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Transcript
Therapies targeting the
Immune System:
 Stimulation
 Suppression
 Modulation
immunhomeostasis
Innate immunity
 Immediate response  Uptake, processing,
presentation of
 Cannot be transfered
antigen/pathogen
to an other individual
 Regulatory
 Recognition of
mechanisms
molecular patterns
 Effector mechanisms
 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
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
Cells of the innate immune system
Myeloid cells:
Bone
marrow
Stem cell
Myeloid
stem cell
Mast cell
Erythrocytes Trombocytes
(platelets)
Pluripotent
stem cell
Lymphoid
Stem cell
Monocyte
Basophil
Eosinophil
Neutrophil
granulocytes granulocytes granulocytes
makrofág
Macrophage
Dendritic
cells
Bone
marrow
Myeloid
stem cell
Lymphoid
cells
Pluripotent
stem cell
Lymphoid
stem cell
B lymphocytes T lymphocytes NK cells
B lymphocytes
Products:
antibodies =
Immunoglobulins, Ig
T lymphocytes
Products:
Cytokines = Interleukins (IL)
CD=Cluster of Differentiation
Lymphocyte
populations in human
blood
The immune response
bacteria parasites
fungi
proteins
virus
Pathogens,
antigens
Physical, chemical barrier
(skin, mucose, etc)
Antimicrobial
peptides
Innate immune system
afferent
Dendritic cell
Complement
activation
NK cell
Granulocyte
Mast cell
Adaptive immune system
Humoral immune
response
Cellular immune
response
central
efferent
Death of microbe
Innate immunity
Adaptive immunity
RNS
DNS
Recognized
structures
Pathogen associated molecular patterns
(PAMP)
Receptors
Sequences of proteins
Pattern recognition receptors (PRR)
mIg
(BCR)
MANNÓZ
TLR1 – TLR10
Genes
csíravonalban kódolt, öröklődő
szekvenciák - limitált specificitás
Somatic recombination
Fine specificity, huge repertoire
Y
Expression
of receptors
Non-clonal – the same structures
for the given cell type
a,b
g, d
(TCR)
Y
Y
Y
Clonal – only T- and B cells
appr. 1010 variations
Clone selection
The immune sytem is a double edges sward
Pathogens
Tumor cells
Bacteria
Viruses,
Fungi
Immune system
allergy
autoimmunity
autoimmunitás
Immunoglobulins
• Membrane bound: B cell’s antigen receptor
(mIgG, mIgM)
• Signalling to B cells (via Igα, Igβ)
• Secreted antibodies by plasma cells, 109
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
CD8
CD4
Main Histocompatibiliy Complex, highly polymorphic, more than 250 allels for
some of the genes! Bind peptides, display them to T cells (CD8+ or 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