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Immuno Test 1
Innate and Adaptive Immunity
141
Immunology
Professional
09/17/2011

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Term
Streptacoccus Equi "strangles"
Definition
Gram positive
extracellular
Term
inate immune system activation time/ details
Definition
0-2 hrs --> 2-5 days depending on the pathogen
not pathogen specific
no memory
Term
inate immune response
Definition
rapid response
fixed
limited number of specificities
constant during response
Term
leukocyte that provides primary defense in inate immunity
Definition
neutrophils
Term
antigen
Definition
any stucture that can be recognized by the adaptive immune system
most commonly proteins and peptides
Term
types of pathogens
Definition
bacteria, virus, protozoa, worms
Term
mechanical barriers of skin, GI, Resp, UG tract and eyes
Definition
flow of fluid
Term
chemical barriers to infection
Definition
defensins
Term
microbiological barriers to infection
Definition
normal flora of the skin, gi, resp, ug and eyes
Term
in absense of barriers burn patients
Definition
infection through skin, no chem, mechanical or microbiological defense
Term
ciliary dyskinesia
Definition
cillia cant move so no mechanical flow of fluids/pathogens out of resp or UG tract
Term
Strangles binds to what on the epithelium
Definition
fibronectin and fibrinogen
Term
Humoral components of innate immune response
Definition
compliment, defensins, CRP
Term
First defense mech mobilized in innate immune response
Definition
compliment cascade
Term
compliment cascade
Definition
enzymatic cascade
multiple compliment proteins
proteins made in the liver
Term
end result of compliment cascade
Definition
cleavage of C3
Term
4 things compliment activation accomplishes
Definition
opsinization of pathogens (coats pathogens so they are more easily recognized by phagocytic cells)
Killing of pathogens
Recruitment of Inflammatory cells
Disposition of immune complexes
Term
complement binding to a cell surface is called...
Definition
Fixation
Term
Compliment activation end results (2)
Definition
recruit inflammatory cells
Bind to Cell surface
Term
Alternative complement pathway
Definition
first to act
pathogen surface creates local environment conducive to complement activation
cleavage of C3 into C3B and C3A
Term
C3B convertase
Definition
formed by initial formed by C3B molecule, plus another proeint called protein B

amplifies the amount of C3B on cell surface
Term
human cells protected by expression of which 2 molecules on self cell surface
Definition
DAF and MCP
Term
what does C3B do on the surface of a pathogen
Definition
Opsinization
initiates the formation of the MAC by activation of C5
Term
Membrane attack complex
Definition
creates a hole in the organism and kills it via recruitment of C5
Term
What happens with no DAF
Definition
PNH (paroxysmal nocturnal Hemoglobinuria)
Term
C3a and C5a
Definition
anaphylotoxins
bind to mast cells causing them to degranulate
bind to endothelial cells, increasing vascular permiability
leads to increased migration of neutrophils out of vessels into tissues and serum out of vessels (more compliment)
Term
components of Mast cell
Definition
(histamine and TNFa)are components of
Term
Defensins
Definition
small molecules produced by epithelial cells throughout the body
these molecules bind to the membrane and disrupt its structure
other humoral component of the innate immune response
Term
CRP
Definition
serum protein produced in response to inflammation that can activate compliment the the CLASSICAL PATHWAY
also called an acute phase protein
Term
of all pathogens, extracellular bacteria are most affected by this type of defense mechanisms
Definition
humoral defenses
Term
Mast cells release their contents when encountered by
Definition
C3a and C5a
Term
Mast cell granules include
Definition
Histamine, TNFa
Term
actions of histamine
Definition
increased vascular permiability
vasodialation
smooth muscle contraction in the bronchiles and intestine
Term
TNFa receptor on endothelial cell does..
Definition
upregulates adhesion molecules to attract circulating neutrophils
Term
Mast cells synthesize (not granular components)
and what do they do
Definition
Leukotrines and prostoglandans from membrane phospholipids
increased vasc. perm.
sm. mm. contraction
mucous production
Term
events in strangles infection
Definition
bacteria enter sub-mucosa
the alternative compliment pathway is activated
bacteria are opsonized by C3b
MAC kills some bacteria
C3a and C5a activate mast cells and cause vasodialation
mast cell products also cause vasodialation, increased vascular permeability, vascular leakage, and mucous production
Term
Macrophage
Definition
tissue based lymphocyte
release pro-inflammatory cytokines upon encounter with pathogen
Term
TLR location and what they recognize
Definition
recognize PAMP which are mostly non protein, non-mammalian molecules

