Lecture 4a

Edward H Sugita

Immunology & Disease

Antigen, the initiator of

the immune system

8a

Introduction

Antigen / Ag = molecules to which Antibodies / Abs bind.

Ag = Antibody generators
Ab mol do not bind to the whole of an infectious agent
each Ab mol binds to one of many mols on the microorganisms surface
each Ab is specific for a particular Ag
different Abs will bind to different Ags
a particular Ag specifically induces the production of the Abs which can bind to it
each Ab binds to a particular part of the Ag called an antigenic determinant or
epitope
a particular Ag can have several different epitopes
or may have several identical epitopes.

foreign mols which generate Abs

antigen

antibody

antigenic determinants / epitopes

the epitopes on one Ag are usually different from those on another

Ag1

recognition

Ag2

recognition

some Ags (Ag3) have repeated epitopes

Ag3

recognition

epitopes are molecular shapes

recognized by the Abs and cells
of the adaptive IS
each cell recognizes one epitope
rather the whole Ag

even simple microorganisms

have many different Ags

8a

Antigen
a foreign substance which induce a detectable immune response when introduce to the body (
Immunogen)

platelets

T-dth

CMI

T-cytotoxic

eosinophil

Immune Reaction
T-helper

neutrophil

Ag

Tolerant
T-suppressor

basophil

Ab (specific)

elicitation depends on the .

way the Ag is presented to
the lymphocytes

B cells
Mast cell
Plasma cell

monocyte
macrophage

3rd population cells

Tolerance: a state of specific immunological unresponsiveness.

8a

Antigenic determinants

c.h

-large molecule but only restricted portions are involved in actual binding with Ab combining site
-determinant area of specificity on Ag molecule varies with size and chemical complexicity
minimum value = valence estimated on the basis of the
n
number of Ab mol bound per mol Ag
e
- 5 Ag determinants for 42.000 MW albumin
- 40 Ag determinants for 700.000 MW thyroglobulin

Haptens

-substances non-immunogenic but can react with Ab of appropiate

specificity
-usually small molecules
Immunogenicity !
Hapten: A small mole which can act as an epitope but which is
incapable by itself of eliciting an Ab response.

Carier

- protein linked to a hapten

- has a set of native / integral determinants + the new determinants
introduced by the conjugated haptens

c.p
Hapten

Carrier: An immunogenic mol or part of a mol which is recognized

by T cells in an Ab response.
a mol which renders a hapten linked to it, able to stimulate Ab production

8a

Epitopes

the simplest form of an antigenic determinant present on a complex antigenic

molecule

Cross reaction

the reaction of an antibody with an antigen other than the one that induced
its formation
X-reaction = The reaction of an Ab directed against one Ag with a 2nd Ag.
This occurs because the 2 Ags possess epitopes in common.

Cross reacting Ag

a type of tumor Ag present on all tumors induced by the same or a similar

carcinogen
Immunodominant : describing the epitope on a mol that
provokes the most intense IR

Size and localization of Ag determinants

- Ab complementary is directed against limited parts of the Ag molecule

Ag determinant is of the order of 4-6 AA or sugar residue

8a

Ab combining site

Antigenic determinant group

Ab subsite
Subunit determinant: AA in peptide chain / Sugar in saccharide chain
Cardinal factor in determinants selection
Evokes Tyr specific AbEvokes Ala specific Ab
L-Glutamic acid

Poly DL Ala
Polylysine backbone

L-Tyr
8a

Immunodominance
the AA subunit of a determinant contributes unequally to bind Ab, the degree
of the influence of the reactivity is a measure of immunodominance of the
Component

Immunogenicity:

the property of a substance making it capable of inducing a detectable immune

response immunogen & antigen
Immunogenicity: The ability of a mol to elicit an IR

Characters for immunogenicity:

* immnogenicity is not an inherent property of a molecule
* immunogenicity is dependent on the systems condition Ag, mode of immunization, immunized organism, sensitivity of the method to detect the
response. Capable to induce cellular immunity mediated by T cell

Conditions for immunogenicity:

