FunctionFunction -- maturationmaturation - differentiation- differentiation - proliferation- proliferation

Primary Primary ((centralcentral)) L.O. L.O. T and B T and B startto express startto express Ag - specific receptorsAg - specific receptors

Secondary (peripheral) L.O.Secondary (peripheral) L.O. LLy y proliferation and differentiation afterproliferation and differentiation after interaction with Aginteraction with Ag

LYMPHOID ORGNSLYMPHOID ORGNS

11) ) ThymusThymus

22)) Bone marrowBone marrow

Primary Primary ((centralcentral)) L.O. L.O.

Morphology: lobular organ Morphology: lobular organ cortex cortex medulla medulla

Function: Function: maturation of maturation of T T cells cells ((only only 1 x 101 x 106 6 of of 5 x 10 5 x 107 7 tymocytovtymocytov mature) mature)

Maturation:Maturation: 3 3 STEPSSTEPS::

11) Migration and proliferation) Migration and proliferation 22)) DifferentiationDifferentiation 33)) SelectionSelection

Thymus 1Thymus 1

11) Migration and proliferation) Migration and proliferation

TThhymocytymocytes react with epithelial cellses react with epithelial cells ( (cortexcortex), dendrit), dendritic cells ic cells and and M Mphph ( (medullamedulla))

22)) DifferentiationDifferentiation

1) step 1) step - 3 negat. t- 3 negat. thhymocytymocyteses (CD3-,CD4-,CD8-) (CD3-,CD4-,CD8-) markers markers CD44+,CD25+,CD117+CD44+,CD25+,CD117+

TCR TCR genes not rearrangedgenes not rearranged 2) step2) step - - differentiationdifferentiation - TCR - TCR

TCR γTCR γ markers markers CD44-, CD25 CD44-, CD25++, CD117+, CD117+ 33) ) tthhymocytymocyteses TCR γ TCR γ T Ly (CD3+, CD4-, CD8-) T Ly (CD3+, CD4-, CD8-) 5%5% of matured T cells of matured T cells

tthhymocytymocyteses TCR TCR Th (CD3+, CD4+, CD8-) Th (CD3+, CD4+, CD8-) Tc (CD3Tc (CD3++, CD4-, CD8+), CD4-, CD8+)

POSITIVE SELECTIONPOSITIVE SELECTION

Only ththymocytymocyteses with affinity with affinity to to „self“-MHC „self“-MHC + Ag + Ag survivesurvive AIMAIM:: Elimination of nonfunctional T cells Elimination of nonfunctional T cells

MHC + epitop-AgMHC + epitop-Ag TCR/CD3TCR/CD3

TTHYHYMUS 2MUS 2

TTHYHYMUS 3MUS 3

NEGATIVE SELECTION

Thymocytes with Thymocytes with high high affinity to MHC + affinity to MHC + selfself Ag Ag are eliminated - are eliminated - clonal deletionclonal deletion or inactivated – clonal anergyor inactivated – clonal anergy

AIMAIM:: Elimination of AUTOREACTIVE T cellsElimination of AUTOREACTIVE T cells

FunctionsFunctions 1.1. Trapping and concntration of AgTrapping and concntration of Ag 2.2. Production of Ab and Ag specific T cellsProduction of Ab and Ag specific T cells

Secondary lymphoid organs:Secondary lymphoid organs:

1.1. Spleen - Spleen - blood born microbs and Agblood born microbs and Ag

2.2. Lymph nodes - lymphatic pathway > skin, mucosaLymph nodes - lymphatic pathway > skin, mucosa

3. 3. Mucosa associated lymphatic tissue Mucosa associated lymphatic tissue (MALT) (MALT) – lining of mucosa surface– lining of mucosa surface Ag invading mucosaAg invading mucosa

Secondary lymphoid organsSecondary lymphoid organs

FunctionFunction - - Ab synthesis and releasing to circulationAb synthesis and releasing to circulation - - hemokaterhemokaterhesis / hesis / TrTr a a ErEr (( StructureStructure:: red red pulppulp

white pulpwhite pulp

SPLEENSPLEEN

Red pulp Red pulp plaplassma cellsma cells, , MaMa, , EEr, r, Tr,Tr, PMNLPMNL a andnd LyLy..

