Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove...
-
Upload
ashlie-simmons -
Category
Documents
-
view
220 -
download
0
Transcript of Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove...
![Page 1: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/1.jpg)
Complement
J. Ochotná
![Page 2: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/2.jpg)
Complement
humoral component of nonspecific immunity
helps remove microorganisms and own altered cells (apoptotic
cells)
complement proteins are synthesized in the liver, less by tissue
macrophages and fibroblasts
![Page 3: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/3.jpg)
system of about 30 serum and membrane
proteins
complement components are present in serum
in inactive form
complement activation has cascade character
Complement
![Page 4: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/4.jpg)
the main complement components: C1-C9 (C3 is the
central component)
other complement components: factor B, factor D, factor P
regulatory proteins: C1 - inhibitor, factor I, factor H, C4bp,
DAF, MCP, CR1, factor S (vitronectin), CD59 (protektin),
anaphylatoxin inactivator
Complement
![Page 5: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/5.jpg)
Biological significance
Opsonization (C3b, C4b)
Chemotaxis (C3a, C5a)
Osmotic lysis (MAC C5b-C9)
Anaphylatoxins (C3a, C4a, C5a)
![Page 6: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/6.jpg)
Riedemann N.C.
Pathways of complement activation
• Classical pathway
• Alternative pathway
• Lectin pathway
![Page 7: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/7.jpg)
Classical and alternative pathway
![Page 8: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/8.jpg)
Alternative complement pathway
C3 component of complement rarely spontaneously
breaks into C3b and C3a
C3b can covalently bind on the surface of a particle (own
cell, microorganism) or reacts with water, thereby
inactivates
![Page 9: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/9.jpg)
to bound C3b joins a factor B, which is cleaved by
factor D to Ba and Bb, resulting complex C3bBb is
stabilized by factor P (properdin) and functions as
an alternative C3 convertase
Alternative complement pathway
![Page 10: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/10.jpg)
C3 convertase cleaves C3 to C3a (chemotaxis)
and C3b, which binds to the surface of the
particles (opsonization), or gives rise to other C3
convertases
Alternative complement pathway
![Page 11: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/11.jpg)
some C3 convertases form C3bBbC3b that act as
an alternative C5 convertase, which cleaves
C5 to C5a (chemotaxis) and C5b (starts terminal
lytic phase)
Alternative complement pathway
![Page 12: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/12.jpg)
Alternative complement pathway
C5b starts terminal lytic phase
![Page 13: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/13.jpg)
Classical complement pathway can be initiated by antibodies IgG ( not by IgG4)
and IgM or by pentraxins (CRP, SAP - acute phase
proteins)
after binding of antibodies to the bacteria
surface, Ab changes its conformation and than
can bind C1 protein
![Page 14: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/14.jpg)
C1 changes its conformation and acquires
proteolytic activity, than cleaves C4 and C2
proteins
Classical complement pathway
![Page 15: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/15.jpg)
fragments C4b and C2a bind to the surface of
microorganism and create the classic C3
convertase (C4bC2a), which cleaves C3 to C3a
and C3b
Classical complement pathway
Description of C3
convertase has
been modified to
C4bC2a
![Page 16: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/16.jpg)
then creates a classic C5 convertase
(C4bC2aC3b) that cleaves C5 to C5a and C5b
Classical complement pathway
![Page 17: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/17.jpg)
Lectin complement pathway
is initiated by serum mannose binding lectin (MBL)
MBL binds to mannose residues on the surface of
some microbes, after this binding starts cleave C4
and C2
this way is similar to the classical pathway
![Page 18: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/18.jpg)
Lectin complement pathway
![Page 19: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/19.jpg)
Terminal (lytic) phase of the complement cascade C5b fragments creates a complex with C6, C7 and C8,
the complex dive into the lipid membrane of the cell and
attache into a circle 13-18 molecules of C9 => MAC
(membrane attack complex), forms a transmembrane
channel, which causes osmotic lysis of the target cell
(G-bacteria, protozoans, some viruses).
