Tolerance and

Tolerance and

regulation

regulation

of immune response.

of immune response.

Consequences in

Consequences in

immunopathology.

immunopathology.

Joanna Makowska

Monika Jędrzejczak

Cellular response

Cellular response

Time from exposition to allergen

T-

d

e

p

e

n

d

e

n

t

re

s

p

o

n

s

e

i

n

te

n

s

it

y

limphocytes T expansion

limphocytes T activation

Apoptosis

activation

Humoral response - IgE

Humoral response - IgE

synthesis

synthesis

B

Y

Th2

Ag

B

Y

CD4

TCR

CD40L

IL4

IL13

MC

IL4

APC

MHC II

CD21 IL4R

CD21

FcERII

CD40

IgM

IgE

Plazmocyt

Y

Y

Y

Y

Y

Y

Y

B

B

B

B

Th

CD40

CD40L

B

Activation

proliferation and

differatiation

HUMORAL
RESPONSE

Il-4

IL-2

IL-5

Cells cooperation in immune

Cells cooperation in immune

response

response



Humoral

Humoral

Lymph Th2 (MHC II)

Lymph Th2 (MHC II)

Surface molecules

Surface molecules

Cytokines (mostly

Cytokines (mostly

Th2)

Th2)



Cellular

Cellular

Lymph Th1

Lymph Th1

Macrofages

Macrofages

Lymph cytotoxic

Lymph cytotoxic

Immunological reaction

Immunological reaction

to antigens has ability to

to antigens has ability to

self-limitation and

self-limitation and

disappears in parallel

disappears in parallel

with antigen elimination

with antigen elimination

and immunological

and immunological

system comes back

system comes back

to its balance.

to its balance.

Regulation

Regulation



Costimulating molecules

Costimulating molecules



Anti-idiotypic antibodies

Anti-idiotypic antibodies



Soluble cytokines receptors

Soluble cytokines receptors



T reg lymphocytes

T reg lymphocytes

CELLULAR RESPONSE

CELLULAR RESPONSE



Against intracellular microorganisms

Against intracellular microorganisms



Against neoplasmatic cells

Against neoplasmatic cells



Th cytokines activity

Th cytokines activity



Tc activity (mostly CD8+, MHC I)

Tc activity (mostly CD8+, MHC I)

CELLULAR RESPONSE

CELLULAR RESPONSE



Develops 24-48 h = late response

Develops 24-48 h = late response



Early response – 2 h

Early response – 2 h

(many cells –

(many cells –

lymphocytes,

lymphocytes,

macrofages

macrofages

produce factors –

produce factors –

RANTES, MCP-1, MCP-2, MIP-

RANTES, MCP-1, MCP-2, MIP-

1

1

α

α

inducing histamine release by mast

inducing histamine release by mast

cells)

cells)



Response amplification – cellular

Response amplification – cellular

infiltration

infiltration

Immature lymphocyte T

APC

CD28

CD80/CD86

For lymphocyte T activation 2 signals are needed:

 MHCII- antigen-TCR binding

 Costimualtory proteins CD28 and CD80/CD86 binding

TCR

MHCII

antigen

APC

CD28

CD80/CD86

Lymphocyt T produces IL-2 and IL-2 receptor expression appears

IL-2

Immature lymphocyte T

APC

CD80/CD86

Immature lymphocyte T

CD28 expression downregulation on activated lymphocyte T

Immature lymphocyte T

APC

Ligand for CD80/CD86 -

CTLA4

increased expression on activated

lymphocytes T.
This molecule is responsible for inhibitory signal transmition.
Lymphocyte T activation is inhibited.

CD80/CD86

CTLA4

ANERGY

T reg

T reg

Treg constutively produced

Treg induced

• CD4+CD25+

•FOXP3 molecule expression

•CTLA4 expression on cell
surface

•Supression effect by direct
contact

• Activated lymphocytes T
may inhibit unspecificaly

• IL10, TGFβ, IL9 production

Tr1

Tr1

Th3

Th3

•IL10
induction

• high amount
in bowels

•

TGF

TGF

β

β

induction

induction

•

high amount in

bowels

Anti-antibodies

Anti-antibodies

antigen

Antigen appearance in the body

Antibody can also be immunogenic
Giving antibody from one to other organism may produce anti-antibody

antibody

Anti-antibodies

Anti-antibodies



Reumatologic factors

Reumatologic factors



Anti-idiotypic antibody

Anti-idiotypic antibody

Reumatologic factor

Reumatologic factor

Antibody

Antibody

IgM

IgM

(85%)

