Lecture 1 Elements of immune system and role in
defense
Chapter 1
Components of immune system
Immune system = diffuse network of interacting cells, cell products and cell-forming tissues that
protects the body. Needs to be able to discriminate between self, non-self and harmless. 2 main
categories:
Innate immunity = existing from birth
o Granulocytes (basophil, eosinophil and neutrophil)
o Monocyte (macrophages and dendritic cells)
Adaptive immunity = during lifetime adapting
o T and B cells
o Antibodies (made by B cells)
Hematopoiesis = development of immune cells, 2 precursors: common myeloid cell precursor (for
innate system) and common lymphoid cell precursor (for adaptive system). Immunity has 3 lines of
defense divided in speed after first time infection: epithelial barriers innate adaptive.
Lymphatic system = primary and secondary lymphoid organs with different functions:
Primary = development of adaptive immune system
o bone marrow = B cells, Thymus = T cells
Secondary = activation of adaptive immune cells, specific sites for T and B cells
o lymph nodes, spleen and gut associated lymphoid tissues (GALT)
innate VS. adaptive immune system
innate
Macrophages and neutrophils are fast responders upon infection and induce inflammation.
Macrophage engulfs bacterium and releases cytokines (=signaling molecules for activation) and
chemokines (= show neutrophils where to go). Macrophages recruit neutrophils from the bone
marrow to collaborate and clear bacterial infection using phagocytosis. However they are aspecific
and cannot keep up, dendritic cells take up pathogen as well and migrate to lymph nodes. There
they activate the adaptive immune cells (T and B cells).
Innate immune cells use pathogen recognition receptors to distinguish self from non-self and get
activated, there is equal expression per cell subset and can differentiate between major pathogen
species. Use associated molecular patterns: pathogen (=PAMPS) and danger (=DAMPS).
Adaptive
Activated by dendritic cells from innate system. Adaptive immune cells use receptors to specifically
detect danger and get activated. B cells have B cell receptor (BCR) and T cells the T cell receptor
(TCR). Antigens are specific for each pathogen and contain epitopes recognized by receptors of
adaptive immune system. Epitope = minimal portion of antigen bound by antibodies or BCR and
recognized by TCR.
,Every T and B cells has a receptor which will bind a different epitope, having different specificity.
Only the ones with the right receptor for ongoing infection will be activated in secondary lymphoid
organs will proliferate and become clone of cells with same receptor.
T cells are cellular response, binding epitope and activation other cells which present epitopes. B
cells can bind whole antigen, differentiation into plasma cells and production of antibodies =
Humoral response. Antibodies have multiple functionalities against infection.
Neutralization = counteract
Opsonization = tagging, macrophages can take it up
Complement activation = extra system activation
Activation innate cells = granulocytes and NK cells
Complement system
Complements ongoing inflammation, consisting of plasma proteins with enzymatic activity. Most
important is C3 = complement factor. C3 is inactive in the plasma, when its cleaved it splits via C3
convertase in:
C3a = anaphylatoxin immune cells recruitment
o Enhance inflammation through activation of endothelium and immune cell
recruitment, increase blood vessel permeability
C3b = complement fixation pathogen binding for phagocytosis and lysis
o Enhanced phagocytosis by binding complement receptors CR1 on
phagocytes, important for formation of membrane attack complex (MAC)
and pathogen lysis
3 pathways lead to C3 activation:
1. Alternative pathway = first to be activated and spontaneous activation C3 activation via
hydrolysis (part 1), second part cut and activated soluble C3 convertase
2. Lectin pathway = activates membrane bound C3 convertase starting with binding MBL to
pathogen surface (protein induced)
3. Classical pathway = activates membrane bound C3 convertase starting with binding C1 or
antibodies to pathogen surface, requires additional protein binding to pathogen surface
(CRP)