Recognize nucleic acids , and lipoprotiens on bac and protozoa
Term
TLRs found on cell surface recognize
Definition
Sugars (carbs) and lipids
Term
TLRs inside cell (on endosomes) recognize
Definition
nucleic acids and lipoprotiens
Term
Role of activated TLR
Definition
causes degredation of IkB by phosphoralation allowing NFkB to be translocated to the nucleus leading to upregulation of pro-inflammatory cytokines
Term
IkB
Definition
holds NFkB in cytoplasm
Term
IL-1, IL6, and TNFa are...
Definition
cytokines cause many of the effects of inflammation.
activate vascular endothelium allowing neutrophils to enter an area of infection.
Responsible for Fever
Term
CXCL8
Definition
Chemokine
allows cells to move
Term
selectins
Definition
bind to carbs,
weak interactions (non covalent bonds)
bind to addressins
Term
addressins
Definition
carb ligand for selectin
diff selectins on endothelium of diff sites (synovial vessels and mucosal vessels)
Term
integrins
Definition
bind Ig family proteins
stronger than selectin bonds
Term
Important integrins / integrin complexes
Definition
CD18 and CD11 (a,b,c)
CD18 always bound to any one of the CD11
Term
what type of integrins are the CD18/CD11(a,b,c)
Definition
B2 integrins
Term
deficiency in B2 integrins will cause
Definition
non healing ulcers caused by
Term
Leukocyte Adhesion Deficiency
Definition
DZ that affects cows, dogs, people
CD 18 not expressed
Neutrophils can no longer adhere firmly and migrate out of tissues
neutrophil counts in serum are very high
Term
process of intracellular killing of bacteria
Definition
phagocytosis of opsonized bacteria
phagosome fuzes with specific granules (lysozyme, defensins, myeloperoxidase, proteases, NADPH oxidase)
rise in PH of phagosome kills bac.
fuses with lysosome to create a phagolysosome and completely degrades bacterium
neutrophil dies by apoptosis and is phagocytosed by macrophage
Term
NADPH + 2 O2 -->
Definition
superoxide
(reactive oxygen intermediate)
Term
Reactive Oxygen Intermediates and why they are important
Definition
Superoxide and Hydrogen Peroxide
essential for defense against fungi and bacteria
without this can get chronic granulomatous disease and chronic infection with extracellular bac and fungi
Term
surface protiens of Parvo
Definition
VP2 and VP1
VP2 makes up 90% of the virus surface
Term
VP2 binds to
Definition
Transferrin receptor on host cell
Term
viruses are coated with
Definition
Proteins and glycoproteins coat these..
Term
Viral Surface proteins Do/Don't bind to surface TLRs
Definition
Dont!
Term
Intracellular TLR
Definition
recognize viral nucleic acids
Stimulates the translocation of NFkB
stimulates translocation of interferon response elements
Term
Production of type 1 interferon mediated by
Definition
Interferon response elements
Term
RIG-like receptors
Definition
Intracellular
recognize viral nucleic acids
stimulate the translocation of NFkB to the nuc.
Does the same thing a TLRs
Not located on endosomes (free floating in cyto)
Term
Action of type 1 interferons
Definition
different than interferon gamma
IFNb and multiple IFNa genes
IFNs bind to IFNRs in autocrine, paracrine fashion
these TFs induce the production of proteins that resist further viral infection
