Term
| X-Linked Agammaglobulinemia (Bruton's) |
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Definition
Presentation
Males
Starts at 3-6 months (maternal IgG gone)
Recurrent infections that don’t respond to antibiotics
Molecular Defect
BTK Gene Defect prevents B cell maturation
Dx
CD19+CD20+ mature B cells absent/reduced
(Very low CD19+)
Near absence of B cells & all antibody classes (immunoglobulins) (Very low CD19+)
No germinal centers in lymphoid tissue
Tx
Antibiotics, IVIG |
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Term
| Transient Hypogammaglobulinemia (of infancy) |
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Definition
Presentation
Both sexes
Starts at 3-5 months, resolves by 2 years
Recurrent pyogenic infections that don’t respond to antibiotics
More common in premature infants
Molecular Defect
B or TH cells
Dx
Normal numbers of B cells (different than seen in XLA)
IgG always low
IgA low
Tx
Antibiotics
IVIG not usually given |
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Term
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Definition
Presentation
Many asymptomatic
Sinopulmonary infections
Repeated infections by encapsulated bacteria
May progress to common variable immunodeficiency (CVID)
Dx
Low IgA (possible TH2 issue via IL-5)
Tx
Antibiotics
NO IVIG (possess IgE directed towards IgA ANAPHYLAXIS) |
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Term
| IgM & IgG Subclass Deficiencies |
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Definition
Presentation Repeated infections by encapsulated bacteria (Streptococcus pneumonia) Often present with asthma
Dx Decrease in either
Measure by RIA
Tx Aggressive Antibiotics, don’t usually need IVIG |
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Term
| Common Variable Immunodeficiency (CVID) |
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Definition
Presentation
1-5y, 15-20y
May follow EBV infection
Associated with IgA def.
Pernicious Anemia
Recurrent pyogenic bacterial infections
Molecular Defects
B-cell (CD19)
No antibodies
Dx
Normal numbers of B cells
Absence of IgM & IgD; CD27 present
IgG, IgA low
Tx
Narrow-spectrum antibiotics (broad leads to infections by fungi)
IVIG |
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Term
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Definition
Presentation
Recurrent respiratory infections @ 1-2y
More common in males
Molecular Defects
No class-switching from IgM to other types
X-linked: CD40L on T cell males only
Autosomal: CD40 & AID enzyme on B cell would be in females
Dx
Reduced IgG (100%)
Reduced IgA (>75%)
Elevated IgM
Tx
Antibiotics, IVIG
New: BMT |
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Term
| X-Linked Lymphoproliferative Syndrome (Duncan Syndrome) |
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Definition
Presentation
Near fatal-EBV infection causing infectious mono
Males only
3-5y @ dx
B-cell lymphomas (Burkitt)
Molecular Defect
Gene that codes for SAP (signaling molecule in T, B, NK cells & eosinophils & platelets)
Dx
Positive heterophile antibody test for infectious mono
Atypical lymphocytes on blood smear
+PCR for EBV DNA
Liver damage in chem profile (AST, ALT)
Tx
Antimicrobials
Prophylactic IVIG
Stem Cell transplant only cure, but success rate is low
Rituximab (monoclonal antibody to CD20) |
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Term
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Definition
Presentation
Susceptible to all types of infections
Diarrhea, pneumonia
Tx
Bone marrow transplant
Subtypes |
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Term
T-B+ (X-linked) (50% of all cases)
T-B+ (autosomal) |
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Definition
Molecular Defect
y chain of receptor for IL-2, 4, 7, 9, & 15
No T or NK cells
Molecular defect
Alpha-chain of IL-7 (No T or NK cells)
JAK3 Tyrosine Kinase (No T cells |
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Term
| T-B- (Adenosine Deaminase Deficiency) |
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Definition
No T or B cells present
Molecular Defect
Adenosine Deaminase
Tx
ADA enzyme supplement, BMT |
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Term
