Flashcards in Immuno CCOM 1 Deck (129):
What do cells of the innate response recognize during an immune response?
structural motifs common to many pathogens: PAMPs
Pattern Recognition Receptors are responsible for this:
Toll receptors - CD14 binds w LPS and complexes with TLR4
What condition might exhibit an elevated CD14 level?
What are Nod-like receptors used for?
they can form inflammasomes that result in the initiation of cell death and cytokine release
What are some example of PAMPs?
What does Mannose binding lectin bind to specifically on bacteria?
What do scavengar receptors recognize?
acetylated low density lipoproteins
old and dying host cells
ex: PSR for phosphatidyl serine during apoptosis
What are some factors in the innate immunity?
Type 1 interferons-cytokines
gamma-delta T lymphocytes
What other cell may have similar function to NK cells?
gamma-delta T lymphocytes
What are exogenous and endogenous pyrogens?
exo: products of microorganisms that induce or act directly on hypothalamus
endo: IL1, IL6, TNFa - cause release of arachidonic acid that metabolizes to PGE2 which acts on hypothalamus
Describe active and passive immunity vs natural and acquired
active natural: pt acquires disease and recovers
active acquired: pt vaccinated
passive natural: mother passes immunity
passive acquired: pt given preformed IGs
Where do all leukocytes originiate from?
Where do lymphocytes first encounter pathogens?
secondary lymphoid tissues
Which cell type does the spleen have the most?
What is the more accurate view of the function of lymph nodes?
trap foreign molecules
concentrate these molecules in same location as appropriate WBC to increase opportunity
How do lymph node cells constantly recirculate?
about 2% of the lymphocyte pool recirculates every hour
to feel out the environment
-surveillance and communication
-80% lymphocytes end up in diff node by end of day
What are properiteis of MALT?
MALT cells recirculate to only other mucosal tissues
describe the markers for T cells
All are CD3
some are CD4 (helper)
somer are CD8 (ctotoxic)
What types of cells do hematopoeitec stem cells give rise to?
What are cytokine made of?
protein or glycoprotein
they act locally
What are the only cells that produce antibodies?
What is biological activity of Abs?
help lyse organisms
clump organisms together
What are some reducing agents of Abs?
mercapto: breaks apart 4 chains at disulfide bonds
Papain: breaks hinge to yield 3 fragments
Pepsin: yields 2 F(ab)2 (divalent)
After papin digests Abs, describe the properties of the fragments
Fab can still bind Ag
Fc cannot bind Ag but is:
What is the order of concentraion of Igs in descending order?
What determines the type of heavy chain? What does the heavy chain define?
heavychain defines isotype of Ig
What is the hypervariable region
Where there is contact with the epitope of the antigen. The regions that contact epitope is the idiotype
How many constant domains are on the light chain and heavy chain?
Which is the only Ab to cross the placenta?
What are the fucntions of IgG?
secreted as pentamer
Ag receptor as a monomer
J chain joins units together
no hinge region
extra constant domian in heavy
What is the first Ab type formed in the primary immune reponse?
a dimer linked by J chain
has a secretory component in secretions-protects from protease
protects on mucosal surfaces
What is the predominant Ab found in bodily secretions?
Which Ab is passed along through breast milk?
simliar to IgM structure
allergic reactions (T1 hypersens)
similar in structure to IgG
not sure of function really
might serve as marker of B cell differentiation
How can Igs be antigens?
because they are glycoproteins
ex: human Ig in mouse Igs.
Do plasma cells produce IgD?
Half life of Igs?
G: 23 days
Where is the site of hematopoeisis throughout life?
until 6 mo gest: yolk sac and liver
What is the cell marker for a hematopietic stem cell?
What is the order of B cell development?
pro B cell
pre B cell
immature B cell
mature B cell
Which cytokines interact w pro B cells to continue differentiation?
(also stromal cells)
What happens when IL 7 and IL 3 interact w pro B cell?