Term
How type 1 IFNs prevent further viral infection
Definition
interference with viral replication
interfere with viral protein synth
production of more interferon
activation of NK cells
Term
NK cells
Definition
large granular lymphocytes
circulating cells (same lineage as lymphs)
activated by T1 IFNs
Have receptors on their surface for proteins expressed on mammalian cells
Recongnize 2 types of ligands on mammalian cells
Healthy mammalian cells express higher levels of inhibiting ligands
Term
types of ligands on mammalian cells recognized by NK cells
Definition
Inhibiting ligands (MHC)
Activating Ligands (MIC)
Term
The response to viral infections Increases/decreases the expression of activating ligands
Definition
Increases!!
Term
MIC ligands
Definition
Activating ligand
expressed on intestinal epithelium
increased upon viral infection
Recognized by NKG2D protein on NK cell
Term
interaction btw NKG2d and MIC causes
Definition
NK cells release granule contents
perforin
granzyme
perforin and granzyme combine to kill the virally infected cell
Term
what cytokine activates NK cells
Definition
IL2
Term
NK cells produce increased amt of what when activated by IL2
Definition
type II interferon, IFNgamma
Term
similar function performed by antibodies and complement
Definition
opsonization and neutralization of bacteria/viruses
Term
by contrast with complement antibodies are/are not specific for a single pathogen
Definition
are
Term
describe antibody design for both B and Tcell receptor / antibody
Definition
both have constant and variable regions
bcell Rs and ABs are Y shaped,
Bcells have Heavy and Light chain
Tcells have alpha and beta chain
Bcells have either lambda or kappa light chains
Term
sequence of events in the lymph node
Definition
bcells are activated by encounter with antigen
beclls migrate to tcell area
tcells which recognize the same antigen help bcells to divide
bcells differentiate into plasma cells, which produce antibody
bcells differentiate into memory cells, which can be reactivated quickly
tcells differentiate into memory cells which can be reactivated quickly
Term
Heavy and light chains combine to form
Definition
antigen binding region (formed by)
Term
true or false
immunoglobulin is flexible and can bind antigen in a number of different conformations
Definition
True
Term
bond that holds Fab region to Fc region
Definition
disulfide bond
Term
Fab and Fc result from
Definition
proteolytic cleavage of Antibody by papain
Term
epitope
Definition
sequence of aa residues that bind to antibody binding complex on antibody
Term
linear epitope
Definition
sequence of amino acids that are in s linear fashion
Term
discontinuous epitope
Definition
antibody binds to amino acid sequence that is not in a linear fashion, tertiary structure... duh
Term
antibodies can to what?
Definition
proteins, carbs, DNA, lipids, metals and Stallions.
Term
types on non-covalent interactions between antibodies and their targets
Definition
Van der waals forces - weak interactions between non charged molecules
Hydrophobic interactions - non charged molecules
hydrogen bonds- e- oxygen, N, Fl. stronger than Vanderwaals, ph of environment changes this interaction

