What is autoimmunity?
Inability to tolerate self antigens (rejection of self).
What is tolerance in immunology?
A state of immunologic unresponsiveness against a potential immunogen.
What does self-tolerance refer to?
Recognition by the immune system that 'self' should not be attacked.
Is self-tolerance a permanent state?
No, it is not always permanent.
What can cause a breakdown of tolerance?
Release of sequestered antigens and alteration of autoantigens.
What are privileged sites?
Sites where the immune system is blind to certain antigens, preventing immune responses.
What can lead to the release of sequestered antigens?
Infection or trauma may allow antigens to enter the blood.
What is an example of a sequestered antigen?
Lens protein of the eye causing endophthalmitis.
What is a soluble immunosuppressive mediator?
Certain cytokines that suppress immune response.
What is an example of an antigen in the CNS?
CNS proteins can induce encephalitis if the blood-brain barrier is compromised.
What is the role of the blood-brain barrier?
It protects CNS proteins from immune responses.
What is a common characteristic of autoimmunity?
Loss of tolerance to self antigens and exogenous antigens.
What can alter or modify self antigens?
1) Mutations or defects in synthesis 2) Combination with a drug 3) Viral infection
What happens with a subtle change in an antigen?
It can be recognized as different from self and seen as non-self.
What is molecular mimicry?
Exogenous substances have epitopes similar to autoantigens.
Which infectious agent is implicated in Rheumatic fever?
Rabies vaccine, E. coli 014, Trypanosoma cruzi, Treponema pallidum.
What is polyclonal activation?
Microbes act as polyclonal lymphocyte activators, causing non-specific T-cell activation.
What are superantigens?
Antigens that clamp to MHC class II and TCR, causing massive cytokine release.
What can induce inappropriate MHC Class II expression?
Release of IFN-γ during viral infection.
What can happen if MHC Class II is expressed on non-expressing tissues?
A self-peptide may be presented, resulting in T cell activation.
What happens when autoimmunity leads to pathological consequences?
It results in autoimmune disease.
What factors affect the clinical presentation of autoimmune diseases?
What are common components involved in autoimmune diseases?
How does age affect autoantibodies?
Low levels are found in the general population; incidence increases with age.
What is molecular mimicry in autoimmunity?
Extrinsic agents have epitopes similar to those in the human body.
What role do genetic factors play in autoimmune diseases?
They influence incidence, onset, and nature of diseases.
What is the pattern of inheritance in autoimmune diseases?
Complex, often involving more than one gene.
Which chromosomes may influence autoimmune diseases?
X or Y chromosome-linked genes and/or sex hormones.
What is the strongest evidence of a genetic nature in autoimmune diseases?
Linkage between autoimmune disease and certain HLA haplotypes.
What are the mechanisms of tissue damage in autoimmunity?
Humoral mechanisms involving type II hypersensitivity.
What do autoantibodies bound to cells cause?
What happens when autoantibodies bind to cell receptors?
How can autoantibodies inhibit cell function?
What can excessive activation of a cell by autoantibodies lead to?
What triggers tissue damage in immune complex formation?
What type of hypersensitivity mechanism is involved in cell-mediated autoimmunity?
What do CD4+ T cells activate against normal cell antigens?
What is the result of CTLs activation against normal cell antigens?
What is an example of an autoimmune disease affecting the multiple systems?
Name an autoimmune disease affecting the blood vessels.
Which autoimmune disease affects the heart?
What is an autoimmune disease of the pancreas?
Which autoimmune diseases affect the liver & biliary tract?
Name two autoimmune diseases related to endocrine disorders.
What are examples of autoimmune diseases in the hematopoietic system?
Which autoimmune diseases affect the skeletal system?
What is an autoimmune disease affecting the lungs?
Name an autoimmune disease affecting the kidneys.
Which autoimmune diseases affect the skin?
What are examples of autoimmune diseases in the central & peripheral nervous systems?
What does the bar graph show regarding autoimmune diseases?
It shows rates per 100,000 of diseases including Graves' disease, rheumatoid arthritis, Hashimoto's thyroiditis, vitiligo, and Type I diabetes.
