Immune Flashcards
Morphology of Acute Transplant Rejection
- humoral (B cell): C4d deposition, neutrophilic infiltrate (PMNs), endotheliitis
- cellular (T cell): lymphocytic (MONOnuclear) interstitial infiltrate and endotheliits
Humoral Response
- bacteria
- neutrophils (PMNs)
- B cells with antibodies
Cellular Response
- viruses
- lymphocytes (mononuclear)
- T cells
Acute Rheumatic Fever
- molecular mimicry
- due to anti group A strep antibodies that cross react with cardiac and nervous antigens
- pancarditis, arthritis, sydenham chorea
- mitral regurg/stenosis
Guillain Barre
- ascending paralysis
- can be caused by campylobacter jejuni
- demyelinating syndrome of peripheral nerves
- characterized by endoneural inflammatory infiltration (lymphocytes and macrophages)
- antibodies from febrile illness cross react with myelin of spinal roots and peripheral nerves
Myasthenia Gravis
- muscle weakness (ptosis, diplopia)
- weakness worsens with activity or at the end of each day
- majority of pts also found to have thymoma or thymic hyperplasia
- antibodies attack the Ach receptor
Lambert Eaton Myasthenic Syndrome
-antibody to Ca channel in presynaptic nerve terminal
-weakness improves with exercise
Associated with malignancy in half of cases (esp. Small cell lung cancer)
Amyotrophic Lateral Sclerosis
- most common motor neuron disease
- combine UMN (spasticity, hyperreflexia) and LMN (weakness, fasciculations) lesions are characteristic
- damage to motor neurons of an. horn and demyelination of corticospinal tract present
- atrophy of lateral corticospinal tracts
IL1
- produced by macrophages and epithelial cells
- pro inflammatory
- commonly secreted by malignant plasma cells in multiple myeloma
- osteoclast activating factor that causes lytic bone lesions
IL5
-secreted by Th2 cells
-promotes humoral response with class switching to IgA.
Calls in eosinophils.
IL12
-secreted by macrophages
-induces differentiation of naive T cells into Th1 helper cells and activation of NK cells
Pts with a def. will have mycobacterial infections and can be tx with IFNgamma
TNFa
- produced by macrophages, NK cells, and T cells
- proinflammatory
- inc. expression of adhesion molecules
- important in septic shock response
IL10
- anti-inflammatory cytokine
- dec. Th1 cytokines and MHC2 expression
- protective effect in Crohns Disease
- Increases TH2 T cells
- Secreted by TH2 cells
Sarcoidosis
- young black women
- malaise, cough, erythema nodosum
- bilateral hilar lymphadenopathy
- transbronchial biopsy of non-caseating granulomas necessary for dx
- inflammatory dz of unknown etiology
- elevated ACE
- CD4 cells predominate
CREST Syndrome
- calcinosis
- raynauds
- esophageal dysmotility
- sclerodactyly (tightening of skin on fingers)
- telangiectasias (dilated capillaries)
- variant of systemic sclerosis
- can lead to pulmonary HTN
IL2
Anti tumor properties through activation of natural killer cells and T cells
Secreted by helper T cells
CD14
Surface marker of monocyte/macrophages.
IL4
Secreted by TH2 cells. Enable class switching to IgE.
Interleukins secreted by TH2 cells?
IL4, IL5, IL10
Cytokines and interleukins secreted by TH1 cells?
Interferon gamma (also secreted by NK cells)
Stimulates macrophages to kill phagocytosed pathogens.
IL2, IFNgamma, IL12
Cytokines secreted by all T cells?
IL2 (stimulates T cells)
IL3 (stimulates bone marrow)
Stimulate and support immune system growth
Cytokines secreted by macrophages?
IL1 (fever) IL6 (stimulates acute phase protein production) IL8 IL12 TNFa (mediates septic shock)
HOT Tbone stEAK
IL1 (fever) IL2 (stimulates T cells) IL3 (stimulates bone marrow) IL4 (stimulates IgE) IL5 (stimulates IgA) IL6 (aKute phase protein production)
Clean up on aisle 8
Neutrophils are recruited by IL8 to clear infections. Produced by macrophages. Causes cont. inflammation.
Pt’s neutrophils fail to turn blue on nitro blue tetrazolium testing?
Chronic Granulomatous Disease
X linked mutation affecting NADPH oxidase, which normally generates ROS to kill bugs.
Pt at inc. risk of catalase positive organisms due to dec. effect of neutrophils.
Citrullinated Peptide Antibodies… Dx?
Rheumatoid Arthritis
TGF beta
-controls cell proliferation, inhibits macrophages
Healing and resolution molecule with IL 10. AtTENunates immune response.
Regulatory T Cell Phenotype
- CD4+
- CD25+
- foxp3+
4 things that attract neutrophils?
leukotriene B4, C5a, IL8, bacterial products
3 Things that activate mast cells?
Tissue trauma
C3a and Ca
Cross linking of cell surface IgE by antigen
Substances that mediate pain?
