pg 120-158 Flashcards
What percentage of the population is affected by autoimmune disease?
2-5%
Failed self-tolerance is referring to what?
Having self-reactive T and B cells- or an immune response to ones one’s own tissue antigens
What is immunologic tolerance?
The unresponsiveness to an antigen that is induced by exposure of specific lymphocytes to that antigen
What is Central Tolerance?
The principal mechanism is the antigen-induced death of self-reactive T and B lymphocytes during their maturation in the central (the places they are generated) lymphoid organs
Where are T cells and B cells generated?
T cells in the Thymus and B cells are generated in the bone Marrow (T=T and B=B)
What does peripheral tolerance refer to?
It refers to the death/deletion or inactivation of self-reactive T and B cells at the peripheries that escape the Thymus and could otherwise wreak havoc in the body
What does the breakdown of self-tolerance and development of autoimmunity result from?
A combination of inherited genes which influence lymphocyte tolerance, and environmental factors, such as infections or tissue injury, that alter the display of self-antigens
What are the prime targets for autoimmune disorders?
Connective tissue and vessels
Several autoimmune diseases are linked with what?
The Human Leukocyte Antigens (HLA) locus of genes are chromosome 6
What is the HLA responsible for?
It regulates the immune system by encoding for antigen-presenting proteins (presents allergen to T-cell, T-cell decides whether or not to kill it)
Is there a greater incidence of the same disease between dizygotic or monozygotic twins?
Monozygotic
The group of people most likely to develop autoimmune disorders are ___ and why?
Women of reproductive age due to high estrogen levels?
The display of tissue antigens may be altered by what 2 things?
Environmental factors and infections
Anergy refers to what?
Self antigens in peripheral tissues becoming functionally inactive
Lupus affects primarily which organs?
Skin, kidneys, serosal membranes, joints, heart, plus CNS
A disease which is described with an insidious inset, unpredictable, and relapsing could be…?
Lupus
Immunologically, Lupus is associated with an enormous array of autoantibodies, including ___
ANA (antinuclear antibodies) as well as IgG
Lupus is most common in…?
Women of childbearing age- more specifically African American woman of child-bearing age
What are some of the most common signs of Lupus? (There are lots)
Fever of unknown origin, photosensitivity (which leads to Malar rash, discoid rash, dermoepidermal degeneration), serositis (pleuritis or pericarditis), hair loss, GI discomfort, Libman-Sacks endocarditis (‘warts’ on Bicuspid valve)… painless oral ulcers, non-erosive arthritis, CNS problems, fatigue, myalgia, pulmonary and liver fibrosis, pancytopenia, splenomegaly
The fundamental defect in SLE is…?
The failure to maintain self-tolerance, leading to the production of large number of autoantibodies that can damage other tissues directly or via immune-complex deposits
The best way to diagnose SLE is to look at ___ which means what? And how specific is the test?
ANA’s, which means that 99% of Lupus patients will show positive for ANA’s. It is 80% specific, meaning that other diseases can show positive for ANA, but 80% of those positive results will be from Lupus
The ANA test uses ___
Immunofluorescence
Most organ damage in SLE is caused by what?
Immune complex deposition
The most common cause of death to Lupus patients is…? Another common cause of death is…? What are they also at risk of?
Renal failure… Coronary artery disease is another cause, which can lead to MI and infection. They are also at an increased risk of B cell lymphoma
What is the survival rate of SLE after diagnosis?
95% 5-year survival
How many Americans have Lupus?
1.5 million
A condition that is secondary to other autoimmune disorders, is most common females aged 35-45, can be triggered by a virus, and is associated with dry eyes and dry mouth would be…?
Sjogren syndrome
Dry eyes and dry mouth when isolated can be called…?
sicca syndrome
Sjogren syndrome patients are also at increased risk of…?
B cell lymphoma
Sjogren syndrome is an autoimmune disease caused by…?
CD4+ T cell reactions against unknown antigens in the ductal epithelial cells of the exocrine glands
Sites of damage from most common to least common in Sjogren syndrome are:
Lacrimal (keratoconjunctivitis sicca and salivary (xerostomia) glands, and less commonly the vagina, nasopharynx (laryngitis), upper airways (bronchitis), kidneys, CNS, muscles
What percentage of Sjogren syndrome patients will test positive for ANA?