, Lecture 2 Innate immunity: induced response to
infection
Chapter 3
Inflammation and infection
Tissue resident cells and first to respond upon infection. They are big eaters and clear pathogens by
phagocytosis, present in all tissues. Alert rest of immune system upon infection. They respond to
bacteria using pathogen recognition receptors bind to it engulfment and uptake merge with
lysosome to form phagolysosome. Also cytokine production is done, to activate other cells. They are
pro-inflammatory cytokines for induction of inflammation. Some alert tissue to make other cells able
to enter (neutrophils and complement), also help of chemokines. Neutrophils need to enter tissue
coming from high speed blood circulation, therefore using anchors of adhesion molecules and
chemokines:
1. Rolling adhesion = along walls blood
vessels
a. Selectins for weak binding
b. Integrins for moderate binding
c. Chemokines for signaling
d. Integrins for tight binding
2. Diapedesis = entering neutrophil into
tissue through CD31 from blood stream
3. Migration = movement through tissue
a. Chemokine gradient
Neutrophils express receptors for phagocytosis and toxic granules for killing, expression of multiple
receptors for pathogen recognition (CR). Neutrophils has multi-lobular nucleus, recruited to infection
site and efficient killers with short life span. Fusion with vesicles and lysosomes to form
phagolysosome. After this the neutrophil dies and cleared by macrophages.
Macrophages induce acute phase response initiating production of MBL and CRP by liver. This
activates complement system and have opsonizing function for enhanced phagocytosis.
Complement activation leads to three modes of action:
C3a = recruitment by anaphylatoxins inflammation leaky blood vessels
C3b = opsonization and induce phagocytosis phagocytes with receptors for C3b engulf
Membrane attack complex induction bacterial lysis
Receptors
Use of pattern recognition receptors (PRR), different types with different functions. Can be
extracellular or intracellular, to also detect inside of the cell. Two main types:
C-type lectin receptors phagocytosis and destruction, CLR recognize sugar on pathogen
Toll-like receptors signaling and immune cell activation, expression by many immune
cells, intra and extracellular with great diversity
defense
Chapter 1
Components of immune system
Immune system = diffuse network of interacting cells, cell products and cell-forming tissues that
protects the body. Needs to be able to discriminate between self, non-self and harmless. 2 main
categories:
Innate immunity = existing from birth
o Granulocytes (basophil, eosinophil and neutrophil)
o Monocyte (macrophages and dendritic cells)
Adaptive immunity = during lifetime adapting
o T and B cells
o Antibodies (made by B cells)
Hematopoiesis = development of immune cells, 2 precursors: common myeloid cell precursor (for
innate system) and common lymphoid cell precursor (for adaptive system). Immunity has 3 lines of
defense divided in speed after first time infection: epithelial barriers innate adaptive.
Lymphatic system = primary and secondary lymphoid organs with different functions:
Primary = development of adaptive immune system
o bone marrow = B cells, Thymus = T cells
Secondary = activation of adaptive immune cells, specific sites for T and B cells
o lymph nodes, spleen and gut associated lymphoid tissues (GALT)
innate VS. adaptive immune system
innate
Macrophages and neutrophils are fast responders upon infection and induce inflammation.
Macrophage engulfs bacterium and releases cytokines (=signaling molecules for activation) and
chemokines (= show neutrophils where to go). Macrophages recruit neutrophils from the bone
marrow to collaborate and clear bacterial infection using phagocytosis. However they are aspecific
and cannot keep up, dendritic cells take up pathogen as well and migrate to lymph nodes. There
they activate the adaptive immune cells (T and B cells).
Innate immune cells use pathogen recognition receptors to distinguish self from non-self and get
activated, there is equal expression per cell subset and can differentiate between major pathogen
species. Use associated molecular patterns: pathogen (=PAMPS) and danger (=DAMPS).