What should we consider about autoimmune diseases?
What is Systemic Lupus Erythematosus (SLE)?
A multisystemic chronic disease characterized by 'flare-ups' and remissions, reflecting a generalized loss of tolerance.
What is the incidence of SLE?
Occurs in 1 per 2,500 population; primarily affects females (90%).
What is the common age of onset for SLE?
Typically in teens or 20s.
What is the 10-year survival rate for SLE?
90% or more.
What genetic factors are associated with SLE?
What environmental factors can trigger SLE?
What are the key autoantibodies in SLE?
How is organ damage mediated in SLE?
What are some clinical manifestations of SLE?
What is the consequence of antibody to phospholipid?
What does increased antibody formation lead to?
Hypergammaglobulinemia (extra antibodies in the bloodstream)
What are autoantibodies that target host cells associated with?
Type II hypersensitivity reaction (T2HRxn)
Where do immune complexes lodge in Type III hypersensitivity?
What is a classic cutaneous sign of systemic lupus erythematosus?
'Butterfly' rash on cheeks and bridge of nose
Who is most often affected by systemic lupus erythematosus?
Young women
What are some signs and symptoms of systemic lupus erythematosus?
What is Rheumatoid Arthritis (RA)?
A progressive inflammatory disease targeting joints, skin, and blood vessels.
What is the prevalence of Rheumatoid Arthritis?
Affects approximately 1% of the world population, more common in females (3:1).
What is a key factor in the pathogenesis of RA?
Increased risk with HLA-DQ and polymorphisms of the PTPN22 gene.
What is the rheumatoid factor?
IgM antibodies against the Fc portion of self IgG, not specific.
What type of immune response do CD4+ Th cells initiate in RA?
Delayed hypersensitivity mechanism.
What mediators are involved in Rheumatoid Arthritis?
What is the earliest medication used for rheumatoid arthritis?
Targets TNF
What are the signs and symptoms of rheumatoid arthritis?
What is Sjögren syndrome?
An autoimmune disease targeting and destroying salivary and lacrimal glands
What percentage of Sjögren syndrome cases occur in women aged 35-45?
90%
What is a common autoantibody in Sjögren syndrome?
What are the dry eye and dry mouth conditions associated with Sjögren syndrome?
What is the effect of xerostomia?
Increased dental caries and opportunistic oral infections
What does Systemic Sclerosis primarily target?
Connective tissue, causing excessive fibrosis
What is the peak age of onset for Systemic Sclerosis?
50 to 60 years old
In Systemic Sclerosis, how much more common is it in women than men?
Occurs in women three times as commonly
What are the autoantibody markers in Systemic Sclerosis?
ANAs
What antibodies are associated with anti-DNA topoisomerase I?
What cytokines are released in response to antigen in pathogenesis?
What is the effect of cytokines on fibroblasts?
They act as growth factors to produce excess collagen.
What are the characteristic changes in the face and hands due to excessive collagen?
What is the common phenomenon associated with this condition?
Raynaud phenomenon is common.
What organs may be affected by visceral involvement?
What is CREST syndrome?
A limited expression of systemic sclerosis, mostly affecting the skin.
What are the defining characteristics of CREST syndrome?
What is the nature of autoimmune hemolytic anemias?
Characterized by autoimmune destruction of red blood cells.
What tests facilitate the diagnosis of autoimmune hemolytic anemias?
Coombs testing: positive direct and indirect tests.
What does a positive direct Coombs test indicate?
Presence of antibodies coating RBCs.
What does a positive indirect Coombs test indicate?
Presence of circulating anti-RBC antibodies.
What do autoantibodies target in autoimmune hemolytic anemias?
Antigens present on RBCs.
What confirms the presence of antibodies complexed to RBCs?
Positive Coombs testing
What are the major mechanisms of RBC destruction?
1) Complement-mediated lysis 2) Phagocytosis by macrophages
What are common signs and symptoms of anemia?
What is the most common type of Autoimmune Hemolytic Anemia (AHA)?
