Table of Contents
Theme 1 Introduction. ...................................................................................................... 4
Three different phases of immune response: ............................................................................ 6
Development B and T cells: ...................................................................................................... 7
Induction phase part I: antigens activate mature naïve lymphocytes. ......................................................... 8
Induction phase II: Effector cells and mediators (antibodies)....................................................................... 9
Antigen recognition and effector mechanisms (overview function B and T cells): ..................... 10
Theme 2 Innate immunity ............................................................................................... 12
1. Phagocytes (cells); Macrophages, Neutrophils, NK cells = patrolling cells. ............................ 13
2. Innate immune receptors; PAMP, DAMP, TLR ...................................................................... 14
3. Complement system........................................................................................................... 16
Classical pathway ........................................................................................................................................ 16
Lectin pathway ............................................................................................................................................ 16
Alternative pathway .................................................................................................................................... 16
Pathway of compliment activation (C3, C3A and C3B + C5A, C5B) ............................................................. 16
4. Cytokines + function ( ......................................................................................................... 17
Local effect .................................................................................................................................................. 17
Systemic effect ............................................................................................................................................ 17
Acute phase reaction (C-reactive protein (CRP)) ........................................................................................ 18
5. Natural killer cells. ............................................................................................................. 18
Theme 3 MHC (Major Histocompatibility) complex and antigen processing ..................... 20
Life of a T cell ......................................................................................................................... 20
MHC = major histocompatibility complex (overview MHC I + II). .............................................. 21
Autoimmune response ................................................................................................................................ 23
Theme 4 T-cell development and T-cell receptor. ............................................................. 24
2. Generation of αß T-cell receptor diversity (VDJ segments, RAG) .......................................... 24
3. T-cell selection processes (+- selection) ............................................................................... 26
4. Survival of T-cells (S1PR1). .................................................................................................. 29
5. γδ T cells and NKT cells + overview ..................................................................................... 30
6. TCR signalling; Tyrosine kinase families, ITAM, ITIM.............................................................. 33
Early events in T cell activation ................................................................................................................... 35
Downstream events in T-cell activation (LAT, PLCy1, IP3) .......................................................................... 35
Functional consequences of TCR signaling............................................................................... 37
Theme 5 B-cell development, B-cell receptor and signalling and antibodies. .................... 38
1. B-cell receptor and antibodies (structure, mono-bi-valent interactions, what happens after
activation) .............................................................................................................................. 38
1
, 2. Generation of BCR diversity: molecular processes (RAG 1 RAG 2, randomly nucleotides
changes) ................................................................................................................................ 39
4. BCR signaling; Src kinases, PLCy, complement receptor 2, C3 ................................................ 43
Consequences of B-cell activation: Inhibitory signaling in B cells: ....................................................... 44
ITIM domains in Fc receptor. ...................................................................................................................... 44
5. Similarities and differences between B and T cell receptor and development....................... 44
Theme 6 Cellular immunity ............................................................................................. 45
1. Presentation of the antigen to T cells. ................................................................................. 45
2. Selective activation of antigen-specific T cells. .................................................................... 46
3. Avoidance of T cell activation in harmless conditions (PAMPs and DAMPs). ......................... 47
4. Activation of the correct type of effector cell (overview CD4+ (Th1 Th2 Th17) CD8+ cytokines
!!!) ......................................................................................................................................... 48
5. Generation of sufficient numbers of effector cells. .............................................................. 52
6. Homing of effector cells to the site of infection; growth factor il-2 (CCR).............................. 52
Killing mechanism of CD8+ cytotoxic T cells: .............................................................................................. 53
7. Contraction of the T cell response (reduction, CTLA-4 (inhibitory signal) + PD-1 ................... 53
8. Generation of memory (central vs effector memory cells) ................................................... 54
Theme 7 Humoral Immunity ........................................................................................... 55
1. Antibody production .......................................................................................................... 55
Upon recognition of the B cell from the T cell (1) the................................................................................. 59
T cell will do two things: .............................................................................................................................. 59
How does the B and T cells know where to go? CCR7 + CXCR5 .................................................................. 60
Theme 8 Infections & Immunodeficiency’s ...................................................................... 68
1. Extracellular surviving bacteria ........................................................................................... 68
Tricks of bacteria to escape the immune system ........................................................................................ 69
Conjugate vaccines...................................................................................................................................... 69
2. Intracellular surviving bacteria............................................................................................ 70
3. Viruses ............................................................................................................................... 71
Viruses have many mechanisms for immune evasion (tricks ..................................................................... 71
4. Fungi.................................................................................................................................. 72
5. Parasites ............................................................................................................................ 72
Theme 9 Tumor Immunology .......................................................................................... 74
Cells of the adaptive immune system involved in anti-tumor immunity ................................... 75
Life cycle of a dendritic cell..................................................................................................... 76
Interaction between Dendritic cell and T cell (signal + tumor use this to inhibit T cells) ...... 76
Immunosuppressive tumor environment: ................................................................................................... 77
Theme 10 Tolerance and autoimmunity .......................................................................... 80
Where does this tolerance induction takes place? ..................................................................................... 80
2
, Autoimmunity type I - IV ............................................................................................................................. 81
Theme 11 Transplantation immunology .......................................................................... 85
Mechanisms of rejection (hyperacute (direct/indirect), acute, chronic) ..................................... 85
Prevention of rejection (HLA matching, screening, cross matching, immunosup.) ...................... 87
Theme 12 Modulation of the immune response............................................................... 89
3
, Abstract Immunology
Theme 1 Introduction.
