Primary lymphoid organs:

- Bone marrow- Thymus

the cells of the immune system originate in and mature here

Secondary lymphoid organs:- Spleen

- Lymphatic vessels- Lymph nodes- Adenoids and tonsils- MALT (Mucosal Associated Lymphoid Tissue) GALT (Gut Associated Lymphoid Tissue) BALT (Bronchus Associated Lymphoid Tissue) SALT (Skin Associated Lymphoid Tissue)

NALT (Nasal Associated Lymphoid Tissue)

not for cell development. (final differentiation, activation may be performed) The cells of the adaptive immune system recognize

here the pathogens

LYMPHOID ORGANS!!

THE TWO ARMS OF THE IMMUNE SYSTEM

Monocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components

B and T cellsMonocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components

!!

MEMORY

Professional phagocytic cellsmacrophagesneutrophyl granulocytesdendrtitic cells

Professional antigen presenting cellsmacrophagesB lymphocytesdendrtitic cells

they express MHCII molecules

the protein degradation products (peptides) can be presented to T lymphocytes by MHC molecules

!!

!!

Cells of innate immune system:

Macrophages: Macrophages are constitutively present in tissues and recognize microbes that enter these

tissues and respond rapidly to these microbes. Initiate the immune response• These cells are phagocytes (eliminate the pathogens)• Activate the innate immune response (by secreted proteins, called cytokines)• Activate the adaptive immune system. Macrophages serve as APCs that display antigens to

and activate T lymphocytes

• Dendritic cellsare constitutively present in tissues and recognize rapidly microbes that enter these tissues. Initiate the immune response.• They have phagocytic capabilities migrate to lymph nodes, and display microbial antigens to T lymphocytes,professional antigen presentimg cells (APC)

Neutrophil granulocytesare phagocytes, the main function to eliminate the pathogensAppear only in the circulation under normal conditionMain actors In inflammatory processes

!!

Recognition is inevitable

Innate immunity as a first line of defence

Innate immune cells recognize frequently found structures of pathogens by PRRs ,

these are not found in human cells!

Examples of recognited structures: duple strain RNA bacterial cell wall components bacterial flagellin….

!!

PRRs (pattern recognition receptors) are responsible for recognize conserved structures of the microbes

Danger signal!The innate immune system also recognizes molecules that are released from damaged or necrotic cells. Such molecules are called damage-associated molecular patterns (DAMPs).

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OPSONIZATION ! !

Main opsonins:antibodiesComplement fragmentsAcute-phase proteins

Opsonization facilitate and accelerate the recognition of the pathogen by phaogocytes,opsonins form a bridge between pathogen and a phagocyte connecting them.

direct connetion between innate cells

and pathogen)(

Specificity of innate immunity

Few receptors (20-30) are responsible for the recognition of all the pathogens

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:• membrane-bound heterodimer composed of an α chain and a β chain, each chain

containing one variable (V) region and one constant (C) region Both the α chain and the β chain of the TCR participate in specific recognition of MHC molecules and bound peptides

! T cell receptor (TCR) The TCR, which recognizes peptide antigens displayed by MHC molecules!

BCR

TCR

!!

B cell Plasma cell

TCRs only function as membrane receptors

T cell

ANTIGEN RECOGNITION BY T-CELLS REQUIRESPEPTIDE ANTIGENS AND ANTIGEN PRESENTING CELLS

THAT EXPRESS MHC MOLECULES

IIT

No T-cell response

soluble Ag

Native membrane Ag

Peptide antigen

Cell surface MHC-peptide complex

T-cell response

Cell surfacepeptides APC

!!

APCAPC

PEPTIDE

1

3

2

2m

STRUCTURE OF CLASS I MHC MOLECULES

MHCI

Expressed by all nucleated cells

!!

2

1

2

1

PEPTIDE

STRUCTURE OF CLASS II MHC MOLECULES

MHCII

Expressed by professional antigen presenting cellsMacrophage, dendritic cell, B cell

!!

ANTIGEN RECOGNITION BY T-CELLS REQUIRESPEPTIDE ANTIGENS AND ANTIGEN PRESENTING CELLS

THAT EXPRESS MHC MOLECULES

IIT

No T-cell response

soluble Ag

Native membrane Ag

Peptide antigen

Cell surface MHC-peptide complex

T-cell response

Cell surfacepeptides APC

!!

APCAPC

MHCI

Displays intracellular antigensto cytotoxic T cells

!!

MHCII

Displays extracellular antigensto helper T cells

!!

Peptides of endogenous proteins (virus, tumor) bind to class I MHC

molecules presented to cytotoxic T cells

Tc

Endogenous Ag

RECOGNITION OF EXOGENOUS AND ENDOGENOUS ANTIGENES BY T-LYMPHOCYTES

Exogenous Ag

Th

Peptides of exogenous proteins (toxin, bacteria, allergen) bind to class II MHC molecules presented to helper T cells

TCR

Peptide

MHCI

TCR

Peptide

MHCII

APC

!!

