IMMUNOLOGICAL MEMORY

The immune system seems to „remember” previous infections,

• Which cells do it and how?• Why?• For how long?• How can we use this to fight infectios diseases?

The concept of immune protection by immune memory memory has probably been known for a few thousand years…..

Parents can take care of sick children if they already had the disease and recovered

History of infection with a pathogen.

• Some infections are stopped by the innate immunity… Adaptive immune response is not induced• Many pathogens are seasonal, repeated infections with viruses during wintertime.•Antibodies produced in response to an infection are present for several months. •Virus neutralization….

!

B cell memory:

Quicker responseIncrease in the number of specific B cellsThe amount of antibody are higherHigher affinity antibodies (‘more specific’)Isotype switch

In case of T dependent B cell activation

!!

Memory B cells

proliferation and differentiation to plasma cell upon re-activation or entry to the GC reaction again

and

Long-lived plasma cellsPlasma cells generated during GC reaction migrate to bone marrow andsurvive for years, producing antibody Much of circulating IgG is produced by long-lived plasma cells, provides initial protection

B cell memory is provided by:

Both effector B and T cells and memory B and T cells are produced during a primary immune

response.

1781: Measles epidemics in the Faroe islands

after the epidemics the island has remained measles free for 65 years

1846: Another epidemic

Those, who were elder than 65 years and were sick in 1781 were not re-infected

1. Life long protection against some viruses exists

2. Maintenance of memory does not require the sustained or intermitting presence of the virus

Inhabitants: 46 000Area: 1 400 km2

Memory can provide protection against pathogens for decades,

5000 inhabitant , 98 survivors were protected

Memory B cells and T cells provide protection against pathogens for decades,

75 years after inoculation (vaccination) with vaccinia virus, vaccinia-specificantibodies are still present.

75 years after inoculation (vaccination) with vaccinia virus, CD4+ and CD8+ T cells are still present.

T-CELL MEMORY

Central memory cells

Effector memory cells

T cell memory:

Quicker responseIncrease in the number of responding cells

!!

Effector T

Citokines/Cytotoxicity

AICD

Naive T

Central memory T

Effector T

Citokines/cytotoxicity

PERIPHERAL LYMPHOID ORGANS

PERIPHERAL TISSUESSkin dermis, gut lamina propria, alveolar space

Tissue-specific migration

Effector memory T

Effector T

Cytokines/cytotoxicity

ANTIGEN/SITE OF INFECTION

The differences between central and effector memory T cells.

Proliferation

cytotoxicity

Functional differences between lymphoid tcm cells and tissue-resident TEM cells

Woodland DL & Kohlmeier JR 2009 Nat Rev 9:153killing

Generation of memory T cells during the response to a virus

infection.

After clearing viral infection about 5% of the cells become memory cells. This is about 100-1000X more than the % of naive virus-specific T cells.

AGE

THYMUS PERIPHERY

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A

I

V

E

IMMUNOLOGICAL EXPERIENCEIMMUNOLOGICAL EXPERIENCE

M

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M

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As we age we rely more on our past experiences with pathogens (Memory cells)

Highly mutable viruses such as influenza gradually escape from immunological memory without stimulating a

compensatory immune response.

The original antigenic sin

Summary

Differences between the primary and secondary immune responses.

A TERMÉSZETES ÉS SZERZETT IMMUNITÁS EGYÜTTMŰKÖDÉSEIDŐBEN

Active and passive immunization

Active: generates memory response

Passive: ensure the protection by premade antibodies(the adaptive immune system of the person is not activated)

!!

Active and passive immunization

active passive

protection slow immediate(2 weeks)

Time-span long short(years)

time

activepassive

injection

protection

!!

Vaccination with cowpox virus elicits neutralizing antibodies that react with antigenic determinants shared with smallpox virus.

Cowpox is very similar to smallpox, similarity is the basis of protection

Most viral vaccines are made of killed or inactivated viruses…But live, attenuated viruses usually generate effective long-lasting protection

The Polio eradication program

1988: Polio endemic in 125 countries350,000 deaths / yearBy 1990 polio is almost eradicated

Time course of the H1N1 influenza pandemic of 2009 and the development

of a vaccine against it.

Anti-viral immune response

Defense:

Innate Immunity: – type I interferons(INFα, β)

– NK cells

Adaptive immunity

B cells – antibody-mediated neutralization

T cells --- cytotoxic T cells, cytokines

!

Anti-viral immune response Type I INTERFERONs

vírus

IFN és IFN

!

!

napok

vírus-titer

2 4 6 8 101 3 5 7 9 1211 13

KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS

Complement

AntibodyCytotoxic T cellsNK cells

IFNα/β, IL-12

days

lev

el/a

cti

vity

VIRUS TITER