto immunity is avoided
B & Th cell interaction activates B cell
Activation initiates B cell proliferation with some cells
being memory cells and some Committed to antibody production
Basic antibody structure
what kind of protein is it?
anitgen binding sites?
what is between the binding sites?
what kind of shape is made?
what holds the chains together?
specific bond between with amino acids? type of bond?
what is key about the light and heavy chains?
describe the light chains ( 2 types)
describe the heavy chains - what determined Ig classes?
Antibody = Immunoglobulin = Glycoprotein
2 identical antigen binding sites
A Hinge ’H’ region flexible spacer between binding
sites
4 polypeptide chains held together by non covalent interactions and by disulphide crosslinks between cysteine a.a residues into a Y shaped molecule
2 identical Light ‘L’
Either kappa ( κ ) or lambda λ
Never both
2 identical Heavy ‘H’ ( Red Blue )
Have carbohydrates attached in Golgi body during assembly
Sequence of Fc section determines 5 Ig classes (isotypes)
Antibody fragments
what is FaB?
what is Fc?
Protease cleavage generates large fragments called
Fab (antigen binding)
Fc (crystallisable)
Fab - variable region binds antigen
Fc - constant region binds to receptors on phagocytes,
activates complement
2 structure of IgM
what is the difference between the 2?
- Monomer of basic sub unit
B cell receptor
Extra Heavy Chain domain that is membrane bound in the B cell
2.Pentamer of basic sub unit in plasma ( secreted Ig)
Contains a J chain a polypeptide involved in pentamer polymerisation
Benefits of pentamer IgM
larger hence can bind to more antigens, can complement in different ways
mops up things + works better
Function of antibody classes: IgG
what is this made by?
special about this and baby?
what is it very good at?
what does it act as? what do these cells recognise?
how long can it be present in body? what may this indicate?
the major class overall (75% of all Ig) the major class made by secondary responses only class able to cross the placenta and protect developing fetus (small enough to pass and as foetus doesnt make own antibodies and needs protection)
very good at activating complement via classical
pathway (removing the
acts as an “ opsonin ” inducing phagocytosis
– Fc region recognised by “Fc receptors” on surface of
immune cells. eg , neutrophils and macrophages
It can be present for long periods in the serum thus IgG antibodies may indicate past exposure and not current infection !!!
Function of antibody classes: IgM
what does it indicate?
what is it excellent at? why?
how does it bind immune cells?
Presence of specific IgM antibodies to an antigen indicates a recent primary response to
that antigen
–Implies a current primary infection
–excellent at activating complement via classical
pathway (ie , because of its pentameric structure)
•higher valency of pentamer increases overall
affinity (ie , by binding higher number of
•binds immune cells via Fc receptor (ie , inducing
phagocytosis)
RESPONSE to PRIMARY INFECTION
speed?
specificity?
why is there a latent period? what happens after that?
what is isotype switching?
The adaptive response to new infections is
SLOW and SPECIFIC with long lasting MEMORY
Gets into cells to stimulate T cells hence latent period. After 10 days, it leads to IgM being made, as IgM declines, IgG is made which is more long lasting + larger response
This is due to isotype switching where it is the same cell and antigen but different heavy chains
Preferred isotype switching
what is used to make variable region?
what causes rearrangement/excision?
what is altered and what isn’t?
Transcription is used to make variable region
Ig heavy chain genes are in a specific order
IgM comes FIRST in the queue
Cytokine signalling causes gene re arrangement/excision New heavy chain alters the class of Immunoglobulin But NOT the Variable region antigen specificity
Secondary response
how does the latent period change? why?
how does the Ig response change?
The adaptive response to re-infection is
FAST and SPECIFIC and ensures long lasting MEMORY
goes from 10 to 3 days as body is primed for antigen due to memory hence less time and more cells primed. Quicker Igm but HUGE IgG response
Antibody antigen interaction
what are the interactions? what does it depend on?
Non covalent interactions
Electrostatic, hydrophobic, van der Waals forces, hydrogen bonds
Depends on the antibody binding site being exactly complementary, sterically and chemically, with a site on the surface of the antigen
A single antigen can have many possible binding sites (epitopes)
Natural immune responses are polyclonal
why is more than one close of B cells generated? more than one Ig sythesised?
More than one clone of B cells is generated • More than one Ig is synthesised • Because – Multiple antigens on organism – Multiple epitopes on each antigen – More than one Ig may recognise the same epitope
How does antibody fight infection?
3 ways?
how does each of these work?
- By coating and neutralising a pathogen
a) E.g. if a virus is coated with Ab it cannot bind to its
receptors on the cell surface - By activating complement
a) Which can then form holes in a bacterial cell
membrane - By opsonisation
– Phagocytes have Fc receptors on their cell
membrane
– Bind to pathogens coated with Ab, and phagocytose
them
Function antibody classes: secretory IgA
where is this most abundant?
what protects this?
where does it act too?
secretory IgA most abundant class in external secretions (milk, sweat, tears, saliva, gut fluids etc
• first line protection at external surfaces
–initiates localised mucosal response different from
more general circulating immune response
–secretory component protects IgA from degradation,
hence it can work in harsh environments ( eg , GI
Function antibody classes: serum IgA
abundance?
what does it do in circulation?
what can it not do?
• second most abundant class in circulation
• circulatory IgA cannot activate complement
• circulatory IgA binds Fc receptor on immune cells
initiates inflammatory reactions
Function of the Ig classes: IgE
where does it have a harmful action? why?
where does it have an useful function? why?
when is this conc raised?
what can ove response lead to?
•harmful function in allergies
-binds to specific Fc receptor on mast cells and basophils releasing histamine
• useful function in response to parasitic worms releases chemicals from mast cells activates eosinophils (via Fc receptor binding)
• normally low concentration in circulation
raised in allergic patients
raised in infections with large parasites
• Over response can cause anaphylactic shock
Function of the Ig classes: IgD
where is it mainly found?
where does it not bind?
•extremely low concentration in circulation
•role is unclear
•mainly found on surface of B cells as antigen
binding B cell receptor
•does not bind complement
•probably helps cell activation
