Immunology-introduction
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the questions.
Immune system
• One of basic homeostatic mechanisms of
the body.
• Its function is the recognition of
foreign/dangerous substances.
• The dangerous substances trigger
complex reactions which result in
elimination of those substances.
Immune system
• Recognizes foreign/dangerous substances
from the environment (mainly microbes)
• Is also involved in elimination of old and
damaged cells of the body.
• Attacks tumor and virus-infected cells.
Functions of the immune system
• Deffence
• Autotolerance
• Immune surveillance
Antigen
• Substance, that is recognised by the
immune system as a foreign and triggers
immune reaction (immunogenicity).
• Products of the immune reaction
(antibodies, T-lymphocytes) react with the
antigen.
Chacteristics of immunogenicity
• Foreign (unknown) for the immune system
• High molecular weight (> 6 kDa)
• Chemical complexity
Antigen – functional components
• Carrier part of the molecule
• Antigenic determinant- epitope (cca 5-7
aminoacids)
Antigen - epitopes, carrier part
Antigen - epitopes, carrier part
Antigen and epitope
Chemical composition of antigents
• Proteins – usually very good antigens.
• Polysacharides- usually only as a part of
glycoproteins.
• Nucleic acids- poor antigenicity, limited to
complexes with proteins.
• Lipids – only exceptionally, best known are
sfingolipids.
Protective and nonprotective
antigens
• Protective antigens – elicit protective
immune response that leads to elimination
of the microbe.
• Non-protective antigens – elicit nonprotective
immune response, but it does
not lead to elimination of the microbe (e.g.
antibodies against HIV).
Hapten
• Low-molecular weight substances that trigger
immune reaction after binding to various
proteins of the body.
• They react with products of the immune reaction.
• Typical examples are metals (Cr, Ni) that trigger
type IV immunopathological reactions. Drugs
(antibiotics, local anestetics) cause type I
immunopathological reaction.
Immunogenicity of hapten
Cross reactivity of antigens
• Products of the immune reaction may, in some
situations, react with substances that are very
different from the initial immunogen.
• Immunological cross-reactivity not necessary
mean similar chemical composition.
• The degree of cross reactivity may be different.
• Cross reactivity is important in pathogenesis of
several autoimmune diseases (eg rheumatic
fever).
• Cross reactivity of allergens is very important in
allergology.
Cross reactivity of anntigens
High affinity Low affinity
Ab1
Ag2
Ab1
Ag1
Adjuvants
• Substances, that, when mixed with antigen, nonspecifically
enhance immune reaction against
the antigen.
• Freud´s adjuvant: killed Mycobacterium
tuberculosis + water-in-oil emulsion. Used in
veterinary medicine.
• Alum precipitate - AL(OH)3 - used in human
medicine.
• Mechanisms: improved prezentaion of the
antigen, fixation of the antigen in the place of
application.
Two branches of the immune
response
• Innate, nonspecific – very quickly
recognizes several foreign substances and
eliminates them. There is no memory.
• Adaptive, specific – high degree of
specificity in distinction between self and
non-self. The reaction requires several
days to be effectively triggered. Immune
memory is induced.
Paul Ehrlich
Adaptive immunity
Eli Metchnikoff
Inborn immunity
Nobel price 1908
Cells of the immune system
• Main cells of the immune system
– Lymfocytes (T a B)
• Accessory cells of the immune system
– Granulocytes
– Monocytes
– Tissue macrophages
– Mast cells
– Dendritic cells
– NK cells
– Endotelial cells
– Thrombocytes, erythrocytes, fibroblasts, epitelial cells
Majority of immune system cell originate in bone marrow
Roitt/Broskoff/Male: IMMUNOLOGy, 4th ed
Differentiation of haematopoetic stem cell is
influenced by the local environment
Auxiliary cells of the immune system
Polymorphonucler (neutrophil)
granulocytes
• Approx. 60-70% leukocytes in peripheral
blood (in adults).
• Present in blood, but predominantly in
various tissues ( approx. 90%).
• Blood half life is several hours only.
• Important phagocytic cells that operate in
early phases of inflammation
• Are important cytokine producers.
• The most significant component of pus.
• Do not present antigens.