Foreigness, Molecular size, Chemical complexity, Genetic constitution of
the living target, Method of Ag administration

Chemical nature of immunogens:

- Macromolecule proteins
- Polysaccharides, Synthetic polypeptides, Synthetic polymers
- Ab which react with Nucleic Acid (nucleoprotein immunization)
8a

Immunogenic determinants:
Immunogens
: normally, large molecule
Immonogenicity : a function of molecular size and complexicity

Characteristic of immunogen:
- Capable to induce cellular immunity mediated by T cell
- Possess at least 2 determinants in order to stimulate Ab formation by B cell

Haptens and carriers

to obtain the optimum secondary response to an antigenic determinant which is not immunogenic by itself (eg hapten), it is necessary to immunize the subject with the same
Ag in both the primary and secondary challenge
it is not sufficient that the Ag share a common antigenic determinant recognized
by the B cells
he determinant must also be attached to the same carrier molecule (= the carrier effect).
this implies that the cells involved in making the
Ab response recognize at least 2 parts of the Ag

8a

The carrier effect

3 groups of mice were immunized (primary Ag) with DNP-BSA (dinitrophenylated bovine serum albumin) and rechallenged (secondary Ag) with either
DNP-BSA, BSA or DNP-OA (dinitrophenylated ovalbumin)
measure
primary Ag
DNP BSA

secondary Ag

(rechallenged)

Ab response to DNP
(=hapten)

DNP BSA

++++
DNP BSA

BSA

optimal Ab response to
DNP (obtained with 2x
immunization with the
same Ag

3 groups
DNP BSA

DNP OA

BSA acts as a specific carrier for the Ab response to DNP

8a

Carrier priming

lymphocyte priming to the carier is required when there was a previous

priming to the carier alone or receives spleen cells from donor primed to
that carier circumvented in the response to hapten-carrier conjugate
3 groups of X-irradiated mice were reconstituted with the Ag-primed
spleen cells and challenged with Ag
experiment
DNP-BSA

OA

spleen cell transfer

DNP-BSA

groups of mice
strong Ab response

DNP-OA
2

++++

DNP-OA
3

Ab response tp DNP

weak Ab response
(demonstrating the carrier effect)

++++

Ags (challengers)
received cells primed to both
DNP-BSA and to OA, then
challenged with DNP-OA
strong response to DNP
demonstrating that the re- .
quirement for carier priming can be circumvented
by supplying carrier-primprimed spleen cells

8a

T cell recognition of carier (OA)

experiment
OA

DNP-BSA
spleen cell transfer

an X-irradiated mouse, if reconstituted with spleen cells

primed to the OA carrier to
DNP-BSA will, on subsequent
challenge with DNP-OA produce a normal Ab response to
DNP
1) this response is unaffected if
the OA-primed cells were previously treated with normal serum and complement

1)

complement and
anti-
normal serum
DNP-OA

assay Ab response to DNP

result of anti-DNP response

2) However, if the OA-primed

cells were treated with anti-T
cell serum (anti-) and complement, which destroys T
cells, the anti-DNP response
is abrogated

response

normal serum

anti-

indicating that T cells recognize the carrier

and give help to the hapten-primed B cells

removing T cells from the carrier-primed donor spleen cells, shows that the T cells are
responsible for recognizing carrier determinant on the Ag and delivering help to the B
cells which recognized the hapten
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In these 2 experiments:
* to determine their immunological activity: Ag-primed cells are injected into irradiated recipient mice
act as living test tubes
detailed analysis of the T cells responsible for this helper effect in the mouse shows
that they carry Ly1 surface markers but do not carry Ly2 or Ly3 markers
(=Ly1+(23)-

Overview of the IR
1.

