DEFINITION AND PROPERTIES OF ANTIGEN IMMUNOLOGICAL DEFINITION Any chemical structure Soluble or...
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Transcript of DEFINITION AND PROPERTIES OF ANTIGEN IMMUNOLOGICAL DEFINITION Any chemical structure Soluble or...
DEFINITION AND PROPERTIES OF DEFINITION AND PROPERTIES OF ANTIGENANTIGEN
IMMUNOLOGICAL DEFINITIONAny chemical structure
Soluble or corpuscle
Simple or complex
Originated from the body or comes from outside
Genetically self or non-self
Natural or artificial
DEFINITIONSDEFINITIONSANTIGEN (Ag) - any substance, which is recognized by
the mature immune system of a given organism
ANTIGENICITY– capability of an antigen to bind to bind specificallyspecifically with certain product of the adaptive immunity: TCR or BCR/antibody,
– immunogenicity - capability of an antigen to induceinduce an (adaptive) immune response,
– tolerogenicity - capability to induce immunological tolerance, specific immune non-responsiveness
FACTORS INFLUENCING FACTORS INFLUENCING IMMUNOGENICITY I.IMMUNOGENICITY I.
• Foreignness
• Size
• Genetics– Species– Individual
• Age
FACTORS INFLUENCING FACTORS INFLUENCING IMMUNOGENICITY II.IMMUNOGENICITY II.
• Dose
• Route subcutaneous > intravenous > oral / intranasalNot true for live vaccines (i.e. oral polio vaccine)
• Adjuvant– substances that enhance an immune response to an
antigen (aluminum salts, LPS, Freund’s adjuvant, TLR ligands)
COMPLEX EFFECTS – depot effect – slower biodegradation, prolonged antigen
intake by antigen presenting cells– activation of innate immunity
FACTORS INFLUENCING FACTORS INFLUENCING IMMUNOGENICITY III.IMMUNOGENICITY III.
• Physical status
– corpuscle (cell, colloid) or soluble
– denatured or native
• Degradability
– antigen presentation by APC
part of the antigen which is recognized by a defined immunoglobulin (BCR / antibody) or by T cell receptor
ANTIGENIC DETERMINANT (ANTIGENIC DETERMINANT (==EPITOPE)EPITOPE)
Ab1Ab2
hidden/revealed determinant
denaturation
new/neoantigen determinant
conformational determinant
cleveage
conformational/linear determinant
TYPES (STRUCTURE) OF ANTIGEN DETERMINANTSTYPES (STRUCTURE) OF ANTIGEN DETERMINANTS
surface/accessible determinants
linear determinantlinear determinant conformational determinantconformational determinant
(TCR, BCR, Ig) (BCR, Ig)
B cell epitopeB cell epitope T cell epitopeT cell epitope
recognized by B cells
• proteins polysaccharides lipids DNA steroids etc. (many artificial molecules)
• cell or matrix associated or soluble
recognized by T cells
• proteins mainly (8-23 amino acids)
• requires processing by APC
ANTIGEN RECOGNITION BY NAIVE T CELLS REQUIRES ANTIGEN RECOGNITION BY NAIVE T CELLS REQUIRES PRESENTATION VIA MHC MOLECULESPRESENTATION VIA MHC MOLECULES
Recognition/No activation
Recognition/Activation
SUPERANTIGENSSUPERANTIGENS
Microbial proteins that bind to and activate all the T cells that express a particular set or family of TCR molecules resulting in a polyclonal activation.
Interaction is not via the peptide binding cleft of MHC molecule.