(85%)

less frequently IgG, IgA or IgE

less frequently IgG, IgA or IgE

against Fc of own

against Fc of own

IgG

IgG

Detectable in serum,

Detectable in serum,

synovial fluid,

synovial fluid,

pleural fluid

pleural fluid

Reumatologic factor

Reumatologic factor

Autoimmunologc diseases – RZS

Acute bacterial, viral infections

Neoplasmatic disorders

Production induced by immunological complexes

Upregulate complement activity and IC removal

Bind to Fc – so bind to antibody with different
specificity

Anti-idiotypic antibody

Anti-idiotypic antibody

antigen

antibody

Ig are produced against antigen

Immunologic response initiation

Anti-idiotypic antibody (Ab2)

Anti-idiotypic antibody (Ab2)

antigen

Anti-idiotypic
antibody

Jerne’a anti-idiotypic network theory

antibody

Within time anti-idiotypic antibody are produced

against Fab

on

antibodies.
Immunological complexes network is build up
(antibody - anti-idiotypic antibody)

Anti-idiotypic antibody

Anti-idiotypic antibody

antigen

Anti-idiotypic
antibody

Jerne’a anti-idiotypic network theory

antibody

Complexes are eliminated by
macrophages

Anti-idiotypic antibody

Anti-idiotypic antibody



Many idiothypic determinant are present in

Many idiothypic determinant are present in

Fab

Fab



Anti-idiotypic antibody may bind to antibody

Anti-idiotypic antibody may bind to antibody

of different classes both soluble and on cell

of different classes both soluble and on cell

surface (BCR, TCR)

surface (BCR, TCR)



1984 – Jerne – Nobel price

1984 – Jerne – Nobel price

Anti-idiotypic antibody

Anti-idiotypic antibody



Present in healthy subjects

Present in healthy subjects



Regulatory function for humoral and

Regulatory function for humoral and

cellular response

cellular response



Depending on:

Depending on:



Concentration

Concentration



Time when they appear

Time when they appear



Other factors like cytokines

Other factors like cytokines

Immunological tolerance

Immunological tolerance

For normal body functioning not only

For normal body functioning not only

effective pathogens and toxin

effective pathogens and toxin

elimination is needed

elimination is needed

but also ability to autoantigens

but also ability to autoantigens

tolerance as well as

tolerance as well as

antigens that are harmless.

antigens that are harmless.

Lack of tolerance leads to severe disorders

Immunological memory

Immunological memory



Ability to quicker and more effective

Ability to quicker and more effective

immunological response after second

immunological response after second

contact with antigen.

contact with antigen.



Positive memory (microorganism

Positive memory (microorganism

disorders)

disorders)



Negative memory (allergy)

Negative memory (allergy)

Immunological memory

Immunological memory

mechanisms

mechanisms



Increasing

Increasing

number of lymphocytes

number of lymphocytes

that can recognise antigen

that can recognise antigen



Lymphocytes with

Lymphocytes with

higher affinity

higher affinity

to

to

antigens

antigens



Survived

Survived

memory lymphocytes

memory lymphocytes

* 90% cells from primary response die in

* 90% cells from primary response die in

apoptosis induced by Apo-1/Fas or cytokines;

apoptosis induced by Apo-1/Fas or cytokines;

* memory cells survive because of increased Bcl-2

* memory cells survive because of increased Bcl-2

expression (antyapoptotic molecule)

expression (antyapoptotic molecule)

How is it possible?

How is it possible?

- hypothesis

- hypothesis

1.

1.

Memory lymphocytes can live for a long time

Memory lymphocytes can live for a long time

2.

2.

Antigen that induce primary immunological

Antigen that induce primary immunological

response is binded for a long time by dendritic

response is binded for a long time by dendritic

cells and can stimulate lyphocytes

cells and can stimulate lyphocytes

3.

3.

