immunology Flashcards
type 4 delayed hypersensitivity reaction moa
doesn’t involve antibodies or complement; occurs 1-2 days after exposure as antigen is taken up by dendritic cells, displayed on MHCII, and stimulate Th1 to release interferon-gamma and attract MO
reactive arthritis triad, age group, and lab finding
urethritis, arthritis, and conjunctivitis; young men; HLA-B27
hep B markers of DNA replication
HBeAg, HBV DNA
hep B chronic infection lab findings
high HBeAg, low anti-HBeAg
eosinophil 2 functions
- defense against parasites: IgE detects parasites, binds and attracts eosinophil via IgE FcR, euosinophil releases major basic protein to kill parasite; 2. regulate type 1 hypersensitivity rxn (mediated by mast/basophils): by releasing histaminase, which helps reduce severity of atopic reaction
EBV nydus of infection
pharyngeal mucosa and tonsillar crypts, then blood
EBV binds to what receptor on what cell?
CD-21 (C3d complement receptor) on mature B-cells
EBV histological giveaway
CD8+ cells that clinically expand to destroy the virus-infected cells; appear much larger with lots of cytoplasm, eccentrically placed nucleus, and cell membrane that conforms to nearby cell bodies
monocotyes and macrophages: signals identity and serves as LPS receptor
CD14
type 1 hypersensitivity: moa
initial exposure: develop a wheal and undergo class-switching to IgE specific to antigen; re-exposure will result in cross-linking on the surface of basophils and mast cells, degranulation, and release of histamine, proteases, leukotrienes, prostaglandins, and heparin
TNF-alpha produced by what cells, does what, and is elevated in what diseases?
mast cells and macrophages; activation of inflammatory cells (CD4, PMN, fibroblasts, endothelial cells) and apoptosis of tumor cells; increased in inflammatory conditions like RA, psoriatic arthritis
Anti-TNF-alpha IG
infliximab, eternacept
toxic shock syndrome moa
superantigen that activates large numbers of helper T-cells (release IL-2) and MO (release IL-1 and TNF); cause capillary leakage, circulatory collapse, hypotension/shock, fever, and skin findings
TB: mycobacteria survival strategy
hide in MO, able to escape killing and replicate w/i phagollysozomes
TB: macrophage response
- present antigen to naive Th cells, 2. secrete IL-12 to induce Th1 differentiation (to produce interferon gamma to help MO), and 3. produce TNF-alpha to recruit additional MO to wall bacteria in
TB: histological hallmark
epithelioid MO
hep C genetic variation: 2 moa
hypervariable region for envelope glycoprotein; no proofreading 3’-5’ exonuclease activity on virion-encoded RNA polymerase
chronic granulomatous dz: moa, pw, dx
inactivation of NADPH oxidase leads to decreased oxidative burst and impaired phagocytic intracellular killing; pw recurrent infection with coag + bacteria, lungs, skin, LN, liver involved, w/ diffuse granulomatous formation; dx by measuring PMN superoxide products (DHR flow cytometry or nitroblue tetrazolium test)
Dihydrorhodamine flow cytrometry test
measures conversion of DHR to rhodamine (fluorescent green); decreased NADPH activity, decreased fluorescence
Nitroblue tetrazolium test
NADPH oxidaises yellow NBT to dark blue; if yellow, then dz positive
What disease presents similarly to chronic granulomatous disease?
myeloperoxidase deficiency (normal DHR/NBT test)
Chediak-higashi syndrome: moa, pw
AR defect in phagosome-lysosome fusino in PMN, leading to abnormal giant lysosomal inclusions visible on light microscopy; pw recurrent pyogenic infectino by strap, strep, albinism, neurological defects (nystagmus, neuropathy)
NK cell (10 percent of all lymphocytes): function, moa
destroy cells w decreased/absent MHCI (virus, tumor); release perforins that punch holes in membranes and granzymes that induce target cell apoptosis
NK cells surface markers
CD16, CD56
NK cells activated by
interferon gamma and IL-12
Th1 cell-mediated adaptive immunity: moa
targets intracellular pathogens, secrets IL-2, interferon- gamma to activates MO and cytotoxic T cells ; also mediates delayed-type hypersensitivity
Th2 cells humoral adaptive immunity: moa
secretes IL-4, IL-13 to promote B-cell IgE production, secretes IL-5 to promote eosinophil activity/IgA synthesis
Hypothesis for asthma
Increased Th2/Th1 activity; type 1 hypersensitivity, increased IgE
IL-1 secreted by who and stimulates what
Secreted by MO to stimulate helper T cells, fever
Acute hemolytic transfusion reaction moa
type 2 reaction (antibody-mediated) in which anti-ABO IgM antibodies binds with corresponding antigens on donor RBC, release C5b-C9 (MAC) and C3a-C5a (vasodilation, shock); pw fever, chills, hypotension, chest/back pain, hemoglobinuria, DIC, renal failure;
thymus and t-cell maturation
