Summary and notes of the lectures of the course Advanced molecular immunology and cell biology. Important supporting images of lectures are included in the summary.
Lecture 1: Introduction course, introduction immunology
To do: add notes from work book
Hematopoiesis: the process from which the blood cells are produces → hematopoietic stem cell
- Adaptive immune cells (B and T cells) are derived from common lymphoid percursos
- Innate immune cells (macrophages, DCs) are derived from common myeloid precursors
The immune system is important for the destruction of pathogens
- Recognition of Innate immune system
o Fast (hours) and Fixed
o Limited number of specificities
o Constant during response
- Recognition of adaptive immunity
o Slow (days to weeks) and variable
o Highly selective specificities
o Improve during the response
Innate response to pathogens
- Macrophages recognize non-self on the surface of bacteria
- NK cells recognizes changes at the surface of humane cells caused by viral infections
- Phagocytosis: macrophage recognizes component and microorganism are bound on the
macrophage surface: with receptors for bacterial surface constituents
o Bacteria is bound → engulfment of the bacteria → degradation of the bacteria in the
macrophage
- Signaling: recognition with the Toll like receptor with the
pathogen-recognition domain
o Bacterial components bind to the signaling receptors →
transcription → inflammatory cytokines are produced
Adaptive immunity response
- Starts in a draining lymph node → macrophages from place of
infection go to lymph node
- Bacterial components and pathogen carrying dendritic cells drain
the lymph node, where other cells are activated →
Dendritic cells
- Immature DCs: take up the antigen in the peropheral tissues →
gets actiavted → antigen processing in the lymphatic circulation
→ Mature DCs: present the antignes in the lymphoid tissues
In the lymphoid tissues the T-lymphocyte and DCs meet
→ adaptive immune response starts
Complement
- Phagocytosis occurs readily when bacteria are covered in
antibodies (specific antibodies for bacteria) → opsonization→
phagocytosis and destruction
- The complement can further stimulate the phagocytosis
Complement factors:
- Factors that are present in the serum, lymph and fluids
- Synthesized by the liver
, - Bind pathogens to help with phagocytosis → for many bacteria complement factors are
necessary to be phagocytosed
Opsonization: Opsonization is a process in the immune system where particles, such as pathogens
(like bacteria or viruses) or other foreign materials, are marked or coated with molecules that make
them more easily recognizable and susceptible to destruction by immune cells. The molecules
involved are mostly antibodies and complement proteins
The adaptive immune system – Specific
- T and B cells recognize antigens and become effector cells → Teffector cells and plasma cells
- Teffectors cells → release soluble factors
- Plasma cells (B) → release antibodies
- Both Cells have different receptors for antigen recognition
- RAG-enzyme expression: required for the rearrangement of immunoglobulin genes → only
expressed by lymphocytes
,B cell receptor diversity
- Diversity by gene rearrangement
- More diversity during immune response by somatic hypermutation
- Also diversity during maturation in germinal centers (affinity maturation)
- High affinity antibodies are selected
T cell receptor diversity
- By gene rearrangement in the thymus
- T cells recognize antigenic peptides and HLA (MHC)
Major histocompatibility complex (Human Leukocyte antigens)
- The antigenic peptides are situated in antigen binding sites non-covalently
- MHCI
o Presents peptides derived from the cytosol (→ ER → ribosome → cell surface)
- MHCII
o Presents peptides: phagosomes → lysosomes → clasII compartments
o
- Variation in MHC allotypes at the site that bind the peptide and T cell receptor
- Peptide binding motifs and sequences of bound peptides
Activation of B and T cells
- DCs take up bacterial antigens in the skin and transport
them to a lymph node → naïve T cells circulate through
, the secondary lymphoid organs, where they monitor antigens presented by DCs
- Two signals to activate naïve T cells
o Signal 1: Recognition peptide in MHC (present on the DCs)
o Signal 2: Costimulation by CD28 and B7 (CD80/CD86)
- T cells that recognize self-antigens in the absence of costimulation become anergic
- Signal 3: the production of cytokines
o Specific cytokines determines what kind of effector CD4 T cell the naïve T cell
becomes → all containing different functions
o The differentiation is induced by different cytokines
o The different effector T cells also produce different cytokines for inflammation
B-cells activation
- Need help from Tfh cells to become activated
- Opportunistic infection → when there is no thymus (DiGeorge syndrome) or an inadequate
antibody production
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