BIO 343 Lecture Notes - Lecture 16: Autoimmune Regulator, Fetus, B Cell
Immunology Chapter 16: Autoimmunity
Hayden Casassa
• Autoimmunity- the response to self
o Against self-components
o It is a breakdown in self-tolerance
o Make Abs against self-antigen as T cells react with self
o Can resemble type 2,3 or 4 hypersensitivity
• Women are more susceptible to Autoimmunity
o Immune Response→ oe’s iue sstes a e oerl aggressie ad roust
o Hormones →Estrogen can overly stimulate immune system
o Genetics → XX may express more genes that play a role in autoimmunity in upping gene expression
• Mechanisms that contribute to self-tolerance
o Negative selection of B cells in marrow
o Failure of AIRE regulator in expression of self-proteins in thymus
o Neg selection of T cells in thymus
o Exclusion of lymphocytes from certain tissues
o Induction of Anergy in autoreactive B and T cells that reach peripheral circulation
o Suppression of autoimmune response by Tregs
• Autoimmune Disease Susceptibility
o Most important genetic factor are genes located in the HLA complex
o Most autoimmune could be specific HLA class 2 genes
o CD4 T cells binds to class 2 so some aspect of it is T cell tolerance
o You could have B cell leave marrow and enter periphery that is specific for self-protein
▪ Nothig happes if T ell does’t help it
▪ That CD4 T cells also has to be specific for self-peptide helps autoreactive B cell to make Abs
▪ Therefore, most autoimmune diseases is involved in T cell tolerance
• HLA associations with autoimmunity reflect the importance of T cell tolerance in preventing autoimmunity
o T cell tolerance breakdown leads to majority of autoimmunity
o T cell tolerance is more important in preventing disease than B cell tolerance
▪ CD4 T cell tolerance is more important as most diseases deal with class 2
▪ B cell-mediated autoimmunity is contingent on loss of T cell tolerance
• Autoimmune Susceptibility factors
o Adverse side-effect of immune response to infection
▪ Rheumatic Fever
o Smoking → leads to increase susceptibility of rheumatic fever
o Senescence of the thymus → involution of thymus as one grows older. New T cell must be
generated by expanding so some are functionally altered
o Trauma
• APECED
o Caused by genetic deficiency of TF AIRE Gene
o AIRE is a TF that promotes expression of genes in thymus that would normally only occur in specific
tissues
▪ If this does’t ork, the u a’t ake speifi tissues ol foud i ertai tissues so u
release naïve T cells specific for self-proteins from tissue
• IPEX
o Genetic Deficiency of FOXP3 which causes lack of functional Tregs
▪ Tregs help with peripheral tolerance
▪ Express CD25 and FOXP3 along with TCR for self-antigens
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Hayden casassa: autoimmunity- the response to self, against self-components. It is a breakdown in self-tolerance: make abs against self-antigen as t cells react with self, can resemble type 2,3 or 4 hypersensitivity, women are more susceptible to autoimmunity. If this does(cid:374)"t (cid:449)ork, the(cid:374) u (cid:272)a(cid:374)"t (cid:373)ake spe(cid:272)ifi(cid:272) tissues o(cid:374)l(cid:455) fou(cid:374)d i(cid:374) (cid:272)ertai(cid:374) tissues so u release na ve t cells specific for self-proteins from tissue. Igg and igm autoantibodies bind to antigenic part of rbc (rh: trigger classical component pathway and mac, hemolysis and anemia, goodpasture"s (cid:455)(cid:374)dro(cid:373)e. Whe(cid:374) (cid:374)eeded tsh is released and binds to receptor. Iodinated thyroglobulin is released as t3 and t4 and feedback on pituitary to inhibit tsh production However, autoabs against tsh receptor induce continuous synthesis of hormones irregardless of tsh regulation. If (cid:455)ou (cid:373)ake a(cid:374) a(cid:271) agai(cid:374)st re(cid:272)eptor the(cid:374) the re(cid:272)eptor (cid:449)ill undergo endocytosis so you will lose receptors on surface. Ab is binding to the acetylcholine receptor not acetylcholine molecule.