Ig genes for variable heavy chain rearranges
Define the Pre B cell
expression of ruly rearranged Ig heavy chain and initiation of light chain rearrangement
Describe the first checkpoint in B cell dev
surrogate light chain interacts w rearranged heavy chain. It goes to cell surface. If they dont interact-> death
if they do-> live/allelic exclusion
What is allelic exclusion?
even though B cell encodes for 2 heavy chains and 2 light chains, only one of the loci will be expressed
Define the immature B cell
expression of surface IgM (sIgM)
What happens if the sIgM interacts w a soluble antigen? an insoluble antigen?
soluble: clonal anergy
Define the mature B cell
expression of both sIgM and sIgD
Describe the specificities of sIgM and sIgD on the developing b cell
they have the same specificity
(different isotype but same idiotype?)
Which transmembrane proteins does Ig associate with in the developing B cell?
(all form BCR)
What must occur for the B cell to develop beyond the matrue B cell?
crosslinking of BCRs through antigen epitopes in secondary lymphoid tissues
What is the Clonal Selection Theory?
differentiating stem cells rearrange their genes for the hypervariable region to produce clones of B cells that respod to a specific epitope. Produces plama cells or memory B cells
What is tolerance?
prevents reaction against self
What are T-independent Ags?
Can activate B cells without help from T cells
any with multiple epitopes
any that crosslinks sIg
What are Type 1 T-indep Ags?
What response do you see?
activate B cells without using BCr
stim polyclonal activation
heterophile Abs-many specificities
B cell mitogens
What are Type 2 T-indep Ags? What response do you see? ex?
activate B cell by using BCR (sIg), and crosslinking sIg's
capping- moves to one pole
B cells with only 1 specificity
ex: carb, peptides, dextran
What class of Ab is synthesized in a Type 2 T-indep response?
What happens if a Type 2 T-indep antigen becomes conjugated to a protein?
Switches to a T-dependent response
IgG2 is major Ab made
Describe the memory response for a T-indep antigen?
there is no memory response
identical to primary response
What are characteristice os T-dependent Ags
proteins, glycoproteins, or conjugated to proteins
Which age group responds poorly to T-indep Ags?
children under 2 years
Describe T-depedend responses
isotype switch occurs
but specificity stays same!
APC, T cell, B cell needed
Which cell surface ligand mediates the development from mature/naive cells to memory or plasma cells?
CD40 (on B cell)
CD40L (on T cell)
Why are memory cells faster to react to second exposure of antigens?
Isotype switch already ocured
At a higher activation state
higher affinity Ag receptors
What is affinity maturation?
increased Ab binding strength somatic mutations in variable
'survival of fittest'
BCRs on B cells are better too
(remember specificity does not change)
Describe the Lag phase of a primary resopnse
B cells undergo clonal selection
What is the first type of Ab produced in a primary response?
secondary: IgG is predominant
What is linked recognition?
eptiopes must be physically linked on same anithgen
What are examples of conjugated vaccines?
influenze type b
pneumococcal conjugate vaccine
What protects infants from disease?
infant Ig after 6 mo
normal gut flora
What types ofinfections does breast feeding protect from
How many V, D, J and C chains in heavy and light chaings?
light: Vk=40 ; Jk=5 ; Vl=40 ; Jl=4
heavy: Vh=50 ; Dh=20 ; Jh=6 ; Ch=9
Desribe how you use a paired sera test
collect serum sample 1 durin illness
and sample 2 after recovery
If titer is 4X increase, then disease
What is sensitivity?
a measure of ability to identigy diseased cases
Most helpful when negative-to rule out
there are false positives
good for screenings
What is specificity?
measure of ability to test non-diseased
Best when it is positive-to rule in
there are false negatives
good for confirmatory
What are the primary binding tests?
4) Flow Cytometry
Add known antigens to well
Add diltued uknown serum
Add 2nd Ab conjugated w enzyme
Add chromagen for color
Descfribe Direct IF
Add tissue specimen to slide
Add Ab w conjugated flourescent
Look under UV scope to see it
Describe Indirect IF
When you dont have tissue, but you have serum (Abs)
Add 2nd Ab w Fluorescent
Detect bound Abs
Compare ELISA and blotting specificities and sensitivities
ELISA: high sense, low spec
Blot: low sense, high spec
What are ELISAs used?
When is IF used?
