Transcript (non-specific) immune system

Introduction to Immunology
Martin Liška
The immune system and its importance
for homeostasis of organism
• The immune system = a system of non-specific and
specific mechanisms protecting the organism from
damage caused by infectious factors of environment
and providing surveillance of own structures
(elimination of damaged and death cells)
• The aim is maintenance of homeostasis and integrity
of macroorganism
Mechanisms of immune system
and their cooperation
1/ Innate (non-specific) immune system
- innate, not developed after the exposition to infection
- uniform response, prompt, no immunological memory
-
mechanical barriers (mucosa, skin)
phagocytic cells (microphages, macrophages)
acute phase proteins (CRP)
complement system
Mechanisms of immune system
and their cooperation
2/ Adaptive (specific) immune system
- adaptability, developed after the exposition to
infection
- the immune response is not inherited,
immunological response
- B and T cells, immunoglobulins
1/ Cells
The components of immune
system
a/ innate immune system
- neutrophils, eosinophils, basophils
- macrophages
- nature killer cells (NK cells)
b/ adaptive immune system
- lymphocytes
The components of immune
system
2/ Organs
- liver, skin etc.
- primary lymphoid organs – bone marrow, thymus
- secondary lymphoid organs - spleen, lymph nodes, mucus
associated lymphoid tissue (MALT)
The components of immune
system
3/ Substances
- The complement system
- Cytokines – molecules which ensure the communication between
the components of immune system (e.g.IFN, IL, growth factors)
- Acute phase proteins (CRP, MBL)
- Hormones (immunostimulatory/immunesuppressive effects)
- Immunoglobulins
The immune system of mucosa
and
skin
1/ Mucosa
- intact surface, clearance of surface (microcillia, saliva, tears, urine)
- lysozyme
- IgA
- lymphoid tissue of mucosa (MALT)
- macrophages (dendritic cells)
The immune system of mucosa
and skin
2/ Skin
- intact surface
- lipid barrier (eczema)
- immunocytes of the skin (e.g. Langerhans cells)
Non-specific immune mechanisms
1/ Barriers
- see above (skin, mucosa)
- secretions (fatty acids, HCl, lysozyme)
2/ Various physiological mechanisms
- body temperature
- hormones
Non-specific immune mechanisms
3/ Phagocytosis
- the process by which particular substances
or cells are ingested and destroyed by
specialized cells
- neutrophils, macrophages (monocytes,
tissue macrophages)
Neutrophils
• The most abundant population of leucocytes
(cca 70%)
• Granulocytes
• They stain a neutral pink when stained by
H&E
• Nucleus divided into 2-5 lobes, cytoplasm
with granules
• Neutrophils participate in defense against
extracellular pathogens
Neutrophils
• The average half-life in circulation is about
12 hours
• Upon activation, they marginate (position
adjacent to the endothelium) → rolling
(selectins) → adhesion to endothelium
(integrins) → diapedesis (integrins) →
chemotaxis (movement toward sites of
inflammation by cytoplasmic streaming in
response to chemotaxins (IL-8, IFN-g, C5a)
→ binding to microbe
Neutrophils - phagocytosis
• Interaction with some surface molecules of
microbes (PAMPs, lectin interactions,
binding of TLR to some surface molecules
of microorganisms)
• Opsonisation (= enhancement of binding of
phagocytes to microbes) – Ig, complement
system components, CRP, MBL
Neutrophils - phagocytosis
• Surrounding of microorganism → forming
of vacuole (phagosome) → fusion with the
lysosome → phagolysosome
• Phagosome formation depends on
contractile proteins action
Neutrophils – intracellular destruction
of microbes
1/ Oxygen independent systems
• substances that are contained in granules
• myeloperoxidase, lysozyme, alkaline
phosphatase, lactoferrin → hydrolysis
microbe’s cell wall components
• defensins → forming of channels in
microbial cell membrane
Neutrophils – intracellular
destruction of microbes
2/ Oxygen-dependent systems
• Respiratory burst
• NADPH oxidase system → production of
reactive oxygen agents (hydrogen peroxide,
superoxide anion, singlet oxygen, hydroxyl
radicals)
• Disorder of this system in CGD
Neutrophils – intracellular
destruction of microbes
2/ Oxygen-dependent systems
• Myeloperoxidase, in the presence of toxic
oxygen metabolites, catalyzes peroxidation
of surface molecules on microorganisms
Macrophages
• Intracellular destruction of microorganisms
mainly by NO synthase (system stimulated
by the action of IFN-g or TNF)
• Production of numerous substances:
lysozyme, some components of the
complement system, oxygen metabolites
(H2O2, NO), cell function regulators (IL-1,
IFN-a), arachidonic acid metabolites,
endogenous pyrogens
Natural killer cells
• Granular lymphocytes, different from T- and Blymphocytes
• Cytotoxicity to tumor cells and virally infected autologous
cells (perforins)
• Play a role in defense against some bacterial, fungal and
helminthic diseases
• Participate in reactions of antibody-dependent cellmediated cytotoxicity (ADCC)
• They are not subject to MHC restriction (= NK-cells do not
need to recognize MHC molecules in the target cells)
Natural killer cells
• They kill target cells by perforins
(formation of channels, abnormal ion flux,
depolarization, essential metabolite leakage,
cell destruction)
• NK cells are protected against perforins by
specialized cell membrane protein
(protectin)
Interferons
• Proteins that induce antiviral activity in cells
• We can distinguish two types:
a/ type I: IFN-a (macrophages and other
cells)
IFN-b (fibroblasts)
b/ type II: IFN-g (T-lymphocytes)
Function of interferons
• Stimulation of cell production of antiviral
proteins (protein kinase, oligonucleotide
polymerase – interference with the
translation of viral mRNA)
• Enhancement of T-cell activity
• Activation of macrophages
• Enhancement of NK cells cytotoxic action
Adaptive immune mechanisms
1/ Humoral
- generation of antibodies (Ig) – B cells (plasma cells)
- in majority of antigens, the cooperation with T helper
cells is necessary
2/ Cell-mediated
- generation of antigen-specific T cells (helper,
cytotoxic)
- antigen presentation is necessary
Adaptive immune mechanisms
• Antibodies → neutralization and
opsonization (specific „adapter“) of
microbes, complement system activation
• T cells → cytotoxic effects to microbes,
help for B cells, macrophages activation,
cytokines
Innate/adaptive immune
mechanisms
• Innate (non-specific) immune system: prompt
reaction x less effective, less directed
• Adaptive (specific) immune system: slower
development of reaction x more effective, more
directed, immunological memory
• Both systems cooperate (complement system is
activated by IC, cytokines recruit other cells to the
site of reaction, antigen presentation)