DISORDERS OF DISORDERS OF IMMUNITY II: IMMUNITY II:

AUTOIMMUNE DISEASESAUTOIMMUNE DISEASES

R. HUGO MARTÍNEZ LOZANO, M.D.R. HUGO MARTÍNEZ LOZANO, M.D.

Aug-12-2009.Aug-12-2009.

LEARNING OBJECTIVESLEARNING OBJECTIVES K & U:K & U:- GENERAL FEATURES- GENERAL FEATURES- IMMUNOLOGIC TOLERANCE- IMMUNOLOGIC TOLERANCE- MECHANISMS OF AUTOIMMUNITY- MECHANISMS OF AUTOIMMUNITY- THE MOST IMPORTANT CHARCT. OF:THE MOST IMPORTANT CHARCT. OF: - LES- LES - RA- RA - SS- SS - SYSTEMIC SCLEROSIS- SYSTEMIC SCLEROSISRef: 223-239 & lecture’s informationRef: 223-239 & lecture’s information

GENERAL FEATURESGENERAL FEATURES

FRECUENCY:FRECUENCY: DISEASE VS NORMALITYDISEASE VS NORMALITY

(Pathologic vs physiologic autoimm.)(Pathologic vs physiologic autoimm.)

CRITERIA FOR DX OF CRITERIA FOR DX OF AUTOIMMUNE DISEASESAUTOIMMUNE DISEASES

AUTOIMMUNE REACTIONAUTOIMMUNE REACTION NOT SECONDARY TO TISSUE NOT SECONDARY TO TISSUE

DAMAGEDAMAGE NO OTHER CAUSENO OTHER CAUSE

IMMUNOLOGIC TOLERANCEIMMUNOLOGIC TOLERANCE

CENTRAL: DEATH OF SELF-R LYMPHCENTRAL: DEATH OF SELF-R LYMPH (APOPTOSIS)(APOPTOSIS) PERIPHERAL:PERIPHERAL: - ANERGY: NO COSTIMULATORS B7- ANERGY: NO COSTIMULATORS B7 INHIBITORY R CTLA-4INHIBITORY R CTLA-4 - SUPPRESSION BY REGULATORY T - SUPPRESSION BY REGULATORY T - CLONAL DEL. BY ACTIVATION OF - CLONAL DEL. BY ACTIVATION OF INDUCED CELL DEATH (FASL-FAS)INDUCED CELL DEATH (FASL-FAS)

MECHANISMS OF AUTOIMMUNE DIS. ROLES: - GENETICS - INFECTION/INFLAMMATION

MUTATIONS:-AIRE-CTLA-4-ETC.

ROLE OF INFECTIONS

ROLE OF INFECTIONS

C. EPITOPE EXPOSITION & SPREAD.

SLE: GENERAL FEATURESSLE: GENERAL FEATURES

INCIDENCE: 1:700INCIDENCE: 1:700 SEX: 9:1SEX: 9:1 ETHNIC GROUPETHNIC GROUP AGE:AGE:

CLINICAL CRITERIA:CLINICAL CRITERIA:(TABLE 6-8. p. 228)(TABLE 6-8. p. 228)

MALAR RASHMALAR RASH DISCOIDE RASHDISCOIDE RASH PHOTOSENSITIVITYPHOTOSENSITIVITY ORAL ULCERSORAL ULCERS ARTHRITISARTHRITIS SEROSITISSEROSITIS RENAL INVOLVEMENTRENAL INVOLVEMENT ANAANA ETC.ETC.

ANAANA

GENERICGENERIC ANTI-DOBLE-STRANDED DNAANTI-DOBLE-STRANDED DNA ANTI-SMITH (Sm)ANTI-SMITH (Sm) ANTIHISTONE (DRUG-INDUCED LE)ANTIHISTONE (DRUG-INDUCED LE) SS-A & B (RNP)SS-A & B (RNP) ANTICENTROMERE (CREST)ANTICENTROMERE (CREST)

RISK FACTORSRISK FACTORS

GENETICGENETIC ENVIRONMENTALENVIRONMENTAL IMMUNOLOGICIMMUNOLOGIC

PATHOGENESIS:VASCULITIS(PHASES)

Lupus erythematosus: skin.

SKIN: ANTI-B.M. INJURY

Idem.

IDEM: (IMMUNEFLUORESCENCE)

Malar rash