Adaptive Immunity Recognition Flashcards
What are the 4 phases of adaptive immunity?
- priming phase
- effector phase
- contraction phase
- memory phase
What is the priming phase?
the first time the adaptive immune system encounters a system
What is the effector phase?
when the activated adaptive cells differentiate into effector cells to eliminate pathogen
What is the contraction phase?
when most of the effector cells die off after clearing pathogen
What is the memory phase?
some long lived memory cells remain to make sure that the immune system can respond faster
What are effector cells?
highly specific, slower response, results in memory
What are the 3 major effector functions?
- antibody production
- cytokine secretion
- cytotoxicity
Where do B cells mature?
bone marrow
What surface biomarker do B cells have?
CD19 positive
all B cells have this, which makes them identifiable
How many BCRs do B cells have (refer to specificity as well)?
around 100 000, all with the same specificity for one antigenic epitope
What does BCR engagement lead to?
proliferation and transition to plasma cells
Where do T cells originate from and mature?
originate from lymphoid progenitor cell in bone marrow
mature in thymus
What co-receptors do T cells express?
CD4 (MHC-II restricted)
CD8 (MHC-I restricted)
meaning, CD4 T cells only detect peptides in MHC-I cells and vice versa
What type of TCR do T cells use to recognise antigen?
alpha/beta T cell receptor
What function do CD4+ help rT cells perform once activated?
regulators of immune responses?
Whta function do CD8+ cytotoxic T cells perform once activated?
cytoxicity, release perforin and granzymes
What 5 types of T helper cells does a CD4+ T cell polarise into?
Th1, Th2, Th17, Treg (Th22), Tfh
What are the two rules of engagement for lymphocytes?
- naive lymphocytes recirculate through lymph node/spleen via blood
- pathogens come from periphery into local lymph nodes
What is an epitope?
antigenic determinant - the part of an antigen that is recognised
Can lymphocytes be specific for more than one epitope?
no, each lymphocyte is specific for one epitope
What is an immunogen?
a substance that induces a specific immune response
thus, all immunogens must be antigens
What are the 4 main factors affecting immunogenicity?
- foreignness
- high molecular weight
- chemical complexity
- degradability
What is foreignness, and how does it affect immunogenicity?
if a substance if more foreign, it will have a higher immunogenic result
How does high MW affect immunogenicity?
higher molecular weight, more immunogenic
How does chemical complexity affect immunogenicity?
more chemically complex, greater immune response
How does degradability affect immunogenicity?
usually affect T cells, as they only recognise antigens which are broken down and presented by APCs
What are haptens?
non-immunogenic organic moiety which can be attached to a larger structure (a carrier)
they become the target to an antibody response
What is a carrier (in a hapten-carrier complex)
usually polypeptide, small to be able to cross link surface BCRs
contains T cell determinants
How do Ab bind to antigens?
bind via contacts in variable regions of Ig which are complementary to size and shape
What are the two forms of Ig?
surface
secreted
Where is surface Ig found and what does it do?
embedded on B cell membrane
BCR
induces activation signals when bound to antigen
Where is secreted Ig found and what does it do?
secreted by B plasma cells
also binds to antigens to perform different functions (neutralisation, opsonisation)
What is the structure of an immunoglobulin?
2 heavy chains
2 light chains
How many Ig domains on L/H chains?
light chains have 2 domains
heavy chains have 4-5 Ig domains (depends on Ab class)
How are the L/H chains held together?
disulphide bonds
What are the two regions of an antibody?
variable region (antigen binding)
constant region (effector function)
What are the functionally distinct part of Ig?