- pro t-cells arrive as “double-negative” without CD4, 8 antigens; 2. rearrangement of beta chain of TCR, production of CD4 and CD8 antigens (“double positive”); 3. @ thymic cortex, positive selection picks out T-cells that can bind with MHC cells on thymic epithelial cells (“positive selection”); 4. @ thymic medulla, deletion of t cells that react strongly to self-MHC antigens; 5. loss of CD4 or CD8 antigen
GVH disease
m/c after BMT, liver transplant, transfusion of non-irradiated blood; host is severely immunodeficient and donor T cells w/i transplanted tissue recognize host MHC as foreign and attack; pw liver dmg (jaundice, elevated transaminases, alk phos, bili), GI symptoms, and skin desquamation
sarcoidosis moa
accumulation of activated MO, formation of noncaseating granulomas (that produce ACE and active vita D), dysregulated cell-mediated immune response (increased CD4/CD8, Il-2, IFN-gamma)
ataxia-telengiectasia moa, pw
ATM mutation responsible for DNA break repair; pw ataxia, telengiectasia, immunodeficiency (both cell and humoral) leads to IgA deficiency and respiratory infections
HIV binds to what receptors
CD4 and CCR5
langerhans cell
derived from myeloid line, dendritic cell in skin/mucosa, professional APC, constitutive expression of MHCII and B7 molecules; histo: “racquet-shaped” cell with intracytoplasmic granules (birbeck)
MO in liver, bone, CNS, kidney, lung
kupffer cells, osteoclasts, microglia, mesangial cells, alveolar MO
melanocyte
NC cells that migrate to epidermal basal layer
IgA protease
produced by neisseria to cleave IgA and penetrate mucosa (gonorrhea - genitals, meningitis - nasopharynx)
IgA secretory form: function, structure
Bind to pili and other membrane proteins that mediates bacterial adherence; IgA dimer bound by peptide J chain and peptide secretory component (produce by epithelial cells); abudant in tears, saliva, mucus, colostrum (1st breast milk fed after birth)
Protein A: bacteria, moa?
Staph A; binds w/ Fc portion of IgG, prevent exposure of C1 domain and direct complement-fixing IgG away from bacteria
polysaccharide capsule: bacteria, moa?
s. pneumo, n meningitis, h.flu, crypto; impairment of opsonization/phagocytosis
interferon type 1 (alpha, beta) moa
secreted by infected eukaryotic cells, binds to nreceptors of neighboring cells where it induces transcription of antiviral proteins RNAse L (endonucleases that degrades viral/cellular mRNA) and protein kinase R (phosphorylate and inactivate EF-2, inhibiting translation); these are only active in presence of dsRNA (viral infection)
Interferon type 2 (gamme)
produced by t cell, nk cells in response to antigens/mitogens; promote TH1 differentiation, improve intracellular killing of MO, increase MHCII enzymes
Both type I and type II interferon do what?
induce HC1 expression in all cells, stimulate NK, cytotoxic T-cell activity
Hyper IgM syndrome: moa, pw, rx
2 possible moa: 1. problems with enzyme needed for class switching (DNA recombinase enzyme), 2. CD40T-lymphocyte ligand needed for class-switching is missing; pw recurrent sinus/airway infection 2/2 IgA deficiency; rx with IG
Erythroblastosis fetalis/hemolytic dz of newborn
if mom is blood-type O, natural antibodies are IgG and can cross placenta (15 percent of pregnancies, and HDN only occurs in 3 percent); can occur with first pregnancy as mom can be exposed to A/B antigen
wickott-aldrich moa, pw, rx
XLR combined B/T cell disorder, weakness to polysaccharide capsule (S, N, H) and PCP/herpes; pw eczema, thrombocytosis, immunodeficiency; HLA-matched BM transplantation
giardia: 2 forms, transmission
cysts (infective): oval, 4 nuclei; trophozoite (pathogenic): pear-shaped, multiple flagella, 2 nuclei (“owl eyes”); contaminated water, FO transmission
giardia: pw, dx, immune reaction
watery diarrhea, malabsorption; stool microscopy for ova, parasites (small bowel biopsy shows villous atrophy); host defends with CD4+ Th cells, secretory IgA production
bruton’s agammglobulinemia: moa, lymphoid tissue finding
X-linked; mutation to bruton’s tyrosine kinase prevents development of pre-B cells (CD19, 20) into mature, circulating B cells (19, 20, 21) in bone marrow; low/absent B cells in circulation, decreased lymphoid tissue (GC w/i lymphoid follicles are not present normally where B-cells go to proliferate and undergo somatic hypermutation), pan-hypogammaglobulinemia
LN structure
paracortical zone: T-cell, dendritic cell; outer cortex: house GC; subcapsular regione: lymphatic vessels
chronic renal allograft rejection pw
worsening HTN, increased Cr, proteinuria
RA factor
IgM antibody specific for the Fc component of self IgG (like protein A), binds igG to form immune complexes that deposit in synovium and cartilage
RA hypothesis
autoreactive humoral response against cartilage
Inflammation: passage of leukocytes into tissue
margination, rolling, activation, tight adhesion, transmigration
Inflammation: rolling binds what receptors?
