Immunologic Tolerance and Autoimmunity (part II)

Question 1

most autoimmune diseases are treated ____ as there are no know cures

Answer 1

symptomatically

Question 2

autoimmuinity is caused by the activaion of ____ and/or ____ in the absnese of an onging infection or other discernible cause

Answer 2

T cells and/or B cells

Question 3

hallmarks of autoimmunity

Answer 3

chronic, progressive, self-perpetuating

Question 4

there is no fundamental difference between the structure of ____ and ____ because all proteins are made up by the same amino acids

Answer 4

self-auto Ags and non-self Ags

Question 5

prevention of autoimminity: 4 processes:

1.

2.

3.

4.

Answer 5

1. immunologic ignorance
2. deletion
3. inhibition
4. suppression

Question 6

prevention of autoimmunity: 4 processes

1. immunological ignorance:
   
   1. accomplished by ____ and physical ____
   2. ex:
2. deletion:
   
   1. Fas/FasL mediating ____ or autoreactive T cells
   2. ex:
3. inhibition:
   
   1. prevent ____
   2. ex:
4. suppression:
   
   1. decreasing ____ and ____
   2. ex:

Answer 6

1. 1. barriers and physical separation
   2. blood brain barrier and blood testis barrier
2. 1. deletion
   2. central tolerance ???? or peripheral????
3. 1. activation
   2. CTLA-4
4. 1. activity and responsiveness
   2. Treg cells secreting inhibitory signals IL-10 and TGF-beta

Question 7

what are the immune priveleged sites

Answer 7

1. eye: cornea, anterior chamber, vireous cavity, an d subretinal space
2. brain: ventricles and striatum
3. pregnant uterus
4. ovary
5. testis
6. adrenal cortex
7. hair follicles

Question 8

immune privelege refers to the observation that tissue grafts placed in certain atatomical sites can survive

Answer 8

for extended periods of time

Question 9

general features of autoimmune disorders:

1. autoimmune disease may be either ____ or ____ specific depending on the distrubution of the auto-Ag involved
2. failure of T and B cells ____ is the cause of all autoimmune diseases
3. examples of tissue specific autoimmune diseases:
4. examples of systemic autoimmune diseases:

Answer 9

1. systemic or organ specific
2. self-tolerance
3. type I diabetes (pancreas); multiple sclerosis (neurons, brain)
4. rheumatoid arthritis (joints, connective tissues); systemic sclerodemra (skin, blood vessels); systemic lupus erythematosus (tissues, DNA Abs)

Question 10

genetics of autoimmunity:

1. most autoimmune disease are complex ____ traits
2. affected individuals inherit multiple genetic ____ that contriubte to disease susceptibility
3. among the genes that are assocaited with autoimmunity, the strongest associations are with ____ genes
4. polymorphisms in ____ genes (such as CTLA-4) are also associated with autoimmunity
5. susceptiblility genes interact with ____ factors to cause the diseases

Answer 10

1. polygenic
2. polymorphisms
3. MHC
4. non-HLA
5. environmental

Question 11

environemental component or infectious triggers include

Answer 11

molecular mimicry

bystander activation

release of previously sequestered Ag

epitope spreading

cryptic/hidden Ag

Question 12

genetic component or non-infectious triggers

Answer 12

MHC class II genes (DQ, DR)

CTLA-4 mutations

Question 13

molecular mimicry:

1. an invading virus carries viral Ags that resemble ____ epitopes
2. this viral-Ag mimics self Ags just close enough that when presented by APCs it results in ____
   
   1. Ag is different enough to be perceived as ____ by APC
   2. Ag is close enough to self-Ag to initiate ____ effects

Answer 13

1. self-Ag
2. autoimmunity
   
   1. foreign
   2. autoimmunity

Question 14

bystander activation:

1. during an immune resopnse or injury, sometimes ____ are relased along cytokines and signal molecules
2. these self-Ags are acidentlly presented on ____ to activate autoreactive lymphocytes

Answer 14

1. self-Ags
2. APCs

Question 15

epitope spreading:

1. ____ infection results in release of new self-Ags
2. contined tissue damage and release of new ____
3. self-Ags are taken up and presented by ____
4. ____ activation of more autoreactive T cells leading to autoimmunity

Answer 15

1. persisent
2. self-Ags
3. APCds
4. nonspecific

Question 16

Hidden/cryptic Ag Release:

1. older theory stating ____ self-Ags are hidden during negative selection and central tolerance
2. therefore, autoreactive cells to these hidden Ags are never ____
3. ____ damage results in the release of these self-Ags and autoimmunity can ensue

Answer 16

1. intracellular
2. deleted
3. tissue

Question 17

autoimmunbe disease are much more common in ____ than in ____

Answer 17

women

men

Question 18

____ exacerbate systemic lupus erythematosus (SLE) in mouse models of the disease by altering the B-cell repertoire in the absence of inflammation