Fc part = tail constant region (isotype) - upper part
Fab part = antigen binding, hypervariable - lower part
How does proteolysis of Ig occur - 2 methods?
papain releases individual Fab and Fc fragments (Fab and Fc are left whole)
pepsin separates both Fab regions from digested Fc region
Where are the hypervariable regions on Ig?
within Vh and Vl, the hypervariable regions form the antigen binding site
most variability in CDR3 region
(CDR = Complementary Determining Regions)
What are the two types of light chain?
kappa
lambda
What determines the isotype of Ig?
constant region of heavy chain
What are 4 properties of Ig
- monomer
- major class in secondary response
- large hinge region
- high affinity
What are 5 properties of IgM?
- has extra constant Ig domain
- pentamer
- Ig oligomerisation via J-chain
- first Ig procuced
- high avidity, low affinity
What is affinity?
strength of binding one molecule to another
What is avidity?
total of strength of binding between two molecules or cells to each other (when multiple binding site involved)
What are 3 properties of IgA?
- dimer
- major Ig for GI rest tracts
- 26aa tail piece
What are 2 properties of IgD?
- low abundance
- mainly cell associated
What are 4 properties of IgE?
- help with parasite resistance
- involved in allergic reactions
- binds mast cells –> degranulation
- extra C domain
What are the 2 types of antibody effector functions?
- direct mechanism, involving antigen recognition - Fab
- indirect mechanism - involving Fc part
Explain neutralisation
Ab binds to attachment proteins on viruses, bacteria, toxins to block surface receptors from taking in pathogen
Explain opsonisation
phagocytosis enhanced by Ab coating
Explain Antibody Dependent Cell-mediated Cytotoxicity (ADCC)
Ab binds to variable region of target cell. Ab binds to NK cell. cross linking of FcR triggers NK cell killing
Explain degranulation
IgE binds to parasite/allergen. IgE binds to FcER on immune cell. cross linking of FcER triggers degranulation.
cells involved: basophils, eosinophils, mast cells
Explain complement activation
complement are a collection of proteins promoting pathogen and infected cell death. Ab bids to C1q via Fc and initiates classical complement cascade
Only IgG and IgM binds C1q
free Ab does not activate C1q
What is an allotype?
variation in constant region - bc of inherited variation due to sequence variation in alleles of Ig loci
What is an idiotype?
variation in variable regions
How is Ab diversity generated?
somatic diversification
Which genes heavy and light chain genes undergo rearrangement
V (variable)
D (diversity)
J (joining)
How many rearrangements for V, D, J in kappa/lambda light chains and heavy chain
k light: 35 V x 5 J = 175 diff ways
l light: 32 V x 5 J = 160 diff ways
heavy: 46 V x 23 D x 6 J = 6348 diff ways
How are ‘rosettes’ used for rearrangement?
V segment forms rosettes to bring V segments into proximity with J or rearranged DJ segments
How is rearrangement of germine V,D,J guided?
rearrangement of germline V, D, J gene segments is guided by flanking DNA sequences called Recombination Signal Sequences (RSS)
Explain the 12/23 rule which joining follows
What are nucleases (with 2 examples)
- Artemis complex
- exonucleases
involved in nicking hairpin sequences OR removal of nucleotides generated by RAGs
What is TdT?
Terminal deoxynucleotide transferases (TdT
involved in insertion of random, non-template-encoded nucleotides
- N-nucleotides/N-regions
What are ligases?
eg. DNA ligase IV
involved in ligating DNA ends together
What are N-regions?
inserted nucleotides between V-D or D-J segments. imprecise because of deletion and insertions
How do N-regions affect joining?
contribute to diversity (any sequence possible)
can lead to failure of rearrangement
What are 3 sources of Ig diversity?
- combinatorial diversity
- junctional diversity
- somatic mutation
Explain combinatorial diversity
diversity through different combinations of V,D,J for one particular chain, and then different combinations of heavy and light chains
Explain junctional diversity
random N-region sequences
Explain somatic mutation
creates diversity as immune response progresses, mostly in secondary response
What are the origins of the 3 sources of Ig diversity?
- combinatorial - primary lymphoid
- junctional - primary lymphoid
- secondary lymphoid organs (varies affinity, not specificity)
