patho Flashcards
▪ Group of immunological disorders characterized by failed B-cell maturation and thus impaired antibody responses
▪ Defective antibody formation = M/C
▪ autosomal recessive or dominant or X-linked
▪ Marked reduction in IgG and IgA serum levels (can also have reduced IgM)
▪ Frequent severe infections especially bacteria
Common Variable Immunodeficiency (CVID)
▪ Congenital T-cell deficiency due to thymic hypoplasia
▪Abnormal development of the 3rd and 4th branchial arches d/t the deletion of part of
chromosome 22
Total absence of cell-mediated immunity
▪ B-cells unaffected
▪ Parathyroid glands are also hypoplastic
▪ Autosomal dominant genetic disorder
▪ Congenital heart malformations, cleft palate, learning disabilities, mildly abnormal
facies, tetany or convulsions d/t hypothyroidsim & hypocalcemia, recurrent viral and fungal infections
▪ Complications include hypocalcemia, issues related to congenital heart malformations, and issues in school.
DiGeorge Syndrome
▪ Total absence/severe deficiency of IgA in the blood serum and secretions.
▪ Autosomal recessive or dominant
▪ Associated with RA, SLE and other autoimmune diseases
▪ Recurrent and chronic infections, asthma (severe), food allergies
Selective IgA Deficiency
▪ Absence of both humoral and cell-mediated immunity
▪ Significant lymphopenia
▪ Thymus atrophy, lack of delayed hypersensitivity, high susceptibility to infections by microorganisms including live vaccines.
- Autosomal recessive
▪ Adenosine deaminase deficiency → causes toxicity to lymphocytes - X-linked
▪ IL-2 receptor gamma gene mutation
▪ Severe infections, high risk of malignancy, failure to thrive
Severe combined Immunodeficieny (SCID)
▪ Affects B cells
▪ Absence/extremely low levels of gamma fraction of serum globulins
▪ Doesn’t present until 6 months post-birth due to the presence of maternal Ab before this time
cannot form ANY ANTIBODY!
▪ Results in the inability to form antibody causing frequent infections of the mucous membranes (lung, sinuses, nose, ear, gastrointestinal tract) but can involve internal organs and blood
Etiology: Pneumococcus, Strep, Staph, H influenzae
X-LINKED AGAMMAGLOBULINEMIA
▪ Various medications are used to suppress the immune system
▪ Corticosteroids, tacrolimus, cyclosporin, azathioprine, biologics
▪ These drugs are commonly used in autoimmune diseases, acute inflammatory syndromes, and after organ transplants.
▪ Increased risk of infection and neoplasms
▪ Chemotherapy also results in immunosuppression through the destruction of bone marrow.
Drug Induced Immunodeficiency
which type of hypersensity?
● Within seconds/minutes of allergen exposure, mediated by IgE
▪ Mediated by previously formed IgE bound to a mast cell/basophil (prior exposure)
▪ Second exposure -> cross-linkages form -> resulting in chemical
mediators that initiate an acute inflammatory response.
● Sx: urticaria, conjunctivitis, rhinitis, asthma
● Complications: anaphylaxis
Type I
● Within hours of exposure; IgG mediated reaction to cell-bound allergen
▪ Antigen-antibody interactions (cytotoxic nature)
▪ Complement-mediated or antibody-dependent cell-mediated cytotoxicity (ADCC)
▪ Involves NK cells
● Cytotoxicity dependent on antibody-antigen interaction
● Examples: Grave’s, drug reactions, Goodpasture’s, hemolytic disease
Type II
this is an example of what type of hypersensitivity:
Pollen allergy, on initial exposure IgE binds w/ mast cell or basophil = No sx, second exposure -> chemical mediators (histamine) released from complex -> inflammatory response
Type I
this is an example of what type of hypersensitivity:
Penicillin allergy, penicillin binds to structure on your cells & makes a new epitope/foreign Ag NK cell reacts to it -> inflam. & complement & killing of cell
Type II
What type of hypersensitivity:
poison oak rash, TB skin test, transplant rejection
Type IV
which type of hypersensitivity: vaccines, infused Abs bind w/ IgG to make immune complex in blood
SLE, RA, polyarteritis nodosa, poststreptococcal
glomerulonephritis
Type III
▪ Mediated by the formation of immune complexes which are deposited on tissue surfaces
within hours of exposure; IgG mediated reaction to soluble antigens (Ags)
▪ Basement membrane of blood vessels, serosal membranes of joints, glomerular basement membranes
▪ SLE, RA, polyarteritis nodosa, serum sickness, post-streptococcal glomerulonephritis
Type III
▪ Delayed cell-mediated response that is T-cell dependent
▪ Reaction occurs several days after exposure
▪Haptens bind to body proteins and become immunogens
Type IV
▪ Autoimmune disease of the skin resulting in epidermal atrophy and dermal thickening.
