Immuno Flashcards
What are the characteristics of allergic asthma?
only leukotrienes (LTC4, LTD4, LTE4) and acetylcholines have pharmalogic receptor antagonists that offer clear therapeutic benefit
What are granulomatous conditions?
- Langhans giant cells are characteristic
- multiple nuclei peripherally organized in the shape of a horseshoe
- the macrophages that form these giant cells are activated by CD4+ TH1 lymphocytes
What is a leukemoid reaction?
leukemoid reaction=benign leukocytosis (>50,000/mms)
- in response to undelying condition
- severe infection/hemorrhage
- malignancy (leukemia)
- acute hemolysis
- Lab: increased/nml leukocyte alk phos levels
- peripheral smear:
- increased bands
- early mature neutrophil precursors (myelocytes)
- granules (Döhle bodies) in neutrophils
What is the job of the spleen?
2-fold
- blood filter=can remove circulating pathogens
- major site of opsonizing Ab synthesis
- asplenic patients are prone to infections caused by encapsulated organisms:
- S. pneumo
- H. flu
- N. meningitides
- spleen=most commonly injured organ with blunt abdo trauma
Precursor proteins/peptides responsible for localized amyloidosis
- cardiac atria: atrial natrieuretic peptide (ANP)
- thyroid gland: calcitonin
- pancreatic islets: islet amyloid protein (amylin)
- cerebrum/cerebral blood vessels: beta-amyloid protein
- pituitary gland: prolactin
- immune globulin LC cause multi-organ ayloid deposition in primary systemic amyloidosis
Isotype switching
- takes place in the germinal center of the lymph node
- interaction of CD40R on B cells (activated) with CD40L (CD154) on T-cells
All of th CDs
- CD4-recognize antigens presented by MHC2
- on the surface of MHC2-restricted T-helper cells
- CD7-multi-chain complex T-cell marker
- CD8-transmembrane protein associated with T-cell receptor
- recognizes antigenic peptide from MHC1
- CD14-surface marker of monocyte-macrophage lineage
- CD19,20,21=mature circulating B lymphocytes
HyperIgM Syndrome
- inabiity of B-lymphocytes to undergo isotype switch from IgM to D,G,E,A
- most commonly results in lymphoid hyperplasia and reurrent sinopulmonary infection
- due to genetic absence of CD-40 ligand on T-lymphocytes OR genetic deficiency in the enzymes responsible for DNA modification
X-linked agammaglobulinemia
- low/absent circulating CD19,20 pan B cells and pan-hypogammaglobulinemia
- CP: increased susceptibility to pyogenic bacteria, enteroviruses, Giardia lambia (due to the absence of opsonizing and neutralizing Ab)
Passage of leukocytes into the inflamed tissue (MR.AT&T)
- Margination
- Rolling
- Activation
- Tight Adhesion and Crawling
- Transmigration
Superantigen Activity
- enterotoxins
- oxfoliative toxins
- toxic shock syndrome toxins (TSST-1)
- super Ag interacts with MHC molecules on APC and the variable region of the TLR which causes non-specific, widespread activation of T-cells, resulting in release of IL-2 from T-cells and IL-1 and TNF from macrophages
- TSS is due to the immune cascade
Reactive Arthritis
- classic triad:
- non-gonococcal urethritis
- conjunctivitis
- arthritis
- HLA-B27 associated arthropathy
- within several weeks after GU or enteric infection
- seronegative spondyloarthropathies
- 20%->sacroiliitis
INF alpha and beta
- produced by most human cells in response to viral infections
- suppress viral replication by inhibiting protein synthesis and stimulating apoptosis of infected cells
- limits the ability of viruses to spread through the tissues
Achondroplasia
- AD gain of function in FGFR3 (fibroblast GFR3) gene
- indiv: hetero and 50% chance of transmitting to their offspring
- CP: short stature, disproportionately short upper and lower extremities, large head, prominent forehead
Chemotactics
- macrophages make IL-8 which induces chemotaxis and phagocytosis in neutrophils
- other chemotactics:
- n-formylated peptides
- leukotriene B4
- 5-HETE
- C5a
GvHD
- occurs after allogeneic bone marrow transplantation, transplantation of organs rich in lymphocytes (liver) or transfusion of non-irradiated blood
- pt usually severely immunodef due to primary dz or immunosuppressive meds
- donor T cells from graft survive, migrate into host tissues, recog host MHC Ag ad foreign and become sensitized