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Definition
Presentation
Red, scaly skin resembling Graft-vs-Host rxn
Massive skin & GI infiltration by eosinophils & TH2 cells
Malnutrition (from protein loss)
Loses weight after birth
Hyper-IgE production
No B Cells present
Molecular Defect
“Leaky” RAG activity |
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Term
| T+B+ (Bare Lymphocyte Syndrome) |
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Definition
Molecular Defect
Lack MHC Class I, II, or both (HLA molecules absent)
Class I (CD4+ TH cells)
no collaboration between APCs & TH cells
Class II (CD8+ Tc cells)
TAP molecules to blame
T-cell: zap-70
Sx: all types of infections
live vaccine = lethal
symptoms earlier than XLA, fatal before 1 y/o if untreated |
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Term
| Hereditary Ataxia-Telangiectasia |
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Definition
Presentation
18 months
Wobbly gait (Ataxia)
Telangiectasia (dilated capillaries) on skin & eyes
Severe sinus & lung infections
Molecular Defect
DNA Repair Gene ATM (ataxia-telangiectasia mutated)
Dx
Elevated alpha fetoprotein (AFP) & carcinoembryonic antigen (CEA)
Low lymphocyte count
Low IgA & IgE
Absent adenoids, thymic shadow
Tx
Antibiotics & IVIG |
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Term
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Definition
Presentation
Males
20 months
Bleeding disorders due to thrombocytopenia
Recurrent bacterial infections
Allergic rxns
Petechiae, eczema, pneumonia
Molecular Defect
WASP (Wiskott-Aldrich Syndrome Protein)
Dx
Very low platelets
High IgE & IgA
Low IgM & IgG
Tx
Antimicrobials & IVIG
Manage acute bleeding with platelet transfusions & packed RBCs
Avoid food allergens |
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Term
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Definition
Presentation
Recurrent “cold” staphylococcal abscesses (not inflamed)
Eczematous dermatitis
Skeletal features
Fractures, coarse facial features, joint hyperextensibility, retained primary teeth
NO bleeding disorder (unlike Wiskott-Aldrich)
Molecular Defect
STAT3 Protein (transcription factor essential for signaling from many IL, IFN, & CSF receptors)
Overproduction of TH2 cytokines hyper-IgE (IL-4, IL-13)
Underproduction of TH1-derived IFNy “cold” abscesses
Dx
VERY high IgE (2 SD above)
Eosinophilia w/ normal lymphocyte & PMN numbers
Tx: Antibiotics |
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Term
| DiGeorge Syndrome (Congenital Thymic Aplasia) |
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Definition
Presentation
No thymus or parathyroid glands
Few or no T cells same infections as SCID
Hypocalcemic Tetany (no PTH to stimulate Ca2+ production)
Congenital heart & kidney problems
Hypertelorism (increased eye distance), low-set ears, shortened philtrum of upper lip
Molecular Defect
22q11.2 deletion (not usually hereditary)
Dx
T cells absent or diminished
Low IgG
Thymic shadow absent on X-ray
Tx
Antibiotics
BMT to restore immunologic function
T-Cell function may be normal by age 5 w/o BMT ectopic thymic tissue |
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Term
| Chronic Mucocutaneous Candidiasis |
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Definition
Presentation
Oral thrush and/or skin infections (diaper rash)
Can affect the nails
Molecular Defect
No T-cells with TCRs that recognize candida antigens
Dx
Identify Candida on skin scrapings
Tx
Antifungal agents
Transfer factor small proteins extracted from human donor lymphocytes sensitized to candida species specific cell immunity may be passively transferred by this approach |
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Term
| Autoimmune Lymphoproliferative Syndrome (ALPS) |
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Definition
Presentation
Thrombocytopenia petechia & bleeding
Neutropenia recurrent infections
Anemia fatigue
Splenomegaly before age 3
Lymphadenopathy (swelling of lymph nodes)
B-cell lymphoma night sweats, fever, pruritis (itiching), weight loss
Molecular Defect
FAS (CD95) activates caspases to induce apoptosis
Dx
Lymphadenopathy or splenomegaly lasting more than 6 months
Elevated CD4-CD8- T cells (possible elevated CD3+??)
