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Core 2 Immunology
Core 2 Immunology
176
Immunology
Graduate
10/11/2011

Additional Immunology Flashcards

 


 

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Term
Mast Cell
Definition
resides in tissues, granulse of histamine and IgE, distinct lineage from HSCs
Term
NK cells
Definition
non-antigen-specific, lyse infected self cells, activate macrophages, NOT THE SAME AS NKT CELLS!
Term
neutrophils
Definition
most abundant leukocytes, phagocytose, also called polymorphonuclear leukocytes
Term
Lymph node outermost cortex
Definition
B cell proliferation, divided into follicles
Term
Lymph node paracortex
Definition
T cells
Term
Lymph node germinal centers
Definition
subdivision of a secondary lymphoid follicle, where intense B cell proliferation happens
Term
Lymph node medullary cords
Definition
macrophages and plasma cells (APCs)
Term
Primary lymphoid follicles
Definition
mostly B cells
Term
Where does the spleen get antigens from?
Definition
bloodstream
Term
Where do lymph nodes get antigens from?
Definition
lymph
Term
IgA
Definition
released by plasma cells in lamina propria of mucosal tissues, secreted into lumen of gut, also found in milk, secreted as dimer. found as monomer in blood.
Term
cytokines
Definition
soluble proteins that target cell receptors, eg: Interleukins, interferons, TNFs, TGFs
Term
Chemokines
Definition
induce lymphocyte migration, share receptor with HIV
Term
B defensins
Definition
in skin, peptide that acts like ABs, innate immunity
Term
Complement
Definition
circulates as inactive precursors, cascade leads to opsonization
Term
Costimulation
Definition
Naive lymphocytes need two signals, memory cells don't.
Term
Innate immunity receptor classes
Definition
Toll Like Receptors (TLRs), N-formyl methionyl receptors, Mannose receptors
Term
PAMPs
Definition
Pathogen associated molecular pattern, recognized by innate immunity
Term
DAMPs
Definition
Damage associated molecular patterns, non-infections inflammatory response, e.g. heat shock proteins, HMGB1, ATP, uric acid, heparin sulfate, DNA
Term
Receptors for HMGB1
Definition
TLR2, TLR4, RAGE
Term
Structures reconized by IIS
Definition
LPS/endotoxin, terminal mannose of glycoproteins, dsRNA, unmethylated CpG nucleotides
Term
principal functions if IIS
Definition
activation of AIS, inflammation and anti-viral defense
Term
TLR-1, -2, -6 ligands
Definition
peptidoglycan, lipoprotein, lipotechoic acid, etc.
Term
TLR-4 ligands
Definition
LPS, fungal mannans, viral envelope ptns.
Term
TLR-5 ligands
Definition
bacterial flagellin
Term
TLR-3, -7, -8, -9 ligands
Definition
microbial nucleic acids (ssRNA, unmethylated CpG dinucleotides)
Term
Defensins
Definition
29-34 AA ptns, cysteine rich, present in neutrophil granules, released in response to IL-1 and TNF, kill bacteria and fungi
Term
cryptocidins
Definition
produced in intestinal epithelium, locally sterilize lumen in crypts of intestines
Term
normal Neutrophil count per cubic mm
Definition
4000-10000
Term
Kupfer cells
Definition
liver differentiated monocytes
Term
Alveolar macrophages
Definition
lung differentiated monocytes
Term
Osteoclasts
Definition
bone differentiated monocytes
Term
What causes rolling?
Definition
resident APCs ingest pg, release cytokines--> endothelial cells produce selectins, ligand for integrins, and chemokines--> blood leukocytes bind weakly to selectins--> blood leukocytes stop when they reach integrins and migrate in.
Term
Inflammation
Definition
accumulation of leukocytes, vascular dilation, increased vascular permeability
Term
Leukocyte adhesion deficiency
Definition
heritable deficiency of integrins and/or selectins--> increased susceptibility to infection
Term
How are phagocytosed organisms killed?