- on activation, donor CD4+ and CD8+ T cell (NOT B-cells) participate in host cell destruction
- skin, liver, GI most freq affected
- early s/s:
- diffuse maculopapular rash-palms and soles, may desquamate
- GI: diarrhea, intestinal bleeding, abdo pain
- liver: abnml LFT
Pus
- thin, protein-rich fluid=liquid puris, and dead leukocytes, primarily neutrophils
- during infection, macrophages and surrounding endothelial cells release cytokines (IL-8) that trigger neutrophils to enter the site of infection via chemotaxis
- IL-8 also induces phagocytosis in neutrophils once they have arrived
- other significant chemotactic agents:
- n-formylated peptides, leukotriene B4, 5-HETE (leukotriene precursor), complement component C5a
SCID
- etiology: gene defect leading to failure of T cell development
- also: B cell dysfxn due to absent T cells
- inheritance: X-linked recessive, AR
- CP:
- recurrent, severe viral, fungal, or opportunistic (Pneumocystis) infxns
- failure to thrive
- chronic diarrhea
- tx: stem cell transplant
Lymphatic system of extremities
- superficial lymphatic vessels-follow venous sytem
- receive lymph from skin and subq tissues
- in lower extremities divided into medial and lateral tracks
- lesions on medial foot cause inguinal lymphadenopathy
- lateral mesions more likely to cause lymphadenopathy in both the popliteal and inguinal areas
- deep lymphatic vessels-follow arterial system
- drain deep muscles and superficial vessels
TNF alpha
- TNF alpha inhibitors impair cell-mediated immunity
- all pts beginning tx with TNF alpha inhibitors should be evlauated for latent TB
What are the steps of leukocyte transmigration
- margination
- vascular leakage into microvasculature=hemoconcentration and DEC wall shear stress=improved contact of neutrophils with endolthelial lining
- rolling
- neutrophils roll on endothelium via losse binding of (sialylated) carb groups:
- sialyl lew X/PSGL-1 –to– L-selectin on neutophils
- E-selectin/P-selectin on endothelial cells
- neutrophils roll on endothelium via losse binding of (sialylated) carb groups:
- activation
- slow roll=leikocytes sample chemokines=activate integrins via signaling cascade=conformation change in integrins needed for binding
- tight adhesion and crawling
- neutrophils firmly attached to endothelium via CD18 beta 2 integrins (Mac-1 and LFA-1) to intercellular adhesio moecule-1 (ICAM-1)
- transmigration
- PECAM-1, at peripheral intercellular junctions of endothelial cells
poison ivy dermatitis
- form of allergic contact dermaitis
- type 4 HSR mediated primarily by T lymphocytes
- CP:
- intensely pruritic erythematous papules, vesicles, or bullae that often form linear patterns
- PP: urushiol [allergenic substance, causes immune resp when attached to proteins (hapten)]
what is the major adaptive immune mech that prevents re-infection with the influenza virus
- anti-hemagglutinin Ab
- -humoral resp with Ab directed against Hemagglutinin can neutralize virus and primarily block its binding to the host cells
Calcineurin
- essential protein (phosphatase) in the activation of IL-2 which promotes the growth and differentiation of T-cells
- once ativated, dephosphorylates nuclear factor of activated T-cells (NFAT)..allows NFAT to enter ncleus and binf to IL-2 promoter
- immunosuppresants such as cyclosporine and tacrolimus work by inhibiting calcineurin activation
Rheumatoid arthritis
- autoimune dz triggered by an unknown Ag
- cartilage components=auto-Ag that activate CD4+ T-cells which in turn stimulate B-cells to secrete rheumatoid factor, an IgM Ab specific for the Fc component of self IgG
IgA protease
- produced by:
- N. mening
- N. gonorrhoeae
- Strep pneumo
- H. flu
- cleaves secretory IgA at its hinge region, rendering it ineffective
- secretory IgA exists on mucosal surface and in secretions
- it acts to bind and inhibit the action of pili as well as other cell surface antigens that normally mediate mucosal adeherence and subsequent penetration
DILE (drug induced lupus erythematosus)
- abrupt pnset of lupus symptoms
- fever, arthralgias, pleuritis with posittive anti-histone Ab
- linked to drugs metabolized by N-aetylation in the liver:
- procainamide, hydralazine, isoniazid
- genetically predisposed individuals who are slow acetylators are at greater risk for developing DILE