electrostatic - neg/pos, very strong
Term
polar aa participate in strong/weak electrostatic interactions
Definition
strong
Term
hydrophobic aa's participate in hydrophobic/hydrophillic interactions
Definition
hydrophobic
Term
the affinity of an antibody for its antigen depends on
Definition
the types of bonds between amino acids at the binding site.
the pH, temp, and ionic strength of the environment
Term
low temperatures decrease/increase the affinity of antigen-antibody interactions
Definition
increase
Term
low/high ph and low/high ionic strength can reduce the affinity of antigen-antibody interactions
Definition
low, high
Term
cold aggluitinin dz in dogs and people
Definition
peripheral blood at its lower temp has stronger non covalent interactions with antibodies
autoimmune dz, make ab's against RBC's
Term
interactions btw. antibody and antigen are mediated by
Definition
the aa in the antibody binding site (mediates)
Term
C gene encodes
Definition
constant region of antibody (is coded for by what)
Term
Describe the V,D,J genes
Definition
V for variable region
D for diversity (heavy chain only)
J for junctional
Term
three mechs that generate AB diversity
Definition
random combos of genes that encode the V portion of the AB (somatic recomb)

Junctional diversity through N-Linked addition of nucleotides

somatic hypermutation
Term
somatic recomb
Definition
random selection of VDJ genes when randomly placed together creates hundreds of thousands of different antibodies
Term
RAG
Definition
(recomb activating genes)
RAG1 and RAG2
enzymes that come together to recombine DNA by recognizing specific DNA sequences that flank the VDJ genes
Term
N-Linked addition
Definition
carried out by the enzyme TdT
additional nucleotides are added to the jxns between V and D, and D and J
Term
What are the different ABs
Definition
IgM, IgG, IgA, IgE, IgD

constant regions define which AB is produced
Term
IgM when secreted is....
Definition
a pentomer joined by disulfide bonds
binds w/ low affinity
secreted by naive b cells
Term
first gene downstream from the VDJ region
Definition
IgM
Term
how many C regions in people
Definition
8 regions in people
Term
Alternative RNA splicing in antibody production determines if
Definition
If IgM is going to be secreted or transmembrane
Term
Binding of IgM by antigen sends a signal to the B cell to
Definition
start dividing
Term
B cell receptor
Definition
IgM plus additional polypeptides spanning the membrane form this
Term
Plasma cell
Definition
final differentiation stage of Bcells
by def they are antibody secreting cells
All ABs produced by these cells have the same VDJ genes
Term
affinity maturation/somatic hypermutation
Definition
happens during DNA replication
needs Thelper cells
Mediated by AID (activation induced deaminase)
changes are introduced at random so they may result in increased or decreased affinity for the antigen
the higher the affinity, the stronger the signal to continue dividing
Term
AID
Definition
Activation induced deaminase
introduces nucleotide changes in the VDJ region, which results in aa changes in the antigen binding region
Term
avidity
Definition
the combined strength of multiple bond interactions (IgM has High avidity and low affinity because it has 10 weak binding sites as opposed to 2 strong binding sites)
Term
Where is IgA secreted
Definition
Accross mucosal surfaces
Term
purpose of IgE
Definition
activates mast cells
Term
purpose of IgG
Definition
patrols the extravascular sites among other fxns.
Term
Isotype switching
Definition
permanent change to the DNA
AID is responsible for removing the intervening C region genes

requires Tcell help
Term
which antibodies/cells stick around for a long time
Definition
IgG, IgA, Memory B cells
Term
CD4
Definition
Thelper cells
provide growth and activating factors for Bcells and other Tcells
required for isotype switching
requires cell-cell w/ cd4 and bcell
activate macrophages to allow them to kill intracellular organisms
Term
CD8
Definition
Tkiller cells
kill other cells that are infected with viruses and other intracellular pathogens
requires cell-cell interaction btw. the CD8 and infected cell
need to be activated by antigen
Term
Tcells only exert their effects when they are activated through...
Definition
Tcell receptor
Term
Tcell Receptor
Definition
tcell equivalent of antibody on Bcell, but..
only expressed on cell surface
it recognizes antigen in a diff form
sends a signal to the other tcell when it recognizes antigen
signal activates the tcell to perform its various functions
Term
Tcell receptor genes
Definition
the alpha chain resembles Ig light chains (Vand J genes only)
the beta chain resembles Ig Heavy chain (VDJ genes)
RAG proteins mediate recomb
Term
2 types of Tcell Receptors
Definition
alpha and beta
Term
How do Tcells recognize antigens
Definition
Cannot bind to free antigen
recognizes peptides found in the peptide binding groove of class I and class II MHC protiens
Term
Class I MHC molecules
Definition
expressed on all cells other than RBC
binds to peptides that are derived from proteins synthesized within the host cell
Term
Class II MHC
Definition
expressed primarily on antigen presenting cells (macrophages, bcells, dendritic cells, thymic epithelial cells)
binds to peptides that are taken in from outside the cell
Term
why can MHC molecules bind a wide variety of peptides
Definition
because only 2 aa residues stabilize the peptide in the groove.

