L20 Autoimmunity Flashcards
What is immunologic tolerance
State of inability of the competent immune system to mount an immune response against a particular antigen
What is self tolerance
Refers to the lack of responsiveness out to an individual zone antigens and it’s underlies her ability to live in harmony with ourselves and tissues
What are the two groups of self tolerance
Central tolerance and peripheral tolerance
What is central tolerance
Clonal deletion [apoptosis] of auto reactive T & B lymphocytes in the thymus or bone marrow
What is peripheral tolerance
Any auto reactive cells that escape central tolerance and migrate to the periphery will be removed or deactivated by Anergy Suppression Deletion Sequestration
Anergy
Irreversible functional inactivation
What is suppression
Suppression of auto reactive lymphocytes by regulatory T cells that inhibit their activation
What is deletion
Deletion of auto reactive lymphocytes by Apoptosis
Deletion of apoptosis genes leads to development of autoimmune lymphoprliferative disorders
Describe antigen sequestration
Certain tissues is brain eye and testis sequester their antigens behind blood tissue barrier to be hidden from auto reactive lymphocytes
traumatic injury may expose these antigens leading to auto immune uveitis or orchitis
What are the mechanisms of auto immunity
Failure of self tolerance
genetic factors
infectious factors
Describe failure of self tolerance
Inheritance of susibility genes which contribute to the breakdown of self tolerance or regulation of immune responses 
1) breakdown of t cell anergy
2) failure of t cell mediated suppression(AIDS)
3) polyclonal b cell activation
4) release of sequestered self ags and exposure of hidden epitopes through tissue trauma or inflammatory destruction eg: lens crystalline of eye, spermatoza in testis
What is polyclonal b cell activation
Several mic organisms and their products are capable of causing polyclonal activation of b cells
some of these simulated lymphocytes may be auto reactive
What is The role of susceptibility genes
Defective pathways in HLA alleles
Defective pathways in non HLA genes that regulate central or peripheral tolerance as NOD-2 gene, apoptotic pathways or regulatory t development
Auto immune diseases with a familial increase of incidence
Systematic lupus erythematous diabetes mellitus type one and other diseases
What is the role of infection
Particularly viral infection through: Modification of self-antigens 1-costiumlators upregulation 2-molecular mimicry 3-polyclonal b cell activation 
Describe co simulators upregulation
Upregulate expression of co simulators on antigen presenting cells resulting in breakdown of anergy and activation of T sells specific for the self antigen
Describe molecular mimicry
Where a microbe shares amino acid sequence with a self-antigens then immunological reactions will cross-react the pathogen and become directed against self antigen leading to tissue injury with activation of non-tolerant lymphocytes mediating an auto immune reaction
What is the best example of molecular mimicry
Rheumatic heart disease in which antibodies against streptococcal proteins cross react with myocardial proteins and cause myocarditis
 describe polyclonal b cell activation
By some viruses
May result in production of auto antibodies leading to tissue injury that may release and structurally modify a self antigence creating non-antigens that are able to activate t cells
How can tissue damage an auto immune disease be mediated through hypersensitivity
Type two hypersensitivity reaction example autoimmune hemolytic anemia
Type three hypersensitivity reaction example systematic lupus erthyematosus and rheumatoid arthritis
Type two anti-receptor antibodies example myasthenia gravis
What are the general features of auto immune diseases
▪️Cellular or organ specific self antigens
▪️Chronic with relapse is in remission and the damage is often progressive
▪️An individual may have more than one autoimmune disease simultaneously in this place symptoms of multiple diseases
▪️Signs and symptoms presented and the disease itself can be influenced by various other factors such as age hormones and environmental factors
▪️There are several organs that are commonly impacted by autoimmune diseases such as blood vessels, underlying connective tissues joint and muscles red blood cells renal glomerulus skin and endocrine glands such as thyroid or pancreas glands