90%? (I have noted)
Explain Rheumatoid Arthritis
It is a systemic, chronic inflammatory disease affecting many tissues but mainly the joints to produce nonsuppurative proliferative synovitis that often destroys the articular cartilage and bone underneath
Systemic sclerosis is defined as…?
An immunologic disorder characterized by excessive fibrosis in multiple tissues, obliterative vascular disease, and evidence of autoimmunity, mainly the production of multiple autoantibodies
Systemic sclerosis affects mainly the ___ but also what else?
Skin (95% with it will have skin disorder), but also the GI, kidney, lungs, heart, and skeletal muscle
Systemic sclerosis can be classified into what 2 groups?
Diffuse scleroderma and Limited scleroderma
Diffuse scleroderma is what?
Initial widespread skin involvement with rapid progression to visceral involvement. More aggressive
What is limited scleroderma?
Mild skin involvement, often confined to fingers and face, viscera involvements occurs later.
What are the characteristics of Limited scleroderma and what are they known as?
CREST syndrome- calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
What group of people is most affected by Systemic Sclerosis?
Women aged 40-60
Immune Deficiency Disorders can be classified as either ___ or ___ and do what to the person?
They can be Congenital (primary) or Acquired (secondary). They make the person more vulnerable to infection or disease, like caner
What characterizes a congenital immune deficiency disorder?
Rare, usually genetic, early onset (6-24 months), and has recurrent infections
Some examples of Primary immune deficiency disorders are: (5 of them)
X-linked agammaglobulinemia (Bruton disease), Common variable immunodeficiency, Isolated IgA deficiency, Hyper IgM Syndrome, Severe combined Immunodeficiency (SCID),
Bruton Disease is characterized by: (population, mechanism, common problems, treatment/prognosis)
an early onset to males (6 months), failed B cell maturation (no antibodies), common occurance of otitis media, pharyngitis, sinusitis. Can be helped be infusions–> has a good prognosis
Common variable immunodeficiency is characterized by: (population, mechanism, common problems)
Males and females aged 10-30 (1/50000), they have normal B cell cells abut no plasma cells (poor antibody response to infections) which leads to GI infections
What is the most common immune deficiency disorder and what are characteristics of it?
Isolated IgA deficiency (1/700 Caucasians). It leads to a decrease in IgA production (in mucous membrane), it is generally asymptomatic or very mild (diarrhea or URTIs),
What are the characteristics of Hyper-IgM syndrome?
Increased levels of IgM, decreased levels of IgA, IgE, IgG–> leading to recurrent bascterial infections, 70% Is X-linked and therefore more common males, occurs in 1/100000 people
What is SCID?
Severe combined immunodeficiency- extremely bad, “bubble boy” syndrome, vulnerable to all microbial infections, decrease in T and B cells, 1/65-100K and the most common in Native Americans
Is primary or secondary immune deficiencies more common?
Secondary
When might secondary ID be encountered most often? Other times?
Most often with therapy-induced suppression of bone marrow or of lymphocyte function. Also with malnutrition, infection (HIV), cancer, renal disease, sarcidosis
How is the HIV virus passed?
Blood, semen, vaginal fluid, breast milk
What is the mechanism of AIDS and what occurs as a result?
destroys CD4+ T cells and macrophages via apoptosis or cytotoxicity. This allows for ‘opportunistic infections’ , tumors, and CNS defects to occur more easily
In declining order, what is the most common form of spread (populations)?
Males-male sex- 48% Male-female sex- 34% IV drug abusers- 17% Blood transfusion recipients- 1% to children (transplacental, childbirth, milk)- 1%
What is the most affected group in Africa and Asia?
Male-female sex
Does semen or vaginal fluid transmit HIV ‘better’?
Semen
What antigen is screened to test for AIDS?
p24 antigen
What are 2 tests to check for AIDS?
ELISA test, Western Blot test
The acute phase of AIDS is characterized by…?
pyrexia, pharyngitis, myalgia, viremia usually (70%) 3-6 weeks after infection, decreases again at about 12 weeks
The chronic phase of AIDS appears when? and looks like…?
2-10 years after infection. Minor features: Lymphadenopathy (MC). A decrease in CD4+ T cells, viremia gradually increases, VZV (chicken pox)
The crisis phase of AIDS is characterized by…?