▪ CREST syndrome = localized and limited form of scleroderma
▪ Skin appears shiny like parchment, tightening of hands (sclerodactyly), eyes,
mouth, heartburn, dysphagia, polyarthralgias, telangiectasia
▪ +ve ANA and anti scl-70
▪ Complications include fibrosis at the mouth corners, GI tract (dysphagia and interrupted peristalsis), blood vessels (renal failure), myocardium (cardiac failure), interstitium of the lung (respiratory failure), premature death
▪ Often accompanied by Sjorgren’s syndrome, Raynaud’s phenomenon and other autoimmune diseases.
PROGRESSIVE SYSTEMIC
SCLEROSIS (SCLERODERMA)
▪ Involves the autoimmune destruction of the salivary and lacrimal glands resulting in a dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca)
▪ Can involved bilaterally enlarged parotid glands
▪ ALWAYS secondary to another autoimmune diseases (most commonly RA)
▪ More common in women and often diagnosed between 40-60 yoa
▪ +ve ANA and anti-SS-B, hypergammaglobulinemia
▪ Associated with an increased risk of lymphoma and leukemia
▪ Corneal ulcers can occur due to the lack of tears.
SJOGREN’S SYNDROME
Primary or secondary AMYLOIDOSIS
● Amyloid protein accumulates in ANY organ of the body; sx vary & dx hard
Immunocytic dyscrasia amyloidosis
▪ Amyloid fibrils(Ig light chains=amyloid light chains) can accumulate in any organ
causing various symptoms.
▪ Example: Renal deposition → hematuria, proteinuria, renal failure
Primary amyloidosis
▪ Due to another disease (reactive systemic amyloidosis)
▪ Multiple myeloma, osteomyelitis, chronic dialysis, RA
▪Same sx as primary form
Secondary amyloidosis
mechanism for which cdx:
▪ HIV virus expresses gp120 -> binds to CD4+ on T-helper cells -> binding = virus’s DNA can be incorporated into host cell’s DNA
▪ The virus can remain latent for a long time and viral production is low
▪ T-helper cells are eventually depleted -> Results in the failure of both humoral and cell-mediated immunity.
Acquired immune deficiency syndrome
which CDX:
Can remain asymptomatic for (years/moths) when in the (latent/active) period.
▪ Last stage is defined as ____ where opportunistic infection and (bengin/malignant) neoplasms are common.
▪ HIV antibodies are evident in the blood within weeks of infection.
▪ (CD4+/CD8) cell decline = important marker of immune health
w/ viral load of HIV particles.
▪ Increased incidence of Kaposi’s sarcoma, B cell non-Hodgkin’s lymphoma, hepatocellular carcinoma, Hodgkin’s disease
asx in latent period
last stage is defined as AIDS = malignant neoplasms
CD4+ cell decline
which cdx
▪ SXs start with acute illness = infectious mononucleosis with persistent
lymphadenopathy.
▪ Chronic fever, weight loss, and chronic diarrhea appear later.
AIDS
Opportunistic infections include for AIDs include: (missing 3)
Pneumocystis carinii, Toxoplasma…
Cytomegalovirus, Candida albicans, Cryptosporidium
Clinical Presentation of AIDS: what is the CD4 count of Stage 2-4
● Stage 1 (ARS): persistent generalized LNs, flu-like sx
● Stage 2 (Latent): mild sx w/ LNs, CD4+ < ??
● Stage 3 (ARC): chronic sx of weight loss, fever, fatigue, nodules, anemia of chronic disease, HSV, CD4+ < ??
● Stage 4 (AIDS): presence of AIDS-defining illness (Kaposi sarcoma, Burkitt or Hodgkin’s lymphoma), CD4+ < ??
Stage 2: <500
Stage3: <300
Stage 4: <200
▪ Idiopathic autoimmune inflammatory myopathies and vasculitis
▪ Dermatomyositis → CD4+ cells invade muscle, as early as 5 yoa
▪ Complement-mediated damage to endomysial vessels and vasculature of the dermis ▪ Polymyositis → CD8+ cells invade muscle, >20 yoa, MC in females
▪ Immune system attack muscle antigens
Dermatomyositis
▪ Heliotrope purple rash around eyes and extremities, periorbital swelling, Gottron’s papules or raised erythematous rash over bony prominences, V-shaped thoracic rash, cracked skin on hands, symmetrical proximal muscle weakness
▪ Elevated serum muscle enzyme levels (CK), often +ve ANA, muscle biopsy is confirmatory
Polymyositis
▪ Symmetric pain and weakness of proximal limb and neck flexor muscles, distal musculature and muscles of deglutination are less commonly involved.
▪ Symptoms develop over several weeks to months and have a waxing-waning course.
