EXAM 5 Flashcards
1
Q
Type I Hypersensitivity
A
- IgE mediated, exogenous antigen
- 15-30 min
- receptor mediated activation and release of vasoactive mediators (basophils and eosinophils)
2
Q
Type II Hypersensitivity
A
- IgG/M mediated
- Ab directed at cell surface antigens via complement activation or ADCC
- minutes to hours
3
Q
Type III Hypersenitivity
A
- IgG/M mediated
- soluble Ags
- Ag/Ab complexes are deposited in tissues and induce complement and a massive infiltration of neutrophils
- 3-8 hours
4
Q
Type IV Hypersensitivity
A
- T cell mediated (Delayed type hypersensitivity)
- T-DTH cells release cytokines that activate macrophages and/or T cells (monocytes and lymphocytes)
- antigen: tissues and organs
- 48-72 hrs
- Th1 response
5
Q
Effector mechanisms of Type I
A
- allergen binds to IgE and attaches to FceR1 on mast cells, basophils and eosinophils and activates tyrosine phosphorylation -> Ca++ influx -> triggering degranulation
- mast cells release mediators that attract basophils and eosinophils
- associated with allergens that promote a Th2 response
6
Q
Type I genetic predisposition
A
- candidate polymorphic genes: IL-4, IL-4 cytokine
- attachment of IgE to its receptors increases its life span
7
Q
Mast cells cause:
A
- GI: increased fluid secretion, increased peristalsis
- Airways: decreased diameter and increased mucus secretion
- Blood vessels: increased blood flow and permeability
8
Q
Basophils initiate:
A
- Th2 responses via IL-4 and IL-13
9
Q
Mediators of Type I
A
- histamine (preformed)
- eosinophil chemotactic factor (preformed)
- prostaglandins and thromboxanes
- leukotrienes
10
Q
Histamine
A
- from mast cells
- causes: allergic rhinitis, urticaria, angioedema, bronchospasm
- constriction of smooth muscles
- dilation of blood vessels
11
Q
ECF-A
A
- preformed in mast cells
- important for migration of eosinophils (CCL11 binds CCR3)
- eosinophils release histaminases and arylsulfatases
12
Q
Prostaglandins and Thromboxanes
A
- derived from arachidonic acid
- prostaglandins: increase capillary permeability and induce bronchoconstriction
- thromboxanes: aggregate platelets
13
Q
Leukotrienes
A
- slow reacting, made after IgE binds receptor
- increases vascular permeability and increases smooth muscle contraction
- major mediators in asthma
14
Q
Triple response of Lewis (Type I)
A
- flush: capillary dilation
- flare: arteriolar dilation
- weal: exudation, edema
15
Q
Systemic anaphylaxis (Type I)
A
- causes dilation of peripheral blood vessels in the microcirculation leading to decreased blood pressure and increased heart rate
- most common is allergy to penicillin
16
Q
Treatment Type I
A
- antihistamines (aspirin, NSAIDs)
- inhalers
- allergy shots ( desensitization)
- Omalizumab (monoclonal Ab for IgE)
- Epi
17
Q
Blood transfusion reaction (Type II)
A
- ABO blood group
- blood transfusion reactions cause systemic inflammation and RBC lysis
18
Q
Erythroblastosis fetalis (Type II)
A
- Rh- mom gives birth to 2 Rh+ babies
- Ab made from first baby stay in moms circulation and attack fetal RBCs of the second baby
- treat mom with Ab to Rh (RhoGAM) after first birth
19
Q
Autoimmune hemolytic anemia (Type II)
A
- autoantibodies attack RBCs carrying foreign substances
- immune system sees Ab bound and stimulates ADCC
- Ex: mycoplasma pneumonia infection, drug rxns (not penicillin)
20
Q
Goodpasture’s nephritis (Type II)
A
- Abs bond to the basement membranes of the kidneys and lungs
- Dx: hematuria, foamy urine, edema, high blood pressure
- Tx: immunosuppressants
21
Q
Myasthenia gravis (Type II)
A
- autoantibody to acetylcholine receptor which leads to skeletal muscle weakness
- weakness in face, arms, eyes, legs
- Tx: acetylcholinesterase inhibitors
22
Q
Arthus Reaction (Type III)
A
- vasculitis
- ruptures blood vessels and hemorrhage
- associated with injections of Ig against diphtheria and tetanus
- Dx: immunization of humans with animal serum that produces a rxn that gets worse with each inoculation
23
Q
Immune complex diseases (Type III)
A
- immune complexes get lodged in tissues and cause problems (frustrated phagocytes)
- foreign or self Ag can trigger
- arthritis
- glomerulonephritis, lupus
24
Q
Rheumatic fever (Type III)
A
- cross reactivity of group A strep antibodies with heart tissue and glomerular basement membrane
25
