chapter 28 autoimmune disorders. behavioral objectives at the end of this lecture, the mls and mlt...

Chapter 28

Autoimmune Disorders

Behavioral ObjectivesAt the end of this lecture, the MLS and MLT

student will be able to:Define toleranceDescribe mechanisms for autoimmunity

MLS MLT

Describe Proposed mechanisms of autoimmunity (Level 1)

Describe proposed mechanisms of autoimmunity (Level 1)

1. Release of sequestered antigens

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2. Escape of tolerance at the T cell level

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The MLS and MLT students will be able to:Describe the clinical symptoms and lab

findings of classic autoimmune diseases:Systemic Lupus erythematosusGraves DiseaseRheumatoid arthitisAddison’s DiseaseDiabetes mellitus

What is Autoimmunity?The breakdown of the immune system’s

ability to discriminate between self and non-self; the body’s immune system therefore mounts immune reaction (i.e. produce antibodies) against self antigens with harmful effects to the individual

Self-Recognition (Tolerance)Tolerance- or self-recognition- is the

lack of immune response to self antigens and is initiated during fetal development.This is our normal state of being- our

immune system tolerates proteins and antigens that belong to us (self).

Central tolerance- develops in thymus during fetal life-

Peripheral tolerance- a process involving mature lymphocytes and occurs in circulation.

Auto-antibodies and RoleNot all autoantibodies are bad or cause

diseaseNormal function of Autoab-

binds with certain antigen to rid of dead cells and defective self-antigens; form complexes which are then rid of from the body

For autoimmune disorder to occur, autoantibodies must be present and damage to organ/s.

Spectrum of Autoimmune Disorders

Over 80 serious chronic diseases All characterized by the immune system that

has gone awry or misdirected. The immune system is always being

activatedUnable to recognize the self that it was

supposed to protect- instead it attacks it.Autoantibody- immunoglobulins in

autoimmune disordersAutoantigens- specific antigens being

attacked

Factors Influencing Development of Autoimmunity

Genetic Factors- not well established, but certain genetic predisposition in some cases-

Autoimmune disorders more likely in women than men

Presence of certain HLAPatient Age- 60-70 years peak ageExogenous Factors- drugs, ultraviolet

radiation, chronic infectious disease

Immunopathogenic Mechanisms

1. Sequestered antigen or Hidden antigen theoryCertain antigen are hidden within the organ,

escapes the detection by the immune system during fetal development- (lack of contact with monophagocyte system, :. No tolerance was developed for it.

However, when the antigen escapes to the circulation (e.g due to trauma), the immune system now detects this and sees it as foreign.

Mechanisms for Autoimmunity, con’t:2. Altered antigens- that arise from

biological, chemical or physical processes3. A foreign antigen- shared or cross-

reactive with self antigens or tissue components

MutationLoss of the immunoregulatory function

by the T lymphs subsets

Systemic Lupus Erythematosus (SLE) - antibodies directed against T lymphs

Grave’s disease- antibodies against thyroidRheumatoid Arthritis (RA)- antibodies

against jointsAddison’s disease- antibodies against

cortical elementsDiabetes mellitus- (IDDM)- antibodies

against pancreatic Beta cells

Select Autoimmune Disorders we will study

Organ Specific DisordersThyroid-

Hashimoto’s; Graves diseaseStomach –

Pernicious anemia

Adrenal- Addison’s disease

Pancreas- Juvenile diabetes

Organ-Non-Specific DisordersKidney- Systemic

Lupus erythematosus

Joints- Rheumatoid arthritis

Hashimoto’s DiseaseSymptoms Lab Findings

Autoimmune disease of the thyroid gland

Damage to the thyroid is mediated b y producing autoantibodies against the thyroid proteins –notably the thryroglobulins and thyroperoxidase

Hypothryoidism- dry skin, intolerance to cold temp. fatigue, weight gain.

Hypothyroidism with bouts of hyperthryoidism

Testing for thyroid-stimulating hormone (TSH)

Free T3, Free T4, Antibodies against:

a. thyroglobulin anti-Tg)thyroid peroxidase(anti-

TPO)microsomal antibodies

Grave’s DiseaseSymptoms Clinical Findings

Too much thyroid hormoneHyperthryroidism

When TSH receptor antibody occupies the receptor sites , there is no negative feedback resulting in increased levels of T3 and T4

Antigens implicated: Thyrothropin receptor; Thyroid peroxidase; Thyroglobulin

Due to autoantibodies that mimic TSH

Addison’s DiseaseSymptoms Clinical Findings

Also called chronic adrenal insufficiency; hypocorticolism, hypoadrenalism

Adrenal atrophy- idiopathic autoimmune process

Women- 2x more affected than men

HLA class II antigens DR3 and DR4against cortical elementsAntibodies against adrenal

cells

Low serum Cortisol with elevated corticotropin

Antibodies

Diabetes mellitusSymptoms – High blood sugar

Clinical Findings

Type 1; Insulin-dependent diabetes mellitus (IDDM); juvenile onset diabetes;

diabetes before 30- IDDMImmune destruction of B

cells in pancreasCongenital Rubella

infectionAssociated with HLA-

DR3, DR4, DQ2, DQ8 antigens

Exogenous insulin injections- to maintain normal blood sugar level

Antibodies: anti-insulin, anti-islet cell antigen 2

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)symptoms Lab findings

SLE - chronic autoimmune disorder that may affect the skin, and other organs

Inflammation and B cell activation.

Characteristic “butterfly rash” of the face

Joint pain and swelling

Tests used to diagnose SLE:�Antibody tests,

including:�

Antinuclear antibody (ANA) panel

�Anti-double strand (ds) DNA

�Antiphospholipid antibodies

�Anti-Smith antibodies

Rheumatoid Arthritis (RA)

symptoms Clinical findings

Chronic Inflammation of the peripheral joints-

Lab testing-ESRRF - IgM markerANA- antinuclear

antibodies - TITERS OF > 1:160 is

indicative of autoimmune disease

Review Questions1-4