Pathology: Autoimmune disorders Flashcards
Diagnosis of AI diseases
Existence of auto-Ab
Evidence that immune mechanisms are causing pathologic-lesions
Evidence of immune nature of disorder
Ab cannot always be demonstrated and pathogenicity often difficult to prove
what is Autoimmune diseases
immune response based on the ability of the body to identify self from non-self
Generally tolerant of Ag expressed on own cells
Numerous control mechanisms to suppress response against self Ag
Breakdown of Auto-tolerance =AI
AI Diseases characteristics
Occur with increased frequency in some families indicating genetic factors
Most AI diseases more common in women
Can be systemic or localized
AI Disease systemic (multi organ)
Systemic (multiorgan): SLE, rheumatic fever, rheumatoid arthritis, systemic scleosis, polyarteritis nodosa
AI Disease limited to single organ
Multiple sclerosis:CNS
Hashimoto’s thyroiditis, Grave’s disease : Thyroid
Pemphigus vulgaris: skin
Myasthenia gravis: muscle
SLE (systemic Lupus Erythematosus)
Prototype of immune disorder
Characterized by multisystemic involvement
Affects 1/2500 persons
10 x more common in women
Can occur at any age but more common in young adults
Most severe among African Americans
Generic components
Pathogenesis of SLE
Poorly understood
Malfunction of T suppressor cells withich allows polyclonal activation of B cells
Plasma cells derived from uncontrolled B cell clones secrete antibodies against autoantigens and foreign antigents
Many antibodies to DNA, RNA and nuclear proteins = called antinuclear antibodies (ANA)
Pathology of SLE
Antibodies react with antigens in tissues and also with those released from cells by other means
Antigens that reach circulation from complexes with antibodies in the serum
Circulating Ab-Ag complexes deposited in membranes e.g. synovial membrane, serous membrane, endocardium, choroid plexus, ant. eye chamber
Immune complexes are large and retained and activate complement, which elicits an inflammatory reaction resulting in many organ-specific inflammatory diseases e.g. glomerulnonephritis, arthritis, etc
SLE clinical features
Highly variable
Inflammation of joints (arthritis) - most common, redness, swelling, pain
Kidney involvement (75%)
Cutaneous lesions (butterfly rash 30-60%)
Damage to RBCs causing anemia
Enlargement of lymph nodes and spleen
SLE treatment
Immunotherapy generally successful
-corticosteroids
-cyclophosphamide
Kidney transplant
what is Immunodeficiency
Primary (congenital) or secondary (due to infections, metabolic diseases, cancer, or treatment, etc)
secondary is more common
AIDS is example of secondary (most prevalent)
Primary or secondary may involve B cells or T cells or may be generalized and involve the whole immune system
ID Diseases
All ID diseases are characterized by lymphopenia - low lymphocyte count in peripheral blood
B cell deficiency associated with low levels of serum antibodies
All ID disorders cause reduced resistance to infections
Primary ID Disorders
Group of genetic disorders affecting differentiation and maturation of T cells and B cells
Can occur at any step along the developmental sequence that leads from stem cells to fully differentiated cells
Leads to heterogenous group of disorders with mild or severe symptoms
Example DiGeorge’s syndrome: T-cell deficiency related to aplasia of thymus, associated with aplasia of parathyroid grands
AIDS (Acquired immune Deficiency Syndrome)
set of symptoms and infections resulting from the damage to the human immune system caused by the human immunodeficiency virus (HIV)
progressively reduces the effectiveness of the immune system and leave individuals susceptible to opportunistic infection and tumours
AIDS transmission
Transmitted through direct contact of a mucous membrane of the bloodstream with a bodily fluid containing HIV
Transmission can involve sex, blood transfusion, contaminated needles, exchange between mother and baby during pregnancy, childbirth, breast-feeding, or other exposure to bodily fluids
Epidemiology of HIV
Etiology: Human immunodeficiency Viruses (HIVs)
RNA retroviruses