2.

antigen

APC

3.

help
TH

proliferation

AFC

T cells recognized separate determinants on the Ag to those recognized by the B cells but they deliver help to the appropriate B cells
B cells are stimulated to differentiate and divide into AFCs (Ab Forming Cells)

APC
AFC
Ab secretion

1. Ag is processed by APC & Ag 2. TH cell recognize the Ag via their 3. B cells are stimulated to proliferate
and divide into AFC (Ab Forming
Fragment is retained on the
surface R and provide help to
surface of APC
Cell) which secrete Ab
B cell. B by their surface R (Ig)
presented in a highly
immunogenic form to
TH cells and B cells

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2 types of signal are required to activate a B cell:

1. Ag interacting with B cell Ig-Rs and X-linking them,
2. A second signal (s) from TH cells.
A variety of T cell stimuli are needed for optimal
growth and differentiation of B cells

T-dep and T-indep Ags

Ag that is capable of activating B cell to
produce Ab independently of T cell help
the response to an Ag depends on both
T cell & B cell recognizing the Ag

* large polymeric molecules with repeating

Ag determinant
* many possess the ability, at high C, to activate B cell clones other than those specific
for that Ag = polyclonal B cell activation
at a lower concentration they activate only those B cells with specific Ag Rs for
them

many of the T-indep Ags are particularly resistant to degradation

8a

T-indep Ags.
the major common properties of some of the main T-indep Ags
antigen

polymeric

polyclonal
activation

resistance to
degradation

+++

Ficoll

+++

+++

dextran

++

++

levan

++

++

poly-D amino acids

+++

+++

polymeric bacterial
flagellin

++

++

lipopolysaccharide
(LPS)

T-dep Ags.

poly-L-amino acids and monomeric bacterial flagellin

the primary Ab responses to T-indep Ags in vitro are generally weaker than
the responses to T-dep Ags and that they peak fractionally earlier

8a

Comparison of the primary IRs to T-dep and T-indep Ags

the response to T-indep Ags is weaker than to T-dep Ags and peaks earlier
* the primary response as assessed by plaque forming cell assay, to a T dep Ag and a T-indep Ag
primary antigen
plaque 2000
forming
cell response
per 106 cells 1000
0
0

9 10 11 12
days

far stronger and

appears earlier

* the secondary response in vitro also differs between T-dep and T-indep Ags
resembles the primary response,
by being weak and almost entirely confined to IgM production
T-indep Ags do not usually induce the maturation of response involving
class switching to IgG and increase in affinity seen with T-dep Ags
memory induction is also relatively poor
8a

Comparison of the secondary IRs to T-dep and T-indep Ags

secondary antigen
plaque 5000
forming
cell response 4000
per 106 cells 3000
2000
1000
0

9 10 11 12
days

the IgM PFC (Plaque Forming Cell) response is similar for T-indep
and T-dep Ags but only T-dep Ags produce an IgG PFC response

Affinity maturation

Affinity maturation involves the selective expansion of clones of high affinity

Ab producing cells since lymphocytes do not change the specificity of their AgRs. Abs produced in a secondary response to a T-dep Ags have a higher
average affinity than those produced in the primary response
associates with the switch from IgM to IgG production
no affinity maturation of IgM response and the degree of affinity maturation
is dependent on Ag dose administered

8a

Affinity maturation

the average affinity of the IgM and IgG Ab responses folowing primary and secondary
challenge with a T-dep Ag
primary Ag
mean Ab
affinity (L/M)

low Ag does produce higher affinity

Ig than high Ag does

secondary Ag

10-11

IgG-low [Ag]

10-9
10-7

IgG-high [Ag]

10-5

IgM

the affinity maturation of the IgG

response depends on the dose
of the Ag
the affinity of the IgM response
is constant throughout

8 9
days

low Ag concentrations: only B cells with high affinity Rs bind the Ag and are triggered to divide
and differentiate
high Ag concentrations: there is sufficient to bind and trigger both high and low affinity B cells

8a

Postulated mechanism of affinity maturation

* low Ag doses bind to, and trigger only those B cells with high affinity Rs
* high Ag doses allow triggering of more B cell clones and therefore produce
Ab responses with lower average affinity
Ag
(low dose)

B cells Ag-Rs
10-11 L/M

B cells
activated

antiserum

high affinity

Ag
(high dose)

