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DR.KRISHNA AGARWAL
ASSISTANT PROFESSOR
GIMSR
ANTIGEN
Universities Press
© Universities Press (India) Private Limited
ANTIGEN
 Substance - introduced parenterally
 Production of antibody
 Reacts specifically and in an observable manner
• Parenteral - outside GIT
• Specifically - particular immunocytes
• Some antigens do not induce antibody
 Sensitise specific lymphocytes
Universities Press
© Universities Press (India) Private Limited
Universities Press
© Universities Press (India) Private Limited
ANTIGEN
 Antigen – Interact specifically with antibodies, B
cell receptors and / or T cell receptors
 Immunogen – Induces detectable immune
response (humoral/cellular). Results in either
production of antibodies or activation of T cells.
Universities Press
© Universities Press (India) Private Limited
Antigenicity
 Immunogenecity
 Immunological reactivity
Universities Press
© Universities Press (India) Private Limited
ANTIGENS - 2 types
Complete antigen:
 Induce antibody - specific and observable
reaction
Hapten
 Incapable of inducting antibody
but react specifically with antibodies
 Hapten - Immunogenic on combining with larger
molecule carrier
Universities Press
© Universities Press (India) Private Limited
HAPTEN
Complex
 Precipitate with specific antibody
 Multivalent
Simple
 Non-precipitating
 Monovalent
Universities Press
© Universities Press (India) Private Limited
EPITOPE
 Smallest unit of antigenicity
 Antigenic determinant / epitope
 Epitope - 4 or 5 amino acids or monosaccharides
 Specific chemical structure , electrical charge &
Steric configuration
 Sensitising immunocyte
 Reacts with complimentary antibody or TCR
Universities Press
© Universities Press (India) Private Limited
Structure of epitope
Universities Press
© Universities Press (India) Private Limited
EPITOPE
 Linear or sequential epitope - single linear
segment of primary sequence.
Epitopes: linearised
Universities Press
© Universities Press (India) Private Limited
EPITOPE
 Conformational epitope – epitopes formed by
being brought together on surface residues from
different sites on peptide chain
Epitopes: conformational
Universities Press
© Universities Press (India) Private Limited
EPITOPE
 T cells recognise sequential epitopes
 B cells recognise conformational epitopes
 Paratope – combining area on antibody
corresponding to epitope
 Antigenic mosaic - bacteria or virus
 Antigenic cross reaction
Universities Press
© Universities Press (India) Private Limited
DETERMINANTS OF ANTIGENICITY
Size:
 Large molecules - highly antigenic
 Low molecular weight - weakly antigen
Chemical nature
 Naturally occurring antigens
Proteins / polysaccharides
 Lipids/Nucleic acid-less antigenic
Universities Press
© Universities Press (India) Private Limited
DETERMINANTS OF ANTIGENICITY
Susceptibility to tissue enzymes:
 Antigens – degraded fragments
 Phagocytosis and intracellular enzymes – antigens,
immunogenic fragments
 Synthetic polypeptides (D-amino acids) - not
antigenic,
 L amino acids - antigenic
Universities Press
© Universities Press (India) Private Limited
DETERMINANTS OF ANTIGENICITY
Foreignness ( non self )
 Induce immune response
 Ehrlich - ‘Horror autotoxicus’
 Tolerance to self antigen - during
development
 Breakdown of mechanism - autoimmunity
Universities Press
© Universities Press (India) Private Limited
ANTIGEN SPECIFICITY
 Determined - single chemical grouping
Species specificity:
 All individual in a species
 Tracing evolutionary relationships - species
 Forensic applications
blood ,seminal stains, etc.