White pulp - White pulp - ((PPerieriAArteriolar rteriolar LLymphoid ymphoid SSheath heath - - PALSPALS).).

T T cells round cells round central arteriacentral arteria B B cells cells in in primary folicules primary folicules (( non stimulated non stimulated)) secondary folicules secondary folicules ((Ag stimulatedAg stimulated))

germinal centre / memory cellsgerminal centre / memory cells

B B LLy represent y represent 50%50% spleen cells, spleen cells, 30-40%30-40% - - T T LyLy. .

SpleenSpleen

Lymph node (LN)Lymph node (LN)

Structure Structure - - cortxcortx - - medullamedulla

Cortex Cortex Primary folicules Primary folicules –– non activated B cells non activated B cells Secondary folicules Secondary folicules - response to Ag - response to Ag

- - Activated B celsActivated B cels – differentiation to plasma cells – differentiation to plasma cells - - TTh support h support B cell differentiationB cell differentiation - - dendritic cellsdendritic cells – – Ag presentationAg presentation

- - FDC FDC - - activation of memory cellsactivation of memory cells- - MMphph

IInterfolinterfolicular space and in paracortex cular space and in paracortex – T – T cells cells ( (mainly mainly T Thh) )

Medulla Medulla Ly, Ly, high number of high number of MMph ph a and dendritic cellsnd dendritic cells

AgAg enters LN and trapped by enters LN and trapped by MMphph a andnd dendrit dendriticic cellscellsDegradation of Ag . Fragments Degradation of Ag . Fragments (epitop(epitopeses) ) are expressed on the are expressed on the surface of APC cells together with MHC molecules surface of APC cells together with MHC moleculesActivation of T cellsActivation of T cells

The first mitotic wave in The first mitotic wave in T T zones is recorded zones is recorded 1-2 1-2 days after days after contact with Agcontact with Ag

prolif. prolif. of of B Ly, B Ly, germinal centrersgerminal centrers

Lymph node (LN)Lymph node (LN)

Immune system of mucosaImmune system of mucosa - MALT - MALT

>50% >50% of of lymlymphphoidoid tissue tissue

- (GALT) gut-associated lymphoid tissues- (GALT) gut-associated lymphoid tissues

- (BALT) bronchus-associated lymphoid tissue- (BALT) bronchus-associated lymphoid tissue

-(GUALT) genitourinary-associated lymphoid tissue(GUALT) genitourinary-associated lymphoid tissue

Exmples of Exmples of MALT: MALT: tontonsilessiles, appendix, Peyer, appendix, Peyer`s patches`s patches, , etc. … etc. …

Mucosa associated lymphatic tissue Mucosa associated lymphatic tissue - MALT- MALT

Structure of Structure of MALTMALT 1.1. Organized Organized MALT (o-MALT) MALT (o-MALT) – – immune cells in immune cells in epithelial layer of mucosa and under epitheliumepithelial layer of mucosa and under epithelium

Induction of immune reactionInduction of immune reaction 2. Dif2. Diffusefuse MALT (d-MALT) MALT (d-MALT) – – various types of lymphoid cells various types of lymphoid cells (B a(B andnd T Ly, Ma, Ne, Eo, Ma) T Ly, Ma, Ne, Eo, Ma) in lin lamina propriaamina propria

Effector phase of immune reactionsEffector phase of immune reactions

OrganizedOrganized MALT (o- MALT) MALT (o- MALT)

PeyerPeyer`s patches `s patches : : 1. 1. Lymphoid folicules Lymphoid folicules ((>> 100) 100)

central part central part - B Ly, FDC, DC, Ma- B Ly, FDC, DC, Ma peripheral part peripheral part - T Ly- T Ly

2. Epit2. Epithelium helium - „M“ - „M“ cells cells – transport – transport of of Ag Ag

- - intra epithelia intra epithelia T LyT Ly – 80% – 80% belong to belong to CD8+ ( CD8+ (regulatory functionregulatory function) )