Most microorganisms are resistant to this lytic effect of
complement (protection by cell wall).
![Page 20: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/20.jpg)
Terminal phase of the complement cascade
![Page 21: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/21.jpg)
Complement activation and efector functions
![Page 22: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/22.jpg)
Complement regulation and protection of own cells
Activation of complement cascade is controlled by the plasma and membrane inhibitors.
MCP DAF Protectin
Anaphylatoxin inactivator
![Page 23: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/23.jpg)
Complement regulation
C1 inhibitor (C1-INH) – inhibits C1; if missing→
HAE
factor I with cofactors: MCP (membrane cofactor
protein), CR1, factor H – C3b, C4b cleavage
DAF (decay-accelerating protein)-degradation of
C3 and C5 convertase
![Page 24: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/24.jpg)
factor S (vitronectin) – inhibits complex C5bC6
CD 59 (protectin) - prevents the polymerization of C9
anaphylatoxin inactivator (CPN)- inactivates
anafylatoxins (C3a, C4a, C5a)
Complement regulation
![Page 25: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/25.jpg)
Complement receptors Bind fragments of complement components
CR1 - on various cells
- promotes C3b, C4b decay
- stimulate phagocytosis
- erythrocyte transport of
immunecomplexes
CR2 - on B lymphocytes and FDC
- activation of B cells
![Page 26: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/26.jpg)
CR3, CR4 - on phagocytes
- participation in opsonization,
adhesion
C3aR, C5aR – receptors for anaphylatoxins
- mast cell activation
Complement receptors
![Page 27: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/27.jpg)
![Page 28: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/28.jpg)
4 basic complement functions
Opsonization (C3b, C4b)
Chemotaxis (C3a, C5a)
Osmotic lysis (MAC C5b-C9)
Anafylatoxins (C3a, C4a, C5a)
![Page 29: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/29.jpg)
Basophils and mast cells
and their importance in
immune responses
![Page 30: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/30.jpg)
Mast cells
Mucosal mast cells - in the mucous membranes of
respiratory and gastrointestinal tract, produce histamine,
serotonin, heparin, tryptase, leukotriene C4 ..., participate
in parasitosis and allergy
Connective tissue mast cells – in the connective tissue,
producing tryptase, chymase, prostaglandinD2 ..., are
multiplicated in fibrosis, in parasitosis and allergy are not
participating
![Page 31: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/31.jpg)
Mast cell functions
Defense against parasitic infections
In pathological circumstances, responsible for the
early type of hypersensitivity (immunopathological
reaction type I)
Apply during inflammation, in angiogenesis, in
tissue remodeling
![Page 32: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/32.jpg)
Mast cell activation
Mast cells can be stimulated to degranulate by:
cross-linking of IgE receptors (FcRI)
anafylatoxins (C3a, C4a, C5a)
TLR
![Page 33: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/33.jpg)
Mast cell activation by cross-linking of IgE Fc receptors
Binding of IgE to highaffinnity Fc
receptor for IgE (FcRI)
Binding of multivalent antigen
(multicellular parasite) to IgE
Aggregation of several
molecules of FcRI
![Page 34: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/34.jpg)
Mast cell activation
Mast cell degranulate (cytoplasmic granules mergers
with the surface membrane and release their contents)
Activation of arachidonic acid metabolism (leukotriene
C4, prostaglandin D2)
Start of production of cytokines (TNF, TGF, IL-4, 5,6 ...)
![Page 35: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/35.jpg)
Secretory products of mast cells
Cytoplasmatic granules: hydrolytic enzymes, histamine, heparin, chondroitin sulphate, serotonin
Histamine - vasodilation, ↑ vascular permeability(erythema, edema, itching), bronchoconstriction, ↑ intestinal peristalsis, ↑mucus secretion in the respiratory tract and GIT (helps eliminate the parasite)
Arachidonic acid metabolites (leukotriene C4, prostaglandin D2)
Cytokines (TNF, TGF , IL-4, 5,6 ...)