Eosinophil granulocytes
• 1-3% of leukocytes in healthy persons.
• Play a critical role in protection against parasites.
• Secrete many toxic substances affecting eucaryotic cells: MBP
(major basic protein), eosinophil peroxidase, ECP (eosinophil
cationic protein)…
• IL-5 is the most important stimulus for their formation.
• Synthetise various cytokines of the Th2 group.
• Involved inphagocytosis but do not present antigens
• Their number is increased in patients with parasitic and allergic
diseases.
• Play a very significant role in allergic inflamation by destruction of
cells and by production of cytokines.
Basophil granulocytes
• Less than 1% of peripheral leukocytes.
• Similar functions as mast cells (binding of IgE,
degranulation, secretion of pro-allergic cytokines).
• Previously considered as precursors of mast cells,
currently these two cells types are considered as products
of two different lineages.
• Enumeration of basophils has no clinical significance in
immuno-allergology.
Lymphpcytes
• 20-40% of leukocytes in adults.
• T- and B- lymphocytes ale the main cells of
the immune response.
• Also NK cell appear like lymphocytes(LGL –
large granulated lymphocytes).
• Not involved in phagocytosis.
• B-lymphocytes belong to the group of antigenpresenting
cells.
Monocytes
• 3-8% of leukocytes
• Circulating precursors of tissue
macrophages and of some types of dendritic
cells.
• Monocytes from the blood have very low
biological activity.
Downloaded from: StudentConsult (on 19 July 2006 06:34 AM)
© 2005 Elsevier
Vývoj makrofágů z monocytů
Antigen- presenting cells
Dendritic cells
• An important component of the innate immunity involved
in activation of acquired immune system cells.
• The main function is antigen processing and its
presentation to T-lymphocytes.
• They are also an important source of costimulatory
signals.
• Langerhans dendritic cells are involved in the transfer of
antigens from the epidermis of the skin.
• Non-activated dendritic cells also have a significant
phagocytic capacity.
Immature dendritic cells
• They phagocytose dead cells, various
other molecules, as well as foreign
particles and pathogenic organisms.
• TLRs are mainly involved in the uptake of
viruses or bacteria.
• Immature dendritic prodominatly supress
immune response leading to formation of
regulatory T lymphocytes.
Mature dendritic cells
They are formed by the maturation of
dendritic cells that have been activated by
PRR.
The mature dendritic cell migrates to the
lymph nodes and exposes fragments of
bacterial / viral antigens to both HLA-II and
HLA-I, thereby activating naïve CD4 + or
CD8 + lymphocytes.
Another cell involved in immune
reactions
• Epithelial cells: produce various cytokines, antibacterial
substances, are part of MALT.
• Endothelial cells: are important in regulation of leukocyte
extravasation and other parts of the inflammatory
process.
• Erythrocytes: express receptors for C3b and C4b – they
are involved in immune complexed elimination.
• Thrombocytes – important in inflammation , mainly as a
source of vasoactive substances.
• Fibroblasts: produce various cytokines.
Organs of the immune system
Thymus
Primary lymphloid organs Secondary lymphloid organs
Bone
marrow
Waldeyer´s ring (lymphs nodes,
tonsilis adenoids
Bronchus-associated lymphoid
tissue
Lymph nodes
Bone marrow
Spleen
Payer´s patch
Mesenteric lymph
nodes
Lamina propria
Urogenital lymphoid tissue
Lymph nodes
Lymph node
Roitt/Broskoff/Male: IMMUNOLOGy, 4th ed
(B-cells zone)
(T-cells zone)
The Spleen
Marginal zone of the spleeen
• Localized between white and red pulp.
• B-lymphocytes of the marginal zone are
responsible for quick response to T- cell
independent, polysacharide antigens.
• The response is mainly in IgM.
Payer ´s Patches
High endotelial venules
• Specialized venules. The site where
lymphpocytes leave the blood stream and
migrate into lymph nodes, spleen, organs
of MALT.
• Adhesion molecules enable selective
attachment of various types of
lymphocytes.
Circulation of Lymphocytes in the body
The role of High Endotelial Venules
Roitt/Broskoff/Male: IMMUNOLOGy, 4th ed