Hypotension
Rash
Desquamation
Fever
conventional antigen
monoclonal/oligoclonal
T cell response
1:104 - 1:105
superantigen
polyclonal
T cell response
1:4 - 1:10
Microbial proteins that bind to and activate all the T cells in an individual that express a particular set or family of TCR molecules
107 – 108 / 1011 1010 / 1011activated T cells
SUPERANTIGENSSUPERANTIGENS
SUPERANTIGENSSUPERANTIGENS
Classification Sources
Endogenous
Exogenous
B cell
1.Mouse mammary tomor virus (MMTV)2.Epstein-Barr virus (EBV) 1.Staphylococcal enterotoxins (SEs): A, B, C1 to C3, D, E, G to Q 2.Staphylococcal toxic shock syndrome toxin-1 (TSST-1) 3.Staphylococcal exfoliative toxins: exoliatin A, exfoliatin B 4.Staphylococcal enterotoxin-like toxins formed due to recombination within enterotoxin gene cluster: U2, V 5.Streptococcal pyrogenic exotoxins (SPEs): A1 to A4, C, G to M 6.Streptococcal mitogenic exotoxins: SMEZ 7.Streptococcal superantigen :SSA 8.Yersinia pseudotuberculosis: Yersinia pseudotuberculosis-derived mitogen (YAM) 9.Mycoplasma species: Mycoplasma arthritidis-derived mitogen (MAM) 10.Cholera toxin: subunit A of cholera toxin 11.Prevotella intermedia*12.Mycobacterium tuberculosis*•Viral superantigens: (a) Mouse leukemia virus (b) IDDMK1222- Ppol-ENV-U3 (c) HIV-Nef (d) Rabies virus-nucleoside protein •Staphylococcal protein A 1.Protein Fv (PFv)
.
T CELLT CELL--DEPENDENT BDEPENDENT B CELL ACTIVATIONCELL ACTIVATION
Polysacharides are not presented!
B cell
cytokines
CD4TCR
MHCII+peptide T cell
2
1
T-INDEPENDENT ANTIGENTI-1
T-INDEPENDENT ANTIGENTI-2
Strong crosslinking of BCRcrosslinking of BCR by repetitive polysaccharide or
protein epitopes
Simultaneous activation of BCR and BCR and other receptorsother receptors on B cells (i.e. LPS
binding protein /CD14) induces the B cells to proliferate and differentiate
B cell
B CELL ACTIVATION (extensive receptor-aggregation)(extra activation signal)
B CELL ACTIVATION WITHOUT THE HELP OF T CELLSB CELL ACTIVATION WITHOUT THE HELP OF T CELLS
Microorganisms have several Microorganisms have several different different cell surface epitopescell surface epitopes
Haptenic/antigen determinant (epitope)
part of the antigen which are recognized by a defined immunoglobulin (B cell receptor or antibody) or by T cell receptor
COMPLEX ANTIGENSCOMPLEX ANTIGENS CONSIST OF THE CARRIER AND CONSIST OF THE CARRIER AND MULTIPLE EPITOPES (=ANTIGEN DETERMINANTS)MULTIPLE EPITOPES (=ANTIGEN DETERMINANTS)
Carrierpart of the antigen directly not involved in connection with the defined Ig/BCR or TCR
These terms can only be used to describe the interaction of particular antigenic determinant and single immunoglobulin or T cell receptor
HAPTENsubstance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Free haptens, however, can react with products of the immune response after such products have been elicited. Haptens have the property of antigenicity but not immunogenicity.
carrier + hapten
Small chemical structures that cannot induce B cell response on their own (e.g. drugs, reactive compounds)
hapten
(i.e. DNP:dinitrophenyl)
-
+
HAPTENSHAPTENS
hapten +
1.
2.
primed
carrier specific hapten specific carrier + hapten specific
carrier + haptenantibodies
Antibody response generated against a hapten-carrier conjugate
INTERACTION BETWEEN INTERACTION BETWEEN MICROORGANISMS AND THE MICROORGANISMS AND THE
IMMUNE SYSTEMIMMUNE SYSTEM
Symbiotic, non-pathogenic microbes– mucosal membrane, skinBacteria, Fungi, Protozoa Gut – colonalization after birth1012 bacteria/g intestinal content1000 species100-times more bacterial genes than eukaryotic
- „peaceful” commensalisms- vitamins (i.e. K1 vitamin)- real ecosystem, survival of the fittest,
competition with pathogenic organism- the few who brake in through the gut epithelium induce local immune response
PatogensBacteria, Fungi, Protozoa,VirusesHelmints
COMPLEX ANTIGENS
Strong immunogens
ANTIGENIC PROPERTIES OF PATHOGENIC ANTIGENIC PROPERTIES OF PATHOGENIC AND NON-PATHOGENIC ORGANISMS AND NON-PATHOGENIC ORGANISMS
Important role in:- development of mucosal and systemic immunity- normal development of peripheral lymphoid organs- maintenance of basic level of immunity
HEALTHY MICROFLORA IS REQUIRED FOR PROPER HEALTHY MICROFLORA IS REQUIRED FOR PROPER DEVELOPMENT OF THE IMMUNE SYSTEMDEVELOPMENT OF THE IMMUNE SYSTEM
THE SKIN AND MUCOSAL EPITHELIUM AS INNATE BARRIERS THE SKIN AND MUCOSAL EPITHELIUM AS INNATE BARRIERS
ACUTE ACUTE IINFLAMMATIONNFLAMMATION
• Acute inflammation is a rapid response to an injurious agent that serves to deliver mediators of host defense — leukocytes and plasma proteins — to the site of injury.
