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Part II

Immunology

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ANTIGEN

• Substance - introduced parenterally


• Production of antibody
• Reacts specifically and in an observable
manner
• Some antigens do not induce antibody
• Sensitise specific lymphocytes

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ANTIGEN

• Antigen – Interact specifically with


antibodies, B cell receptor and/or T cell
receptor
• Immunogen – Induces detectable immune
response (humoral/cellular). Results in
either production of antibodies or activation
of T cells.

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ANTIGEN

Parenteral - outside GIT


Specifically - particular immunocytes
antigenicity:
• Induction of immune response
(Immunogenecity)
• Specific reaction with antibodies
(Immunological reactivity)

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ANTIGENS

• Complete antigen: Induce antibody-specific


and observable reaction
• Hapten - Incapable of inducting antibody
• Hapten – Greek for to fasten
• Hapten - Immunogenic on combining with
larger molecule carrier

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HAPTEN

• Complex - precipitate with special antibody


multivalent
• Simple - non-precipitating monovalent

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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

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EPITOPE

• Linear or sequential epitope - single linear


segment of primary sequence.

Epitopes: linearised

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EPITOPE

• Conformational epitope – epitopes formed


by being brought together on surface
residues from different sites on peptide
chain

Epitopes: conformational
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EPITOPE

• T cells recognise sequential epitopes


• B cells recognise conformational epitopes
• Paratope – combining area on antibody
corresponding to epitope
• Antigenic mosaic - antigens such as
bacteria or virus carry different types of
epitopes, presenting an antigenic mosaic

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DETERMINANTS OF ANTIGENICITY

Size: Related to molecular size, large


molecules - highly antigenic
Low molecular weight - weakly antigen
Chemical nature:
• Naturally occurring antigens
• Proteins/polysaccharides
• Lipids/Nucleic acid-less antigenic

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DETERMINANTS OF ANTIGENICITY

Susceptibility to tissue enzymes:


• Antigens – degraded fragments
• Phagocytosis and intracellular enzymes –
antigens, immunogenic fragments synthetic
polypeptides, D-amino acids-not antigenic
• Amino acids - antigenic

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DETERMINANTS OF ANTIGENICITY

Foreignness - Induce immune response


Ehrlich - ‘Horror autotoxicus’
Tolerance to self antigen, during development
Breakdown of mechanism - autoimmunity

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ANTIGEN SPECIFICITY

Determined - single chemical grouping


Species specificity: All individual in a species
Forensic application - blood stains, etc.
Isospecificity: lso antigens found in some but not
all members
Example: Human erythrocyte antigen - blood
groups

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ANTIGEN SPECIFICITY

Auto specificity: Self-antigens, sequestrated


antigens – not recognised as self-antigens
Organ specificity: Some organs – brain kidney,
lens protein of different species share same
antigen

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HETEROPHILE SPECIFICITY

Closely related antigens - different biological


species, classes, kingdom
Heterogenetic/heterophile antigens:
• Frossman antigen
• Weil–Felix reaction - typhus fever
• Paul–Bunnel - infectious mononucleosis
• Cold agglutinin - primary atypical
pneumonia

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BIOLOGICAL CLASSES OF ANTIGEN

T cell dependent (TD) antigens


T cell independent (TI) antigens

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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

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BIOLOGICAL CLASSES OF ANTIGEN

T cell independent antigen


• Structurally simple - composed of limited
number of repeating epitopes as seen with
pneumococcal capsular polysaccharide,
bacterial lipopolysaccharide
• Does not require preliminary processing
• Antibody response limited to IgM and IgG3
• Do not show immunological memory

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SUPERANTIGENS

• Superantigens are certain protein molecules


such as staphylococcal enterotoxins, that
activate a large number of T cells,
irrespective of their antigen specificity

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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

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SUPERANTIGENS

Schematic diagram of a superantigen

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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

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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.

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