Memory lymphocytes are constitutively

Memory lymphocytes are constitutively

activated by cross-reacting antigens, mitogens

activated by cross-reacting antigens, mitogens

and superantigens

and superantigens

The role of nodules dendritic cell

The role of nodules dendritic cell

(FDC) in immunological memory

(FDC) in immunological memory

Y

Y

Y

Y

Y

Y

Y

Y

No immature lymphocytes
activation

Immunological reaction duration
Ig against antibody high concentration
Blocking of antigen binded on FDC surface

Immunological reaction inhibition
Ig downregulation,
antigens presentation – can activate immature lymphocytes B

Lymphocytes stimulation
Antibody production

Y

Y

Y

Memory lymphocytes B

Memory lymphocytes B

compared to immature

compared to immature

lymphocytes B

lymphocytes B



More

More



BCR have higher affinity to antigen

BCR have higher affinity to antigen

(mature Ig affinity – VDJ genes recombination)

(mature Ig affinity – VDJ genes recombination)

usually IgG, IgA, IgE

usually IgG, IgA, IgE





IgM, IgD

IgM, IgD



Have more MHCII

Have more MHCII



Are easier activated

Are easier activated



Live longer – often present in spleen, bone-marrow

Live longer – often present in spleen, bone-marrow

Memory lymphoctes T

Memory lymphoctes T

compared to immature

compared to immature

lymphocytes T

lymphocytes T



Same affinity

Same affinity



High CD45RO expression – phosphatase

High CD45RO expression – phosphatase

responsible for lymhocytes activation

responsible for lymhocytes activation



Adhesion molecules increased expression

Adhesion molecules increased expression



IL-2 receptor expression activation

IL-2 receptor expression activation



Costimulatory molecules role is smaller

Costimulatory molecules role is smaller

comparing to primary response

comparing to primary response



Other circulation: more frequently in

Other circulation: more frequently in

nonlymphatic organs, specially in inflammatory

nonlymphatic organs, specially in inflammatory

places

places

vaccination

Immunologic

Immunologic

al

al

tolerance

tolerance

Unresponsiveness of the immunologic

Unresponsiveness of the immunologic

al

al

system to an antigen that is induced by

system to an antigen that is induced by

previous exposure to that antigen

previous exposure to that antigen

(humoral and cellular)

(humoral and cellular)

.

.

Antigens

Antigens



Tolerogence/

Tolerogence/

tolerogenic

tolerogenic

Induce tolerance

Induce tolerance



Immunogens

Immunogens

generate immunity

generate immunity

Autotolerance

Autotolerance



is a tolerance to own antigens.

is a tolerance to own antigens.



is a part of the normal immune

is a part of the normal immune

system

system

T

T

Immunogen
ic
antigen

Tolerogenic

antigen

T

T

T

Proliferation and
differentiation

T

Deletion (cell death)

Anergy (functional
unresponsiveness)

+

No
respons
e

Immunogen
ic
antigen

Why is it so important?

Why is it so important?



Tolerance to own antigens

Tolerance to own antigens

- we all have the same antigen receptors genes, later expressed in

- we all have the same antigen receptors genes, later expressed in

lymphocytes

lymphocytes

- self antigens are present on the cells and in the circulation

- self antigens are present on the cells and in the circulation

- self/nonself discrimination

- self/nonself discrimination



Foreign antigens may be administered in ways that

Foreign antigens may be administered in ways that

inhibit immune response

inhibit immune response

- immunisation methods to enhance the immunogenicity

- immunisation methods to enhance the immunogenicity



Therapeutic approach for preventing harmful

Therapeutic approach for preventing harmful

immune response

immune response

- organ transplant rejection

- organ transplant rejection

- autoimmune and allergic disorders treatment

- autoimmune and allergic disorders treatment

- tolerance in gene theraphy

- tolerance in gene theraphy

- proteins injection in protein deficienies (factor VIII in hemophiliacs)

- proteins injection in protein deficienies (factor VIII in hemophiliacs)

Mechanisms of tolerance

Mechanisms of tolerance



C

C

lonal

lonal

d

d

eletion

eletion



C

C

lonal

lonal

a

a

nergy

nergy



Autoantygen seqestration

Autoantygen seqestration

- anatomical

- anatomical

- molecular

- molecular



Active supression

Active supression

- anti-idiothypic antibody

- anti-idiothypic antibody

- regulatory lymphocytes

- regulatory lymphocytes

Clonal deletion

Clonal deletion



Process that leads to death

Process that leads to death

of

of

lymphocytes

lymphocytes

capable to autoantigen

capable to autoantigen

recognition

recognition

l

l

y

y

m

m

ph

ph

ocyt

ocyt

es

es

T

T

–

–

in thymus

in thymus

and in

and in

peripheral

peripheral

l

l

y

y

m

m

ph

ph

ocyt

ocyt

es

es

B

B

–

–

in bone marrow

in bone marrow

and

and

in peripheral

in peripheral

Positive selection Negative

Positive selection Negative

selection

selection

4-8- 4+8+

4+8+

4+8+

4+8+

4+8+

4+8+

MHC I

MHCII

No

MHC

binding

Cell death

8+

8+

4+

4+

Epithelium (cortex)

no

autoantigen

recognition

autoatigen

recognition

no

autoantigen

recognition

Cell death

8+

4+

Dendritic cells
Macrophages

Epithelium (core)