Warm Autoimmune Hemolytic Anemia
What causes Warm Autoimmune Hemolytic Anemia?
Warm-reactive autoantibodies (IgG) against Rh antigen active at 37°C
What are signs of Warm Autoimmune Hemolytic Anemia?
What characterizes Cold Autoimmune Hemolytic Anemia?
Cold-reactive autoantibodies (IgM) against ABO RBC antigens active at 30°C and below
What are the symptoms of Cold Autoimmune Hemolytic Anemia?
What is Myasthenia Gravis?
An uncommon disorder of neuromuscular transmission
What autoantibody is involved in Myasthenia Gravis?
IgG autoantibody against acetylcholine (ACh) receptor
What are signs and symptoms of Myasthenia Gravis?
What is Goodpasture Syndrome?
An autoimmune disease targeting the lungs and kidneys, causing damage to the basement membranes.
What autoantibodies are present in Goodpasture Syndrome?
Autoantibodies against the glomerular basement membrane.
What is a key feature of the pathogenesis of Goodpasture Syndrome?
Linear deposits of IgG and complement detectable by immunofluorescence.
What are the acute signs and symptoms of Goodpasture Syndrome?
Rapidly progressive glomerulonephritis, proteinuria, hypertension, azotemia, pulmonary hemorrhage.
What is Multiple Sclerosis (MS)?
A chronic demyelinating disease characterized by relapsing and remitting neurologic deficits.
What is the epidemiology of Multiple Sclerosis?
Occurs in about 1 in 1,000 persons in the US, affecting women twice as often as men.
What is involved in the pathogenesis of Multiple Sclerosis?
Autoantibodies against the myelin sheath and cytotoxic T lymphocytes attacking nerve tissue.
What are common symptoms of Multiple Sclerosis?
Motor weakness, clumsiness, vertigo, visual impairment, ataxia, cognitive deficits.
What is Pemphigus vulgaris?
An autoimmune disease affecting the skin and mucous membranes, causing blisters.
What is Mucous membrane pemphigoid?
An autoimmune condition that leads to blistering of the mucous membranes.
What is Pernicious Anemia?
An autoimmune disorder that affects the absorption of vitamin B12, leading to anemia.
What is Immune Complex Nephritis?
An autoimmune disease causing inflammation in the kidneys due to immune complexes.
What is Type I Diabetes Mellitus?
An autoimmune disease where the immune system attacks insulin-producing cells in the pancreas.
What is Graves Disease?
An autoimmune disorder that causes hyperthyroidism due to overstimulation of the thyroid gland.
What is Hashimoto Thyroiditis?
An autoimmune disease where the immune system attacks the thyroid gland, leading to hypothyroidism.
What kind of course do some patients have?
A steady down-hill course.
What is the first anti-inflammatory drug mentioned for autoimmune diseases?
Prednisone (Steroids)
Which anti-inflammatory drug is used for SLE and rheumatoid arthritis?
Salicylates
What is an example of an anti-mitotic drug?
Azathioprine
Which anti-mitotic drug is used for rheumatoid arthritis?
Cyclophosphamide
What are TNF inhibitors used for?
They target TNF, such as Adalimumab, Etanercept, Infliximab, Golimumab.
What is Rituximab used for?
It is a B-cell–depleting agent.
What does Dupilumab inhibit?
It inhibits interleukin IL-4 and IL-13.
What is the role of plasmapheresis in autoimmune treatment?
It is used as a therapeutic procedure.
What is crucial for organ-specific autoimmune diseases?
Metabolic control
Which disease is associated with Type I diabetes mellitus?
It is an autoimmune disease.
What are two examples of autoimmune diseases?
What is the topic of Chapter 5 in the textbook?
Diseases of the Immune System
What pages cover autoimmune diseases in the required reading?
Pages 149-153
What concept is discussed under Immunologic Tolerance?
Mechanisms of Autoimmunity
What is covered in pages 131-139 of the recommended reading?
Who contributed to this topic?
Daila S. Gridley, Ph.D.
What is tolerance in immunology?
