Therapies targeting the Immune System:  Stimulation  Suppression  Modulation

immunhomeostasis Innate immunity Immediate response Cannot be transfered to an other individual Recognition of molecular patterns No memory Adaptive immunity Requires same days to be activated Can be transfered to an other individual with antibodies or cells High degree of specificity Immunological memory Uptake, processing, presentation of antigen/pathogen Regulatory mechanisms Effector mechanisms

Elements of innate immunity (rapid response) Elements of adaptive immunity (slow response)

Cells of the immune system Innate immune system: –Granulocytes: Eosinophils Basophils Neutrophils –Monocytes – macrophages –Dendritic cells –Mast cells Adaptive immune system: –B lymphocytes –T lymphocytes –NK cells

makrofág Myeloid cells: Cells of the innate immune system Bone marrow Stem cell Myeloid stem cell Mast cell Pluripotent stem cell Lymphoid Stem cell Erythrocytes Trombocytes (platelets) Basophil granulocytes Eosinophil granulocytes Neutrophil granulocytes Monocyte Macrophage Dendritic cells

Bone marrow Lymphoid cells B lymphocytes T lymphocytes NK cells Myeloid stem cell Pluripotent stem cell Lymphoid stem cell

CD=Cluster of Differentiation Products: antibodies = Immunoglobulins, Ig Products: Cytokines = Interleukins (IL) B lymphocytes T lymphocytes

Lymphocyte populations in human blood

The immune response Humoral immune response Cellular immune response Physical, chemical barrier (skin, mucose, etc) Pathogens, antigens bacteriaparasitesfungi proteins virus Innate immune system Adaptive immune system Anti- microbial peptides Complement activation afferent central efferent Mast cell Granulocyte Dendritic cell NK cell Death of microbe

Expression of receptors Non-clonal – the same structures for the given cell type Clonal – only T- and B cells appr variations Receptors csíravonalban kódolt, öröklődő szekvenciák - limitált specificitás Somatic recombination Fine specificity, huge repertoire Recognized structures Innate immunityAdaptive immunity Pathogen associated molecular patterns (PAMP) Sequences of proteins Genes YYYY mIg (BCR)   (TCR) Pattern recognition receptors (PRR) TLR1 – TLR10 MANNÓZ RNS DNS

Clone selection

Tumor cells autoimmunitás Y YY Y allergy Pathogens Immune system The immune sytem is a double edges sward Bacteria Viruses, Fungi autoimmunity

Immunoglobulins Membrane bound: B cell’s antigen receptor (mIgG, mIgM) Signalling to B cells (via Igα, Igβ) Secreted antibodies by plasma cells, 10 9 different specificities! 5 classes (isotypes: IgM, IgD, IgG, IgA, IgE) Effector functions eliminate antigen

Complementarity determined regions

Monoclonal antibody production – biological therapies

Effector functions I:

Effector functions II:

Effector functions III:

Antigen recognition by the T cell receptors Recognize MHC-bound peptides Mediate activation signal for T cells as part of TCR complex) Stimulate T cell proliferation and cytokine secretion

Structure of MHCI and MHCII Main Histocompatibiliy Complex, highly polymorphic, more than 250 allels for some of the genes! Bind peptides, display them to T cells (CD8+ or CD4+). CD8 CD4

Class I: bind 8-11 amino acid peptide, class II binds up to 30 amino acid peptides, structurally related (anchor amino acids)

Helper T cells

TH1 cells

TH2 cells

T cell cytotoxicity