Clonal anergy

Clonal anergy



Inactivation of autoreactive lymphocytes

Inactivation of autoreactive lymphocytes

that avoided clonal deletion

that avoided clonal deletion



„

„

second

signal”

is

needed

for

second

signal”

is

needed

for

lymphocytes activation ( CD28 i CD80)

lymphocytes activation ( CD28 i CD80)



Only one signal leads to lymphocyte

Only one signal leads to lymphocyte

anergy – in this situation lymphocyte

anergy – in this situation lymphocyte

can produce some cytokines but can not

can produce some cytokines but can not

proliferate

proliferate

Immature lymphocyte T

APC

CD28

CD80/CD86

TCR

MHCII

antigen

Lack of

II signal leads to anergy

APC

B7

CTLA4

T

The role of costimualting molecules

The role of costimualting molecules

CD28 and CTLA4

CD28 and CTLA4

APC

CD28

B7

T

IL2

Tolerance mechanisms of lymphocytes B

Tolerance mechanisms of lymphocytes B

B

YY

Y

IgM

Polivalent antigens;
peptidoglikans

Clonal deletion

Anergy

Poly IgM binding

Apopotosis

Fagocytosis

B

B

Y Y

Y

Mature
lymphocytes B

B

Y

Y Y

soluble
autoantigens
high concentration

B

Y

IgM
ekspression

B

O

N

E

M

A

R

R

O

W

P

E

R

IP

H

E

R

A

L

S

PA

C

E

AUTO-ANTIGEN

AUTO-ANTIGEN

SEQUESTRATION

SEQUESTRATION



Anatomical

Anatomical



Molecular

Molecular

Molecular sequestration model

Molecular sequestration model

thymus

Th

Th

Lymphocyt that
recognise
„hidden” epitop

„dominating
” epitop

„hidden”
epitop

Virus

IFN γ

Disclosure of

„hidden”