Highest prevalence in Africa
35 million world wide
100,000 new cases per year in US
1% of all college-aged people (18-25 years old)
Pathogenesis early stage
Transmitted through the transfer of body fluids
Virus can’t survive outside host cell
HIV has affinity for T helper cells and monocytes
Macrophages can also become infected
Fixed tissue phagocytic cells can also become infected (e.g. microglia)
infected cells can serve as reservoir for virus
HIV virus is cytotoxic thus infected cells often die
initial infection stimulates B cells to produce antibodies within weeks
Pathogenesis later
Latent infection can persist for years
As virus replicates and destroys more helper T cells, symptoms of AIDS begin to appear
Pathogenesis end stage
Cell mediated immunity becomes depressed and humans can not defend against infections (opportunistic)
Death generally occurs due to infection but can also occur due to tumours
Clinical presentation of HIV (Group 1)
Phase of Acute illness Usually 3-6 weeks after exposure Symptoms typically non-specific, include fever, night sweats, nausea, myalgia, headache, sore throat, skin rash, lymph node enlargement Symptoms last 2-3 weeks, then disappear Patients may develop antibodies to HIV
Clinical Presentation of HIV (group II)
Phase of asymptomatic infection
Variable duration, months to years
Asymptomatic patients carries virus and is infectious
Approx 50% of HIV + patients develop AIDS within 10 years of initial diagnosis
Clinical presentation of HIV (Group IV)
Patients shows signs of AIDS which reflects opportunistic disorders including GI disorders, CNS involvement, neoplasia
Clinically ratio of CD4+/CD8+ cells decrease
In the last stages, almost no CD4+ cells present
What HIV does to Lymph nodes?
Initially Lymph nodes enlarge and show hyperplasia
After time, lymph nodes become depleted of lymphocytes and eventually become infected
What HIV does to Brain?
Microglia in the brain and multinucleated giant cells from nodules
Opportunistic infection leads to meningitis or encephalitis (CMV, herpes, fungi, protozoa)
May destroy part of the brain directly or through infarct
What HIV does to respiratory tract?
Initially localized to Upper respiratory tract but often progresses to Lower respiratory tract (pneumonia or TB) -Pneumocystis jiroveci/carinii
What does HIV does to GI?
Infections are similar to respiratory tract and can also include parasites
Diarrhea and malabsorption of nutrients can also be present
What does HIV do to Skin?
can include dermatitis or infections (fungi, herpes, bacteria)
What kind of Cancers does HIV cause?
Kaposi’s sarcoma and lymphomas (lymph nodes, spleen, liver, brain, etc)
Kaposi’s sarcoma
Malignant disease of endothelial cells
Caused by herpesvirus
Often occurs in skin and internal organs
Nodules composed of anastamosing vascular spaces filled with blood
Can cause bleeding or compress vital organs
Diagnosis of HIV
Presence of HIV antibodies in blood (HIV+)
T-cell count decreased ratio of CD4+/CD8+
AIDS diagnosed by presence of opportunistic infection and tumours
Treatment
Meds- replication inhibition of virus
Expensive and not readily available worldwide
Vaccines unsuccessful
Death can be postponed by vigorous treatment of opportunists
Amyloidosis
caused by deposition of a fibrillar substance called amyloid
multi-factorial disease
Often related to abnormalities of the immune system or an abnormal response to chronic infection
Amyloid: any fibrillar protein that forms a beta-plated sheet
Amyloid is deposited in the extra-celluar spaces
Changes the function of tissues and cells
Leads to proteinuria in kidney
Vessels in liver and adrenal grands becomes solid
Atrophy and loss of cell function
Amyloid in heart causes weakened contractions
Amyloid in brain causes dementia
Clinical presentation is variable and depends on the organ system involved
No effective treatment
Clinical presentation of Amyloid deposition
Systemic amyloidosis: usually caused by deposition of AA or AL amyloid in various organs (e.g. liver, kidneys, adrenals, spleen, heart)
Localized organ: specific amyloid deposits (e.g., Alzeimer’s disease)