Definition
fusion of lysosomes with phagosomes, production of ROIs and NO
Term
Dendritic cells
Definition
Antigen presenting cells, produce cytokines that activate leukocytes
Term
NK cells produce___
Definition
IFN-gamma (macrophage activating cytokine)
Term
What activates NK cells and how?
Definition
Macrophages, with IL-12
Term
How do NK cells kill?
Definition
discharge granules with perforins, also induce apoptosis
Term
MHC I
Definition
expressed on nearly all host cells, inhibits NK cells, absence activates NK cells.
Term
3 ways complement cascade can be activated?
Definition
alternative pathway (AB independent), Classical pathway (AB mediated), or Lectin pathway (Mannose binding lectin)
Term
2 cytokines that function in innate & adaptive immunity?
Definition
TGF-Beta and IFN-gamma
Term
TNF
Definition
comes from MPs, T cells, causes inflammation, fever, apoptosis, activates NPs
Term
Interleukin-1
Definition
comes from MPs, endothelial and some epithelial cells, causes inflammation, fever, Th-17 differentiation
Term
chemokines
Definition
comes from MPs, dendritic cells, endothelial cells, T cells, fibroblasts, platelets, increases integrin affinity and chemotaxis
Term
IL-12
Definition
Comes from Dendritic cells and MPs, increases IFN-g production and cytotoxic activity, TH-1 differentiation. Infected MPs produce this to get them killed.
Term
IFN-gamma
Definition
comes from T cells and NK cells, activates MPs and stimulates some AB responses
Term
IFN-alpha
Definition
comes from dendritic cells and MPs, anti-viral state, increased MHC 1, activates NK cells, a type I IFN
Term
IFN-beta
Definition
comes from fibroblasts, causes antiviral state, increased MHC-1, activates NK cells, a type I IFN
Term
Mannose binding lectin
Definition
binds bacteruial carbs, targets for phagocytosis and/or complement cascade
Term
C-reactive protein (CRP)
Definition
binds phosphocholine on microbes, targets for phagocytosis by MPs
Term
Acute phase response
Definition
elevated plasma levels of many proteins in response to infection
Term
Pneumococcus adaptation to IIS?
Definition
capsular polysaccharide inhibits phagocytosis
Term
staphylococci adaptation to IIS?
Definition
produces catalase to breakdown ROIs
Term
Neisseria meningitides adaptation to IIS?
Definition
sialic acid expression inhibits C3 and C5 convertases in complement cascade
Term
Streptococcus adaptation to IIS?
Definition
M protein blocks C3 binding to organism, C3b binding to complement receptors
Term
Pseudomonas adaptation to IIS?
Definition
modified LPS resists peptide antibiotics
Term
humoral immune response
Definition
antobody and B cell mediated for blood borne microbes
Term
adjuvant
Definition
substance that elicits the same IIS reaction that a microbe would (vaccines need this)
Term
Describe B cell antigen receptors
Definition
membrane bound antibodies
Term
What do B cell antigen receptors recognize?
Definition
a wide range of macromolecules in soluble and cell-surface-associated form
Term
Describe T cell receptors
Definition
membrane bound receptor, recognizes only small peptide fragments bound to MHC
Term
Determines graft rejection
Definition
HLA
Term
CD8 T cells recognize which MHC and which pathogens?
Definition
MHC I, cytosolic polypeptides degraded by proteasome, viral antigens
Term
CD4 T cells recognize which MHC and which pathogens?
Definition
MHC II, vesicular peptides
Term
CD8 T cells differentiate into?
Definition
Cytotoxic T cells
Term
MHC I expressed by which cells?
Definition
All but RBCs
Term
MHC II expressed by which cells?
Definition
APCs, also thymus
Term
MHC II structure?
Definition
a1,a2,B1,B2, 2 transmembrane domains
Term
MHC I structure?
Definition
a1,a2,a3, B2 microglobulin, 1 transmembrane domain
Term
How do cytosolic polypeptides get from proteasome to RER?
Definition
Transporter for Antigen Processing (TAP)
Term
TAP allows which MHC to bind antigen?