Answer 18

estrogens

Question 19

drugs can alter the immune repertoire:

____ and ____ can bind to RBC membrnae and generate a neoantigen that elicits an auto-Ag that causes hemolytic anemia

Answer 19

peniclillins and cephalosporins

Question 20

the blockade of ____ can induce antinuclear Abs and even SLE and MS in certain persons

TNF-a has inhibitory effects on activated ____

Answer 20

TNF-alpha

T cells

Question 21

systemic lupus erythematosus is the prototypic

Answer 21

immune complex-mediated disease (type III hypersensitivity)

Question 22

systemic lupus erythematosus (SLE):

1. clues
   
   1. skin
      
      1. ex:
   2. kidneys
      
      1. ex:
   3. joints
      
      1. ex:
2. diagnositc test: ____ ____

Answer 22

1. 1. 1. rash/vasculitis
   2. 1. glomerulonephritis
   3. 1. arthritis
2. anti-nuclearn (DNA) Abs

Question 23

rheumatoid arthritis:

1. inflammation of the ____ associated with destruction of the joint cartilage and bone
2. cells involved: ____ and ____
3. type ____ hypersensitivity due to Th17
4. diagnostic test
   
   1. presence of ____ ____ (IgM or IgG) that autoreact with ____ portion of ____
      
      1. result in activation of ____

Answer 23

1. synovium
2. Th1 and Th17
3. IV (4)
4. 1. rheumatoid factor (RF) Fc IgG
      
      1. complement

Question 24

multiple sclerosis (MS):

1. inflammatory response to ____ in the ____
2. cytokines play an important role in MS
   
   1. ex of cytokines:
      
      1. trigger an inflammatory response in the ____ matter of the brain
3. development of ____ (the characteristic pathology of MS) in the white matter by stripping ____ from neurons
4. most popular tx for individuals with MS is the cytokine ____ which is thought to attentuate the action of the proinflammatory cytokines
5. type ____ hypersensitivity due to Tcell mediation

Answer 24

1. white matter CNS
2. 1. TNF-a, IL-6, IL-17, TGF-b, IFN-g
      
      1. white
3. plaques myelin
4. IFN-beta
5. IV (4)

Question 25

characterstics of type I Diabetes

Answer 25

• ketoacidosis
• autoantibodies towards pancreatic B-cell or markers of B cell destruction
• high risk HLAs
  
  • DQ2, DQ8, DR3, DR4
• hyperglycemia

Question 26

type I diabetes:

1. immune mediated destruction of ____ beta cells leading to insulin ____
2. type ____ hypersensitivity due to Tcell mediation
3. threshold effect:
   
   1. symptoms manifest around when ____ of beta cells are destroyed
4. onset of T1D is associated with infiltration of the islets of langerhands by mononucelar cells and CD8+ T cells; this infiltrate is termed ____

Answer 26

1. pancreatic deficiency
2. IV
3. 1. 60-80%
4. insulitis

Question 27

irritable bowel disease (IBD):

1. IBD is a broad term used to describe 2 disorders that involve ____ inflammation of the GI tract
   
   1. ____ ____ is characteriec by chornic inflammation and ulcers in the innermost lining of the colon and/or rectum
   2. ____ ____ is characterized by inflammation of the lining of the GI which often spreads deep into affected tissues and may occur in any part of the GI
2. type ____ hypersensitivity due to T cell mediation
3. in 40% of patients with CD, the ____ is spared from inflammation in contrast to the universal rectal involved in UC
4. patients with IBD have been shown to have increased ____ permeability
5. ____ hypothesis of allergic and autoimmune disease has been invoked to explain an increased incidence of IBD

Answer 27

1. chronic
   
   1. ulcerative colitis (UC)
   2. crohn’s disease (CD)
2. IV
3. rectum
4. intestinal
5. hygiene

Question 28

IBD:

disruption of the barrier function - mainly in ____

dysfunction of microbe sensing - mainly in ____

changes in immunoregulation of innate and adaptive immune resonses - both disorders

Answer 28

UC

CD

Question 29

the mucosal barrier and IBD:

1. IBD is associated with increased ____ of the epithelial barrier caused by impaired formation of tight junctions
2. the ____ bacteria of the normal intestinal microbiota cause inflammation reactios leading to selfsustained mucosal inflammation
3. bacterial components cross the ____ barrier , contact with immune cells and induce innate and adatpive resopnses

Answer 29

1. permeability
2. commensal
3. mucosal

Question 30

IBD results from an inappropriate perturbation of highly regualted interaction between the immune system and ____ bacteria of the nomral microbiome resulting in: ____ and ____ inflammation

Answer 30

commensal

dysbiosis and mucosal inflammation