5. General effector functions of antibodies Flashcards
which part of the immune system is humoral part of; acquired or innate?
acquired
In a primary response to pathogen - what cell is activated and what does it do?
B cell
proliferates + differentiates into plasma cells which secrete antibodies
which Ab are secreted in the primary response?
IgM
what can IgM class switch into in the primary response?
IgG
where are long lived plasma cells stored?
bone marrow
which Ab are produced in the secondary response?
IgG, IgE, IgA
which has a higher Ab affinity; primary or secondary response?
Secondary
Describe the B cell receptor complex
- Ig in membrane
- Heterodimer; Ig-alpha + Ig-beta
- Immunoreceptor Tyrosine-based Activation Motifs tails (ITAM tails)
what is the function of the B cell receptor complex
Attaches pathogen to stimulate B cell activation
what reaction takes place in the B cell for activation?
tyrosine phosphorylation
name 2 other ways B cells are activated - other than the epitope of the pathogen?
- cd3 attaching to CR2 receptor
2. PAMPs attaching to TLR
what causes B cell differentiation?
cytokines
4 different cells B cell differentiates into and their roles
- Plasma cell = secrete Ab IgM
- IgG-expressing cell = secrete IgG
- high affinity IgG expressing cell = secrete high affinity IgG
- memory B cell
what is a T helper cell?
Thymus helper cell
which B cells are involved in T-dependent antibody response?
Follicular B cell
which B cells are involved in T-independent antibody response?
b1 cells, marginal zone B cells
what attaches to IgM antibodies on B cell in the T-dependent response?
protein antigens
what attaches to IgM antibodies on B cell in the T-independent response?
non-protein antigens (polysaccharides, glycolipids, nucleic acids)
the helper t cell activates the B cell in the T-dependent response. What activates the B cell in the T-independent response?
microbe (epitope, PAMPs) and complement
what Ab does isotype switching produce in T-dependent?
high affinity - IgG,E,A
is there class switching in T-independent response? if s which Ab are involved?
a little bit - IgM to IgG - but low affinity
2 cells produced in T-dependnent response?
memory b cell and long lived plasma cells
what 3 things cause Ab isotype switching
- cytokines
- receptors expressed by B cells
- CD40 ligand
what stimulates IgG production (isotype switching)?
Various Interleukin
what stimulates IgE production (isotype switching)?
IL-4
what stimulates IgA production (isotype switching)?
cytokines which are produced in mucosal tissue - such as transforming growth factor Beta TGF-b and B-cell activating factor BAFF)
principal effector function of IgM
complement
principal effector function of IgG (3)
- Fc-receptor dependent phagocytosis
- complement
- Neonatal immunity
principal effector function of IgE (2)
- immunity against helminths
2. mast cell degranulation (immediate hypersensitivity)
principal effector function of IgA
mucosal immunity
Difference in y-globulin in normal pt and immunised pt
immunised will have higher y-globulin level in blood
why is inactivation of B cell needed?
- pathogen killed
- save energy
- prevent autoimmune disease
in b cell inactivation, what receptor does the Secreted Ab attach to?
Fc receptor
when the Ab attaches to the Fc receptor what occurs to inactivate the B cell?
ITIM inactivates ITAM - stops signal
name 6 Ab effector functions - state which 3 are caused by compliment
- Neutralisation
- opsonisation + phagocytosis
- ADCC (antibody-dependent cellular cytotoxicity)
complement - cell lysis
- inflammation
- phagocytosis of opsonised microbes with C3b
which fragment of an Ab has the ag binding site?
fab fragment
which part of the Ab is involved in isotype switching and why?
fc region - has variation in AA sequence
Give an example of a type of antibody assay which uses Ab as reagents to bind to the Fc region?
ELISA - enzyme linked immunosorbent assay
4 ways in which Ab act as adaptor molecules?
- activate complement
- activate other cells
- attach to pathogens to allow phagocytosis via recognition killing
- activate the cell
what are Ab secreted into?
blood - systemic circulation
which Ab effector function is not isotype and Fc dependent?