A state of immunologic unresponsiveness against a potential immunogen.
What does self-tolerance refer to?
Recognition by the immune system that 'self' should not be attacked.
What can cause a breakdown of tolerance?
Release of sequestered antigens and alteration of autoantigens.
What are privileged sites?
Sites where the immune system is blind to certain antigens, preventing immune responses.
What can lead to the release of sequestered antigens?
Infection or trauma may allow antigens to enter the blood.
What is an example of an antigen in the CNS?
CNS proteins can induce encephalitis if the blood-brain barrier is compromised.
What is a common characteristic of autoimmunity?
Loss of tolerance to self antigens and exogenous antigens.
What can alter or modify self antigens?
1) Mutations or defects in synthesis 2) Combination with a drug 3) Viral infection
What happens with a subtle change in an antigen?
It can be recognized as different from self and seen as non-self.
Which infectious agent is implicated in Rheumatic fever?
Rabies vaccine, E. coli 014, Trypanosoma cruzi, Treponema pallidum.
What is polyclonal activation?
Microbes act as polyclonal lymphocyte activators, causing non-specific T-cell activation.
What are superantigens?
Antigens that clamp to MHC class II and TCR, causing massive cytokine release.
What can happen if MHC Class II is expressed on non-expressing tissues?
A self-peptide may be presented, resulting in T cell activation.
What happens when autoimmunity leads to pathological consequences?
It results in autoimmune disease.
What factors affect the clinical presentation of autoimmune diseases?
What are common components involved in autoimmune diseases?
How does age affect autoantibodies?
Low levels are found in the general population; incidence increases with age.
What is molecular mimicry in autoimmunity?
Extrinsic agents have epitopes similar to those in the human body.
What role do genetic factors play in autoimmune diseases?
They influence incidence, onset, and nature of diseases.
What is the pattern of inheritance in autoimmune diseases?
Complex, often involving more than one gene.
Which chromosomes may influence autoimmune diseases?
X or Y chromosome-linked genes and/or sex hormones.
What is the strongest evidence of a genetic nature in autoimmune diseases?
Linkage between autoimmune disease and certain HLA haplotypes.
What are the mechanisms of tissue damage in autoimmunity?
Humoral mechanisms involving type II hypersensitivity.
What happens when autoantibodies bind to cell receptors?
What triggers tissue damage in immune complex formation?
What type of hypersensitivity mechanism is involved in cell-mediated autoimmunity?
What is an example of an autoimmune disease affecting the multiple systems?
Name an autoimmune disease affecting the blood vessels.
Which autoimmune diseases affect the liver & biliary tract?
Name two autoimmune diseases related to endocrine disorders.
What are examples of autoimmune diseases in the hematopoietic system?
Which autoimmune diseases affect the skeletal system?
What are examples of autoimmune diseases in the central & peripheral nervous systems?
What does the bar graph show regarding autoimmune diseases?
It shows rates per 100,000 of diseases including Graves' disease, rheumatoid arthritis, Hashimoto's thyroiditis, vitiligo, and Type I diabetes.
What should we consider about autoimmune diseases?
What is Systemic Lupus Erythematosus (SLE)?
A multisystemic chronic disease characterized by 'flare-ups' and remissions, reflecting a generalized loss of tolerance.
What genetic factors are associated with SLE?
What environmental factors can trigger SLE?
What are the key autoantibodies in SLE?
What are some clinical manifestations of SLE?
What is the consequence of antibody to phospholipid?
What does increased antibody formation lead to?
Hypergammaglobulinemia (extra antibodies in the bloodstream)
What are autoantibodies that target host cells associated with?
Type II hypersensitivity reaction (T2HRxn)
Where do immune complexes lodge in Type III hypersensitivity?
What is a classic cutaneous sign of systemic lupus erythematosus?
'Butterfly' rash on cheeks and bridge of nose
What are some signs and symptoms of systemic lupus erythematosus?
What is Rheumatoid Arthritis (RA)?
A progressive inflammatory disease targeting joints, skin, and blood vessels.