2 polar aa's form H+ bonds anchor the peptide in the MHC, the remaining residues contact the Tcell receptor binding groove
Term
distance btw aa's to stabilize MHC (class I and II)
Definition
Class I = 8-10 aa residues
Class II = up to 20 aa residues because it extends beyond MHC mol
Term
how Class I MHC presents peptides
Definition
mRNA comes out of nucleus into cyto
proteins are synth'd by ribosomes
degredation by the proteosome into peptides
peptides transported to ER throuh TAP transporters
peptide is loaded onto class I MHC
peptide+MHC transported via golgi
(self and viral proteins can be loaded onto class I)
Term
How class II MHC presents antigen to surface
Definition
endocytosed/phagocytosed proteins/pathogens put into endosome
formation of endolysosome (lysosome has class II MHC in membrane)
proteolytic enzymes degrade proteins to peptides
peptides bind class II MHC
exocytosis puts MHC/peptide back onto surface
(anything can be loaded onto MHC including self proteins etc.)
Term
CD4 interacts with which MHC
Definition
Class II
Term
CD8 interacts with which MHC
Definition
Class I
Term
what happens when a Tcell Receptor is activated
Definition
Leads to Tcell proliferation via phosphorylation of ITAM (a CD3 Molecule)causing CD4/8 to bind to MHC complex.
this aids in further activation/proliferation of Tcell
Term
NF-AT
Definition
TF that when dephosphorylated via TCR activation is translocated to the nucleus and transcribes IL2 alpha chain
Term
IL-2 alpha chain
Definition
upregulated by NF-AT
binds to IL-2 receptor to induce Tcell proliferation
autocrine or paracrine
Term
cyclosporine affect
Definition
prevents NF-AT dephosphorylation and subsequent translocation to the nucleus
= no IL-2 alpha chain
used to prevent transplant rejection
Term
Tcells are only activated when in contact with which antigen presenting cell
Definition
dendritic cell
Term
2 basic fxns of dendritic cells
Definition
pick up antigen at the site of infection and carry it to the lymph nodes

only dendritic cells carry antigen to the draining lymph nodes

to present antigen to Tcell in the lymph node and activate them
Term
where do dendritic cells and macrophages pick up antigen and how
Definition
in the periphery

through phagocytosis and micropinocytosis
Term
type of naive tcell activated upon endocytosis and micropinocytosis
Definition
CD4
Term
Dendritic cell activation results in
Definition
increased expression of class II MHC
increased expression of ICAM
increased expression of CCL7 and CCL21 which attract the dendritic cell to the lymph node
Production of various cytokines affecting Tcell differentiation including IL-6 + 12
increased expression of costimulatory molecules CD80 and CD86 (B7.1/2
Term
Dendritic cells will only activate naive Tcells if what is expressed
Definition
CD80 (B7 molecule) that binds to CD28 on the naive Tcell
Term
what happens if a tcell encounters peptide but no CD28 binding
Definition
the tcell is anergized (non fxnal)
Term
CD40
Definition
ligand expressed on the tcell binds to cd40 on the bcell
responsible for isotype switching and somatic hypermutation
Term
activated tcell produces cytokines that stimulate bcell growth, what else do those cytokines do
Definition
they determine which class of antibody is produced
Term
patients lacking CD40 or CD40ligand will not be able to make antibodies other than..
Definition
IgM and it will be low affinity because CD40 activates isotype switching and somatic hypermutation.
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