B cells Ag-Rs

B cells
activated

antiserum

10-11 L/M

10-10 L/M

10-10 L/M

10--9 L/M

10--9 L/M

10--8 L/M

10--8 L/M

10--7 L/M

10--7 L/M

moderate affinity

Ag presentation
B and T cells are normally required for responses to T-dep Ags, which constitute the majority of the Ags encountering IS
Ag encountering the IS is presented to the lymphocytes
which react to it
in vivo this phase is complicated by the structural
organization of the lymphoid tissue
8a

* Ag from the periphery moves via the lymphatics to the local lymph nodes.
the Ag may be carried free in solution or it may be carried
on the surface of the APCs

on reaching the lymph node different Ags selectively

move to different areas and are thus capable of stimulating different populations of lymphocytes

some Ags remain within the lymph node for long periods providing a constant source of antigenic stimulation while others are
fairly rapidly degraded or lost via the efferent lymphatics

Localization of Ag in lymph nodes

area

Ag

persistence

subcapsular
(marginal) sinus

marginal zone MOs

polysccharides Ficoll (T-indep)

++++

follicles and
B cell areas

dendritic cells

Ag/Ab Complement
fixing complexes

medulla

classical MOs

most Ags

T cell areas

interdigitating cells

skin sensitizing Ags

++

efferent

T
T&B

afferent

APC

+++

8a

schematic lymph node showing afferent and efferent lymphatics follicles, outer cortical B cells
areas and the paracortical T cell area
lymphatic folicle

Ag/Ab complex
FcR

outer cortical B cell area

para-cortical T cell area
different APCs predominate
in these areas, although the
demarcation is not absolute

taken up

C3R

efferent

T
T&B

FDC

may persist for months or years

= with recirculating MOs (classIcal MO; medulla) which last
only for a few days or weeks

the different APCs selectively take afferent

up different types of Ag which then
persist on the sur face of the cells
for variable periods
circulating veiled cells (Langerhans cells) thought to arise from skin change their
morphology to become interdigitating cells within the secondary lymph node
both these and the dendritic cells (skins MO) have long processes in intimate
contact with lymphocytes
the persistence of the different Ags varies between species
the major APCs (based on Abs production): follicular dendritic cells
MOs and marginal zone MOs of the skin appear to be more important presenting Ag to T
cells involved in delayed hypersensitivity reactions
8a

the presentation of Ag to responding lymphocytes is MHC restricted

thus, responding B cells only recognize Ag on the MO surface provided that both the B
cell and the MO share determinants of the HLA class 2 mol

Ag presentation by Macrophage

presentation of Ag by MO to T cells is MHC restricted individually or as a combination of determinants (lymphocyte will recognizes it as altered self
independent recognition

associate recognition

T cell

T cell

Ag-R
Ag

Ia-R

Rs on the lymphocytes are responsible

Ag/Ia-R for recognition of MHC products on the

Ag/Ia

Ia
MO

it is not known whether the T cell recognizes

Ag and MHC independently (dual recogninition)

MO

MO and thus for the MHC restriction

observed in Ag presentation
the exact MHC restriction observed is deare I nitially educated to discriminate self
from non-self during their development in
the thymus by association with cells bearing
self MHCAgs

evidence suggests thatAg MOs has been extensively degraded and occur in the
form of small highly immunogenic peptides which are recognized in association
with the HLA class 2 region gene products
8a

removal of surface Ag from MOs does not lead

to replenishment from an intracellular Ag pool
phagocytosis of Ag and Ag presentation are 2 distinct functions
MOs lacking MHC 1 region products are limited in function to phagocytsis

Clonal expansion
T & B cells derived from a single common precursor stem cell
common
precursor
proliferation
maturation
T lineage

B lineage

subset

the binding of Ag to particular

lymphocytes is not necessary
sufficient to produce an IR

the repertoire of B and T cells is generated before contact with Ag to

produce a range of cells with different Ag binding specificities

subset

antigenic
stimulation

antigen specific clone

subsequent contact with Ag induces selective expansion of Ag specific clones

in this sense the Ag selects the
particular lymphocytes which
will be evolved in the response
against it

