Pathology: Autoimmune disorders

Question 0

Diagnosis of AI diseases

Answer 0

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

Question 1

what is Autoimmune diseases

Answer 1

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

Question 2

AI Diseases characteristics

Answer 2

Occur with increased frequency in some families indicating genetic factors
Most AI diseases more common in women
Can be systemic or localized

Question 3

AI Disease systemic (multi organ)

Answer 3

Systemic (multiorgan): SLE, rheumatic fever, rheumatoid arthritis, systemic scleosis, polyarteritis nodosa

Question 4

AI Disease limited to single organ

Answer 4

Multiple sclerosis:CNS
Hashimoto’s thyroiditis, Grave’s disease : Thyroid
Pemphigus vulgaris: skin
Myasthenia gravis: muscle

Question 5

SLE (systemic Lupus Erythematosus)

Answer 5

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

Question 6

Pathogenesis of SLE

Answer 6

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)

Question 7

Pathology of SLE

Answer 7

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

Question 8

SLE clinical features

Answer 8

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

Question 9

SLE treatment

Answer 9

Immunotherapy generally successful
-corticosteroids
-cyclophosphamide
Kidney transplant

Question 10

what is Immunodeficiency

Answer 10

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

Question 11

ID Diseases

Answer 11

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

Question 12

Primary ID Disorders

Answer 12

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

Question 13

AIDS (Acquired immune Deficiency Syndrome)

Answer 13

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

Question 14

AIDS transmission

Answer 14

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

Question 15

Epidemiology of HIV

Answer 15

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)

Question 16

Pathogenesis early stage

Answer 16

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

Question 17

Pathogenesis later

Answer 17

Latent infection can persist for years

As virus replicates and destroys more helper T cells, symptoms of AIDS begin to appear

Question 18

Pathogenesis end stage

Answer 18

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

Question 19

Clinical presentation of HIV (Group 1)

Answer 19

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

Question 20

Clinical Presentation of HIV (group II)

Answer 20

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

Question 21

Clinical presentation of HIV (Group IV)

Answer 21

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

Question 22

What HIV does to Lymph nodes?

Answer 22

Initially Lymph nodes enlarge and show hyperplasia

After time, lymph nodes become depleted of lymphocytes and eventually become infected

Question 23

What HIV does to Brain?

Answer 23

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

Question 24

What HIV does to respiratory tract?

Answer 24

Initially localized to Upper respiratory tract but often progresses to Lower respiratory tract (pneumonia or TB) -Pneumocystis jiroveci/carinii

Question 25

What does HIV does to GI?

Answer 25

Infections are similar to respiratory tract and can also include parasites
Diarrhea and malabsorption of nutrients can also be present

Question 26

What does HIV do to Skin?

Answer 26

can include dermatitis or infections (fungi, herpes, bacteria)

Question 27

What kind of Cancers does HIV cause?

Answer 27

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

Question 28

Diagnosis of HIV

Answer 28

Presence of HIV antibodies in blood (HIV+)
T-cell count decreased ratio of CD4+/CD8+
AIDS diagnosed by presence of opportunistic infection and tumours

Question 29

Treatment

Answer 29

Meds- replication inhibition of virus
Expensive and not readily available worldwide
Vaccines unsuccessful
Death can be postponed by vigorous treatment of opportunists

Question 30

Amyloidosis

Answer 30

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

Question 31

Clinical presentation of Amyloid deposition

Answer 31

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)