Diseases of the immune system 2
Autoimmunity= pathological state where there has been a breach in tolerance to self and
the immune system attacks one’s own tissue
Response to self =normal damaging effector response=not normal
Chronic autoimmune disease=positive feedback loop
Inflammation- presentation of self peptides-inability to clear self antigen-damage-
broadening of the immune response-presentation of more self peptide=more cells recruited
Development of autoimmunity:
Genetic: MHC,AIRE,FOXP3
Environmental: smoking,chemicals,gas,UV,infection
Occurrence runs in families
Susceptibility can be increased by specific genes which:
Disrupt tolerance, apoptosis
Promote inflammation,cell activation
Monogenic-one predominant genetic risk
Complex-multiple risks- interaction between genetic and environmental
MHC genes
Polygenic- Locus of a gene contains a set of several different MHC I and II so an individual
expresses several MHC I and II with different peptide binding specificities
Polymorphic-different alleles for each gene
These affect the TCR and antigen/MCH complex binding and antigen and MHC
Expression of a type of HLA can be contributing factor to autoimmunity
Why are females more susceptible to
autoimmunity:
Stronger humeral response
Higher levels of antibodies
Oestrogen can enhance B cell responses
High levels inhibit inflammation
Testosterone- negatively regulates BAFF gene-
survival factor for B cells in the spleen
Overcoming peripheral tolerance: adjuvant
effect-injection of tissue extracts with microbial products (danger signals)
Autoimmunity= pathological state where there has been a breach in tolerance to self and
the immune system attacks one’s own tissue
Response to self =normal damaging effector response=not normal
Chronic autoimmune disease=positive feedback loop
Inflammation- presentation of self peptides-inability to clear self antigen-damage-
broadening of the immune response-presentation of more self peptide=more cells recruited
Development of autoimmunity:
Genetic: MHC,AIRE,FOXP3
Environmental: smoking,chemicals,gas,UV,infection
Occurrence runs in families
Susceptibility can be increased by specific genes which:
Disrupt tolerance, apoptosis
Promote inflammation,cell activation
Monogenic-one predominant genetic risk
Complex-multiple risks- interaction between genetic and environmental
MHC genes
Polygenic- Locus of a gene contains a set of several different MHC I and II so an individual
expresses several MHC I and II with different peptide binding specificities
Polymorphic-different alleles for each gene
These affect the TCR and antigen/MCH complex binding and antigen and MHC
Expression of a type of HLA can be contributing factor to autoimmunity
Why are females more susceptible to
autoimmunity:
Stronger humeral response
Higher levels of antibodies
Oestrogen can enhance B cell responses
High levels inhibit inflammation
Testosterone- negatively regulates BAFF gene-
survival factor for B cells in the spleen
Overcoming peripheral tolerance: adjuvant
effect-injection of tissue extracts with microbial products (danger signals)