Definition
MHC I
Term
Invariant chain
Definition
prevents MHC II from binding to antigen until it is fused with endocytic vesicle
Term
Cross presentation
Definition
antigen-presenting cells can take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells. Important for viruses that don't infect APCs and tumors.
Term
HLA-DM
Definition
helps MHC II degrade invariant chain, bind ag. in endosome
Term
location of MHC I polymorphism
Definition
mostly in the peptide binding cleft. Structurally significant regions are well conserved.
Term
hFcRn
Definition
protein shaped like MHC I but not coded on MHC, peptide binding cleft is closed, transports IgG across placenta, maintains adult [IgG] by recycling endocytosed IgG to plasma
Term
CDI
Definition
binds glycolipids for presentation to T cells and NKT cells, deep narrow cleft, not polymorphic, not in MHC
Term
HIV adaptation to MHC I
Definition
enhances internalization of membrane MHC I
Term
HSV adaptation to MHC I
Definition
inhibits TAP
Term
HCMV adaptation to MHC I
Definition
promotes MHC I degradation in ER
Term
Adenovirus adaptation to MHC I
Definition
delays MHC I trafficking to membrane
Term
papain cleavage of IgG
Definition
breaks into two Fab fragments (fragment antigen binding) and one Fc fragment (fragment crystallyzable)
Term
kappa and lambda chains
Definition
light chain loci of Ig; 65:35 ratio is normal
Term
Ig light chain gene segments
Definition
V, J, and C recombine
Term
Ig Heavy chain gene segments
Definition
V,D, J, and C segments recombine
Term
when does recombination occur?
Definition
Before B or T cells encounter antigen
Term
most variable region of Ig and TCR genes and why
Definition
CDR3, due to imprecise cutting and joining of DNA and addition/deletion of nucleotides between gene segments during goining
Term
epitope
Definition
site recognized on antigen. AKA antigen determinant
Term
structure of IgG
Definition
Two heavy chains, two light chains, held together by disulfide bonds
Term
Ig heavy chain structure
Definition
three constant regions (C1,2,3) and one V region
Term
Ig light chain structure
Definition
One constant region, CL, and one variable region, VL
Term
scFv
Definition
single chain variable fragment: a fusion protein of the variable regions of the heavy and light chains; the antigen binding site
Term
TCR structure
Definition
2 transmembrane domains, two alpha and two beta regions, resembles Fab of Ig, held together by disulfide bonds
Term
4 mechanisms of generationg diversity for ag. receptors
Definition
1.multiple gene segments in germline 2.combinatorial association: VDJ and VJ joining 3. Random assortment of H/L and Va/VB chains 4. junctional diversity
Term
TCR alpha gene segments
Definition
V and J segments recombine with C
Term
TCR beta gene segments
Definition
V,D, and J segments recombine with C
Term
cross reaction of Ig example
Definition
antibodies against M protein on group A strep also attack heart muscle causing rheumatic fever
Term
TCR cross reactivity example
Definition
Multiple sclerosis: some patients have a TCR that binds both Epstein Barr virus peptide and a myelin protein
Term
Somatic hypermutation: which cells, when, why, where
Definition
B cells, after encountering ag., to increase binding affinity, in germinal centers of lymph nodes
Term
AID
Definition
Activation Induced cytidine Deaminase, converts cytidine into uridine, completely randomly. B cell then has to attempt repair, which is error prone--> variability. Involved in somatic hypermutation and isotype switching
Term
sequence of TCR recombination
Definition
Beta chain is recombined until functional protein can be combined with surrogate alpha chain. When complete, beta chain is set and alpha chain recombination begins.
Term
sequence of T cell CD development
Definition
double negative, large active double positive, small resting double positive (apoptosis for >95%), single positive CD4 or CD8
Term
Positive selection of T cells
Definition
T cells in the thymus that cannot bind either MHC I or II will not receive survival signals and will die.
Term
Negative selection of T cells
Definition
T cells in thymus that bind MHC too strongly will receive signal to die, preventing binding to self.