Universities Press
© Universities Press (India) Private Limited
Isospecificity:
• lso antigens found in some but not all members
eg :Human erythrocyte antigens- blood groups
Applications
• Blood transfusion
• Isoimmunisation - pregnancy
• Disputed paternity cases
• Anthropology
• HLA antigens
Universities Press
© Universities Press (India) Private Limited
Auto specificity: Self-antigens
Sequestrated antigens – not recognised as self-
antigens
Eg ; eye lens protein , sperm
Organ specificity:
Some organs – brain kidney, lens protein of
different species share same antigen
Eg . Neuroparalytic complications – rabies
vaccine
Universities Press
© Universities Press (India) Private Limited
HETEROPHILE SPECIFICITY
Closely related antigens - different biological
species, classes, kingdoms
Heterogenetic /h eterophile antigens:
 Frossman antigen
Heterophile reactions
 Weil- Felix reaction : Typhus fever
 Paul-Bunnel test : Infectious mononucleosis
 Cold agglutinin test- primary atypical pneumonia
Universities Press
© Universities Press (India) Private Limited
BIOLOGICAL CLASSES OF ANTIGEN
T cell dependent (TD) antigens
T cell independent (TI) antigens
Universities Press
© Universities Press (India) Private Limited
BIOLOGICAL CLASSES OF ANTIGEN
T cell dependent (TD) antigens
 Most natural proteins are T cell dependent
 Require preliminary processing
 Induce a full gamut of immunoglobulin types IgM,
IgG, IgA and IgE
 Show immunological memory
 Rapidly metabolised in the body
Universities Press
© Universities Press (India) Private Limited
BIOLOGICAL CLASSES OF ANTIGEN
T cell independent antigen
 Structurally simple - composed of limited number
of repeating epitopes
Eg : Pneumococcal capsular polysaccharide,
bacterial lipopolysaccharide
 Does not require preliminary processing
 Antibody response limited to IgM and IgG3
 Do not show immunological memory
Universities Press
© Universities Press (India) Private Limited
Differences :
T cell independent
 Antigens directly stimulate
antibody production by B
cells without apparent
participation of T cells.
 Structurally simple
 Eg: capsular
polysaccharides.
 Immune response is
critically dose dependent.
 Metabolise slowly .
 Immunological memory is
absent.
 Ab response is limited to Ig
M & Ig G3
T cell dependent
 Require T cell participation to
generate immune response.
 Structurally complex.
 Eg:erythrocytes , serum
proteins
 Immunogenic over a wide
dose range & do not cause
tolerance readily.
 Rapidly metabolise.
 Immunological memory is
present.
 Induce Ig M, Ig G, Ig A, Ig E.
Universities Press
© Universities Press (India) Private Limited
SUPERANTIGENS
 Superantigens are certain protein molecules
such as staphylococcal enterotoxins, that
activate a large number of T cells, irrespective of
their antigen specificity
Universities Press
© Universities Press (India) Private Limited
SUPERANTIGENS
 Superantigens bind outside the antibody binding
groove directly to the lateral aspect of the TCR β
chain
 Conventional antigen fragments bind to the άβ
heterodimer groove of the MHC molecule
through the V region of the TCR ά and β chains
Universities Press
© Universities Press (India) Private Limited
SUPERANTIGENS
Schematic diagram of a superantigen
Universities Press
© Universities Press (India) Private Limited
Consequences :
Shock : mediated by massive release of
cytokines.
Immunosupression -- due to uncoordinated
activation of immune system.
Autoimmunity – due to bypass of
autoreactive T & B cells.
Universities Press
© Universities Press (India) Private Limited
Superantigens
• Staphylococcal superantigens :
Staphylococcus enterotoxin A – E
Staphylococcus enterotoxin G – P
Toxic shock syndrome toxin 1.
• Streptococcal superantigens -
Str pyogenes exotoxin A,B,C,E & G1
Streptococcal mitogen exotoxin Z
(most potent of superantigens)
Universities Press
© Universities Press (India) Private Limited
• Pseudomonas - Exotoxin A
• Yersinia pseudotuberculosis -
Yersinia pseudotuberculosis mitogen (YPM)
Universities Press
© Universities Press (India) Private Limited
Disease associated with superantigen
production:
• Toxic shock syndrome
• Scarlet fever
• Kawasaki disease
• Eczema
• Psoriasis
• Rheumatic arthritis
Universities Press
© Universities Press (India) Private Limited
DETERMINANTS RECOGNISED BY INNATE IMMUNE
SYSTEM
 Innate immune system recognise unique
molecular patterns - pattern recognition
 Pathogen associated molecular patterns
(PAMPs) - broad molecular patterns
 Pattern recognition receptors (PRRs) –receptors
for PAMPs
Universities Press
© Universities Press (India) Private Limited
PATTERN RECOGNITION RECEPTORS
TYPES
 Toll-like receptors (TLRs) – transmembrane
receptors present on macrophages and dendritic
cells
 Scavenger receptors – include CD 36, CD 68
and SRB-1
 Mannose receptors - receptors on the surface
of phagocytes bind mannose-rich glycans found
in microbial glycoproteins.