Mutations in Fas gene
Decreased RBC, Platelets, Neutrophils
Tx
Antibiotics, IVIG
Corticosteroids for anemia & thrombocytopenia
Sargramostim for neutropenia |
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Term
| Chronic Granulomatous Disease (CGD) |
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Definition
Presentation
2y, more common in males (x-linked & autosomal forms)
Repeated infections by staph, serratia, aspergillus
Granulomas
Pneumonia
Lymphadenitits
Abscesses in skin, liver, & viscera
Molecular Defect
Phagocytes lack of functional NADPH oxidase
X-linked: CYBB gene for gp91phox
Autosomal: other subunits
Dx
Nitroblue tetrazolium (NBT) reduction test
CGD fails to reduce NBT to formazan
No color change from yellow to purple
Tx
Antimicrobials
IFNy induces synthesis of opsonizing & complement activating cells (good for encapsulated bacteria) |
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Term
| Leukocyte Adhesion Deficiency 1 (LAD1) |
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Definition
Presentation
Impaired wound healing
Soft tissue bacterial infections of mouth & GI tract
Cannot form pus efficiently
Molecular Defect
Defective CD18 common to LFA-1, CR3, CR4
Dx
Leukocytosis
Absence of CD18
Tx
Antibiotics
BMT or Stem Cell transplant |
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Term
| Leukocyte Adhesion Deficiency 2 (LAD2) |
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Definition
Presentation
Infections
Growth & mental retardations
Molecular Defect
Fucose metabolism
Lack of CD15/Sialyl Lewis X
Dx
Flow cytometry for CD15
Phagocyte migration & chemotaxis assays
Tx
Antibiotics
Fucose replacement therapy |
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Term
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Definition
Presentation
Recurrent staph, strep, and pseudomonas infections of skin, lungs, respiratory tract
Partial albinism of skin, hair, eyes
Giant granules (lysosomes), defective melanosomes
Molecular Defect
LYST Gene Defect (giant lysosomes)
Dx
Giant granules in granulocytes apparent on stained blood smears
Neutropenia
Elevated Ig’s
Tx
Antibiotics
BMT |
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Term
| IL-12/IL-23/IFNy Deficiency |
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Definition
Presentation
Especially susceptible to weakly pathogenic mycobacteria
Susceptible to other intracellular bacteria (salmonella enteriditis)
Irregular skin lesions all over body
Molecular Defect
IFNy receptor on macrophage
STAT1 transcription factor
IL-12 receptor on TH1 & NK cells |
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Term
| Hereditary Angioedema (HAE) |
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Definition
Presentation
Local edema of hands, face, arms, legs, genitals
Laryngeal edema suffocation
Stomach, GI abdominal pain, constipation, diarrhea
Molecular Defect
Type 1 (85%): low levels of C1INH (C1 esterase inhibitor)
Type 2: Normal/high levels of dysfunctional C1NH
Dx
Low levels of C4
Tx
Fresh frozen plasma before dental/surgical procedure
Maintain airway, pain management |
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Term
| Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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Definition
Presentation
Dark urine
Budd-Chiari syndrome: severe abdominal pain
Weakness, dyspnea, pallor, splenomegaly, Fe deficiency, severe headaches & eye pain, chronic infections
Molecular Defect
GPI anchors of complement regulators
Decay-accelerating factor (DAF) & CD59
Dx
Assess DAF & CD59
Low RBC, WBC, & Platelets
Tx
Prednisone/eculizumab for RBC lysis
Stem cell transplant
Treat anemia & thrombosis |
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Term
| Pernicious Anemia (Stomach) |
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Definition
Presentation
Beefy, red, smooth, sore tongue
Weakness, dyspnea, anorexia, fever, diarrhea
“Megaloblastic madness”: delusions, hallucinations
