Immunology 3: Autoimmunity Flashcards
Autoimmunity
Inappropriate response of the immune system against self components.
- A breakdown of central tolerance or peripheral tolerance in B cells or T cells.
What types of hypersensitivity is autoimmunity related to?
ALL types
- Type 1,2,3,4
What is type 1 hypersensitivity of autoimmunity
Eosinophilic Esophagitis
What is type 2 hypersensitivity of autoimmunity
Autoimmune hemolytic anemia
What is type 3 hypersensitivity of autoimmunity
Systemic lupus erythematosus
What is type 4 hypersensitivity of autoimmunity
Type 1 diabetes
Two types of autoimmune thyroiditis
Attacking the thyroid
- Hypothyroidism
- Hyperthyroidism
What are autoimmune skin diseases?
- Psoriasis (dry skin)
- Pemphigus (bumps with fluid)
- Vitiligo (Depigmentation)
- All involve self antigens and are organ specific
What is autoimmune hemolytic anemia?
- Organ-specific
- IgG targeting RBC self-attacking.
*Different from transfusion reaction.
Examples of non-organ specific
Systemic autoimmune disease
- Lupus
- Rheumatoid Arthritis
- Multiple sclerosis
Multiple sclerosis targets what?
-Targets myelin of CNS
Rheumatoid Arthritis affects what?
-affects joints, cardiovascular, neurological, renal
Sex bias of autoimmune disease?
Much more common in females
Is type 1 diabetes organ specific or organ non-specific?
Organ-specific
Difference between type 1 and type 2 diabetes
Type 1 is autoimmune disease
Type 2 is not
What is type 1 diabetes
Chronic autoimmune disease with strong inflammation
Type 1 diabetes stage one characteristics?
- Induced by PRR (pattern recognition receptor) ligands triggers
- Production of type 1 interferons (Anti-viral, inflammation promoting)
Type 1 diabetes stage two characteristics
- Activation of macrophages and t-cells by type-1 interferons
- Recruiting of pancreatic b cells in inflammation by macrophages
- Amplification of inflammation
Type 1 diabetes stage three characteristics
Maintenance or resolution depending on fate of b cells
What is type 1 diabetes type 4 hypersensitivity?
Because it includes the t cell and b cell production
Steps between communication of immune cells and pancreatic b cells
- activation of b cells via PRR
- Release of cytokines and chemokines that recruit and activate immune cells
- up-regulation of MHC-1 and activation of T cells
- Activation of b cell apoptosis and MHC-II presentation on APCs leading to more t cell activation
- Pro-inflammatory cytokines produced by immune cells to further activate b cells.
** Detrimental cycle of inflammation**
How does inflammation affect b cells?`
Detrimental or beneficial
Detrimental affects of inflammation onto b cells?
- Suppression of B cell function
- Continued B cell death
- Maintenance of disease
Beneficial affects of inflammation onto b cells.
- Stimulus of B cell proliferation
- For individual with mild insulitis, inflammation might resolve and normal b cell function can be regained
Is lupus organ specific or non-organ specific?
Non-organ specific. It is a systemic issues.
Systemic lupus erythematosus key concepts
- 20 to 150 cases per 100,000
- More common in women of childbearing age
- Diverse manifestation
- 50% of patients can get lupus nephritis (Leads to mortality)
- Treated with non-selective immunosuppressants (Severe side-effects)
Etiology of SLE?
** Exact cause is unknown **
Genetics
Environment
Hormones
Genetics effects on SLE
The disease is not linked to a single gene. People with lups often have family members with autoimmune condition
Environment effects of SLE
Triggers are UV light, Certain medication (affecting microbiome), viruses, physical or emotional stress, Trauma
Hormones effects on SLE
Women of childbearing age most vulnerable
Clinical sings/Diagnosis requirements of lupus
4/11 needed to diagnose
-Malar rash
-discoid rash
-Photosensitivity
-oral ulcers
-Arthritis
-Serositis
-Kidney disorder
-Neurological disorders
-Blood disorder
-Immunologic disorder
Abnormal antinuclear antibodies (can also naturally exist)
Immunological mechanisms steps
- Self DNA, cell death releases nucleic acids
- Nucleic acid picked up by NETs of neutrophils
- Triggers interferon response
-Nucleic acid can also be picked up by antibodies
-Forms immunocomplex (type 3 hypersensitivity)
-Recognized by Fc receptor on plasmacytoid dendritic receptor
-Stimulated more Type 1 interferon
- Type 1 IFN stimulated myeloid dendritic cells
- Myeloid dendritic cells stimulates T and B cells
- Leads to recruitment of inflammatory cells
Three categories of autoimmune disease
-Genetic factors
-Immune regulation
-Environment factors
What are genetic factors of autoimmune disease?
-HLA genes
- non-HLA genes
Genes on MHC that help code for self vs non-self antigens
What are Environment factors of autoimmune disease
- Drugs
- Infection
-Smoking
-Hormones
-nutrition
What are the immune regulation factors of autoimmune disease
A breakdown of immunological self-tolerance
What is self-tolerance?
A deficit response to self organs. (AKA lack of response)
What is central tolerance?
Deletion of lymphocytes that react to self in the lymphoid organs (BONE MARROW and THYMUS)
- Attempt at regulation of lymphocytes that will attack self.
What is peripheral tolerance?
Deletion of lymphocytes that recognize self-tissues in the periphery.
– Attempt at regulation of lymphocytes that will attack self.
What happens upon activation of the autoimmune system?
May cause a vicious cycles of injury tissues causing more inflammatory responses
Early stage autoimmune disease will have more of what kind of lymphocyte?
B cells
Late stage autoimmune disease will have more of what kind of lymphocyte?
T cells
Autoimmunity is caused by what type of cell
T helper 17- play an essential role in the clearance of extracellular pathogenic bacteria and fungi but can be directed toward self
Autoimmunity is balance or “capped” by what type of cell?
Tolerance is mediated by Treg cells
-suppressing inflammatory events in an antigen-specific manner