autoantigen

Th

Recognition of

„hidden” autoantigen

Lymphocyt that
recognise
„dominating”
epitop

Active supression

Active supression



Limphocytes T reg

Limphocytes T reg



Anti-idiotypic antibodies

Anti-idiotypic antibodies

Anti-idiotypic antibody

antigen

Anti-idiotypic
antibody

Jerne’a anti-idiotypic network theory

antibody

* Can mimic autoantigens

* Can mimic autoantigens

for example tyreotropin in Graves-Basedove disease

for example tyreotropin in Graves-Basedove disease

* Defficiency may lead to clinical manifestation – lack of regulation

* Defficiency may lead to clinical manifestation – lack of regulation

Factors that can influence

Factors that can influence

autoregulation

autoregulation



immunological

immunological



genetical

genetical



environmental

environmental



hormonal

hormonal

Immunological factors

Immunological factors



Clonal deletion disturbances

Clonal deletion disturbances



Autoantigen depending factors

Autoantigen depending factors



Lyphocytes T depending factors

Lyphocytes T depending factors



Lyphocytes B depending factors

Lyphocytes B depending factors



Anti-idiotypic regulation

Anti-idiotypic regulation

disturbances

disturbances

Clonal deletion disturbances

Clonal deletion disturbances

• Autoreactive lymphocytes
getting out of
to peripheral space

• mutation of genes coding
APO1/Fas i APO1/FasL

-

SLE- circulating of mutated Fas

- apoptosis antagonists

- Hashimoto- Fas expression on

thyreocytes

Autoantigen depending factors

Autoantigen depending factors



Auroantigen sequestration removal

Auroantigen sequestration removal

np. heart infarctus, posttraumal eye inflammation

np. heart infarctus, posttraumal eye inflammation



Increased autoantigen presentation

Increased autoantigen presentation

- influenced by IFNγ increased MHC II expression

- influenced by IFNγ increased MHC II expression

collitis ulcerosa, diabetes,

collitis ulcerosa, diabetes,

autoimmune inflammatory thyroid disease

autoimmune inflammatory thyroid disease



Change of autoantigen structure

Change of autoantigen structure

drug-dependent SLE, inflammatory and traumal

drug-dependent SLE, inflammatory and traumal

influence

influence

Lyphocytes T depending

Lyphocytes T depending

factors

factors



Immunological deviation

Immunological deviation



Cross-reactivity between autoantigen

Cross-reactivity between autoantigen

and egzogenic antigen

and egzogenic antigen



Supression disturbances

Supression disturbances

miasthenia, thymus inflammation, SM, DM

miasthenia, thymus inflammation, SM, DM

no Ts production for DNA in S LE

no Ts production for DNA in S LE



Cytokine depending disturbances

Cytokine depending disturbances





IL2 and IL2R - SLE,

IL2 and IL2R - SLE,

sclerodermia

sclerodermia

, SM

, SM

Th

Th

Autoreaktywna

komórka B

Autoantigen

Egzogenic, cross-reactive
antigen

No Th cell

Th lymphocyte specific
for egzogenic antigen

HELP

Cross-reactivity between autoantigen

Cross-reactivity between autoantigen

and egzogenic antigen

and egzogenic antigen

*

adenovirus A2 and mielin protein -

SM

* ant p69 kom.β pancreas and cow’s milk albumin -

DM t I

IMPORTANT:

correlation with relative HLA haplotyp!

Th1

Th2

IFNγ

Macrophages

activation

IL4
IL5

IL10

B

eosinophil

Mast cell

Immunological deviation

Immunological deviation

RZS
SM
DM t I

SLE
miasthenia gravis

Lyphocytes B depending

Lyphocytes B depending

factors

factors



Policlonal activation

Policlonal activation

-lipopolisacharyd

-lipopolisacharyd

-EBV

-EBV

-HSV

-HSV

-HIV

-HIV

-Trypanosoma cruzi

-Trypanosoma cruzi



Lymphocytes B function disturbances

Lymphocytes B function disturbances

Superantigens and policlonal limphocytes B activation

Superantigens and policlonal limphocytes B activation

Th

APC

Superantigen

* Superantigens- antigens that stimulate limphocytes T

with different antigen specificity

B

Y

B

Y

Policlonal
activation:

-

EBV

- H I V
- LPS
- HSV

TCR

MHC II

Genetical factors

Genetical factors



HLA

HLA

- allows autoreactive limphocytes elimination in thymus

- allows autoreactive limphocytes elimination in thymus

- influence antigen presentation to limphocytes T

- influence antigen presentation to limphocytes T



Other genes:

Other genes:

- genes oding TCR-

- genes oding TCR-

RZS, SLE

RZS, SLE

- genes for APO1/Fas i Fas L

- genes for APO1/Fas i Fas L

- genes coding complement proteins C2, C4

- genes coding complement proteins C2, C4

Environmental

Environmental

factors

factors



Bacterial infections

Bacterial infections

- cross-reactivity

- cross-reactivity

(streptoccoccal protein M and

(streptoccoccal protein M and

miosine

miosine

,

,

Clebsiella

Clebsiella

and HLA B 27)

and HLA B 27)

- bacterial superantigens

- bacterial superantigens

- staphylococcal toxins

- staphylococcal toxins



Viral infections

Viral infections

- cross-reactivity

- cross-reactivity

- policlonal lymphocytes B activation

- policlonal lymphocytes B activation

Cell infected by virus

IFNα/β

NK

IFN γ

Increased

expression of

MHC II and

autoantigen

presentation to
limphocytes Th

NK

Th

Th

Activated Th

limphocyte

do not need

professional APC

help

Tc

Cells damage and

Autoantigens removal

Cytokines increase
cytotoxicity

The role of viral infection in autoimmunisation induction

The role of viral infection in autoimmunisation induction

Virus

Cytotoxic effect

B

Y

Policlonal activation

Virus proteins expression on
cells

Cross-reactivity

* H BV and mielin
* Polio and AchR

The role of viral infection in autoimmunisation

The role of viral infection in autoimmunisation

induction

induction

Hormonal factors

Hormonal factors



Higher frequency of

Higher frequency of

autoimmunologic disorders in women

autoimmunologic disorders in women



Increased estrogens concentration in

Increased estrogens concentration in

women with autoimmunologic

women with autoimmunologic

disorders

disorders



Estrogens increase IFNγ synthesis –

Estrogens increase IFNγ synthesis –

increased MHC kl II expression

increased MHC kl II expression

Autotolerance

Autotolerance



is a tolerance to own antigens.

