Immunology Flashcards
What does delayed separation of the umbilical cord suggest?
LAD (leukocyte adhesion deficiency)
Defect in integrins normally expressed on leukocytes (CD18)
Chediak Higashi Syndrome
Defect in microtubules prevents neutrophil phagosome-lysosome fusion
Inc risk of pyogenic infections, neutropenia, giant granules in leukocytes, defective primary hemostasis, partial albinism (melanocytes can’t pass pigment to keratinocytes), peripheral neuropathy, nystagmus
DiGeorge syndrome
Maldevelopment of the 3rd and 4th pharyngeal pouches
Thymic and parathyroid hypoplasia, abnormalal facies, and cardiac defects
T cell deficiency = immunosuppression
CATCH 22 Cardiac defects Abnormal facies Thymic dysplasia Cleft palate Hypocalcemia Deletion in chromosome 22
Chronic Granulomatous Disease Cause? Susceptible to? Test? Treatment?
Neutrophils have a defect in NADPH oxidase and can’t kill catalase positive organisms
Most common: pseudomonas and staph aureus and aspergillus
Test: nitroblue tetrazolium dye test or Dihydrorhodamine flow cytometry test
Treatment: IFN gamma
Nitroblue tetrazolium dye test
Used to evaluate for chronic granulomatous disease
Turns blue if NADPH oxidase works
Stays clear if NADPH oxidase is defective
HLA B27
PAIR: Psoriatic arthritis Ankylosing spondylitis Inflammatory bowel disease Reactive arthritis
HLA DR4
Rheumatoid Arthritis
4 walls in a “rheum”
Hyper IgE syndrome
Deficiency of Th17 cells - impaired recruitment of neurotrophils and decreased IgG production and decreased IFN-gamma
FATED course Facies staph Abscesses retained primary Teeth inc igE Dermatologic problems (eczema)
Foscarnet
Anti-viral (pyrophosphate analog)
Inhibits DNA polymerase in herpes virus and reverse transcription in HIV.
*Does not require intracellular activation by viral OR cellular kinases
Enteracept
TNFa inhibitor that impairs cell-mediated immunity. Before starting this medication, important to screen for latent TB to prevent reactivation
Mechanism of fever
- Macrophages release IL1 and TNF in response to a pyrogen (ex. LPS on bacteria)
- Inc COX activity in hypothalamus
- Inc production of PGE2
- Inc body temp (fever)
What are the anaphylatoxins in the complement cascade?
C3a and C5a
Trigger mast cell degranulation resulting in vasodilation and increased vascular permeability
What is the mechanism of the mast cell DELAYED response?
Production of arachidonic acid metabolites
Especially leukotrienes that cause increased bronchial tone/bronchospasm
What in the arachidonic acid pathway leads to increased chemotaxis of neutrophils?
LTB4
“Neutrophils arrive B4 others”
Where does vasodilation in inflammation occur?
Arterioles
Which prostaglandin mediates fever?
PGE2 (FEEEver)
Also mediates pain
Which prostaglandins mediate pain?
PGE2 and bradykinin
Where does vascular permeability occur during inflammation?
Post capillary venules
What causes inc susceptibility to recurrent Neisseria infections?
MAC complex (C5-C9) deficiency
Pathogenesis of granuloma formation (cells and products involved)
TH1 cells release IFN gamma –> activates macrophages
Macrophages release TNF alpha –> induces and maintains granuloma formation
Considerations when starting a patient on TNFa inhibitors (Enteracept)
Test for latent TB – lack of TNF alpha can lead to granuloma breakdown and leads to systemic disease
Hypercalcemia and granulomas
Granulomas produce calcitriol (1,25 OH2 vitamin D3) which causes an increase in calcium levels
c-ANCA
p-ANCA
(Anti-neutrophil cytoplasmic antibodies)
c-ANCA: target antigen is proteinase 3
p-ANCA: target antigen is MPO
Child is being evaluated for an eczematous skin rash. His past medical hx is significant for several bouts of severe respiratory infections. Initial evaluation reveals increased bleeding time. His CBC shows a WBC count of 9,000 and a platelet count of 40,000. His platelets are small and deformed on blood smear. What is the most likely diagnosis?
Wiskott Aldrich syndrome: X linked, combined B and T cell immunodeficiency.