DFA: rabies, herpes
IFA: assay Abs
When is blotting used?
measure number of cels w certain surface markers
CD4:CD8 ratios of HIV pts
tumor cells w markers
What is the CD4:CD8 ration in normal patients?
less in AIDS patients. Treatment returns to normal
What is the prozone effect?
antibody excess zone-none
equivalence zone- formed
antigen excess zone-none
Describe the Ouchterlony test
3 wells: 1) pt sample 2) known lab sample w tested Ag 3) Ab against Ag
3 interpretations: 1) complete identity-rainbow 2) Non-Identitiy- X 3) Partial Identity-spur
for fungal diseases
Which molecules are opsonins?
Which molecules are anaphylatoxnis? What do they do?
C5a > C3a > C4a
degranulation of mast cells and release of histamine/vasoactive
Which molecules are for margination? What do they do?
allows WBCs to adhere to vessels
Which is for chemotaxis?
C5a > C3a
What is the function of the membrane attack complex?
permeablizing membranes by adding pores to break it down via osmotic pressure
Which molecules regulate vascular tone?
How are immune complexes removed in the complement cascade?
in plasma: via RBCs (via CR1)
in liver: phags
Describe the stains of basopphils, eosinophils, and neutrophils
basophil: dies w basic dyes
eosinophil: dyes w acid dyes
neutro: noes not stain w either
What are cells of the mononuclear phagocytic system?
monocytes, macrophages and their derivatives
What is the main signal to activate monocytes for phagocytosis?
What activates M1 macrophages?
what do they secrete?
IFN-gamma, TLR ligands
secrete IL-1beta, IL-6, TNF
What activates M2 macrophages? What immune responses are they involved in?
activated by IL-4, IL-13
parasitic immunity, allergies, wounds, tissue remodel
What are some positive chemotactic signals?
Proinflamm. cytokines:IL1, TNF-a
LTB4 (lipoxygenation/arach acid)
What can cytotixic chemo drugs induce?
What are the 4 stages of phagosytosis?
name some adherence molecules for phagocytosis
Fc of Abs (IgG1, IgG3)
What are the 3 mechanisms for digestion in phagocytosis?
1. Respiratory burst
2. phagosome-lysosome fusion
3. Toxic nitrogen oxides
Describe Respiratory burst
superoxide formed via NADPH oxidase
H2O2 formed via superoxide dismutase
OCl- formed via myeloperoxidase
Describe phagosome-lysosome fusion
lysosomes from granules
defensins and protegrins disrupt mmbrane
lactoferrin chelates iron
Describe toxic nitrogen oxides
the cNOS and iNOS pathways produce NO.
No inhibits iron enzymes and damages pathogen DNA.
(iNOS and resp burst form peroxynitrite)
What are the main cytokines that induce inflammation?
Which cytokines induce fever?
Which receptors/ligands are involved in rolling adhesion?
sialyl_Lewisx on the neutrophil:
E-selectins on endothelials
Which receptors/ligands are involved in tight binding?
integrins on neutrophil:
ICAM-1 on endothelials
Which receptors/ligands are involved in diapedesis?
integrins on neutrophil:
Which complement pathway inhibitors can cause meningitis?
What cels are the major producers of IFN-gamma?
CD4 helper T cells
What type of surface oplarity of bacteria enhance phagocytosis?
hydrophobic surfaces enhance phagocytosis
ex: M. tuberculosis
ex: s. pneumoniae
What is the acute phase response?
a systemic resopnse to local inlammation
increased hormone (ACTH)
acute phase proteins
name some actue phase proteins
What can an elevated CRP level indicate?
unstable coronary artery disease
if in healthy: higher risk of CV disease
What is ESR?
erythrocyte sedimentation rate
Bigrinogen reduces charge on RBC so they clump.
ESR~ level of inflamm response
TB, tissue necrosis, rheumatic, MI, malignancy
What is the hallmark of local acute response?
influx of PMNs
What are the 3 enzyme cascades that are activated when endothelial cells are damaged?
blood clotting/kinin system
What are matrix metalloproteinases?
degrade ECM proteins so free moveement of inflammatroy cells can occur
Describe the effedct of adenosine in inflammation
A1 receptor: enhances inflammation
-activated at low concentrations
A2 receptor: suppresses inflammation
-activated at high concentrations
What is the hallmark of chronic inflammation?
accumulation/activation of macrophages
enlargement and replacement of normal tissue
M1 center, M2 periph