L8 Antigens and Immune regulation

Immunogen

Substance that induces a specific immuner esponse

antigen (Ag)

substance that reacts with the products of a specific immune response

Hapten

Non-immunogenic, but can react with the products of a specific immune response

Epitope (antigenic determinant)

Portion of the antigen that combines with the products of a specific immune respons

Antibody (Ab)

protein that is produced to an immunogen and which reacts with an antigen

Factors influencing immunogenicity

Contibution of the antigen

Foreigness

Size, large > small

Chemical composition

Physical form, solubility, naitve or denatured

Degradability

Factors influencing immunogenicity

Contirbution of the biological system

Genetic factors

Age

Factors influencing immunogenicity

Method of administration

Dose, optimum

Route, e.g. subcutaenous, intravenous

AdjuvantsC

Chemical nature of immunogens

Proteins

Polysaccharides

Nucleic acids

Lipids

Haptens

An incomplte immunogen, which is unable to induce an immune response, but can react with components of the immune system (e.g. antibodies)

Haptens are small molecules (<10 kDa)

Haptens need to be boudn to a carrier molecule to induce an immune response (hapten-carrier model)

Carrier - hapten

INjection with, antibodies formedS

hapten-carrier conjugate:

antibodies to hapten, antibodies to carrier, antibodies to conjugate of hapten and carrier

Protein + haptne

hapten induced conformational change

ahpten cross-linked conjugate

multi-hapten conjugate

addition of hapten (alpha-gal( to enhance vaccine potential

Alpha-gal as hapten

Knock-out mouse has no alpha-gal epitopes and therefore high levels of alpha-gal antibodies

WT mouse has alpha-gal epitopes and therefore no alpha-gal antibodies

Immunization with GP120 or GP120-alpha-gal

Mechanism immune enhancement by haptens

Anti alpha-gal immunoglobulins form immune complexes with GP120alpha-gal

Immune complexes are more effciently internalized by APC (enhanced antigen presentation)

APC cause increased Thelper cell activation resulting in more antibodies and cytotoxic T cells

Primair

Val, glu, ser, pro, gly, etc

Secondari

Alpha helix, or beta sheet

Tertiar

Domain

Quarternair

Protein

Seocondary structure

Quaternary structure

Immune function and dysfunction (pathology)

Foreing antigen from pathogen

• immune activation, recovery from infection

• Tolerance, persistent infection

Foreign antigen from environemnt (harmless)

• tolerance, remain healthy

• immune activation, allergic disease

Self antigen

• tolerance, remain health

  • Immun activation, autoimmune diseases

Tolerance, central and peripheralS

Immunoregulation

Communication between immune cells

Tolerance

Antigens

immunoglobulins, idotypic networks

Neural regulation

Regulatory T cells, hygiene hypothesis

Tolerance

Immunological tolerance is the lack of an adaptive response to a specific antigen

T cell tolerance

Neg en pos selection (central tolerance in thymus)

T cell anergy (absence of co-stimulation)

B cell tolerance

clonal abortion (central tolerance in bone marrow)

clonal anergy

Tolerance of T and B cells - schematic

Mucosal tolerance (oral tolerance)

Oral tolerance in broilesr

Central tolerance vs peripheral tolerance for the T cell

schematic

pre-T cell → Thymocyte → T-cell

Thymocyte → responses within the thymus → clonal deletion → central tolerance

T cell → low doses of antigen, lack of costimulation → clonal anergy → peripheral tolerance

negative and positive selection in the thymus - schematic overview

T cell - anergy?

schematic overview

antibody production and tolerance, vs the amount of doses

B cell and clonal abortion, clonal exhaustion, functional delection and receptor blockade

schematic overviewS

Immature B cell → Mature B cell → Plasma cell

immature cell → low doses of antigen →clonal abortion

Mature b cell → exhaustive antigen challenge → clonal exhaustion

Mature B cell → absence of costimulation, excessive suppressor cell activity, excessive T-independent antigen → functional deletion

Mature B cell → excessive T-independent antigen → receptor blockade

Antibody mediated suppresion (page 257,258 days vet)

a

Antibody titer vs maternal antibdoy, newborn antibody production

Schematic overviewS

Negatie feedback mechanism antibodies by FcgammaRIIB(CD32b)

Negative feedback antibodies by FCgammaRIIB

Examples

Maternal antibodies, poor vaccination efficacy

Antibody therapy in rhesus mothers

The effect of stress on the central nervous system

From innate cells to cell mediated immunity, IgG2a, inflamamtion and Immune regulation tolerance and humoral immunity, IgG1, IgA, IgE

Hygiene hypothesis

Improved hygiene hypothesis

Lifestyle changes modify these factors

• microbial inputs, allergesn, detergents and cytotoxins

• Treg, dendiritc cells, effector T cells, dsDNA, cGAS, inflammatory cytokine

  • Unsufficient exposure to microbes (old friends) in early life results in too low numbrs of regulatory T cells (Treg)

Immune reactions influenced by

Environemnt

Hygiene

Genotype

Prenatal experiences

Stress

Nutrition

Physiolgoical status

Age