WATER Wiskott Aldrich Thrombocytopenia Eczema Recurrent infections
What protein deficiency can cause SCID? (Most common cause is X linked)
Adenosine deaminase deficiency – adenosine accumulation is toxic to lymphocytes and leads to widespread death of T and B lymphocytes
Part of the lymph node
Follicle: B cells
Paraxcortex: T cells
Parts of the thymus and role in T cell maturation
Cortex: immature T cells
- Positive Selection: T cells expressing TCR’s capable of binding self-MHC on cortical epithelial cells survive
Medulla: mature T cells
- Negative Selection: T cells expressing TCR’s with high affinity for self-antigens undergo apoptosis
What cells are responsible for the destruction of cells with decreased or absent MHC class I proteins on their surfaces
NK cells
Function of CD40 on B cells
promotes class switching of immunoglobulins. If there is no CD40, then the cells can only produce IgM (complement fixation)
Hyper-IgM syndrome
Due to defective CD40L on Th cells → Leads to severe pyogenic infections early in life; opportunistic infection with Pneumocystis, Cryptosporidum, and CMV
What causes immunodeficiency in ataxia telangiectasia? What is the genetic mutation in this disorder?
IgA deficiency
DNA break repair
Hypersensitivity type: Serum sickness
3
Hypersensitivity type: Goodpasture syndrome
2
Hypersensitivity type: multiple sclerosis
4
Hypersensitivity type: autoimmune hemolytic anemia
2
Hypersensitivity type: rhinitis
1
Hypersensitivity type: eczema
1
Hypersensitivity type: polyarteritis nodosa
3
Hypersensitivity type: contact dermatitis
4
Hypersensitivity type: myasthenia gravis
2
In what transplants do you see GVHD?
Bone marrow and liver transplants
Mechanism of apoptosis
Bcl2 in the cytoplasm is inactivated, cytochrome c can exit the mitochondria and enter the cytoplasm where it activates caspases that initiate apoptosis
o Caspases are proteolytic enzymes that destroy cell components. They contain cysteine and are able to cleave aspartic acid residues (cysteine-aspartic-acid-proteases)
Stem cell locations (skin, bowel, and bone marrow and lung):
skin – basal layer
bowel – mucosal crypts
bone marrow – hematopoietic stem cells
lung – type 2 pneumocytes
What do macrophages secrete to recruit more neutrophils?
IL-8
“clean up on aisle 8”
Interferon alpha and beta in viral infections
A part of innate host defense gainst DNA and RNA viruses
Cause transcription of antiviral enzymes capable of halting protein synthesis
Which cytokines are anti-inflammatory?
IL-10 and TGF-B
What attracts neutrophils?
Il-8 (macrophages)
C5a (complement cascade)
LTB4 (lipooxygenase pathway)
C1 esterase inhibitor deficiency
causes hereditary angioedema due to unregulated activation of kallikrein (Inc bradykinin)
**ACE inhibitors are contraindicated because will lead to accumulation of even more bradykinin
C3 deficiency:
inc risk of severe, recurrent pyogenic sinus and respiratory tract infections
C5-C9 deficiencies:
terminal complement deficiency increases susceptibility to recurrent Neisseria bacteremia due to inability to form MAC complex
Which complement is involved in neutrophil chemotaxis?
C5a
What stimulates class switching to IgE?
IL-4
What stimulates eosinophils?
IL-5
What stimulates class switching to IgA?
IL-5
What cytokines cause fever?
IL-1
IL-6
B cell deficiencies vs T cell deficiencies
B cell deficiencies tend to produce recurrent bacterial infections, whereas T cell deficiencies produce more fungal and viral infections
Calcineurin inhibitors
Cyclosporine and Tacrolimus
block T cell activation by preventing IL-2 transcription
Sirolimus
block T cell activation and B cell differentiation by preventing response to IL-2 – mTOR inhibitor
Daclizumab and Basiliximab
monoclonal antibodies that block IL-2 receptor
Mycophenolate:
reversibly inhibits IMP dehydrogenase, preventing purine synthesis of B and T cells
Role of Fas
The Fas receptor acts to initiate the extrinsic pathway of apoptosis.
Mutations involving the Fas receptor or Fas ligand can prevent apoptosis of autoreactive lymphocytes, thereby increasing the risk of autoimmune disorders such as SLE
What is released from mast cells during anaphylaxis
Histamine and tryptase
Which part of the complement cascade is deposited on antigen and acts as opsonin for phagocytosis? Which immunoglobulin has the same function?
C3b
IgG
Dihydrorhodamine flow cytometry test
Used for diagnosis of chronic granulomatous disease – will show absence of green fluorescence that is characteristic of normal neutrophils
What are people with ileal resection at risk of?
Patients with an ileal resection are at greater risk of infection due to loss of peyers patches (normally in the ileum) and dec ability to differentiate B cells to secrete IgA in response to gut pathogens
Also vitamin B12 deficiency as that is where is is absorbed
Killed vs Live vaccines induce which part(s) of the immune response?
Killed – humoral response only
Live – humoral and cell mediated immune responses
What enzymes can eliminate free radicals?
Superoxide dismutase
Glutathione peroxidase
Catalase
What increases ESR?
IL-6, IL-1 and TNF alpha induce the release of acute phase reactants –> release of fibrinogen causes an inc in ESR