!!T cell receptor (TCR) recognizes peptide antigen and

simultaneously also recognizes the MHC molecule that is displaying that peptide

Specificity of innate immunity

Specificity of T cells

Tc

APC

Tc

APC

peptid

MHCPeptides derivedfrom different microbes

Distinct T cell receptors

direct connetion between innate cells

and pathogen

No direct connetion

between T cell and pathogen

APC-T cell connectionAPC

T

APC

peptid

MHC

T

Peptides derivedfrom different microbes

Distinct T cell receptors

)(

Specificity of innate immunity

Specificity of T cells

Immunoglobulin STRUCTURE

• 2x identical Heavy chain (light blue)

• 2x identical light chain (dark blue)

• Variable regions antigen binding

• Constant regions

hinge region

carbohydrate

disulfide bond

CH1

VL

CL

VH

CH2 CH3

!!

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effektor funkciók

konstans domének

antigénkötés

variábilis domének

ANTIBODY DOMAINS AND THEIR FUNCTIONS

!!

Constant domain

Effector functions

Antigen recognition

Variable domain

AntibodyBCR (B cell receptor) !!

MEMBRANE BOUND!

Associated chains for signaling

Transmembrane domain

Cytoplasmic domain

Antigen recognition and B cell activation

SOLUBLE (freely circulating)

Antigen recognition and effector functions.

Produced by plasma cells

B cell epitop T cell epitop

B cells recognize:

proteinspolysaccharideslipidsDNSsteroidsdrugs, etc

Tissue or soluble antigens

T cells recognize:

peptides (8-23 amino acid)

only when these peptides are presented by MHC molecules on APC cells

!!

Receptors responsible for the recogniton of pathogens in the immune system

Caracteristics of innate immune system,macrophage, dendritic cells

PRR Pattern recognition receptors

Danger signal and Pathogen recognition mainly in the innate immun system

B cells BCR (B cell receptor) Antigen recognition of B cell

T cells TCR (T cell receptor) Antigen recognition of T cell

All nucleated cells in human

MHC (MHCI) Major Histocompatibility Complex

Do not recognise pathogens, but present intracellular peptides required for T cell receptor

professional antigen presenting cells:macrophages, DC, B cells

MHCII Do not recognise pathogens, but present extracellular peptides required for T cell receptor

THE TWO ARMS OF THE IMMUNE SYSTEM

Monocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components

B and T cellsMonocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components

!!

MEMORY

AntibodyBCR (B cell receptor) !!

MEMBRANE BOUND!

Associated chains for signaling

Transmembrane domain

Cytoplasmic domain

Antigen recognition and B cell activation

SOLUBLE (freely circulating)

Antigen recognition and effector functions.

Produced by plasma cells

Several antibodies are expressed on B cells, (arround 100.000) but all of them with the same specificity

!!

Antigen

Activation of specific B cells

1. Clonal expansion

Antigen Antigen

2.Differentiation

Plasma cells, antibody production

MEMORY B CELLS

Antigen

!

Antigen

Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells. !

Effector funtions

InnateAdative B cells T cells

ExtracellularIntracellular pathogens

INNATE IMMUNITY II

Effector functions, elimination of pathogens

1. Phagocytosis2. Killing with soluble mediators

3. Complement system4. NK cell activation

!!

EFFECTOR FUNCTIONS OF ANTIBODIES

Antibody-mediated immune responses

• NEUTRALIZATION• OPSONIZATION• COMPLEMENT FIXATION• ADCC• MAST CELL DEGRANULATION

!!

T helper cells (TH cells) assist other white blood cells in immunologic processes

Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells

!!

Activation of helper T cells results in cytokine production

!!

Cytokines are the most important mediators of indirect cell communication in the immune system („hormones” of the immune system).

THE MOST IMPORTANT FEATURES OF CYTOKINES

!!

!!MHCI is present in all the nucleated cells

Intracellular pathogens can be presented on all the cellsAny cell is infected, can be killed by cytotoxic T cells

MHCII present extracellular antigens to helper T cells. Helper T cells direct the immun eresponse by the pruduced cytokines.

THE TWO ARMS OF THE IMMUNE SYSTEM

Monocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components

B and T cellsMonocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components

!!

MEMORY

B cell memory:

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

In case of T dependent B cell activation

!!

T cell memory:

Quicker responseIncrease in the number of responding cells

!!

!!

Active and passive immunization

active passive

protection slow immediate(2 weeks)

Time-span long short(years)

time

activepassive

injection

protection

!!