Autoimmunity Flashcards

1
Q

Describe the general principle of autoimmunity.

A

-random gen of antigen binding receptors ensures that lymphocytes capable of binding & responding to self antigens are made
-self reactive cells suppressed

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2
Q

Describe the two categories of autoimmune diseases.

A

spontaneous
1. normal immune response to an abnormal Ag
2. abnormal immune resp to normal Ag

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3
Q

Describe normal immune responses.

A

-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

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4
Q

Describe antigens hidden in cells/tissues (cryptic antigens). (normal)

A

-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

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5
Q

Describe antigens generated by molecular changes. (normal)

A

-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

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6
Q

Describe receptor editing (B cells). (normal)

A

-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

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7
Q

Describe molecular mimicry. (normal)

A

-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

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8
Q

Describe failure of regulatory control. (abnormal)

A

-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

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9
Q

Describe infection-induced autoimmunity. (abnormal)

A

-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

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10
Q

Describe microchimerism. (abnormal)

A

-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

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11
Q

Describe autoimmune disease & vaccination.

A

-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

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12
Q

Describe genetic predisposition.

A

-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

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13
Q

Describe immune mediated inflammatory diseases.

A

-extensive & uncontrolled inflam = caused by innate autoimmunity or autoinflammatory diseases
>SLE
>discoid lupus erythematous
>sjorgens syndrome
>autoimmune polyarthritis
>immune vasculitis

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14
Q

Describe organ specific autoimmune diseases.

A
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