Megaloblastic anemia
May be associated with Helicobacter pylori infection
Onset: 30y+
Tx
Vitamin B12
Organ Target
Stomach
Molecular Target
Intrinsic factor
Type II Hypersensitivity Rxn |
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Term
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Definition
Presentation
Glomerulonephritis
Pulmonary hemorrhage
Tx
Acute
Intubation, assisted ventilation, hemodialysis
Long-term
Corticosteroids
Cyclophosphamide (immunosuppression)
Plasmapheresis
Target Organ
Lungs, Kidney
Molecular Target
Complement fixing auto-antibodies (for Type IV collagen)
Type II Hypersensitivity Rxn |
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Term
| Insulin-dependent Diabetes Mellitus |
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Definition
Presentation
Onset: 11-12y, late 30s/40s
Hyperglycemia & ketoacidosis
Polyuria, polydpsia
Polyphagia with weight loss
Fatigue, weakness, muscle cramps
Blurred vision
Tx
Diet & exercise
Insulin
Organ Target
Pancreas
Molecular Target
Glutamic Acid Decarboxylase & alpha/beta cells
HLA-DR3/DR4
Type IV Hypersensitivity |
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Term
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Definition
Presentation
Muscle fatigue with exercise
Progressive muscular weakness
Chewing, swallowing, breathing
Diplopia & ptosis (double vision & drooping eyelids)
Women (common), 20-40y
Tx
Cholinesterase inhibitors
Corticosteroids
IVIG
Organ Target
Muscles
Molecular Target
ACh receptors in motor end plates of neuromuscular junctions
Type II Hypersensitivity Rxn |
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Term
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Definition
Presentation
Darkening of the skin
Due to overproduction of corticotropin (stimulates melanocytes)
Weight loss, diarrhea, vomiting, abdominal pain
Muscle weakness, fatigue, low blood pressure
Depression, irritability, loss of concentration
Tx
Hormone replacement (cortisone)
Organ Target
Adrenal glands
Molecular Target
ACTH Receptors
Type II Hypersensitivity Rxn |
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Term
| Bullous Diseases – Pemphigus Vulgaris |
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Definition
Presentation
Erosion of skin & mucous membranes
Painful, non-itchy blisters
Tx
Prednisone, immunosuppressives, or plasmapheresis
Organ Target
Skin and/or mucoa
Molecular Target
Desmogleins
Type II Hypersensitivity Rxn |
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Term
| Bullous Diseases – Bullous Pemphigoid |
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Definition
Presentation
Subepidermal blistering
RARELY involves mucous membranes
Tense, itchy blisters
Eotaxin in basal layer of epidermis recruits eosinophils
Onset: 65y
Tx
Prednisone, immunosuppressives, tetracycline
Organ Target
Skin and/or mucosa
Molecular Target
Hemidesmosomal antigens
Type II Hypersensitivity Rxn |
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Term
| Graves Disease/Thyrotoxicosis |
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Definition
Presentation
Hyperthyroidism (Increased T3 & T4)
Myxedema, Exophthalmos
Sweating, smooth moist skin
Frequent bowel movements, Diarrhea, Weight loss
Goiter, Rapid heart rate, palpitations widened pulse pressure
Tremor
Women (common); 30s & 40s
Tx
Anti-thyroid drugs, surgery
Organ Target
Thyroid
Molecular Target
TSH Receptors
Thyroperoxidase & thyroglobulin
Type II Hypersensitivity Rxn |
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Term
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Definition
Presentation
Goiter made of WBCs
Dry skin, decreased sweating, cold intolerance
Constipation, Weight gain
Fatigue, memory deficits
Hoarseness
Joint pain, muscle cramps
Tx
Thyroxine
Organ Target
Thyroid
Molecular Target
TSH Receptors
Thyroperoxidase & thyroglobulin |
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Term
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Definition
