Autoimmunity

Question 0

Normal anti-autoimmunity mechanisms

Answer 0

Treg cells
Inactivation (anergy) of T helpers
Anti-idiotype antibodies
Glucocorticoids

Question 1

Overview of autoimmunity

Answer 1

Immune response against self tissue (usu antibody)
Normally exists but subclinical
Can be innate or acquired (infections, drugs, etc)

Question 2

Initiation mechanisms of autoimmunity

Answer 2

Cross-reactive epitope
- Group A strep -> heart, joints, brain -> rheumatic fever,
- EBV -> myelin -> MS
Adjuvants
- infection (EBV, Coxsackie) -> cytokines, receptors
- IFN-g in pancreas -> diabetes mellitus
- lymphocytic choriomeningitis virus (LCMV) fatal dt immune response
- hapten-carriers - drugs, infection -> anemia, low platelets
Antigen complexes - cause local inflammation
Sequestered antigens - no tolerance developed (ex vasectomy)
Immune deficiency - CVID -> inflammation -> autoimmune disease

Question 3

Mechanisms of autoimmune destruction

Answer 3

Cell destruction (ITP, anemia)
Alter receptor function (MG, Graves)
Alter endocrine function (Graves, Hashimotos)
Immune complexes (lupus)

Question 4

Cellular destruction diseases

Answer 4

Autoimmune hemolytic anemia (AIHA)
Idiopathic thrombocytopenia (ITP)

IgG antibodies -> Fc receptor phagocytosis (and complement)
Goal is to decrease Fc interaction with macrophages
- ex IV IG - saturates Fc receptors

Question 5

Myasthenia gravis

Answer 5

Antibodies to neuromuscular junction (Ach) receptor -> weakness

• complement activating (IgM, IgG1-3)
• complement non-activating (IgG4, IgA)
• may block, disable, destroy receptor or destroy cell

Question 6

Graves disease

Answer 6

Autoantibodies to TSH receptor -> endocrine disfunction

• usu overstimulate (thyroid growth stimulating immunoglobulin - TGSI)
• can also have block (thyrotropin binding inhibitory immunoglobulin - TBII)
• can cross placenta -> temporary hyperthyroid in newborn

Question 7

SLE

Answer 7

Systemic lupus erythematosus
Broad auto-antibodies -> complexes -> damage (kidneys, etc)
- generalized regulatory defect
- antibodies vs Treg cells

Question 8

Thyroid diseases

Answer 8

Graves = stimulation of TSH receptor -> hyperthyroid
- treat with ablation
Hashimoto’s - function inhibited by antibodies and cell-mediated
- treat with replacement hormones

Question 9

Risks for autoimmunity

Answer 9

Genetics - HLA type
Microbiome
Sex - more common in females due to hormone interactions?
Age - less immunoregulation
Infections - Strep, Klebsiella, Malaria, Borellia (lyme)
Drugs - act as haptens

Question 10

Treatment for autoimmunity

Answer 10

Broad immunosuppression
- NSAIDs, glucocorticoids, TNF-blocker (Humira), cytotoxic, irradiation
Targetted suppression
- anti CD20 (rituximab -> B), anti CD3 (-> T), CTLA-4/anti CD28
Plasmapheresis - temporarily removes antibodies
IV IG - interferes with Fc, complement, etc

Trying to target specific idiotope (Fab) region on autoreactive B cells