Autoimmunity

Question 1

tolerance

Answer 1

absence of pathogenic autoimmunity ideally achieved w/o systemic immunosuppresion

Question 2

mechanisms maintaining tolerance

Answer 2

ignorance

autoimmune t cells destroyed- negative selection

t cells destroyed in periphery prior to Ag encounter (apoptosis)

t cells inactivated if inapporpriately stimulated (anergy)

T regs

Question 3

positive/negative selection

Answer 3

positive- thymocyte must recognize thru TCR MHC/peptide above a certain threshold of affinity (90%)

negative- too much affinity for MHC/peptide leads to deletion (5%)

Question 4

mechanisms for autoimmunity

Answer 4

molecular mimicry

escape of autoreactive clones

release of sequestered antigen

epitope spreading

polyclonal B cell activation

Question 5

role of infections

Answer 5

possible mechanisms- 
adjuvant effect (enhances immunogenicity of another antigen) (costimulator)

molecular mimicry

polyclonal b cell activation

tissue injury releases self antigens

Question 6

general features of autoimmunity

Answer 6

progressive- relapses/remissions

epitope spreading- tissue damage release self Ags and exposes epitopes previously hidden- triggers new autoimmine cells

clinical and pathologic manifestation determined by the underlying immune response

overlap- different diseases show substantial overlap

Question 7

SLE symptoms

Answer 7

malar rash- high cheek rash
discoid rash
photosensitivity
oral ulcers
arthritis
renal disorders
hematologic disorders
immunologic disorders
antinuclear disorders

Question 8

SLE eitology

Answer 8

contributions from MHC genes and runs in families

compliment deficiencies

defective elimination of self reactive b cells

immune system reactive towards nuclear Ags

Question 9

SLE environmental factors

Answer 9

exposure to UV light
sex hormones
drugs(hydralazine, procainamide, d-penicillamine)

Question 10

libman sacks

Answer 10

sterile valve disease d/t SLE

Question 11

rheumatoid arthritis

Answer 11

chronic systemic inflammatory disease

affects many organs- skin, blood vessels, heart but main target is joint

non suppurative proliferative/inflammatory synovitis

Question 12

RA symptoms

Answer 12

fatigue
weight loss
myalgias
excessive sweating
low grade fever
morning stiffness
swollen joints

Question 13

RA changes in the joints

Answer 13

infiltrate of inflammatory cells - T cells, b cells, plasma cells, DC, marcrophages

increased vascularity

fibrin

neutrophils

osteoclastic activity in underlyin bone

pannus formation- mass of synoviium and stroma w/ inflammatory cells, granulatino tissue, fibroblasts grows over articular cartilage

Question 14

RA risk factors

Answer 14

HLA DRB1 alleles

rheumatoid factor- not causitive- autoAbs to Fc portion of IgG

Anti CCP Abs

TNF

Question 15

type 1 diabetes

Answer 15

caused by destruction of B cells in pancreas

T cell mediated

genetic predisposition

Ag: insulin, others

Question 16

nephrotic syndrome

Answer 16

proteinuria, hypoalbumenemia, edema

Question 17

amyloidosis

Answer 17

nonspecific protein distribution in a wide variety of tissues, causing problems

primary amyloidosis- multiple myeloma- deposition of kappa or lambda light chain

secondary- protein A

familial amyloidosis- mutant prealbumin or protein A

senile systemic amyloidosis- prealbumin

dialysis amyloidosis- microglobin

Question 18

congo red stain

Answer 18

stains amyloid apple green