overview
1.Intro and definition immunotoxicity
2.Immunogenicity related to biopharmaceuticals
3.Immunotoxic effects
*Immunosuppression
*(Immunostimulation)
*Autoimmunity
*Hypersensitivity
*Infusion reactions
what is immunotoxicology
is a study of the interaction between xenobiotics and immune system resulting in adverse effect
the science of poison to the immune system
what is immunotoxicity
is inappropriate change in the structure and function of immune system
what is the challenge to achieve clear toxicity
variation in immune response among the population
what is the different between morbidity and mortality
mortality refers to immune enhancement that can lead to hypersensitivity and autoimmunity
morbidity refers to immune suppression that can lead to infections and cancer
what is immunogenicity
refers to ability of substance to provoke the immune response in the body.
why do we need biopharmaceutical closer to human mAb
to lower the risk of allergic response
between mouse and human where is immunogenicity low
in human mAbs
what cause anti-drug antibodies
patient related and drug related
what is the effect of anti-drug antibody formation may lead to:
- loss/reduction of efficacy
- adverse/inappropriate immune reaction
can biopharmaceutical elicit events that results in multiple form of immulogical risk
yes
what are the type of immune toxicity and the diseases example
-autoimmunity; induction of immunity against self-antigen triggered by biopharmaceutics. by triggering the immune response against own self this can cause the production of auto-antibody or cause autoimmune disease. which can led to development of lupus.
ex; drug-induced lupus
-hypersensitivity: has different type and it depends on the immune response type
* type I, type II, type III, type IV
* always mediated by antibody production for typeI,II, and III and T cells for type IV.
-immunosuppression: reduce capacity to neutralize external organism which may result in prolonged infection and increase cancer development.
ex: IFN-alpha therapy, inhibit tumour cells which is good but they also inhibit normal cells including hematological bone marrow cells which results in reduction of white and red blood cells, platelets production causing bone marrow suppressions.
-infusion reaction: any sign that occurs during the infusion of the drug or on the day of administration.
* IgE(type I) and non-IgE(we use IgG instead)-mediated hypersensitivity reaction
* non IgE: come from direct activation of mast cells
* cytokine -release syndrome: inflammatory response and is non-allergic reaction caused by release of large amount of cytokines in immune cells in response to the drug
what are different type of hypersensitivity and cells involved
- type I: take place within a minute
- immediate reaction
*IgE mediated - mast cells and basophils
- infusion related reaction
- immediate reaction
- type II: take place within 5-8 hrs
*antibody-mediate cytotoxic reaction
*IgG and IgM dependent reaction- red blood cells, white blood cells or platelets
- Ig production are against cellular antigen
-type III: take place within 2-8 hrs
* immune complex mediate reaction
* IgG or IgM mediated reaction, Ig are against soluble antigen in the serum
* cause serum sickness
-type IV: take place within 24-72hrs
*delayed hypersensitivity reaction
*cell-mediated via antibody production and T cells
* there reaction can be due to the CD8+ activation that cause the apoptosis reaction.
what are the 3 steps of hypersensitivity type III
- immune complex formation: when we are exposed to the drug our body create antibody against it and antibody binds to the antigen forming the immune complex
- immune complex deposition: immune complex can settle in various tissues of our body and the way they settle depends on the balance btn the antibody and antigen.
- in antibody excess: they form big or large complex and it will not be able to circulate in the body so this will lead to the elimination of the complex by immune cells like macrophage.
*in antigen excess: if they are to many antigen the they small complex and this can be able to pass through the body tissue or joints which can lead to joint pain or kidney disfunction.
- in antibody excess: they form big or large complex and it will not be able to circulate in the body so this will lead to the elimination of the complex by immune cells like macrophage.
- inflammatory reaction: after the complex settle in the tissue our body see it as a threat that’s why it activate the immune response against it. this will lead to activation of classical pathways that cause the body to release C3a and C5a which attract the formation of macrophage which cause inflammation and tissue damage.
what are the two challenges for the Hypersensitivity
sensitization phase; is the initial of the exposure to the antigen that lead to the activation of immune system
elicitation phase: re-exposure to the same antigen that leads to the immune activation again.
what is immunotoxicants
are the substances that negatively affect the immune response’s function
what are the key characteristics of immunotoxicants
- break down the immune tolerance lead to inflammation and autoimmunity
- covalently binding to form novel antigen lead to hypersensitivity
what does allergic contact dermatitis (ACD) cause
cause skin allergy, after induction phase and inflammation response