PMN (sialyl lewis X/L-selection) to endothelium (E,P selectin)
Inflammation: tight adhesion binds what receptors?
CD 18/beta-2 integrin (mac-1, LFA-1) on PMN to intercellular adhesion molecule 1 (ICAM-1) on endothelium
Inflammation: transmigration requires adhesion to what molecule?
platelet endothelial adhesion molecule (PECAM-1)
leukocyte adherence deficiency (LAD) type 1 moa
absence of CD 18 results in recurrent skin infection w/o pus, delayed umbilical cord detachment, poor wound healing
diptheria organism descrption
nonmotile, unencapsulated GP rod with metachromatic granules that stain with aniline dyes like methylene blue
anti-RH(D) IG
IgG anti-Rh antibodies given to Rh- females at 7 months and immediately post-partum to bind with potential Rh factor in children
myasthenia gravis: moa
circulating antibodies bind with post-synaptic ACh receptor and cause complement-mediated destruction; pw muscle weakness that worsens throughout day; thymus abnormalities
Immune system dysfunction in GBS
T-cell and macrophage destruction of PNS
Immune system dysfunction in polymyositis
Tc-mediated SK muscle damage
Immune system dysfunction in SLE, RA, CT d/o
deposition of immune complexes
type II hypersensitivity d/o:
MG, good pasture
type III hypersensitivity d/o: examples
PSGN, hypersensitivity pneumonitis, churg-strauss
hypersensitivity pneumonitis
IgG precipitates actinomyces antigen, leads to interstitial alveolitis/bronchiolitis
type IV hypersensitivity d/o: examples
sarcoidosis, contact dermatitis, PPD, candida test
complement cascade
C1 binding to 2 molecules of IgG or IgM at the Fc region of heavy chain (but only exposed when bound to antigen); easier to begin with IgM
silicosis moa, increases susceptibility to what dz?
internalized silica particles may disrupt MO phagolysosomes; impair MO killing of intracellular mycobacteria, increased susceptibility to TB
Immune system response to TB
Mo activates Th1, which releases IFN-gamma to stimulate MO and IL-2 to stimulate cytotoxic T-cell; create caseating granuloma with epithelioid cells, langhans multinucleated cells, fibroblasts, collagen
What complement components are needed for formation of MAC? deficiency of these results in increased risk for:
C5b - C9; recurrent neisseria infection
SCID: 2nd most common cause, rx
AR deficiency of adenosine deaminase, which causes toxic levels of adenosine accumulation in lymphocytes; rx retroviral vectors to infect pt stem cells w/ adenosine deaminse gene
acute serum sickness: moa, pw, histo, lab
type III hypersensitivity; fever, pruritic skin rash, arthralgias 7-14 days after exposure; small vessel vasculitis with fibrinoid necrosis with intense PMN infiltration; decreased C3 level (2/2 IgG/IgM deposition + localized complement consumption)
live attenuated flu vaccine moa
Stimulate MHCI antigen cells and cytotoxic CD8+ cells
FAS sequence: initiator caspases
8, 10
FAS sequence: executor caspases
3, 6 (cleave cellular proteins and activate DNAase)
anti-apoptotic signals
Bcl-2, Bcl-x
Pro-apoptotic signals
Bak, bax, Bim (mitocondria becomes permeable and release cytochrome c)
This cytokine is produced by macrophages induces PMH chemotaxis and phagocytosis
IL-8
Granulocytes, present in RS cells
CD-15
IL-2 secreted by, function?
Thcell, growth factor for cytotoxic, helper t cells (via autocrine reaction with IL-2R); also activates monocytes, NK, B-cells; has anti-tumor effects 2/2 increased effectiveness of NK and T cells; rx for metastatic melanoma and RCC
Neonatal prophylaxis of tetanus
Give pregnant mom shot before birth! IgG antitoxin antibodies across placenta
Inhibitory cytokines
TGF-beta and IL-10
Candida two-part immune response
- T cells for cutaneous/superficial infection; 2. PMN prevents hematogenous spread
polymyositis: two-part injury sequence
- initial injury releases muscle antigens and triggers inflammatory response 2/2 MO and CD4+; 2. increased expression of MHC on muscle cells increases CD8+ that destroy muscle (thus, histologically see CD8+ lymphocytes and MO in endomyseum); increased creatinine kindase, anti-JO-1 antibodies
MHCI structure
heavy chain (highly polymorphic) + beta2-microglobulin
DiGeorge syndrome moa
22q deletion, maldevelopment of 3rd, 4th brachial cleft/pharyngeal pouch; T-cell deficiency 2/2 absence of thymus
Asthma MOA and rx for treatment-resistant asthma
high IgE response; anti-IgE antibodies (omalizumab)