What is the prevalence of Rheumatoid Arthritis?
Affects approximately 1% of the world population, more common in females (3:1).
What is a key factor in the pathogenesis of RA?
Increased risk with HLA-DQ and polymorphisms of the PTPN22 gene.
What mediators are involved in Rheumatoid Arthritis?
What are the signs and symptoms of rheumatoid arthritis?
What is Sjögren syndrome?
An autoimmune disease targeting and destroying salivary and lacrimal glands
What are the dry eye and dry mouth conditions associated with Sjögren syndrome?
In Systemic Sclerosis, how much more common is it in women than men?
Occurs in women three times as commonly
What antibodies are associated with anti-DNA topoisomerase I?
What is the effect of cytokines on fibroblasts?
They act as growth factors to produce excess collagen.
What are the characteristic changes in the face and hands due to excessive collagen?
What are the defining characteristics of CREST syndrome?
What is the nature of autoimmune hemolytic anemias?
Characterized by autoimmune destruction of red blood cells.
What tests facilitate the diagnosis of autoimmune hemolytic anemias?
Coombs testing: positive direct and indirect tests.
What are the major mechanisms of RBC destruction?
1) Complement-mediated lysis 2) Phagocytosis by macrophages
What are common signs and symptoms of anemia?
What causes Warm Autoimmune Hemolytic Anemia?
Warm-reactive autoantibodies (IgG) against Rh antigen active at 37°C
What characterizes Cold Autoimmune Hemolytic Anemia?
Cold-reactive autoantibodies (IgM) against ABO RBC antigens active at 30°C and below
What are the symptoms of Cold Autoimmune Hemolytic Anemia?
What autoantibody is involved in Myasthenia Gravis?
IgG autoantibody against acetylcholine (ACh) receptor
What are signs and symptoms of Myasthenia Gravis?
What is Goodpasture Syndrome?
An autoimmune disease targeting the lungs and kidneys, causing damage to the basement membranes.
What autoantibodies are present in Goodpasture Syndrome?
Autoantibodies against the glomerular basement membrane.
What is a key feature of the pathogenesis of Goodpasture Syndrome?
Linear deposits of IgG and complement detectable by immunofluorescence.
What are the acute signs and symptoms of Goodpasture Syndrome?
Rapidly progressive glomerulonephritis, proteinuria, hypertension, azotemia, pulmonary hemorrhage.
What is Multiple Sclerosis (MS)?
A chronic demyelinating disease characterized by relapsing and remitting neurologic deficits.
What is the epidemiology of Multiple Sclerosis?
Occurs in about 1 in 1,000 persons in the US, affecting women twice as often as men.
What is involved in the pathogenesis of Multiple Sclerosis?
Autoantibodies against the myelin sheath and cytotoxic T lymphocytes attacking nerve tissue.
What are common symptoms of Multiple Sclerosis?
Motor weakness, clumsiness, vertigo, visual impairment, ataxia, cognitive deficits.
What is Pemphigus vulgaris?
An autoimmune disease affecting the skin and mucous membranes, causing blisters.
What is Mucous membrane pemphigoid?
An autoimmune condition that leads to blistering of the mucous membranes.
What is Pernicious Anemia?
An autoimmune disorder that affects the absorption of vitamin B12, leading to anemia.
What is Immune Complex Nephritis?
An autoimmune disease causing inflammation in the kidneys due to immune complexes.
What is Type I Diabetes Mellitus?
An autoimmune disease where the immune system attacks insulin-producing cells in the pancreas.
What is Graves Disease?
An autoimmune disorder that causes hyperthyroidism due to overstimulation of the thyroid gland.
What is Hashimoto Thyroiditis?
An autoimmune disease where the immune system attacks the thyroid gland, leading to hypothyroidism.
What are TNF inhibitors used for?
They target TNF, such as Adalimumab, Etanercept, Infliximab, Golimumab.
What is covered in pages 131-139 of the recommended reading?
Are you sure you want to delete 0 flashcard(s)? This cannot be undone.
Select tags to remove from 0 selected flashcard(s):
Loading tags...