8a

Mechanisms of cell cooperation

the crucial event which determines the Ag specificity of an IR is the triggering
of particular clones of lymphocytes via their Rs for Ag
B cells responding to a T-dep Ag require T cell help to produce
an optimum response and in these IRs the T dep Ig is recognized effectively via two different antigenic determinants
IS will have greater specificity in discriminating foreign Ag
effective cooperation between the lymphocytes recognizing the different determinants is essential
mechanism of B cell activation could be studied with T ind Ags
T-ind Ags have the inherent ability to deliver all necessary activating signals to B
cells Properties of the T-ind Ags suggest a number of ways in which they could
themselves supply the 2nd signal

8a

2 mechanisms of B cell activation by T ind Ags

R X-linking

mitogenic action

Ag

polymeric Ags (Ag) Xlink the cell surface

Ig of the B cells

Ag

Ig
signal
B cell

Ig

Ags with inherent mitogenic

activity are bound to the B
mitogen-R
cells via the surface Ig and
signal activation through a
signal
postulated R on the B cell
B cell

1. T ind Ags are polymeric can X-linked the B cells Ag-Rs

2. most T ind Ags are mitogenic, it is possible that 2nd signal is delivered via the B cells
mitogen R. (Ag-R serves to focus the mitogen onto the surface of the particular B cell.
however mitogen-Rs of B have not yet been identified, and this effect may be due to
IL-1 released from MOs)
3. some of the T ind Ags fix comlement (C) by the classical or alternative pathways
(B cells have C-Rs, 2nd signal may be delivered in this way)
these hypothesis are not mutually exclusive. It is possible that
different mechanisms are valid for different Ags or B cells
the way in which T cells activate B cell shows evidence that some forms of
interaction may be mediated by Ag specific T cell helper factors.(Released
from T cells and subse-quently induce B cell activation

8a

2 mechanisms of Ag spec B cell activation by T-dep Ags

helper factors (TH) speT cell factors
cific for carrier determinant on the Ag and
Ia mols bind to the Ag APC
and delivers a help sigTH factor
nal, which in conjunchelp
tion with the signal Ag
Ia
from the B cells Ag R
Ig
triggers activation
signal
B cell

cellular interaction
T cell

T and B cells bind Ag via

their Rs (TR and Ig) and
help is delivered directly
to B cell

Ia-R
Ag

TR
Ia

Ig

help

this requires cell / cell

contact and recognition
of Ia

signal
B cell

T cell factors
the evidence for the existence of Ag specific T helper factors come from culture
systems in which the Ag-stimulated TH cells are separated from the target B
cells by a membrane permeable to mols, but impermeable to cells

8a

Demonstration of Ag induced T cell helper factors.

Cultures were set up containing DNP-primed (DNP) B cells and:

all cultures contain

KLH-DNP

1) KLH-primed T cells
2) KLH-primed T cells separated from B cells by a protein permeable membrane
3) CGG (Chicken Glob) primed T cells similarly separated from the B cells
the number of activated T cells initially
introduced into the culture is varied &
the B cell response depends in this

the help given to the B cells was

measured by plaque forming cell
(PFC) assay
IgM-PFC
response 2000
to DNP

1
2

DNP+ + KLH+
B
T
DNP+ KLH+
B
T

1000

the response is unaffected by preventing

direct cell/cell contact, implying the presence of helper factors

DNP+ CGG+
T
B

the effect of Ag specificT cells primed to

CGG cannot substitute for KLH-primed
0
104
105
107 cell culture
106
cells
of activated T cells system
the eventual decline in response may
be due to TS cells
Separation of B and T cells does not affect cooperation.
3

there is an optimum ratio of T:B cells to produce a maximum response

8a

* TH factors were shown not to be genetically restricted (i.e recognizing Ia Ags on

their targets) but like TH cells, they are restricted
* there is also evidence for the action of Ag non-specific T cell helper factors
= factors released during T cell activation and act on

the factors can be demonstrated in supernaall clones of B cells

tants from MLC consisting of all allogeneic
cells. in this system T cells are stimulated by contact with allogeneic lymphocytes