Universities Press
© Universities Press (India) Private Limited
THANK YOU

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Antigen - Copy.pptx

  • 2. Universities Press © Universities Press (India) Private Limited ANTIGEN  Substance - introduced parenterally  Production of antibody  Reacts specifically and in an observable manner • Parenteral - outside GIT • Specifically - particular immunocytes • Some antigens do not induce antibody  Sensitise specific lymphocytes
  • 3. Universities Press © Universities Press (India) Private Limited
  • 4. Universities Press © Universities Press (India) Private Limited ANTIGEN  Antigen – Interact specifically with antibodies, B cell receptors and / or T cell receptors  Immunogen – Induces detectable immune response (humoral/cellular). Results in either production of antibodies or activation of T cells.
  • 5. Universities Press © Universities Press (India) Private Limited Antigenicity  Immunogenecity  Immunological reactivity
  • 6. Universities Press © Universities Press (India) Private Limited ANTIGENS - 2 types Complete antigen:  Induce antibody - specific and observable reaction Hapten  Incapable of inducting antibody but react specifically with antibodies  Hapten - Immunogenic on combining with larger molecule carrier
  • 7. Universities Press © Universities Press (India) Private Limited HAPTEN Complex  Precipitate with specific antibody  Multivalent Simple  Non-precipitating  Monovalent
  • 8. Universities Press © Universities Press (India) Private Limited EPITOPE  Smallest unit of antigenicity  Antigenic determinant / epitope  Epitope - 4 or 5 amino acids or monosaccharides  Specific chemical structure , electrical charge & Steric configuration  Sensitising immunocyte  Reacts with complimentary antibody or TCR
  • 9. Universities Press © Universities Press (India) Private Limited Structure of epitope
  • 10. Universities Press © Universities Press (India) Private Limited EPITOPE  Linear or sequential epitope - single linear segment of primary sequence. Epitopes: linearised
  • 11. Universities Press © Universities Press (India) Private Limited EPITOPE  Conformational epitope – epitopes formed by being brought together on surface residues from different sites on peptide chain Epitopes: conformational
  • 12. Universities Press © Universities Press (India) Private Limited EPITOPE  T cells recognise sequential epitopes  B cells recognise conformational epitopes  Paratope – combining area on antibody corresponding to epitope  Antigenic mosaic - bacteria or virus  Antigenic cross reaction
  • 13. Universities Press © Universities Press (India) Private Limited DETERMINANTS OF ANTIGENICITY Size:  Large molecules - highly antigenic  Low molecular weight - weakly antigen Chemical nature  Naturally occurring antigens Proteins / polysaccharides  Lipids/Nucleic acid-less antigenic
  • 14. Universities Press © Universities Press (India) Private Limited DETERMINANTS OF ANTIGENICITY Susceptibility to tissue enzymes:  Antigens – degraded fragments  Phagocytosis and intracellular enzymes – antigens, immunogenic fragments  Synthetic polypeptides (D-amino acids) - not antigenic,  L amino acids - antigenic
  • 15. Universities Press © Universities Press (India) Private Limited DETERMINANTS OF ANTIGENICITY Foreignness ( non self )  Induce immune response  Ehrlich - ‘Horror autotoxicus’  Tolerance to self antigen - during development  Breakdown of mechanism - autoimmunity
  • 16. Universities Press © Universities Press (India) Private Limited ANTIGEN SPECIFICITY  Determined - single chemical grouping Species specificity:  All individual in a species  Tracing evolutionary relationships - species  Forensic applications blood ,seminal stains, etc.