Presentation
Morning stiffness, gets better in late day
Arthritis of 3 or more joints
SubQ rheumatoid nodules
Serum Rheumatoid Factor (RF)
Reactive with Fc fragment of IgG
Females (common)
Initial trigger; mycoplasma, EBV, parvovirus, rubella
Tx
NSAIDs, Corticosteroids, COX-2 inhibitors, anti-TNFa agents
Organ Target
Joints (fingers, wrists, elbows, shoulders, knees)
Molecular Target
HLA-DR4, TH1 & TH17 cells
Type IV Hypersensitivity |
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Term
| Systemic Lupus Erythematosus (SLE) |
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Definition
Presentation
Arthritis, Glomerulonephritis, Erythema (AGE)
Malar (butterfly) rash over nose & cheeks
Fever, headache, pericarditis
“Lumpy-bumpy” pattern on immunoflorescence
Severe cases
Hemolytic anemia
Thrombocytopenic purpura
Renal damage
Hair loss
Discoid rash & mouth sores
90% are women estrogen worsens disease
African, Caribbean, Asian, & Hispanic descent more likely
Onset: 20-40y
Dx
Anti-dsDNA antibodies very specific for SLE
Correlates with renal damage
Tx
Avoid sunlight to prevent flairs
NSAIDS, steroids
Methotrexate
Type III Hypersensitivity |
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Term
| Sjogren Syndrome (Sicca Syndrome) |
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Definition
Presentation
Dry eyes, mouth, vaginal mucosa
Sometimes dry nose, larynx, bronchi
Usually associated with RA or SLE
Salivary gland enlargement
Dx
Anti-SS-A/Ro & anti-SS-B/La antibodies
Tx
Symptomatic
Type IV Hypersensitivity |
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Term
| Guillain-Barre Syndrome (GBS) |
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Definition
Presentation
Ascending paralysis affecting peripheral nerves
Weakness & diminished reflexes
Paresthesia, numbness, facial droop, double vision
Commonly occurs after infectious disease or vaccination
Campylobacter jejuni most common antecedent
Inflammatory cellular response controlled by CD4+ TH cells
Autoantibodies to nerves (myelin sheath)
Tx
Keep airway clear, plasmapheresis
IVIG
Physical & Speech therapy
Type IV Hypersensitivity |
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Term
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Definition
Presentation
Chronic relapsing paralysis that affects CNS
Most common neurologic disease of young adults
Peak incidence at 35y (females more likely)
Paresthesias (prickling, tingling) in extremities
Weakness or clumsiness, Partial blindness, Bladder control issues, Vertigo & ataxia
Emotional disturbances
Due to demyelination of CNS tissue
TH1 cells specific for myelin basic protein
Tc, macrophages, & microglia attack oligodendrocytes
Initiating inflammatory stimulus via viral infection
Dx
MRI plaques of demyelination with perivascular inflammation primarily in white matter
Oligoclonal IgG bands detected
Elevated myelin basic protein (MBP)
Tx
Corticosteroids
ABC’s (avonex, betaserone, copaxone)
Natalizumab
Regular exercise & PT
Type IV Hypersensitivity Rxn |
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Term
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Definition
Presentation:
Early: Fever (IL-1), Cachexia (TNF@), night sweats and diarrhea
Later: Significant loss of CD4+ T cells with decrease in humoral and cell mediated immune functions.
CD4/CD8 is normally 2:1 but it reverses to 1:2
Kaposi's Sarcoma, P. Jerovi pneumonia, cryptosporidium (small bowel), cerebral toxoplasmosis, lymphomas by EBV, vericella zoster virus
Transmission: Sexual contact, transfer of blood, transfer by contaminated needles, mother-child during birth or breast feeding
HIV infects all cells that infect CD4 (TH, monocytes, Macrophages, Dendritic cells, microglial cells)
M tropic: CCR5 prefer binding to macrophages in early in disease.
T-tropic viruses: CXCR4.
No vaccine or cure
TX: HAART (highly active retro antiviral therapy) |
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