Non-specific T cell helper factors

a nude mouse (= mouse lacking T cells) has its spleen cells removed
2 cultures of these spleen cells are set up:
nude

spleen cells
SRBC

sspleen cells +
sheep red blood cells
(SRBCs; = a T-dep Ag)
the spleen cells are unable
to produce an Ab response

SRBC

spleen cells

supernatant
24 hr MLC

culture 1

culture 2

+++

Ab response to SRBC

the cells stimulated in the

MLC participates in a CM IR

spleen cells + SRBCs + the supernatant

of MLC produced by cultivating spleen
cells from 2 different mouse strains for
24 hours
the supernatant stimulates the spleen cells
to produce Ab against the SRBCs
Conclusion: the supernatant contains non-specific
T cell helper factors

8a

only augment the response to some Ags

* the T cell factors produced are not Ag specific, ie, a T cell triggered by Ag X produces
factors which can help a B cell produce Ab to Ag Y
particular B cells clones may be selectively stimulated by n on-specific factors due to their
close proximity to T cells releasing the factors (might occur in an Ag stimulated lymph node)

other Ags still require Ag specific help before an Ab response is generated

thus, Ab to particulate SRBC is enhanced by non-specific factors alone whereas
the response to most protein Ags is not
helper factor that interacts directly with B cells,
can have affinity for MOs and other APCs
these factors act initially by binding to the APC before exerting their effect on the
target cell
TS cells may exert their suppressor factors which act
in similar way to the helper factors

8a

The action of T cell helper factors

2.

1.

3.

THF
Ag factor release
Il-1
Ia

APC

T
Ag

T cells encountering Ag on the

APC recognize the Ag through
their Rs (TR) and release Ag
specific helper factors (THF)

THF
Ag

factors bind to the

APCs possibly in
association with
Ag

Ia

B
Ig

a B cell encountering the APC is

stimulated by the matrix of Ag
and T helper factor and also possibly by IL-1, release from the activated APC (MO).

the interactions is thought to be MHC restricted

some of the factors carry determinants of The H-2I region
in mice or its equivalent in humans (HLA-D)

8a

Characteristics of factors carrying I-region determinants

the three factors here are genetically restricted factor (GRF) produced by MOs, helper factor
produced by TH cells (carrying the Ly1 marker) and suppresor factor produced by TS cells
(carrying the Ly2, Ly3 marker)
V
GRF

helper
factor

supressor
factor

source

macrophage

Ly1+ T cell

Ly23+ T cell

target

Ly1+
Ly123+ T cell

macrophage
B cell

T cell

effect

induces
TH cells

induces
B cells

suppresses
T cells

55 75K

55 80K

55 80K

+
I-J

Ag specificity
mol. wt.

this characteristic
refers to their reactivity with antisera

serology V/C
MHC 1

I-A

I-A (I-J)

MHC restriction

+ or

these antisera detect both V and C regions (= with V & C

regions of Ig; but analogous) on T cell factors but not
on MO factors
the factors also share determinants in
common with MHC-subregion mols

+ or

MHC restriction refers to the possible

requirement for the cells interacting
through these factors to be matched
with respect to the MHC mols diplayed
on their surfaces
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Ag nonspecific factors

previously these factors had been defined by their effect in different assay systems A single factor with several biological actions could be known by various names
these factors appear to fall into groups each with their own properties

IL-1 ( = LAF, Lymphocyte Activating Factor) acts during Ag

priming of lymphocytes
IL-2 (= TCGF, T Cell Growth Factor)
is essential for long term growth of
activated T cells
TRF (= T cell Replacing Factor)
is required for optimal B cell
differentiation in response to Ag
BCGF (= B Cell Growth Factor) is
a signal for B cell activation

source

target

effect

Interleukin 1
(LAF)

macrophage
& other cells

T & B cells

promotes
multiplication
& activation

Interleukin 2
(TCGF)

Ly1+.23- T cell
in presence of
macrophage

T cells

proliferation of
activated T cells

T cell replacing
factor (TRF)

Ly1+.23- T cell
in presence of
macrophage

B cells

B cells
differentiation

B cell growth
factor (BCGF)

