Immune system

Lecture 2011

Immune system

Innate - non-specific(no immunisation required)o physical barriers (skin,

mucosa, cilia)o biological barriers

(symbionts)o chemical barriers (pH,

mucus)o soluble factors

(lysozyme, interferons, proteins ac.ph., complement)

o Cells: phagocytes, granulocyteso (rapid answer,

restrictive flexibility, non-specific reaction, no memory)

adaptive – specific(immunisation required)o Cells: T - lymfocytes(directly kill cells/ virus-

infected, foreign cells, microorganisms)

o B – lymfocytes (produce)o Antibodies(delayed answer, high

flexibility, high specifity, memory and immunity)

Organs and cells of immune system

internet

Bone marrow Thymus Tonsils and adenoids Lymph nodes Spleen Peyer´s patches Appendix Lymphatic vessels

Cells of immune system (effect)

non-specific intracelullar killing

macrophages (mononuclear phagocyte system)

“activating macrophages“! produce cytokins

APC! neutrophils extracellular killing NK-cells (CD16, CD56), “large, granular lymfocytes“ (perforins, apoptosis), not

MHC restricted eosinophils (granules with

cytotoxic proteins)

specific B-lymphocytes (receptor: Ig)o T-lymphocytes (receptor:TCR in complex with

CD, Ag split in peptide fragments in complex with MHC presented by APC

(Tc) MHC I+Ag

(TH) Ag +MHC II presenting by APC

Cell origin: Hemocytoblast (pluripotent stem cell)

Myeloid lineageErythrocytesPlateletesGranulocytesMonocytes

Dendritic cells Mast cells Lymphoid lineageB-lymphocytesT-lymphocytesNK-cells

Tissues and organs of immune system

cells: blood, lymph, lymphoid tissue lymphoid tissue: lymphoid nodules,MALT primary or central lymphoid organs: thymus bone marrow secondary or peripheral: encapsulated: lymph

nodes spleen

non-capsulated: Peyer´s patches

appendix tonsils

Cells of immune system LYMPHOCYTES

Can exist without contact with another cells (cytokines!)

Migrate through tissues, blood and lymph

2kg in organism/ 2-3 grams in blood

Lymphocytes

organ T-lymph % B-lymph %

thymus 100 0

bone marrow 10 90

spleen 45 55

lymph nodes 60 40

blood 80 20

NK

Cells of immune system Antigen presenting cells (APC)

heterogenous group of cells macrophages dendritic cells Langerhans´ cells (skin) B-lymfocytes M-cells (GIT)

Dendritic cells

APC originate in bone marrow, progenitor c. precursors are seeded through the blood to

(T-regions) or to non-lymphoid organs (Langerhans cc. in the skin)

high ability to be attracted to sites of antigen challenge and travel via lymph vessels to peripheral organs, presenting Ag to T-lymph (satelite lymph node, initiate immune response)

X folicular dendritic cc – origin just in stroma of nodes, not presenting Ag, but retain Ag/Ab in membrane – B-lymph and i. memory

Thymus

immature lymphocytes from bone marrow settled the thymus pre- and postnatally, undergoing -terminal differentiation and proliferation

elimination 95% (apoptosis), negative selection and positive selection

cortex (blood-thymus barries) x medulla (postcapillary venules – mature lymphocytes leave thymus to T-regions in peripheral organs)

reticular epithelial stroma, reticular cells!

Dual embryonic origin - endoderm (3rd pair of pharyngeal pouches) + mesenchym (lymphocytes),

Intensive growth till puberty Inborn defect: di George syndrom- thymus aplasia

Thymus anatomy

Superior and anterior inferior mediastinum lobus dx. et sin. lobuli, cortex, medulla (lobuli thymici accessorii) weight at birth (12-14g)

Thymus – cortex (85% T-cells)

epithelial cells – cortical (stromal cells) secretory granules,desmosomes,3D network, express MHC I, MHC II T-cells double negative, proliferation,gene rearrangement

pre-TCR along with coreceptors CD4 and CD8

double positive (CD4 and CD8), positive selection( CD4 or CD8)

macrophages negative selection, apoptotic T-cc

dendritic cells

corticomedullary venules (functional thymocytes exit to circulation to T-regions

Thymus – medulla (25% T-cells)

Fully matured T-cells (single positive)

Epithelial cells Hassal´s corpuscles (onion –like structures,

degenerated cells Macrophages Dendritic cells NO blood-thymus barrier

Blood – thymus barrier

Cortical epithelial cells Basal lamina Basal lamina Endothelial cells

Macrophages

Only present in cortex

Thymus involution

Gradual involution from puberty After 50th year, adipose tissue

Lymph node

organs of lymphoid tissue in the course of lymphatics

filter of Ag (microorganisms, tumor cells) coming in the lymph before its return to blood circulation

recirculation: lymphocytes return to node via high endothelial venules

reticular connective tissue stroma cortex (lymphatic nodules, B-lymph)

paracortex (T-lymph)

Lymph node

Cortex: Subcapsullary sinuses Lymphatic follicules Interfollicular sinuses

Paracortex Medulla

Lymphatic cords Medullary sinuses

Spleen

largest lymphoid tissue accumulation filter of Ag (microorganisms, tumor

cells) that penetrate blood, producing antibodies and activated lymphocytes

White pulp , PALS (T-lymph) + lymhatic nodule (B-lymph)

Marginal zone (between red and white pulp, active macrophages)

Red pulp – lymphatic cords of Billroth + venous sinuses

Vascular supply

Splenic artery Trabecular artery Central artery (surrounded by PALS) Penicilar artery (in red pulp) Venous sinuses Trabecular veins Splenic vein

Spleen – proliferation in germ center of lymhatic follicle (PCNA)