Describe, in general, the 2 phases of AIDS
The acute phase occurs within 3-6 weeks of initial infection and is accompanied by moderate-mild symptoms and discomfort that go away within 12 weeks. A chronic phase follows for 2-10 and is characterized by relatively normal rates of infection and a slightly decreased level of CD4+ T cells. Crisis phase occurs after the chronic phase and is characterized by CD4+ T cells being below 200/microliter- this is the bad stage with lots of infection and leading to death fairly quickly
Opportunistic infections account for what percentage of AIDS deaths?
80%
What characterizes the transition from acute phase AIDS to chronic phase AIDS?
Dissemination of the virus, viremia, development of host immune response
What occurs during the chronic phase of AIDS?
Lymph nodes and the spleen are sites of continuous HIV replication and cell destruction
How does HIV enter cells?
It requires the CD4+ molecule, which acts as a high affinity receptor for the virus
What are infections that occur in the CNS due to AIDS?
Toxoplasmosis, CMV, and cryptococcosis
What type of tumor are AIDS patients more likely to develop?
Kaposi Sarcoma- a vascular tumor that is otherwise rare
What is amyloidosis?
It is fundamentally a disorder of protein misfolding associated with a number of inherited and inflammatory disorders in which fibrillar proteins are responsible for tissue damage and functional compromise
What type of dye is used to identify the presence of amyloids?
Congo red
Which 2 general categories do proteins that form amyloids fail?
normal proteins have an inherent tendency to misfold, associate to form fibrils, and do so when they are formed in increasing amounts; mutant proteins that are prone to misfolding are subsequent aggregation
How does failed phagocytosis affect the formation of amyloids?
misfolding proteins accumulate that should be broken down (amyloids), these buildups damage tissue and disrupt function
What is an amyloid?
A series of non-branching fibrillar proteins (that got there via mutation)
What does Congo Red dye do to the amyloid bodies?
Polarized light a Congo Red stained amyloid show apple-green birefringence
A common organ for amyloid bodies to accumulate is the…
kidney
What are 4 types of amyloid proteins?
Amyloid light (AL), Amyloid-assoctiated (AA), Beta-amyloid (AB), Transthyretin
How are AL proteins produced?
By plasma cells (Beta cell proliferation)… and is made of immunoglobulin light chains and Bence-Jones proteins
What are AA proteins associated with?
The Liver (serum associated amyloids- SAA)–> leads to chronic inflammation like TB, RA, Inflammatory bowel disease, osteomyelitis
What is associated with Beta Amyloids (AB)?
Alzheimer’s disease. It is associated with cerebral lesions and deposition of cerebral plaques in cerebal blood vessels and is derived from Amyloid Precursor Protein (APP)
Other than Alzheimer’s Disease, what other disorder is associated with Beta-amyloids?
Down Syndrome
What is Transthyretin associated with?
Senile Systemic Amyloidosis- they deposit in the heart of older people
In systemic amyloidosis, what are the 3 kinds and which is most common?
Primary, secondary, and aging. Primary is more common and involves malignant plasma cells and Amyloid Light chains. Secondary leads to chronic inflammation and deals with Amyloid Associated proteins. Aging occurs in the elderly and deals with Senile systemic amyloidosis
What are common organs affected by Localized Amyloidosis and which protein is associated with it?
Amyloid-Light chains, and the single organs often affected are the brain, heart, kidney, tongue, lung, skin, larynx
Name the effects of amyloidosis on: tongue, kidney, brain, spleen, liver, heart, wrist ligaments
tongue- macroglossia;
kidney- (MC), enlarged and decreased function;
Brain- AB plaques, Alzheimer’s;
Spleen- splenomegaly, decrease function;
Liver-hepatomegaly, decrease function;
Heart- cardiomegaly, decrease function- Restrictive cardiomyopathy;
Wrist ligaments- dialysis, CTS
What are the most common non-specific features of amyloidosis?
weakness, fatigue, cachexia
When is amyloidosis most likely to be fatal?
when it involves the kidneys (renal disease/kidney failure) or the heart (arrhythmia, restrictive cardiomyopathy)
What is the prognosis when amyloidosis is systemic?
Poor–> 1-3 years after diagnosis (worse with multiple myeloma)