Ly1+.23- T cell
in presence of
macrophage

B cells

synergizes
with IL-1 in
B cells activation

TRF and BCGF are really groups of mols and not necessary single entities

8a

Adjuvants
= substances which non-specifically enhance the IR to Ag.
in certain circumstances it is possible to completely change the mode
of response (Tolerance vs Immunity; by administering Ag together
with adjuvant
it is possible to break self tolerance to a large number of self Ags by injecting them into the host animal in an appropriate adjuvant
Most frequently used adjuvant:
- water-in-oil (w/o) emulsions with the Ag in the aqueous phase
eg. Freunds incomplete adjuvant

Effect of adjuvants on the Ab rsponse following injection of Ag (KLH).

Ab responses toAgs in adjuvants are :
Keyhole Limpet Haemocyanin
-greater
-more prolonged
- frequently consist of different classes to the response obtained without
adjuvant
Ag
primary
Ab
response

the response is greater

and more prolonged

KLH + adjuvant

KLH

8
9
weeks

8a

Mechanism of adjuvant:
1. the Ag in emulsion is resistant to dispersal, and it therefore acts as a depot for
longed Ag stimulation
pro2. microbial products activate MOs thus leading to the production of Ag non-specific
factors which will enhance the response
3. the Ag somehow bypasses the requirement for the T cell signals in B cell differentiation leading to maturation of the response with class switching

Summary:
Ab response is a coordinated reaction of B cells, T cells and APCs, communicating either directly or via Ag specific and non-specific factors.
communication between the cells involves products of the MHC and other
gene products
failure to produce a properly coordinated response may lead to tolerance

8a

Hypothesis to explain the T cell recognition of

the MHC class 2 restricted cells (eg TH) possess a molecule, T4, which recognizes
Ag
MHC protein and the Ag

Tr, T cell receptor, recognizes

the MHC protein and the Ag

the activation signal is transmitted to the T cell via the T3

peptide, which is associated with Tr (T cell receptor)
T
T4

T
T3

Tr

MHC
class 2

Ag

T8
MHC
class 1

T3

Tr
Ag

antigen presenting cell

APC

class 1 restricted cells have a molecule,

T8, which recognizes MHC class 1 Ags
MHC molecules(both classes) have 4 globular domains and the T4 and T8 molecule
recognize different domains to those recognized by the T cell receptor
8a

Chief characteristics of different

APC
characteristics

antigen presenting cell

APC
APC
B cells do not need to recognize Ag in association with
MHC but can be stimulated by
free Ag or complexed Ag
which have bound to APCs
with Fc and C3 receptors

marginal zone
macrophages

Fc/C
receptor

follicular
dendritic cells
dendritic cells

these cells which present Ag

to T cells have class 2 MHC
molecules

monocytes/
macrophages
Langerhans cell

class 2
MHC ex- present to
pression

phagocytosis

+
+

+
+

+/

T
T&B

8a

Activation of T cells by APC

the activation of T cells is thought to occur in 3 phases
2) this in association with Ag stimulation induces IL-2-Rs on 3) which drives Ag activated
cells into proliferation
the T cells (possibly a separate
1) following binding the T cell to subset (3) from that which inthe Ag-presenting cell (APC) an duced L-1 production) and stiunknown factor (?) from the T mulates T cells to release IL-2
IL-1)
proliferation

T
?

MHC class 2

IL-2

T
IL-2-R

IL-1

IL-1

Ag

antigen presenting cell

2

8a

Cell mediated
4cytotoxicity
different types of cell binding in cell-mediated cytotoxicity
effector cells
TC
MHC/Ag
receptor
Ag

MHC

NK
NK-R

FC-R

IgG
NK
determinant Ag

cytotoxic
cell

surface
glycoproteins

lectin

4
(experimental)

target cells
(1) Cytotoxic cell (TC) bind (2) NK cells recognize (3) K cells recognize (4) experimentally glycoproteins on the surface of eftheir target which recogthe Fc of IgG Ab
determinants exfector and target can be
nizies Ag and MHC depressed on neoplasbound to Ag on
cross-linked
by lectins
terminants
tic cells
the target surface

8a

Thank You

8a