Autoimmunity Flashcards
Describe the general principle of autoimmunity.
-random gen of antigen binding receptors ensures that lymphocytes capable of binding & responding to self antigens are made
-self reactive cells suppressed
Describe the two categories of autoimmune diseases.
spontaneous
1. normal immune response to an abnormal Ag
2. abnormal immune resp to normal Ag
Describe normal immune responses.
-autoimmune resp = normal immune resp to antigen (prev hidden) OR result of cross reactivity between infectious agent & normal body component
-naturally occurring autoantibodies = role in homeostasis & regulation
-low titer, low affinity IgM or IgG antibodies against protein frag, or proteins damaged by oxidation/enzymes
Describe antigens hidden in cells/tissues (cryptic antigens). (normal)
-autoimmune resp triggered when nontolerant T cells meet prev hidden autoantigens
-T cells only tolerant to autoantigens if T cells first exposed to antigens
-autoantigens dont induce tolerance bc theyre hidden in cells/tissue
-not all autoimmune resp bad
>some autoimmune resp have physiological functions
anion transport protein = CD233 - IgG autoAb
-autoantigens in places where they never encounter circ lymphocytes
-testes = new antigens at puberty - long after T cell system developed & become tolerant to autoantigens
-injury to testes = permit proteins from damaged tissues to reach bloodstream, encounter antigen sensitive cells, & stim autoimmunity
-hidden antigen in cells
-after heart attack = autoantibodies made against mitochondria of cardiac muscle cells
-chronic hepatitis = (dogs) animals develop antibodies to liver membrane proteins
-trypanosomiasis/Tb = (tissue damage) autoantibodies to diff tissue antigens detected in serum
Describe antigens generated by molecular changes. (normal)
-make some antibodies triggered by development of new epitopes on normal proteins
>EX: rheumatoid factors (RF) & immunoconglutinins (IK)
-RFs = autoantibodies against other immunoglobulins
>antibody binds to antigen & shape of Ig molecule changes = new epitopes on Fc region
>made in diseases where IC are made = autoimmune diseases
–rheumatoid arthritis & systemic lupus erythematosus (B cells resp to diff autoantigens)
-IKs = autoantibodies against complement C2, C4, C3
>epitopes that stim IK formation exposed when complement components activated
Describe receptor editing (B cells). (normal)
-B & T cell antigen receptors gen by random gene arrangement
>results in gen of nonfunctional & autoreactive antigen receptors
>complete antigen formed = rearrange receptor gene seg cont
-if immature B cell makes receptor that binds to self antigen = cont development of B cell is blocked while light chain receptor chains cont recombination
-replacement of one light chain = change receptor specificity -> cells no longer autoreactive
-receptor editing only in immature B cells !!!
>mature B cells that bind autoantigens dont undergo receptor editing THEY DIE VIA APOPTOSIS
Describe molecular mimicry. (normal)
-share epitopes between infectious agent or parasite & an autoantigen
-B cells may bind a foreign epitope that cross react w autoAg
-response -> only when receiving T cell help
-once B cell triggered to resp -> infectious agent removed -> autoimmune resp cont
-trypanosoma cruzi -> mammalian neurons & cardiac m
-integrin CD11a/18 = shares antigenic determinant w Borrelia burgdorferi
Describe failure of regulatory control. (abnormal)
-autoimmunity triggered by resp to hidden epitopes (sustained resp for disease to develop)
-result from failure of normal control mechanisms of IS -> demonstrated by injected mice w rats RBCs
-autoimmune diseases associated w lymphoid tumors
-myasthenia gravis = associated w thymic carcinoma
-humans = increase incidence of rheumatoid arthritis in ppl w malignant lymphoid tumors
Describe infection-induced autoimmunity. (abnormal)
-autoimmune disease triggered by environ factors & infectious agents
-infections common & autoimmune disease rare
-NZB mice = persistent infection w type C retrovirus -> make autoantibodies against nucleic acids & RBCs
-bacteria like strep pyogenes, borrelia burgdorferi, leptospira interrogans = trigger autoimmune heart disease, arthritis, uveitis
Describe microchimerism. (abnormal)
-during preg = mother & fetus exchange cell
-fetal cells persist in mom body for yrs after preg -> mother cell in offspring
-accepted by tolerant immune system = fetal microchimerism
-Y chromosomal DNA -> in golden retrievers = persistent fetal microchimerism
Describe autoimmune disease & vaccination.
-guillain barre syndrome = triggered by influenza virus
-immunization of beagle puppies w rabies vaccine trigger antithyroglobulin antibodies (6 mo later)
-case control study: link between vaccination & development of auto immune hemolytic anemia in dogs (few wks later)
-vaccines w potent adjuvants = trigger development of low levels of autoantibodies
Describe genetic predisposition.
-genetic analysis of mice = ID of 25 genes that contribute to autoimmunity if deleted/overexpressed
-most imp genes = influence naturally occurring autoimmune disease in MHC
-studies in human pop = almost all autoimmune dieases linked to MHC alleles
-domestic dogs (rare breeds) = inbred & show restricted MHC polymorphism -> increase autoimmune susceptibility
-diabetes mellitus = DLA-A3, A10, DLA-B4
Describe immune mediated inflammatory diseases.
-extensive & uncontrolled inflam = caused by innate autoimmunity or autoinflammatory diseases
>SLE
>discoid lupus erythematous
>sjorgens syndrome
>autoimmune polyarthritis
>immune vasculitis
Describe organ specific autoimmune diseases.