Systemic Lupus Erythematosus (Type III)
- chronic activation of lymphocytes
- sx: fatigue, arthritis in hands, butterfly rash
- Dx: presence of antinuclear Abs
- Tx: corticosteroids
26
Steps of Type IV
- sensitization stage: ag-specific Th1 and Th17 cells made, takes 1-2 weeks
- elicitation stage:48-72 hrs after re-exposure
27
Cytokines and chemokines of DTH
- chemokines: recruit macrophages
- IFN-gamma: activates macrophages, induces expression of vascular adhesion molecules
- TNF alpha and beta: local tissue destruction, increase adhesion molecules
- IL-3 and GM-CSF: stimulate monocyte production
28
Contact dermatitis (Type IV)
- lipophilic compounds penetrate the skin and attach to cells
- eczema at site of contact
29
Granulomatous Hypersensitivity (DTH)
- forms giant cells (granulomas)
- 21-28 days
- Ex: TB
30
Graft vs. Host disease (DTH)
- transplanted immune cells recognize host cells as foreign and donor T cells are activated
31
Grave's Disease
| Dr. Gregg's autoimmunity lecture
- agonist autoantibodies bind to TSH receptor and induce overproduction of thyroid hormones
- Sx: enlargement of thyroid, bulging eyes, nervousness, heat intolerance, tachycardia, weight loss
- genetics: HLA-DR3/CTLA-4 mutant --> Th2 response --> Ig4
32
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Myasthenia gravis
(Dr. Gregg's autoimmunity lecture)
```
- antagonistic autoantibodies (IgG) bind to ACh receptors leading to progressive muscle weakening
- Sx: drooping eyelids, double vision, weak facial muscles and chest muscles
- genetics: HLA-A01, HLA-B08, HLA-DQ2, HLA-DR3/ CTLA-4 mutant/ higher TNF-alpha/ decreased Th2 response
33
Hashimoto's thyroiditis
| Dr. Gregg's autoimmunity lecture
- autoantibodies (IgG) bind TPO and thyroglobulin expressed by thyroid cells leading to hypothyroidism
- Sx: enlargement of thyroid, fatigue, muscle aches, weight gain, huskiness to voice
- genetics: HLA-DR3/ CTLA-4 mutant / decreased Tregs
34
Systemic lupus erythematous
| Dr. Gregg's autoimmunity lecture
- autoantibodies (IgG) produced against a number of self Ags that form immune complexes and deposit in blood vessels, kidneys, and other tissues
- Self-Ags derive from an inability to dispose of apoptotic cells (deficiencies in pentraxins, C1, C2, C4), complement fixation leads to immune cells recruitment
- Sx: leaky blood vessls, butterfly rash, proteinuria and hematuria, joint swelling
- genetics: HLA-Dr2 and HLA-DR3 / low Treg numbers and loss of function / increased IL-6 / CTLA-4 and Fas/FasL mutants
35
X-linked agammaglobinemia (XLA)
- pathogenesis: mutation of the Bruton's tyrosine kinase which is important for B cell differentiation, maturation and signaling --> lack of B cells and plasma cells in the blood and tissues, normal levels of pro-B cells
- decreased IgM, IgA, IgE, IgG
- histology: lack of germinal centers, normal thymus, adenoids, tonsils, LN hypoplastic
- clinical presentation: recurrent infections of the sinuses and resp tract by pyogenic bacteria, otitis media, chronic diarrhea
- Dx: flow cytometry for lack of B cells in peripheral blood, DNA sequence for BTK
- note that IgG may be normal d/t maternal IgG
36
Hyper-IgM syndrome
- pathogenesis: failure of B cells to undergo Ig class switch recombination, X-linked mutation of CD40 ligand or CD40 --> AID not induced
- low levels of IgG, IgA, IgE
- elevation of IgM
- clinical presentation: develops in first 5 yrs, increased frequency of pyogenic bacteria, neutropenia, increased risk for PJP and cryptosporidium diarrhea
- Dx: serology shows high levels of IgM, low levels of other Abs, flow cytometry shows normal to elevated B and T cells
37
Combined variable immunodeficiency (CVID)
- pathogenesis: most common form of hypogammaglobinemia diagnosed in adults, B cells have immature markers and cannot differentiate into plasma cells, mutations in inducible costimulatory molecule (ICOS) which promotes TFH cells to make IL-21
- clinical presentation: recurrent sinus and resp tract infections by pyogenic bacteria, otitis media, giardia, celiac disease
- generally all Ig are reduced, but may only be one isotype
- histology: lymphoid tissues may be enlarged
- Dx: Ab deficiency developing >2 yr + poor Ig development following vaccination, B and T cells are normal to elevated
38
Selective IgA deficiency (IgAD)