• Acute inflammation has three major components:
1) alterations in vascular caliber that lead to an increase in blood flow
2) structural changes in the microvasculature that permit plasma proteins and leukocytes to leave the circulation
3) emigration of the leukocytes from the micro-circulation, their accumulation in the focus of injury, and their activation to eliminate the offending agent
ACUTE INFLAMMATORY REACTIONS ARE ACUTE INFLAMMATORY REACTIONS ARE TRIGGERED BY A VARIETY OF STIMULITRIGGERED BY A VARIETY OF STIMULI::
• Infections (pathogenic microbes and microbial toxins)
• Trauma (blunt and penetrating)• Physical and chemical agents (thermal
injury e.g. burns or frostbite; irradiation; some environmental chemicals)
• Tissue necrosis (from any cause)• Foreign bodies (splinters, dirt, sutures)• Immune reactions (hypersensitivity and
autoimmune reactions)
The classic symptoms of inflammation:
redness (rubor), swelling (tumor), heat (calor), pain (dolor),loss of function (functio laesa)
CHEMICAL MEDIATORS OF CHEMICAL MEDIATORS OF INFLAMMATIONINFLAMMATION I. I.
• Vasodilation– prostaglandins, nitric oxide
• Increased vascular permeability– vasoactive amines (histamine, serotonin),
C3a and C5a, bradykinin, leukotrienes, PAF
• Chemotaxic leukocyte activation– C3a, C5a, LTB4, chemokines
CHEMICAL MEDIATORS OF CHEMICAL MEDIATORS OF INFLAMMATIONINFLAMMATION II. II.
• Fever– IL-1, IL-6, TNF, prostaglandins
• Pain– prostaglandins, bradykinin
• Tissue damage– neutrophil and macrophage products
• lysosomal enzymes• oxygen metabolites• nitric oxide (NO)
ENDOTHELIAL ADHESION MOLECULES DURING INFLAMMATION ENDOTHELIAL ADHESION MOLECULES DURING INFLAMMATION
Pus is a whitish-yellow, yellow, or yellow-brown exudate produced by vertebrates during inflammatory pyogenic bacterial infections. Pus consists of a thin, protein-rich fluid, known as liquor puris, and dead cells.
PUS PUS
CONSEQUENCECONSEQUENCESS OF OF MACROPHAGE AMACROPHAGE ACTIVATIONCTIVATIONSYNTHESIS OF SYNTHESIS OF CCYTOKINESYTOKINES
Liver
Mannose binding
lectin/proteinMBL/MBP
Fibrinogen
Serum amyloid protein (SAP)
C-reactive protein (CRP)
UNDER THE INFLUENCE OF IL-6 THE LIVER PRODUCES A BUNCH OF ACUTE-PHASE PROTEINS
ComplementIL-6
ACUTE PHASE REACTIONACUTE PHASE REACTION
SEPTIC SHOCKSEPTIC SHOCK
Triggering factors : • systemic infection (bacteraemia)• microbial cell wall products and/or
toxins released from the pathogens
Result: Systemic activation of
neutrophils and macrophages
High level of cytokine (TNF-alpha) production: „cytokine storm”
Excessive inflammatory response
SEPTIC SHOCKSEPTIC SHOCK
The key molecule of the process: TNF-alpha
TNF-alpha and other inflammatory cytokines
capillar permeability blood pressure
DIChigh fever multiorgan failure
Therapy: anti-TNF-alpha antibody
disseminated intravascular
coagulation
DICDICDDisseminated isseminated IIntravascular ntravascular CCoagulationoagulation
• pathologic activation of thrombotic process
• distress of thrombotic process, bleeding
• other causes: snake bite, septic abortion, acute obstetric complications, malignant tumors, leukemias