PG E2
Bradykinin
Cytochrome C
Mitochondrial enzyme that leads to cell death through apoptosis.
Polymyocitis
Symmetrical proximal muscle weakness (difficulty combing hair). Elevated muscle enzymes (CK) and autoantibodies against histidyl tRNA synthetase (anti Jo). Over expression of MHC class 1 on the sarcolemma leads to CD8 T cell invasion. Leads to patchy muscle fiber necrosis. Lacks characteristic skin findings of dermatomysitis.
IL10
Healing and resolution molecule secreted with TGFbeta. AtTENuate immune response.
Acute Graft Rejection
Usually cell mediated pathway. Expect to see dense interstitial lymphocyte infiltrate.
Where do T cells live in the lymph node?
Paracortex
Schaumann Bodies, Noncaseating Granulomas, and Asteroid Bodies?
Sarcoid
What causes green color of sputum?
-myeloperoxidase released by neutrophils during infection
2 Tests for CGD
- nitroblue tetrazolium test: no blue = CGD
2. dihydrorhodamine flow cytometry: dec. green fluorescence = CGD
What disease is HLA DR2?
MS
Calcineurin
- protein phosphatase in T cells that is essential to IL2 activation
- dephosphorylates nuclear factor of activated T cells (NFAT) that leads to inc. immune response
- inhibited by cyclosporine and tacrolimus in pts with organ transplant
Langerhans Cell Histiocytosis
- disorder of langerhans cells
- lytic bone lesions, skin rash, otitis media,
- S100
- birbeck granules
IFNgamma
- produced by T cells and recruits leukocytes and activates phagocytosis
- type 2 interferon
- promotes Th1 differentiation
- inc. expression of MHC class 2
- important for mycobacterial infections, and def. will cause infection with these bugs
What cytokines mediate septic shock response?
TNF-a, IL1, IL6
Interferon alpha and beta
- type 1 interferons
- synthesized by most human cells in response to viral infection
- autocrine/paracrine signaling halts protein synthesis in presence of dsRNA (viral RNA)
- inc. MCH class 1 expression
Anti-dsDNA
-specific for SLE
Anti-histone Antibodies
- drug induced lupus
- procainamide, hydralazine, isoniazid, D-penicillamine
Anti-Ro/SSA and anti-La/SSB antibodies
-sjogren syndrome
Anti-phsopholipid Antibodies
-SLE and antiphospholipid antibody syndrome
Anti-DNA topoisomerase
-highly specific for systemic sclerosis-diffuse type
Anti-centromere Antibodies
CREST syndrome-systemic sclerosis limited type C-calcinosis R-raynauds E-esophageal dysmotility S-sclerodactyly T-telangectasias
Leukemoid Reaction
- benign leukocytosis in response to underlying condition like severe infection/hemorrhage, malignancy, or acute hemolysis
- leukocyte alk phos can be normal or elevated
- smear shows inc. bands, mature neutrophil precursors, and granules (dohle bodies) in neutrophils (not hypersegmented nuclei)
Systemic Mastocytosis
- abnormal proliferation of mast cells and inc. histamine release
- histamine causes inc. gastric acid as well as hypotension, flushing, and pruritis (with rash)
Leukocyte Adhesion Deficiency
- due to absence of CD18 antigens necessary for formation of integrins
- recurrent skin infections without purulence
- delayed separation of umbilical cord
- persistent leukocytosis
- ICAM deficiency
What immune cells are involved in the candida skin test?
-CD4+ T lymphocytes and macrophages
Graft Vs. Host Disease
- fever
- cytolytic destruction of mucous membranes such as GI and skin (maculopapular rash)
- follows organ transplant
- T lymphocytes from graft reject host cells
Cytokines involved in rheumatoid arthritis?
- IL1
- IL6
- TNFa
Myeloperoxidase Deficiency
- dec. myeloperoxidase
- pt cannot form HOCl- (bleach/ hypochlorus acid.hydroxyl halide radicals)
- inc. risk candida infections
Bence Jones Proteins
- monoclonal globulin protein found in the urine
- suggestive of multiple myeloma
What happens to endothelial tight junctions during inflammation?
-the tight junction permeability increases to allow for white cell migration to site of injury
IgE Independent Degranulation
- some medications (opioids, radiocontrast agents, vancomycin) induce granulation via protein kinase A and PI3 kinase
- IgE mediated degranulation is associated with environmental exposures and beta lactam and sulfonamide antibiotics
Caspases
- common to both intrinsic and extrinsic apoptosis pathways
- proteolytic enzymes that cleave cellular proteins
- stand for cysteine aspartic acid proteases
Maternal Antibodies
- type A or B mothers make IgM antibodies that can’t cross placenta if blood type is not compatible
- type O mothers make IgG that can cross placenta
Chediak Higashi
- defect in lysosomal trafficking regulator gene
- AR
- recurrent pyogenic infections
- partial albinsim
- progressive neurodegeneration
- pancytopenia
- mild coagulation defects