Neutralisation
3 ways in which neutralisation stops infection
when Ab attaches to pathogen:
- pathogen cannot pass through epithelia - too large
- pathogens cannot bind to body cells
- block exotoxin
explain opsonisation and phagocytosis in steps
- Ab attaches to Fc receptor on cell
- Epitope attaches to binding site on Ab
- Fc receptor sends signals into the cell
- stimulates phagocytosis
- Cell killed - ROS, NO, proteolytic enzymes
why is agglutination helpful? which Ab is most useful for this and why?
limits activity of pathogen, IgM - lots of Ag binding sites
which Ab involved in opsonisation and phagocytosis?
IgG
describe ADCC
- IgG attaches to epitope
- IgG fc region attaches to Cd16 Fc receptor on Natural killer cells
- NK cells secrete perforin to kill cell
How and why can Ab be used to treat cancer by the means of ADCC?
Ab attach to tumour cells - NK kill.
Tumour cells express more receptors or may have a mutation which will allow Ab to attach.
where are complement proteins produced?
liver
3 types of complement proteins
- 3 x C1 + C2-C9
- Factor B+D
- regulatory proteins
what are the 3 different complement pathways
classical, lectin, alternative
what is the classical comp pathway activated by?
IgM/IgG attaching to Ag
what is the lectin comp pathway activated by?
MBP attaching to mannose residues on microbial cell surface
what is the altenative comp pathway activated by?
microbial cell surface
Describe the steps in which C4 is activated in the classical complement pathway
- Ag attaches to IgG/IgM
- conformational change in Fc region
- Fc region binds to C1q
- C1r activation
- C1s activation
- C1s activates C4
Describe the steps in which C4 is activated in the lectin complement pathway
- serum MBP binds to MBP associated protease (MASP)
2. MBP:MASP complex activates C4
Classical : what attaches on top of C4b ?
C2
what cleaves C2 ?
i) classical
ii) lectin
i) C1s
ii) MBP:MASP complex
what does C3 convertase consist of in…
i) classical
ii) lectin
iii) alternative
i) C4b:C2b
ii) C4b:C2b
iii) Bb:C3b
what does C5 convertase consist of in…
i) classical + lectin
ii) alternative
i) C4b:C2b:C3b
ii) C3b: Bb:C3b
in all complement pathways, what binds to C6?
C5b
which complement pathway is part of the innate system
alternative
Alternative comp: why is c3b not broken down?
it attaches to Factor B
Alternative comp: how is factor B cleaved?
Factor D
Alternative comp: which complex binds to the pathogen membrane?
C5 convertase or C3b:Bb:C3b
describe steps in formation of MAC
- C5b, C6, C7 attach to membrabe (via C7)
- C8 attaches
- C9 attaches
- All 1-16 molecules of C9 bind to membrane to form a pore
Other function of C3b
acts as opsonin to attach to receptors on neutrophils, macrophages and monocytes to stimulate phagocytosis
What complement proteins cause inflammation of mast cells and capillary endothelial cells?
C3a, C4a, C5a
function of C5a
chemoattractant of neutophils, monocytes, eosinophils
what 2 things regulate complement?
- unstable active proteins
2. regulatory proteins
which Ig is involed in mast cell degranulation?
IgE
Briefly describe steps in mast cell degranulation
- IgE attaches to helminths
- IgE Fc region attaches to Fc receptor on eosinophils
- TH2 cells release IL-5
- IL-5 stimulates degranulation process- release of toxins (histamine, heparin)
- parasites are killed
which specific site is IgA produced?
plasma cells in lamina propria of GI and resp tracts
explain neonatal immunity in
a) foetus
b) baby
a) IgG transported across placenta
b) IgA transported in colostrum/milk through gut
3 mechanisms of immune evasion
- antigenic variation
- inhibition of complement
- coating of hyaluorinc acid
which type of B cells recognise antigens but dont secrete Ab?
Naive B lymphocytes
which 2 Ab are inserted on naive B cells?
IgM and IgD
what do B1 cells respond to?
non-protein Ag in mucosal tissue and peritoneum
what do marginal zone B cells respond to?
polysaccharides and lipid antigens
function of IgM antibodies (2)
- clear apoptotic cells
2. protect against bacterial infection
where are memory B cells stored?
blood, mucosal tissues
which Ig is involved in B cell inactivation?
IgG
what allows the transportation of IgG through the placenta?
FcRn
name 2 regulatory proteins of complement
- plasma - C1 inhibitor
2. Decay accelerating factor (DAF)
function of c1
inhibits C1r and C1s serine protease activity
function of DAF
Inhibits c3 convertase formation