Immunology Flashcards
IL-10
anti-inflammatory bc it attenuates pro-inflammatory Th1 cytokines (IL2 and IFN gamma) and MHC II expression
inhibits activated dendritic cells and macrophages
released by Th2 cells and Treg
IL-1
produced by macrophages and epithelial cells
proinflamm. :
- endothelium activation
- increased chemokine expression (promoting leukocyte recruitment)
- induction of fever
IL-5
secreted by Th2 cells
promotes humoral response –> stim differentiation of BCs and IgA production
promotes growth and differentiation of eos –> possible role in allergies
IL-12
secreted by macros and BCs
induces differentiation of Th1 cells and activation of NK cells
Interferon-y
secreted by Th1
pro-inflamm:
- activates macros
- inc Ag presentation
- inducing apoptosis of epithelial cells
TNF-alpha
produced by macros, NK, TCs
pro-inflamm.
- leukocyte recruitment
- activates endothelium (inc adhesion molecules and leuk recruitment) –> vascular leak
Mediates septic shock
Bradykinin
vasodilation, inc vascular permeability, stimulates smooth muscle contraction, mediates pain
leukotriene B4
metabolite of arachidonic acid
stimulates neutrophil migration to site of inflammation
Platelet-activating factor
vasoconstriction, bronchoconstriction, platelet stimulation
small amounts = vasodilation and inc vascular permeability
enhances leukocyte adhesion to endothelium, chemotaxis, phagocytosis and degranulation
Acute-phase reactant production
IL-1, IL-6, TNF-a stimulate hepatic secretion of APRs like fibrinogen –> ESR hence marker of inflammation
Pneumococcal polysaccharide vaccine (PPSV23)
TC independent BC response that’s less effective in children
Pneumococcal conjugate vaccine (PCV13)
covalently attached to recombinant, inactivated diphtheria toxin –> induces active immunity via a TC dependent BC response
better immunogenicity and formation of higher affinity Ab and memory cells even in children
capsular polysaccharide vaccines
PPSV23 (pneumococcal), neisseria meningitidis, HiB
killed bacteria vaccines
oral cholera
require multiple inoculations or boosters to induce and maintain immunity
Live attenuated bacterial vaccines
BCG and oral typhoid
can revert to virulent strains
contraindicated in immunocompromised hosts
recombinant surface protein vaccine
HBV
insert relevant DNA into a host organism (e.g. baker’s yeast) –> produces Ag in desired quantity
require boosters or multiple inoculations to achieve and maintain sufficient immunity
Inactivated toxin (toxoid) vaccines
diphtheria and tetanus vaccines
useful when toxin is the cause of morbidity and mortality –> produce neutralizing Ab to toxin
CD15
present on granulocytes and all Reed-Sternberg cells –> used in dx Hodgkin lymphoma
CD16
low-affinity Fc receptor found on NK cells, neutrophils, and macrophages
i.e. weak role in opsonization
Graft-versus-host disease
after allogeneic bone marrow transplant or transplant of organs rich in lymphocytes (eg, liver) or transfusion of non-irradiated blood
donor TC from graft survives –> migrates to host tissues –> recognize host MHC Ag –> sensitized –> activation –> donor CD4 and CD8 cells destroy host cells –> typically affects skin, liver, GI tract
sx = diffuse maculopapular rash of palms and soles, desquamation, diarrhea, intestinal bleeding, abdominal pain, abnormal LFTs 2/2 liver damage
Acute and chronic graft rejections mechanism
host T and B cel sensitization against graft MHC Ag –> graft failure w/o involvement of other organ systems
Mechanism of susceptibility to encapsulated organisms postsplenectomy
dec IgM –> dec complement activation –> dec C3b opsonization –> inc susceptibility
Encapsulated organisms
SHiN SKiS
Streptococcus pneumoniae Haemophilus influenzae type B Neisseria meningitidis Salmonella Klebsiella pneumoniae Group B streptococci
postsplenectomy findings:
Howell-Jolly bodies (nuclear remnants)
Target cells
Thrombocytosis
costimulatory signal on dendritic cells that activate immature TC
B7 on DC binds CD28 on TC
signal 2 in activation of BCs
CD40 ligand on TC binds CD40 receptor on BC
BC class switching
dictated by cytokines released by Th cell –> class switching, affinity maturation, Ab production
Treg cells
promote immune tolerance
express CD3, CD4, CD25 (alpha chain of IL2 receptor)
secrete IL-10 and TGF-beta = anti-inflammatory cytokines
Fc region
- Constant
- Carboxy terminal
- Complement binding at CH2 = second fragment of heavy chain (IgM and IgG only)
- Carbohydrate side chains
- Determines isotype (IgM, IgD, etc)
Ab methods of generating diversity
- VJ recombination = light chain
- VDJ recombination = heavy chain
- Somatic hypermutation = after Ag stimulation
- Terminal deoxynucleotidyl transferase = adds nucleotides during recombination
Alternative complement pathway
activated spontaneously or by microbial surfaces
C3–>C3b –> C3 convertase + other crap –> c3a and C3b –> c3b activates C5 convertase –> C5b + C6-9 –> MAC
Lectin complement pathway
activates by microbial surfaces e.g. mannose
MBL –> C1-like complex –> C4b –> C3 convertase –> C3b –> C5 convertase –> C5b + C6-9 –> MAC
Classic complement pathway
Ag-Ab mediated; only IgG and IgM
C1–> C1 complex –> C2 split –> C2a activates C3 convertase –> C3b –> C5 convertase –> C5b + C6-9 –> MAC
C3b
opsonization
C3a and C5a