Adaptive
Activated by dendritic cells from innate system. Adaptive immune cells use receptors to specifically
detect danger and get activated. B cells have B cell receptor (BCR) and T cells the T cell receptor
(TCR). Antigens are specific for each pathogen and contain epitopes recognized by receptors of
adaptive immune system. Epitope = minimal portion of antigen bound by antibodies or BCR and
recognized by TCR.
,Every T and B cells has a receptor which will bind a different epitope, having different specificity.
Only the ones with the right receptor for ongoing infection will be activated in secondary lymphoid
organs will proliferate and become clone of cells with same receptor.
T cells are cellular response, binding epitope and activation other cells which present epitopes. B
cells can bind whole antigen, differentiation into plasma cells and production of antibodies =
Humoral response. Antibodies have multiple functionalities against infection.
Neutralization = counteract
Opsonization = tagging, macrophages can take it up
Complement activation = extra system activation
Activation innate cells = granulocytes and NK cells
Complement system
Complements ongoing inflammation, consisting of plasma proteins with enzymatic activity. Most
important is C3 = complement factor. C3 is inactive in the plasma, when its cleaved it splits via C3
convertase in:
C3a = anaphylatoxin immune cells recruitment
o Enhance inflammation through activation of endothelium and immune cell
recruitment, increase blood vessel permeability
C3b = complement fixation pathogen binding for phagocytosis and lysis
o Enhanced phagocytosis by binding complement receptors CR1 on
phagocytes, important for formation of membrane attack complex (MAC)
and pathogen lysis
3 pathways lead to C3 activation:
1. Alternative pathway = first to be activated and spontaneous activation C3 activation via
hydrolysis (part 1), second part cut and activated soluble C3 convertase
2. Lectin pathway = activates membrane bound C3 convertase starting with binding MBL to
pathogen surface (protein induced)
3. Classical pathway = activates membrane bound C3 convertase starting with binding C1 or
antibodies to pathogen surface, requires additional protein binding to pathogen surface
(CRP)
, Lecture 2 Innate immunity: induced response to
infection
Chapter 3
Inflammation and infection
Tissue resident cells and first to respond upon infection. They are big eaters and clear pathogens by
phagocytosis, present in all tissues. Alert rest of immune system upon infection. They respond to
bacteria using pathogen recognition receptors bind to it engulfment and uptake merge with
lysosome to form phagolysosome. Also cytokine production is done, to activate other cells. They are
pro-inflammatory cytokines for induction of inflammation. Some alert tissue to make other cells able
to enter (neutrophils and complement), also help of chemokines. Neutrophils need to enter tissue
coming from high speed blood circulation, therefore using anchors of adhesion molecules and
chemokines:
1. Rolling adhesion = along walls blood
vessels
a. Selectins for weak binding
b. Integrins for moderate binding
c. Chemokines for signaling
d. Integrins for tight binding
2. Diapedesis = entering neutrophil into
tissue through CD31 from blood stream
3. Migration = movement through tissue
a. Chemokine gradient
Neutrophils express receptors for phagocytosis and toxic granules for killing, expression of multiple
receptors for pathogen recognition (CR). Neutrophils has multi-lobular nucleus, recruited to infection
site and efficient killers with short life span. Fusion with vesicles and lysosomes to form
phagolysosome. After this the neutrophil dies and cleared by macrophages.
Macrophages induce acute phase response initiating production of MBL and CRP by liver. This
activates complement system and have opsonizing function for enhanced phagocytosis.
Complement activation leads to three modes of action:
C3a = recruitment by anaphylatoxins inflammation leaky blood vessels
C3b = opsonization and induce phagocytosis phagocytes with receptors for C3b engulf
Membrane attack complex induction bacterial lysis
Receptors
Use of pattern recognition receptors (PRR), different types with different functions. Can be
extracellular or intracellular, to also detect inside of the cell. Two main types:
C-type lectin receptors phagocytosis and destruction, CLR recognize sugar on pathogen
Toll-like receptors signaling and immune cell activation, expression by many immune
cells, intra and extracellular with great diversity