is a tolerance to own antigens.



is a part of the normal immune

is a part of the normal immune

system

system

Autoimmunological

Autoimmunological

mechanisms

mechanisms



Autoantigens

Autoantigens

(intracellular, secretogenous)

(intracellular, secretogenous)



Autoreactive lymphocytes T

Autoreactive lymphocytes T

(CD4+; MHC restriction)

(CD4+; MHC restriction)



Autoreactive lymphocytes B

Autoreactive lymphocytes B

(soluble antigens, APC)

(soluble antigens, APC)



Autoantibody

Autoantibody

(soluble or cellular surface antigens)

(soluble or cellular surface antigens)

Autoimmunological disordes

Autoimmunological disordes



Chronic disorders with

Chronic disorders with

remissions leading to

remissions leading to

disability and death

disability and death



70 diseases

70 diseases



5% of population

5% of population

Autoimmunological disordes

Autoimmunological disordes



Depending on autoantigen location

Depending on autoantigen location

*

*

organ specific

organ specific

* systemic

* systemic



Depending on patomechanism

Depending on patomechanism

* limph CD4+

* limph CD4+

* immunological complexes

* immunological complexes

* antibody

* antibody

Organ specific disorders

Organ specific disorders



Hashimoto

Hashimoto



Graves-Basedov

Graves-Basedov



Pernicious anaemia

Pernicious anaemia



Addison

Addison



Diabetes mellitus I

Diabetes mellitus I



Miasthenia gravis

Miasthenia gravis



Multiple sclerosis

Multiple sclerosis

Systemic disorders

Systemic disorders



Systemic lupus erythromatosus SLE

Systemic lupus erythromatosus SLE



Sclerodermia

Sclerodermia



Musculo-cutaneus inflammatory

Musculo-cutaneus inflammatory

diseaese

diseaese



Sjogren syndrome

Sjogren syndrome



Primary billary cirrhosis

Primary billary cirrhosis



Autoimmunohemolitic anemia

Autoimmunohemolitic anemia

Autoimmunological disordes

Autoimmunological disordes



Cellular response

Cellular response

Hashimoto

Hashimoto

MD I

MD I

Multiple sclerosis

Multiple sclerosis

albinism

albinism



Humoral response

Humoral response

Miasthenia gravis

Miasthenia gravis

Graves-Basedov

Graves-Basedov

Autoimmunohemoliti

Autoimmunohemoliti

c anemia

c anemia

Systemic lupus

Systemic lupus

erythromatosus

erythromatosus

SLE

SLE

Multiple sclerosis

Multiple sclerosis

myelin sheath destruction by:

myelin sheath destruction by:



Macrofages (NO, TNF, free radical)

Macrofages (NO, TNF, free radical)



CD8+ cytotoxic (MHC I, granzymes, perforynes)

CD8+ cytotoxic (MHC I, granzymes, perforynes)



Lymphocytes B (antibodies against complement)

Lymphocytes B (antibodies against complement)



Cytokines (IFN-

Cytokines (IFN-

γ

γ

, TNF)

, TNF)



Chemokines for Th1

Chemokines for Th1

Humoral response

Humoral response



Antigen opsonisation

Antigen opsonisation

(fagocytosis,

(fagocytosis,

complement)

complement)

- erythrocytes in

- erythrocytes in

autoimmunohemolitic anemia or platelets

autoimmunohemolitic anemia or platelets



Autoantibody binded to cell surface antigens

Autoantibody binded to cell surface antigens

- complement activation, neutrophils, macrophages infiltration

- complement activation, neutrophils, macrophages infiltration

- Goodpasture’a syndrom

- Goodpasture’a syndrom



Autoantibody binded to important receptor

Autoantibody binded to important receptor

- Graves Basedov – TSHR tyreotropine receptor stimulation

- Graves Basedov – TSHR tyreotropine receptor stimulation

- miasthemia gravis – AChR blocking

- miasthemia gravis – AChR blocking

Immunological complex

Immunological complex

disorders

disorders



IgM antibodies bind to intracellular

IgM antibodies bind to intracellular

antigens released after cell death

antigens released after cell death



Activate complement

Activate complement



Eliminated by macrophages in liver

Eliminated by macrophages in liver

and spleen

and spleen



Pathological IgG antibodies

Pathological IgG antibodies

Thank
you