anaphylaxis
C5a
neutrophil chemotaxis
C5b-9
MAC and cytolysis
C1 esterase inhibitor deficiency
hereditary angioedema
normally C1 esterase inhibitor helps prevent complement activation on self cells like RBCs
ACEi contraindicated
C3 deficiency
severe, recurrent pyogenic sinus and respiratory infections
inc susceptibility to type III hypersensitivity reactions bc C3b also helps clear immune complexes in addition to its job of opsonization
C5-9 deficiencies
recurrent neisseria bacteremia
DAF (GP1 anchored enzyme) deficiency
complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)
bc DAF1 usually helps prevent complement activation on self cells like RBCs
IL-8
major chemotactic factor for neutrophils
“clean up on aisle 8”
IL-6
endogenous pyrogen –> fever and production of acute phase reactants
secreted by Th2
IL-2
stimulates growth of helper, cytotoxic and regulatory TCs
IL-3
supports growth and differentiation of bone marrow stem cells
fxns like GM-CSF
secreted by TCs
INF-gamma
secreted by Th1 cells
suppresses Th2 cells
antiviral and antitumor properties
inc MHC I and II expression and Ag presentation in all cells
IL-4
induces differentiation into Th2 cells Promotes growth of BCs enhances class switching to IgE and IgG
TGF-beta
anti-inflammatory similar to IL-10
Mneumonic for important cytokines
“Hot T-Bone stEAk”
IL 1 = fever IL 2 = TC stimulation IL 3 = BM stimulation IL 4 = IgE production IL 5 = IgA production
Interferons
INTERfere with viruses
alpha and beta = inhibit viral protein synthesis via ribonuclease that’s specific for viral mRNA
gama = inc MHC I and II expression and Ag presentation in all cells
activates NK cells to kill virus-infected cells
what is the EBV receptor on BCs?
CD21
serum sickness
sx = fever, urticaria, arthralgias, proteinuria, LAD 5-10 days after exposure
Ab produced against foreign protein, takes ~5 days –> immune complex deposited in membranes –> fix complement –> tissue damage
more common than Arthus reaction
Arthus reaction
local subacute type III reaction
intradermal injection of Ag –> Ab induction –> immune complexes in skin –> edema, necrosis and activation of complement
Type IV hypersensitivity reactions
cell-mediated, not transferable by serum
4 T’s:
- TC mediated
- transplant rejection
- TB skin tests
- touching (contact dermatitis)
Allergic reaction to blood transfusion
Type I hypersensitivity
sx - urticaria, pruritus, wheezing, fever
tx - antihistamines
anaphylactic reaction to blood transfusion
severe. IgA deficient individuals must reveice blood products lacking IgA
sx = dyspnea, bronchospasm, hypotension, respiratory arrest, shock
Febrile nonhemolytic transfusion reaction (FNHTR)
Type II hypersensitivity reaction
host Ab against donor HLA-Ag and leukocytes
sx = fever, HA, chills, flushing
Acute hemolytic transfusion reaction (HTR)
Type II hypersensitivity reaction
intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host Ab reaction against foreign Ag on donor RBC)
sx = fever, HoTN, tachypnea, tachycardia, flank pain, Hb-emia (intravascular), jaundice (extravascular hemolysis)
Hyper IgE Syndrome (Job’s syndrome)
Th1 cells don’t produce IFN-gamma –> neutrophils can’t respond to chemotactic stimuli
FATED: coarse Facies cold (noninflamed) staph Abscesses retained primary Teeth inc IgE Derm problems (eczema)
Wiskott Aldrich Syndrome
x-linked, WAS gene on X chromosome
TCs can’t reorganize actin cytoskeleton
Triad (TIE):
Thrombocytopenic purpura
Infections
Eczema
low IgM, high IgE and A, thrombocytopenia
Cyclosporine
blocks differentiation and activation of TCs by inhibiting calcineurin –> prevents production of IL-2 and receptor
use for organ rejection and AI d/o
SE = nephrotoxicity, gingival hyperplasia, hirsutism (also HTN, HLD, hypergly)
Tacrolimus
binds FK-binding protein –> inhibits calcineurin and secretion of IL-2
use for organ transplant rejections
SE = same as cyclosporine but NO GINGIVAL HYPERPLASIA OR HIRSUTISM
Sirlomius = rapamycin
inhibits mTOR –> inhibits TC proliferation in response to IL-2
use for kidney transplant immunosuppression + cyclosporine and steroids; also drug-eluting stents
SE = HLD, thrombocytopenia, leukopenia
Azathioprine
precursor to 6MP
interferes with metabolism and synthesis of nucleic acids –> inhibits lymphocyte proliferation
use for kidney transplant, glomerulonephritis, hemolytic anemia
SE = bone marrow suppression – worsened by allopurinol because the active metabolite 6MP is also degraded by xanthine oxidase
Muromonab = OKT3
monoclonal Ab binding CD3 –> blocks TCR transduction
immunuosuppression after kidney transplant
SE = cytokine release syndrome, hypersensitivity reaction
Digoxin immune Fab
antidote for digoxin intoxication
infliximab
targets TNF-alpha
Crohn’s, RA, psoriatic arthritis, ankylosing spondylitis
adalimumab
targets TNF-alpha
Crohn’s RA, prosiatic arthritis
Abciximab
targets glycoprotein IIb/IIIa
unstable angina and percutaneous coronary intervention
Omalizumab
targets IgE severe asthma
Bone marrow recovery
Filgrastim (GCSF)
Sargramostim (Granulocyte-macrophage colony-stimulating factor)
alpha interferon
HBV, HCV, Kaposi sarcoma, leukmia, malignant melanoma
beta interferon
MS
gamma interferon
chronic granulomatous disease
thrombocytopenia cytokine tx
oprelvekin (IL-11), TPO