![Page 36: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/36.jpg)
Basophils Differentiate from myeloid precursor
Receptor equipment, content of granules, the
mechanisms of stimulation and functions are very
similar to mast cells
Play a role in parasitic infections and allergies
Basophil activation markers: CD 63, (CD 203)
![Page 37: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/37.jpg)
Immune mechanisms
of inflammation
(Local and systemic
reactions)
![Page 38: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/38.jpg)
Inflammation
Is a protective physiological response leading to
protection against infection in damaged sites,
localization of damage, elimination of necrotic
cells and tissue repair.
![Page 39: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/39.jpg)
Local body's response to inflammation
Classical signs - pain (dolor), fever (calor), redness (rubor), swelling (tumor)
![Page 40: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/40.jpg)
Inflammation
• The first signals for the development of inflammatory
response come from mast cells, phagocytes, and the
substances released from damaged cells and
components of extracellular matrix.
• With longer duration of local inflammation are
activated an antigen-specific mechanisms (T and B
lymphocytes).
![Page 41: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/41.jpg)
Inflammation
![Page 42: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/42.jpg)
Inflammation – local reaction
• vasodilation, ↑ vascular permeability (histamine, serotonin,
bradykinin, complement components C3a, C5a, leukotrienes ,
prostaglandins, …) → rednes, swelling
• ↑expression of adhesion molecules on endothelia
(TNF, IL-1) → leukocyte adhesion to the endothelium
• influence of local nerve endings via prostaglandins → pain
• Increased local temperature (IL-1, IL-6, TNF, prostaglandins)
![Page 43: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/43.jpg)
Inflammation - systemic reaction
• Leukocytosis
• Fever (TNF, IL-1, IL-6, IFN
↑ tissue metabolism
↑ mobility of leukocytes
↑ formation of IFN, cytokines, Ig
↑ expression of Hsp
• Acute phase proteins (IL-6, TNF, IL-1)
CRP, SAP - opsonization and complement
activation
![Page 44: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/44.jpg)
Inflammation - systemic reaction
• Septic shock - the massive penetration of
microorganisms into the bloodstream (TNF)
• Anaphylactic shock - basophil and mast cells
activation with allergen (histamine)
![Page 45: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/45.jpg)
Tissue repair
• elimination of damaged cells with phagocytes
• activation of fibroplastic mechanisms
• activation of angiogenesis
• regeneration and tissue remodeling
![Page 46: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/46.jpg)
Antigens
![Page 47: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/47.jpg)
Antigen (immunogen)
substance which provokes specific immune response
usually proteins or polysaccharides (lipids and nucleic acids only in the combination with proteins or polysaccharides)
molecules > 5 kDa (optimal size of the antigen molecules is about 40 kDa)
![Page 48: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/48.jpg)
Hapten small molecules, that are able to induce specific
immune response only after the attachment
to the macromolecular carrier
separate haptens are not immunogenic
typically drugs (eg penicillin antibiotics, hydralazin)
![Page 49: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/49.jpg)
Epitope (antigenic determinant)
part of the antigen which is recognized by
immune system (lymphocytes- BCR, TCR, Ig)
cross-reactive antigens - shares one or more
identical or similar epitopes
![Page 50: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/50.jpg)
Interaction antigen – antibody
Binding site of antibody (paratop)
form non-covalent complexes with
the corresponding part on antigen
molecule (epitope)
participation: the hydrogen bonds,
electrostatic and hydrophobic
interactions, van der Waals forces
antigen-antibody complex is reversible
![Page 51: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/51.jpg)
Antigen
endogenous antigens - autoantigens (self Ag)
exogenous antigens - foreign substances from the
environment
allergen is exoantigen that in the susceptible individuals
can cause pathological (allergic) immune response
![Page 52: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/52.jpg)
