Unit 3

Autoimmune Disorders

MLAB 1335 – Immunology

 Autoimmunity
• Autoimmunity can be defined as breakdown of mechanisms
responsible for self tolerance and induction of an immune response
against components of the self. 
• Antibody directed against “self”, termed autoantibody

• Considered abnormal but usually does not result in disease

• May occur in healthy individuals.

• Precise etiology of autoimmunity is unknown

 Autoimmunity
• Autoimmune disease occurs when the immune system attacks
self-molecules as a result of a breakdown of immunologic
tolerance to autoreactive immune cells.
• Can be caused by T-cell mediated immune responses or
autoantibodies
• Disorder in which tissue injury is caused by an immunologic
reaction of the host to its own tissues.
• Comprising multiple disorders and symptoms ranging from
organ-specific to systemic.
 Autoimmunity
• What is tolerance?
• Do not mount immune response to
“self” antigens
• Immune system constantly
challenged to discriminate between
self and non-self and make
right choice
• Under NORMAL circumstances
immune system will not destroy
self-antigens
 Mechanisms of Autoimmunity
• Genetics
• Endogenous and Environmental Factors
• Hormones
• Tissue Trauma and Release of Cryptic Antigens
• Microbial Infections
• Epigenetics
• Interactions between Factors – results in breakdown of immunologic tolerance
• Evidence leans toward a combination of these factors
• Certain genes thought to make you more susceptible
• Gender
• Tissue injury
• Exposure to infectious microorganisms
 Mechanisms of Autoimmunity - Genetics
• Genetics
• Often more prevalent among family

• Research has found an association between certain HLA and a risk of developing
certain autoimmune disorders
• People who have the HLA-B27 have a 100 x greater chance of developing ankylosing spondylitis

• Class II MHC molecules may be abnormally expressed on cells

• Results in presentation of self-antigens and no self-tolerance established

• Inheritance of specific genes may make someone more susceptible to an

autoimmune disorder
• Add the variation of environmental or other factors and the two together can trigger autoimmunity
 Mechanisms of Autoimmunity - Hormones
• Hormonal Influence – Hormones may influence the following
• Women are 2.7 x more likely to develop an autoimmune disorder!
• Women develop autoimmune disorders at an earlier age
• Women may acquire even more than one disorder
• Women have higher CD4+ T cell counts
• Women have higher level of circulating antibodies than men
• Estrogen directs the immune system to develop more Type 2 T-helper
cells
• Provides more B cell activation; therefore an increase in ab production
• Prolactin stimulates both humoral and cell-mediated immune responses
 Mechanisms of Autoimmunity – Tissue Trauma
• Immunologic tolerance that occurs in early development of lymphs
• Occurs in thymus and bone marrow
• Some self-antigen may be hidden (sequestered) or cryptic within the host tissue
• T and B lymphs are shielded from the sequestered antigens
• Therefore, they are not “taught” to be tolerant of these antigens
• If tissue trauma occurs, the sequestered antigens are exposed, leading to an immune response
• Tissue damage can be from
• Infections
• Contact with environmental toxins
• Physical injury
• UV radiation
• Known as immunologic ignorance – producing autoantibodies to “hidden” antigens
 Mechanisms of Autoimmunity – Microbial Infections
• Microorganisms such as bacteria and virus may trigger autoimmune
response
• Molecular mimicry – bacteria or viruses may contain antigens similar to the amino acid sequences of self-
antigens

• Exposure to the foreign antigens may trigger immune responses that CROSS-REACT with human self-
antigens

• Example – Streptococcus pyogenes and rheumatic fever (autoimmune disorder that affects joint and the
heart). Patients not treated for the strep infection with antibiotics may develop scarlet fever or pharyngitis.

• This leads to rheumatic fever – caused by production of antibodies to the M protein and N-acetyl
glucosamine (components of bacteria)
• These antibodies CROSS REACT with cardiac myosin (heart muscle) – leads to damage of the heart
 Mechanisms of Autoimmunity – Microbial Infections
• Superantigens
• Proteins that are produced by some microorganisms which have the ability to bind class II MHC molecules
and TCRs

• Activate a large number of T cells with different antigen specificities

• Examples include staphylococcal antigens that cause food poisoning and toxic shock syndrome

• If some of the T cells possess self-antigen specificity

• Autoimmune responses may result

• Viruses such as EBV and CMV can cause polyclonal activation of B cells
 Mechanisms of Autoimmunity – Epigenetics
• Refers to modifications in gene expression that are NOT caused by
changes in the original DNA sequence
• May be triggered by
• Environmental toxins
• Ingestion of toxic food or drugs
• Aging process
• Leads to over or under-expression of certain genes resulting
• Homeostatic imbalance leads to
• Breakdown of self-tolerance leads to
• Autoimmunity disorder
• In addition, may have exposure to environmental factors at the protein level
• Involved the biochemical reactions, which lead to an alteration of the immunogenicity of an antigen
• End up with an autoimmune situation
• Examples include RA and MS
 Classification of Autoimmune Diseases
• Systemic
• The autoimmunity is directed against an antigen that is present at many
different sites and can include involvement of several organs 
• Organ-specific
• Organ-specific means the autoimmunity is directed against a component of
one particular type of organ.
• May overlap systemic and organ specific
• Excellent chart on classification
https://www.palpath.com/MedicalTestPages/autoimclass.htm   
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