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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).
!!
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
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
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
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. !
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
!!
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
!!
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