A concise ppt about autoimmunity. It incudes information about tolerance, etiology behind autoimmune diseases, types of autoimmune diseases and few examples of diseases.

1. Immunology
Autoimmunity
Monu Raj
III B.Sc. Biotechnology

2. Introduction
• Autoimmunity is defined as an immune response leading to reaction with self
antigen, i.e. any molecule that is a normal body constituent.
• These components are called autoantigens or self-antigens and typically consist of
proteins (or proteins complexed to nucleic acids).
• The antibodies and T lymphocytes that recognize autoantigens are called
"autoantibodies" and "autoreactive T cells".
• The etiology behind autoimmune diseases is multifactorial, with genetic,
hormonal, and environmental factors all playing a role.
• Autoimmunity is benign and present in all individuals and increases with age;
however, autoimmune disease occurs only in those individuals in whom the
breakdown of one or more of the basic mechanisms regulating immune tolerance
results in self-reactivity that can cause tissue damage.

3. Tolerance
• Immune tolerance refers to the
unresponsiveness of the immune
system to self-antigens.
• Tolerance is induced and maintained
both centrally and peripherally.
• Central Tolerance refers to deletion
of autoreactive T and B cells during
their development in Thymus or Bone
marrow. This process is normally
referred as Negative selection.

4. Peripheral Tolerance
• Peripheral tolerance mechanisms prevent autoimmunity from arising in the case
that autoreactive lymphocytes made it through all central tolerance processes.
• Four main mechanism in peripheral tolerance are:
• Anergy is the first main peripheral tolerance mechanism. It refers to a lack of
immune response due to the absence of costimulatory signals.
• Clonal deletion (Apoptosis): The association of autoreactive T-cells with self-
antigen complexes triggers activation of the Fas-Fas ligand system. Both Fas and
its ligand are found on T-lymphocytes, and their interaction induces cell death of
the T-lymphocyte by triggering the caspase cascade.
• Ignorance: T-cells ignore certain self-antigens because they are located in
immune-privileged sites or because they have low immunogenicity.
• Immune Regulation: Immune regulation is achieved by the action of Treg’s

5. Factors affecting Autoimmunity
• Although underlying molecular etiologies
remain elusive for most autoimmune diseases,
it is thought that autoimmunity is
multifactorial, resulting from a complex
interplay between genetic susceptibility,
environmental triggers, and aberrant immune
regulation.

6. Genetic Factors
• Certain autoimmune disorders are familial.
• Single gene mutations lead to autoimmunity (monogenic
diseases, e.g. ALPS), but most autoimmune diseases are
polygenic (30+ genes contribute)
• Genes shown to have a strong association with many
autoimmune diseases are within the MHC locus.
• Genetic associations outside the MHC locus include the
autoinflammatory disorders (e.g. genes for FcγR have a
moderate association with SLE)
MHC-I association
Ankylosing spondylitis (HLA-B27)
Reactive arthritis (HLA-B27)
Psoriasis (HLA B-13, B-16, B-17)
MHC-II association
Systemic diseases
Systemic lupus erythematosus (HLA-DR2 and
DR3)
Rheumatoid arthritis (HLA-DR4)
Organ-specific diseases
Type 1 diabetes mellitus (HLA-DR3 and DR4)
Multiple sclerosis (HLA-DR2)

7. Environmental Factors
• Bacterial and viral infections can lead to a phenomenon known as 'molecular mimicry,' in which
antigens on certain pathogens may have determinants that cross-react with self-antigens. An
immune response against these determinants may lead to effector cells or antibodies against tissue
antigens.
• For example, a membrane protein on the P-hemolytic streptococcus bacterium has a high degree of
homology with cardiac myosin, and antibodies that target the bacterium also cross-react with
cardiac muscle and induce rheumatic fever.
• Drugs or degradation products of self-antigens may bind to tissue constituents forming a hapten-
carrier complex which then triggers autoimmunity.
• Women are much more prone to autoimmune disease compared to men.
• Type 1 diabetes is most common in children, accounting for two thirds of new cases in children of
all ethnic groups.