Properties of antigen
immunogenicity
proteins> carbohydrates> macromolecule
complexes (glycoproteins, nucleoproteins, and
glycolipids)> lipids
specificity
![Page 53: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/53.jpg)
Factors affecting immunogenicity
Physical:
solubility - insoluble Ag more immunogenic
molecular weight - ideal 5-40 kDa
Chemical:
structure - the number of determinants
degradability - "ease" of uncovering the determinants
in antigen presenting cells (APC cell)
![Page 54: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/54.jpg)
Biological:
biological heterogeneity
genetic and physiological disposition of the body
Properties of antigen
![Page 55: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/55.jpg)
Degree of foreignness Autogeneic - antigens of the same individual
Syngeneic - antigens of genetically identical
individuals (eg twins)
Allogeneic (alloantigens) - antigens genetically
different individuals of the same species
Xenogeneic (heterologous) - antigens derived
from individuals of different species
(eg monkey kidney transplant man)
![Page 56: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/56.jpg)
Types of antigens according to antigen presentation
T- dependent antigens
T- independent antigens
![Page 57: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/57.jpg)
Thymus dependent antigens
more frequently, mostly protein Ag
for specific humoral immune response to antigen
is necessary assistance of TH lymphocytes
(or response isn´t enough effective)
assistance implemented in the form of cytokines
produced by TH lymphocytes
![Page 58: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/58.jpg)
T- independent antigens
can stimulate B cells directly
mainly bacterial polysaccharides,
lipopolysaccharides and polymer forms of
proteins (e.g. Haemophilus, Str.pneumoniae)
![Page 59: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/59.jpg)
T-independent pathway
![Page 60: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/60.jpg)
Superantigens
stimulate T cells polyclonaly and massively
(massive cytokine release)
massive activation of T cells can cause shock
e.g. bacterial toxins (Staph.aureus, Str.pyogenes,
Pseud.aeruginosa)
![Page 61: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/61.jpg)
• Proteins (microbial products) which have 2
binding sites, one interacts with the epitope
presented on all MHCgpII, second interacts with
other structures presented in many different TCR
molecules (connection of T lymphocyte with APC)
Superantigens
![Page 62: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/62.jpg)
Differcence between antigen and superantigen binding
![Page 63: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/63.jpg)
Sequestered antigens
autoantigens, that are normally hidden to
immune system and therefore unknow (e.g. brain,
the lens of the eye , testes)
if they are "uncovered" by demage, exposed to
the immune system, are recognized as foreign
(one of the theories of autoimmune processes)
![Page 64: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/64.jpg)
Immunologically privileged sites
brain, eye, gonads
are protected from potentially damaging
inflammatory immune responses
this tissues are far less rejected in allogeneic
transplant (cornea)
this privileged position is not absolute
![Page 65: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/65.jpg)
Immunologically privileged sites
Mechanisms of protection from the immune system:
isolation from the immune system (blood-brain barrier)
preferences of Th2 and suppression of Th1-response
production of immunosuppressive cytokines (TGFβ)
FasL expression -active protection against effector
T-lymphocytes
increased expression of membrane complement
inhibitors
![Page 66: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/66.jpg)
Thank you for your attentionThank you for your attention
![Page 67: Complement J. Ochotná. Complement humoral component of nonspecific immunity helps remove microorganisms and own altered cells (apoptotic cells)](https://reader036.fdocuments.us/reader036/viewer/2022062409/5697bff31a28abf838cbca3a/html5/thumbnails/67.jpg)
• Komplement – klasická cestahttps://www.youtube.com/watch?v=vbWYz9XDtLw
• Komplement – klasická a alternativní cestahttps://www.youtube.com/watch?v=aNh5A0gtuLE
• Komplement – alternativní cestahttps://www.youtube.com/watch?v=qga3Wn76d9w
• Akutní záněthttps://www.youtube.com/watch?v=suCKm97yvyk