2-Autoimmunity

Question 1

tolerance breached

Answer 1

1. central- autoreactive lymphs not deleted in marrow and thymus
2. peripheral- normal inhib mechanisms fail (anergy, apop, suppression

Question 2

famililal trends

Answer 2

-autoimm thyroid dis + vitiligo in same person
-lupus + sjogrens in diff members of same fam
-insulin dependent diabetes in families
-identical twin has dis then other twin high risk

Question 3

predisposition factors

Answer 3

1. abnormal lymphs and APCs
2. genetic
3. microbial infections

Question 4

tissue injury causes

Answer 4

1. autoreactive CTLs
2. circulating autoantibodies
3. immune complexes

Question 5

vertical transmission of Ab

Answer 5

maternal autoimmune IgG affect dev fetus
-effects dissapear after birth when Ab catabolized
-organ damage irreversible like heart > bradycardia

Question 6

theories behind autoimmunity

Answer 6

1. mircobes- molecular mimicry so resemble self antigen close enough to break tolerance
   -mycoplasma infections when Ab cross react with antigen on RBC and destroy
2. inapprop expression of MHC proteins

Question 7

autoimmune hemolytic anemia

Answer 7

-RBC Ab vs RBC membrane proteins
-cause RBC lysis and anemia
-opsonization > removal by phagocytic cells in spleen

Question 8

goodpasture’s syndrome

Answer 8

autoAb to alpha3 chain of type IV collagen (@ basement mem) in alveoli and glomeruli
-acts complement so kidney damage, pulmonary hemorrhage, death
-will show smooth, ribbon like appearance of BM

Question 9

pernicious anemia

Answer 9

autoAb to intrinsic factor (transports B12) and/or gastric parietal cells
=dec absorption of vit B12 so abnormal erythropoiesis/anemia

Question 10

hashimoto’s thyroiditis

Answer 10

hypothyroid state
-autoAb and autoreactive T cells to thyroid gland proteins

Question 11

idiopathic thrombocytopenia purpura

ITP

Answer 11

platelets destroyed by autoAb to platelet membrane proteins
-‘purpura’ bc purple skin lesions from epidermal hemorrhage
-IVIG prevent destruction of platelets

Question 12

vitiligo

Answer 12

depigmentation of skin by destruction of melanocytes

Question 13

grave’s disease

Answer 13

autoAb vs TSH receptor in thyroid
-hyperthyroidism bc Ab stims receptor without ligand so lots of hormones

Question 14

myasthenia gravis

Answer 14

autoAb to alpha chain of nicotinic acetylcholine receptor on skeletal muscle cells @ nueromusc junctions

blocks neuromuscular transmission by inhib binding of ligand to receptor so muscle weak and paralysis

Question 15

type 1A diabetes

Answer 15

autoAb to insulin secreting beta cells, autoreactive T cells mediate destruction

dec insulin so inc blood glucose

Question 16

multiple sclerosis

Answer 16

autoimm demyelinating dis of CNS
-TH1 and TH17 get act so drive macro act and damage to myelin containing nerve cells bc specific for myelin antigens

either be relapsing-remitting or progressive

treat with interferon-beta1b every other day or interferon-beta1a weekly or steroids

Question 17

systemic lupus erythematosus

SLE

Answer 17

multisystem dis from broad loss of reg control that sustains self tolerance
-skin, joints, kidney most common
-autoAb vs numerous antigens for DNA, RNA, proteins, ribonucleoproteins
-more women

Question 18

SLE mechanism

Answer 18

mediated by immune complexes (hypersens III) targets kidneys thru glomerulus and podocytes
PLUS
hypersens II with autoAb vs RBCs, WBCs, and platelets

Question 19

SLE predisposition

Answer 19

1. genetic- family members inc incidence
2. drugs and some viruses- drug induced lupus coplex with nucleoproteins = autoimm
3. immunologic- B cell hyperactivity, inc T helper activity, dec Treg activity

Question 20

rheumatoid arthritis

Answer 20

progressive inflamm dis of joints so destroy joint cart and synovium, pulmonary/cardiac/ocular symptoms
-associated with HLA-DR4 haplotype

TH1, TH17, macros, B cells/plasma cells = inflamm environ with secretion of leukocyte recruiting cytokines

rheumatoid factor = IgM/IgG to Fc of IgG = immune complex

Question 21

biologic agents of RA

rheumatoid arthritis

Answer 21

TNF-alpha important

1. etanercept- TNF-a type II receptor fused to IgG1 Ab
2. infliximab- chimeric mouse/human anti TNF-a monoclonal Ab
3. adalimumab- recombinant human IgG1 monoclonal

Question 22

sjogren’s syndrome

Answer 22

dry eyes and mouth from destruction of lacrimal/salivary glands
-B and T cells influx in glands
-can be alone or with RA and SLE
-women
-inc risk of dev lymphoid malignancies

Question 23

scleroderma

Answer 23

progressive systemic sclerosis

xs collagen deposit in skin, kidneys, GI tract, heart, muscles, lungs
-antinuclear Ab in most cases but dk why
-T cells infiltrate dermis so hypersens to collagen > release IL1 and TNF-a > collagen syn = vicious cycle

Question 24

polymyositis-dermatomyositis

Answer 24

polymyositis= muscle injury from CD4+ and CD8+ T lymphs inflitrate muscles

dermatomyositis = skin rash usually with poly

25% have autoAb to histidyl tRNA synthetase so use for dx

maybe with coxsackie B virus

Question 25

corticosteroids | treatment

Answer 25

prednisone = anti inflamm but bone mineral loss, weight gain, diabetes, fluid retention, skin thinning

Question 26

cytotoxic drugs | treatmen

Answer 26

azathioprine and cyclophosphamide -interfere with DNA syn so elim dividing lymphocytes -bone marrow suppression and damage to intestinal epi

Question 27

cyclosporine and tacrolimus

Answer 27

nonspecific immunosupp that blocks activity of acalcineurin so block transcription of IL-2 both are nephrotoxic

Question 28

plasmapheresis treatment

Answer 28

removes Ag-Ab complexes but only short term alleviation

Question 29

antagonists of TNF-alpha

Answer 29

1. infliximab- humanized anti TNF-a monoclonal Ab 2. etanercept- soluble TNF-a receptor fusion protein binds to TNF-a 3. adalimumab- recombinant human IgG1monoclonal 4. potent anti-inflamms- treat Crohns, RA, juvenile chronic arthritis, ankylosing spondylitis