8. Immune system Dysregulation
• The negative selection in the thymus may not be fully functional to eliminate self reactive cells and
can lead to the presence of autoreactive T cells.
• Similar mechanisms can lead to proliferation of autoreactive B-cells.
• Defective apoptosis and impaired Treg activity can also lead to autoimmune diseases.
• For example, Autoimmune polyendocrine syndrome type I (APSI) or (APECED) due to defects in
AIRE induced apoptosis in central tolerance and Immunodysregulation polyendocrinopathy
enteropathy X-linked (IPEX) syndrome due to Foxp3 mutation leading to and absence of Treg.

9. Autoimmune diseases
• Autoimmune diseases develop when
the auto-reactive B lymphocytes and T
lymphocytes causes a pathological
and/or functional damage to the
organ/tissue containing the target
autoantigen(s).
• Types of Autoimmune diseases:-
1. Organ Specific
2. Systemic (non-organ specific)

10. ORGAN-SPECIFIC AUTOIMMUNE
DISEASES
• The immune response is directed to a target antigen unique to a single organ or
gland, so that the manifestations are largely limited to that organ.
• The cells of the target organs may be damaged directly by humoral or cell
mediated effector mechanisms.
• Gradually, the damaged cellular structure is replaced by connective tissue
(fibrosis), and the function of the organ declines.
• Alternatively, anti-self antibodies may overstimulate or block the normal function
of the target organ.

11. SYSTEMIC AUTOIMMUNE DISEASES
• In systemic autoimmune diseases, the immune response is directed toward a broad
range of target antigens and involves a number of organs and tissues.
• These diseases reflect a general defect in immune regulation that results in
hyperactive T cells and/or B cells.
• Tissue damage is typically widespread, both from cell-mediated immune
responses and from direct cellular damage caused by auto-antibodies or by
accumulation of immune complexes.

13. Type 1 Diabetes Mellitus
• T1DM is caused by an autoimmune attack against insulin-producing cells (beta
cells) scattered throughout the pancreas.
• This results in decreased production of insulin and consequently increased levels
of blood glucose.
• The attack begins with cytotoxic T lymphocyte (CTL) infiltration and activation of
macrophages, frequently referred to as insulitis, followed by cytokine release and
the production of autoantibodies, which leads to a cell-mediated DTH response.
• Genetic factors include both MHC and non-MHC genes.
• The most common environmental factors linked with T1DM are viral infections
(such as CMV and Coxsackie) and vitamin deficiency.
• Three major auto-antigens have been identified in T1DM: insulin, GAD65 and
IA2.
• The most common therapy for T1DM is daily administration of insulin

14. Rheumatoid Arthritis
• It is a common autoimmune disorder, most often
diagnosed between the ages of 40 to 60 and more
frequently seen in women.
• The major symptom is chronic inflammation of the
joints, although the hematologic, cardiovascular, and
respiratory systems are also frequently affected.
• Individuals with RA produce a group of auto-antibodies
called rheumatoid factors that are reactive with
determinants in the Fc region of IgG.
• The classic rheumatoid factor is an IgM antibody that
binds to normal circulating IgG, forming IgM-IgG
complexes that are deposited in the joints.
• These immune complexes can activate the complement
cascade, resulting in a type III hypersensitivity reaction,
which leads to chronic inflammation of the joints.

15. References
• Kuby immunology Owen, Judith A; Punt, Jenni; Stranford, Sharon A; Jones, Patricia P; Kuby, Janis.7th ed. New York :
W.H. Freeman, c2013.NLM ID: 101607504 [Book]
• Kurup S, Pozun A. Biochemistry, Autoimmunity. [Updated 2022 Dec 19]. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576418/
• Lucier J, Weinstock RS. Type 1 Diabetes. [Updated 2023 Mar 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507713/
• Mackay IR. Tolerance and autoimmunity. West J Med. 2001 Feb;174(2):118–23. PMCID: PMC1071274.
• Smith DA, Germolec DR. Introduction to immunology and autoimmunity. Environ Health Perspect. 1999 Oct;107 Suppl
5(Suppl 5):661-5. doi: 10.1289/ehp.99107s5661. PMID: 10502528; PMCID: PMC1566249.

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