- pathogenesis: most common Ab deficiency, B cell differentiation abnormalities, IgG1 (Th1) is produced while IgG4 (Th2) and IgA are not, some have anti-IgA Abs that lead to its removal by the liver
- clinical presentation: most are asymptomatic, sinusitis and giardia are common
- Dx: pt > 4 y/o with low IgA
39
Transient hypogammaglobulinemia of infancy
- pathogenesis/clinical presentation: as maternal IgG is catabolized, infant IgG production cannot keep up. Lowest point of maternal IgG and newborn production is at 6 months, if drops to > 2 SD from normal then criteria is met
- increased frequency/severity of infections
40
DiGeorge syndrome (DGS)
- pathogenesis: abnormal migration of neural crest tissue from 3rd and 4th pharyngeal arches in the 4th week of development, most have chromosomal deletion 22q11.2, results in thymic hypoplasia, T cell deficiency, hypoparathyroidism, facial dysmorphism, cardiac defects
- clinical presentation: hypocalcemia, learning difficulties, can be completely missing thymus, or have low T cell numbers, elevated CD4/CD8 ratio
- Dx: absence or reduction of thyroid size (reduced thymic shadow on x-ray), decreased CD3+ T cells
41
Severe combined immunodeficiency (SCID)
- pathogenesis:
1) Deficiencies in cytokine receptors - lack of common gamma chain which is the signaling chain, deficiency in JAK3 can also give same phenotype
2) Defects impacting differentiation of progenitor cells - mutation of RAG 1,2,3 genes, mutations in ZAP-70, defects of TCR complex or CD3
3) Deficiencies of purine salvage enzymes - deficiency of adenosine deaminase (ADA)
- clinical presentation: sx initiate by 4 mo, usually don't live past 1 yr, persistent lung infections, chronic diarrhea, mucocutaneous candidiasis
- histology: absence of all lymphoid tissue, absence of thymic shadow
- Dx: very low levels of lymphocytes, absent T cell response to skin tests, genetic evaluation
42
Bare lymphocyte syndrome
- pathogenesis: MHC class I deficiency, loss of expression of TAP
- clinical presentation: persistent infections with PJP and pyogenic bacteria
- Dx: all Ig's decreased, no CD8 cells
43
MHC class II deficiency
- pathogenesis: mutations associated with transcription factors of MHC II expression, nearly absent CD4 population
- clinical presentation: persistent infections with candida or cryptosporidium
- Dx: all Ig's decreased, no CD4 cells
44
Ataxia-telangiectasia
- pathogenesis: deficiency of DNA repair enzymes, generalized defect in tissue maturation
- histology: thymic hypoplasia
- clinical presentation: progressive cerebella ataxia, dilated blood vessels in the conjunctiva
- Dx: all Ig's decreased, T cell deficiency
45
Wiskott-Aldrich syndrome (WAS)
- pathogenesis: loss of function mutation of WASP which is needed for actin polymerization so cells have abnormal size and shape, especially platelets and lymphocytes, abnormal Th2 response --> severe eczema
- clinical presentation: eczema, thrombocytopenia, frequent infections, hemorrhage
- Dx: abnormally shaped platelets, normal lymphocyte counts
46
Chronic granulomatous disease
- pathogenesis: most frequent phagocytic disease, mutation in alpha-chain phosphoprotein of cytochrome b558 leading to a nonfunctional NADPH oxidase
- clinical presentation: recurrent bacterial and fungal infections, esp in lungs, LN, liver, skin, and soft tissues, all have formation of microabscesses and granulomas, lymphadenopathy and hepatosplenomegaly
- Dx: increased Ig, oxidative burst by neutrophils
47
Chediak-Higashi syndrome
- pathogenesis: deficiency of lysosome trafficking regulator (LYST) necessary for assembly of cytoplasmic granules and fusion with phagosomes. No fusion with giant secondary lysosomes --> no melanin transport or pigmentation
- clinical presentation: albino, fevers, peripheral neuropathy, bruise easily, recurrent infections
- Dx: giant lysosomes in neutrophils
48
Early complement deficiencies
- lack of C1, C2, and/or C4
- infections with pyogenic bacteria
- autoimmune susceptibility: SLE
49
C3 deficiency
- lack of C3 synthesis
- infections with pyogenic bacteria
- autoimmune susceptibility: vasculitis, glomerulonephritis
50
Late complement deficiencies
- lack of C5, C6, C7, C8 and/or C9
- infections with polysaccharide encapsulated bacteria, especially Neisseria
- no autoimmune susceptibility