  • 17. Universities Press © Universities Press (India) Private Limited Isospecificity: • lso antigens found in some but not all members eg :Human erythrocyte antigens- blood groups Applications • Blood transfusion • Isoimmunisation - pregnancy • Disputed paternity cases • Anthropology • HLA antigens
  • 18. Universities Press © Universities Press (India) Private Limited Auto specificity: Self-antigens Sequestrated antigens – not recognised as self- antigens Eg ; eye lens protein , sperm Organ specificity: Some organs – brain kidney, lens protein of different species share same antigen Eg . Neuroparalytic complications – rabies vaccine
  • 19. Universities Press © Universities Press (India) Private Limited HETEROPHILE SPECIFICITY Closely related antigens - different biological species, classes, kingdoms Heterogenetic /h eterophile antigens:  Frossman antigen Heterophile reactions  Weil- Felix reaction : Typhus fever  Paul-Bunnel test : Infectious mononucleosis  Cold agglutinin test- primary atypical pneumonia
  • 20. Universities Press © Universities Press (India) Private Limited BIOLOGICAL CLASSES OF ANTIGEN T cell dependent (TD) antigens T cell independent (TI) antigens
  • 21. Universities Press © Universities Press (India) Private Limited BIOLOGICAL CLASSES OF ANTIGEN T cell dependent (TD) antigens  Most natural proteins are T cell dependent  Require preliminary processing  Induce a full gamut of immunoglobulin types IgM, IgG, IgA and IgE  Show immunological memory  Rapidly metabolised in the body
  • 22. Universities Press © Universities Press (India) Private Limited BIOLOGICAL CLASSES OF ANTIGEN T cell independent antigen  Structurally simple - composed of limited number of repeating epitopes Eg : Pneumococcal capsular polysaccharide, bacterial lipopolysaccharide  Does not require preliminary processing  Antibody response limited to IgM and IgG3  Do not show immunological memory
  • 23. Universities Press © Universities Press (India) Private Limited Differences : T cell independent  Antigens directly stimulate antibody production by B cells without apparent participation of T cells.  Structurally simple  Eg: capsular polysaccharides.  Immune response is critically dose dependent.  Metabolise slowly .  Immunological memory is absent.  Ab response is limited to Ig M & Ig G3 T cell dependent  Require T cell participation to generate immune response.  Structurally complex.  Eg:erythrocytes , serum proteins  Immunogenic over a wide dose range & do not cause tolerance readily.  Rapidly metabolise.  Immunological memory is present.  Induce Ig M, Ig G, Ig A, Ig E.
  • 24. Universities Press © Universities Press (India) Private Limited SUPERANTIGENS  Superantigens are certain protein molecules such as staphylococcal enterotoxins, that activate a large number of T cells, irrespective of their antigen specificity
  • 25. Universities Press © Universities Press (India) Private Limited SUPERANTIGENS  Superantigens bind outside the antibody binding groove directly to the lateral aspect of the TCR β chain  Conventional antigen fragments bind to the άβ heterodimer groove of the MHC molecule through the V region of the TCR ά and β chains
  • 26. Universities Press © Universities Press (India) Private Limited SUPERANTIGENS Schematic diagram of a superantigen
  • 27. Universities Press © Universities Press (India) Private Limited Consequences : Shock : mediated by massive release of cytokines. Immunosupression -- due to uncoordinated activation of immune system. Autoimmunity – due to bypass of autoreactive T & B cells.
  • 28. Universities Press © Universities Press (India) Private Limited Superantigens • Staphylococcal superantigens : Staphylococcus enterotoxin A – E Staphylococcus enterotoxin G – P Toxic shock syndrome toxin 1. • Streptococcal superantigens - Str pyogenes exotoxin A,B,C,E & G1 Streptococcal mitogen exotoxin Z (most potent of superantigens)
  • 29. Universities Press © Universities Press (India) Private Limited • Pseudomonas - Exotoxin A • Yersinia pseudotuberculosis - Yersinia pseudotuberculosis mitogen (YPM)
  • 30. Universities Press © Universities Press (India) Private Limited Disease associated with superantigen production: • Toxic shock syndrome • Scarlet fever • Kawasaki disease • Eczema • Psoriasis • Rheumatic arthritis
  • 31. Universities Press © Universities Press (India) Private Limited DETERMINANTS RECOGNISED BY INNATE IMMUNE SYSTEM  Innate immune system recognise unique molecular patterns - pattern recognition  Pathogen associated molecular patterns (PAMPs) - broad molecular patterns  Pattern recognition receptors (PRRs) –receptors for PAMPs
  • 32. Universities Press © Universities Press (India) Private Limited PATTERN RECOGNITION RECEPTORS TYPES  Toll-like receptors (TLRs) – transmembrane receptors present on macrophages and dendritic cells  Scavenger receptors – include CD 36, CD 68 and SRB-1  Mannose receptors - receptors on the surface of phagocytes bind mannose-rich glycans found in microbial glycoproteins.
  • 33. Universities Press © Universities Press (India) Private Limited THANK YOU