Cells can be part of Innate and acquired (adaptive) immune system:
4
Theme 1 Introduction. ...................................................................................................... 4
Three different phases of immune response: ............................................................................ 6
Development B and T cells: ...................................................................................................... 7
Induction phase part I: antigens activate mature naïve lymphocytes. ......................................................... 8
Induction phase II: Effector cells and mediators (antibodies)....................................................................... 9
Antigen recognition and effector mechanisms (overview function B and T cells): ..................... 10
Theme 2 Innate immunity ............................................................................................... 12
1. Phagocytes (cells); Macrophages, Neutrophils, NK cells = patrolling cells. ............................ 13
2. Innate immune receptors; PAMP, DAMP, TLR ...................................................................... 14
3. Complement system........................................................................................................... 16
Classical pathway ........................................................................................................................................ 16
Lectin pathway ............................................................................................................................................ 16
Alternative pathway .................................................................................................................................... 16
Pathway of compliment activation (C3, C3A and C3B + C5A, C5B) ............................................................. 16
4. Cytokines + function ( ......................................................................................................... 17
Local effect .................................................................................................................................................. 17
Systemic effect ............................................................................................................................................ 17
Acute phase reaction (C-reactive protein (CRP)) ........................................................................................ 18
5. Natural killer cells. ............................................................................................................. 18
Theme 3 MHC (Major Histocompatibility) complex and antigen processing ..................... 20
Life of a T cell ......................................................................................................................... 20
MHC = major histocompatibility complex (overview MHC I + II). .............................................. 21
Autoimmune response ................................................................................................................................ 23
Theme 4 T-cell development and T-cell receptor. ............................................................. 24
2. Generation of αß T-cell receptor diversity (VDJ segments, RAG) .......................................... 24
3. T-cell selection processes (+- selection) ............................................................................... 26
4. Survival of T-cells (S1PR1). .................................................................................................. 29
5. γδ T cells and NKT cells + overview ..................................................................................... 30
6. TCR signalling; Tyrosine kinase families, ITAM, ITIM.............................................................. 33
Early events in T cell activation ................................................................................................................... 35
Downstream events in T-cell activation (LAT, PLCy1, IP3) .......................................................................... 35
Functional consequences of TCR signaling............................................................................... 37
Theme 5 B-cell development, B-cell receptor and signalling and antibodies. .................... 38
1. B-cell receptor and antibodies (structure, mono-bi-valent interactions, what happens after
activation) .............................................................................................................................. 38
1
, 2. Generation of BCR diversity: molecular processes (RAG 1 RAG 2, randomly nucleotides
changes) ................................................................................................................................ 39
4. BCR signaling; Src kinases, PLCy, complement receptor 2, C3 ................................................ 43
Consequences of B-cell activation: Inhibitory signaling in B cells: ....................................................... 44
ITIM domains in Fc receptor. ...................................................................................................................... 44
5. Similarities and differences between B and T cell receptor and development....................... 44
Theme 6 Cellular immunity ............................................................................................. 45
1. Presentation of the antigen to T cells. ................................................................................. 45
2. Selective activation of antigen-specific T cells. .................................................................... 46
3. Avoidance of T cell activation in harmless conditions (PAMPs and DAMPs). ......................... 47
4. Activation of the correct type of effector cell (overview CD4+ (Th1 Th2 Th17) CD8+ cytokines
!!!) ......................................................................................................................................... 48
5. Generation of sufficient numbers of effector cells. .............................................................. 52
6. Homing of effector cells to the site of infection; growth factor il-2 (CCR).............................. 52
Killing mechanism of CD8+ cytotoxic T cells: .............................................................................................. 53
7. Contraction of the T cell response (reduction, CTLA-4 (inhibitory signal) + PD-1 ................... 53
8. Generation of memory (central vs effector memory cells) ................................................... 54
Theme 7 Humoral Immunity ........................................................................................... 55
1. Antibody production .......................................................................................................... 55
Upon recognition of the B cell from the T cell (1) the................................................................................. 59
T cell will do two things: .............................................................................................................................. 59
How does the B and T cells know where to go? CCR7 + CXCR5 .................................................................. 60
Theme 8 Infections & Immunodeficiency’s ...................................................................... 68
1. Extracellular surviving bacteria ........................................................................................... 68
Tricks of bacteria to escape the immune system ........................................................................................ 69
Conjugate vaccines...................................................................................................................................... 69
2. Intracellular surviving bacteria............................................................................................ 70
3. Viruses ............................................................................................................................... 71
Viruses have many mechanisms for immune evasion (tricks ..................................................................... 71
4. Fungi.................................................................................................................................. 72
5. Parasites ............................................................................................................................ 72
Theme 9 Tumor Immunology .......................................................................................... 74
Cells of the adaptive immune system involved in anti-tumor immunity ................................... 75
Life cycle of a dendritic cell..................................................................................................... 76
Interaction between Dendritic cell and T cell (signal + tumor use this to inhibit T cells) ...... 76
Immunosuppressive tumor environment: ................................................................................................... 77
Theme 10 Tolerance and autoimmunity .......................................................................... 80
Where does this tolerance induction takes place? ..................................................................................... 80
2
, Autoimmunity type I - IV ............................................................................................................................. 81
Theme 11 Transplantation immunology .......................................................................... 85
Mechanisms of rejection (hyperacute (direct/indirect), acute, chronic) ..................................... 85
Prevention of rejection (HLA matching, screening, cross matching, immunosup.) ...................... 87
Theme 12 Modulation of the immune response............................................................... 89
3
, Abstract Immunology
Theme 1 Introduction.
Cells can be part of Innate and acquired (adaptive) immune system:
4
