OIA1010 ANTIGEN & IMMUNOGENECITY

Antigen, Epitopes & Haptens

Epitope (Antigenic Determinants)

Antibody don't bind whole infectious agent but only part produced by specific antibody: antigenic determinant

Expose active areas of molecules with antibody can combine

Antigen vs. Immunogen

Antigen: any agent capable of binding specific to component of immune response (antibodies or lymphocytes)

Stimulating formation of antibody (humoral immune response) & develop cell-mediated immune response

Reacting specifically with antibodies (humoral immune response) or T-lymphocytes (cell-mediated immune response)

Immunogen: any agent capable of inducing immune response

Antigenicity: property of Antigen to react with product of specific immune response (antibody or specific sensitised T-lymphocytes)

Immunogenicity: property of immunnogen that endows with capacity to provoke specific immune response: contain surface grouping (amino acids, polysaccharides = epitotes)

Haptens (low MW): immunogenic when conjugated with high MW carrier

Requirements for Immunogenicity

Foreigness

Ability of immune system to distinguish "self" and "non-self"

Requires higher MW, more

More foreign: more immunogenic -> stronger immune response

Exception in some disease: immune system attack own body tissues (autoimmunity)

High Molecular Weight (MW)

Need minimal molecular weight to be recognised:

<1000Da (e.g., penicillin, progesterone, aspirin) not immunogenic

1000-6000Da (e.g., Insulin, ACTH) may not immunogenic

> 6000Da (e.g., albumin, tetanus toxin) general immunogenic

Chemical Complexity

Must certain physicochemical complexity

Homopolymers of amino acids (big enough but non-immunogenic)

Complexity increases: add various moieties

Primary: amino acid sequence;

Secondary: polypeptide chain backbone (alpha-helix or beta-pleated sheet);

Tertiary: 3d configuration of protein, folding of polypeptide chain & held by disulfide bridges, H-bonds, hydrophobic interaction, etc.)

Degradability

Antigens processed by APC (enzymatic degradation) & presented to T cells via MHC

Must susceptible to partial enzymatic degradation

D-amino acids (stable ) & L-isomers

Antigenicity

Bind specific to components of immune response

Requires specific receptors

Epitope: antigen portion that binds specifically to binding site

Type of Immune Response

Humoral Immune Response

Bacteria engulf by phagocytes -> expose to specific B cells & recognise antigen -> differentiate into plasma cells -> produce antibodies -> antibodies inactivate bacteria & attract phagocytes

Cell-mediated Immune Response

Infected cells engulf by phagocytes -> form APC

Viral antigen expose to specific T cells -> differentiate into Tc cells (contain toxic proteins) -> bind and release cytokines into infected cells -> destroy infected cells & repeats

Type of Antigen

Tolerogens

Provoke specific immune non-responsiveness due to molecular form

Induces tolerance (specific suppression of immunoresponsiveness due to prior exposure to certain antigen)

Unresponsiveness to antigen -> immunological reaction (e.g., Grafting)

*If molecular form changed -> Tolerogens become immunogen (autoimmune disease)

Immunological Tolerance

Natural tolerance for own antigens & proteins, but when fail self tolerace -> autoimmune disorder

Induced tolerance due to external antigens due to manipulation such as medications

*Organ transplantation: body forced to accept an external organ (if fail -> transplant rejection)

Allergen

Specialised class of immunogens: induce hypersensitivity type I

Origin of Antigen

Exogenous Antigen

Entered body through inhalation, ingestion or injection

Phagocytosis: antigens taken to APC & processed into fragments to T helper cells (CD4+) using Class II MHC molecules on their surface

Activate Th cells -> secrete cytokines -> activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages & other cells

T Helper Cells (Th cells)

Unusual: no cytotoxic or phagocytic activity

Involved in activate & directing other immune cells (important for acquired immunity)

Important: determine B cell antibody switching, activation & growth of cytotoxic T cells and maximise bactericidal activity of phagocytes

Mature Th cells: always express surface protein CD4 -> form CD4+ T cells

*HIV infect CD4+ (including Th cells) -> decrease functional CD4+ T cells -> AIDS

Major Histocompatibilty Complex (MHC) aka. HLA molecules

Matured MHC molecules anchored in cell membrane: display short polypeptide to T cells via T cell receptors (TCRs)

Polypeptides: may be "self" or "non-self" (bacteria, virus, Allergen & etc.)

Overarching design of MHC-TCR interaction: T cell ignore self peptides

Protein act as "signpost": display fragment pieces of Antigen on host cell Surface

*If infected foreign: class I MHC molecule (endogenous pathway) -> engulf by leukocyte and destroyed -> display Class II MHC molecule (exogenous pathway)

Endogenous Antigen

Generated within cells due to normal cell metabolism or infection

Fragments presented on cell Surface of Class I MHC -> activated CD8+ T cells recognise and secrete cytotoxins -> infected cell lysis or apoptosis

Cytotoxic T Cell (Tc or killer T cells)

Induce death of infected somatic (damage or dysfunctional) or tumor cells

Most express T-cell receptors (TcRs): recognise specific peptide antigen bound to Class I MHC molecules

Express CD8: attract to portion of Class I MHC -> affinity keeps Tc cell and target cell bound closely during antigen-specific activation

Tc cells with CD8 surface protein: CD8+ T cells -> predefined cytotoxic role

Autoantigen

Usually normal protein or complex of protein (sometime DNA or RNA) recognised by immune system of autoimmune disease

Normal not target, but lost immunological tolerance to these antigens due genetic & environmental factors