Term
sequence of B cell Ig rearrangement
Definition
germline DNA--> Heavy chain D-J--> V-DJ--> HC binds surrogate LC and goes to membrane--> proliferation--> LC V-J until functional Ig is made (or cell dies)
Term
Ig allelic exclusion
Definition
each B cell only expresses one Ig receptor
Term
receptor editing
Definition
if a B cell Ig binds self, it dies or produces a new LC with new specificity
Term
significance of aberrant kappa/lambda LC ratio
Definition
one line of cells may be proliferating too much, potentially malignant
Term
TCR allelic exclusion
Definition
Beta chain is subject to allelic exclusion, alpha chain is technically not
Term
gamma/delta TCRs
Definition
abundant in epithelia, recognize both protein and non-protein ag.s on non-classical MHCs
Term
IgM
Definition
First Ig expressed by developing B cells with μ constant region, membrane bound, can form pentamer w/ J chain
Term
IgD
Definition
Second Ig expressed by developing B cells, alternative splicing of HC for IgM makes δ chain. Membrane bound, co-present with IgM on naive B cells. Secreted in resp. tract.
Term
avidity
Definition
total strength of binding at MULTIPLE sites
Term
affinity
Definition
strength of binding at a SINGLE site
Term
IgG
Definition
most abundant, longest lasting Ig. neutralizes toxins + viruses, opsonizes pathogens, preps for NK cells to kill, activates complement, cross placenta via active transport
Term
IgE
Definition
low concentration, binds mast cells. When antigen encountered, triggers degranulation and inflammation-->allergic rxn or response to parasite. Activates eosinophils too.
Term
Isotype switching
Definition
A naiive B cell may switch from IgM/IgD to IgG, IgA, or IgE. Always successful, after ag. encounter, involves AID, cytokines from CD4 T cells determine which class.
Term
IFN-gamma--> which Ig class?
Definition
IgG
Term
IL-4 --> which Ig class?
Definition
IgE
Term
TGF-Beta --> which Ig class?
Definition
IgA
Term
Determines whether an Ig protein is secreted or membrane bound
Definition
RNA processing (splicing). All isotypes can be either.
Term
Classical Complement Pathway (Adaptive)
Definition
C1q binds 2+ antibodies (IgM or IgG) --> C4bC2bC3b
Term
Alternative Complement Pathway (Innate)
Definition
C3b binds microbe --> factor D cleaves Factor B -->> C3bBbC3b
Term
Complement terminal pathway
Definition
C5 cleaved to C5a + C5b; C5b + C6 + C7 --> C8 joins and penetratees membrane --> C9 makes extra dead: C5a --> inflammation
Term
Covalent regulation of complement
Definition
C4b and C3b will get quickly hydrolized if they don't bind antibody or complement quickly
Term
Th1 turned on by?
Definition
IFN-y, IL-12 (Tbet, Stat4 TFs)
Term
Th1 funcitons
Definition
Secretes IFNy; Control intracellular pathogens, tumors, mediate transplant rejections, make macrophages more active by secreting IFNy
Term
Th2 turned on by?
Definition
IL-4 (Gata3, Stat 6 TFs)
Term
Th2 functions
Definition
Secretes IL-4 & IL-5; Induce B cells to switch classes & proliferate; mediated by CD40L, fight parasites; mediates allergic dx & asthma
Term
Th17 turned on by?
Definition
TGFB + IL6 (in absence of IFN, IL-12, IL-4)
Term
Th17 functions
Definition
Recruit & stimulate neutrophils; important for antibacterial & antifungal infections
Term
Treg turned on by?
Definition
TGFB, IL-2 (FoxP3, Stat 5)
Term
Treg functions
Definition
secretes TGF-B, IL-10; Expresses CD25 (a IL-2R) which soaks up the IL-2 and takes it away from activating other Th's, B cells, and macrophages
Term
Lymph node organization
Definition
B cells: follicle (attracted there by chemokines)
Antibodies / mature B cells in germinal center of follicle
T cells in paracortex
Term
Naive T cell receptor
Definition
CCR7
-recognizes chemokines from lymph & spleen
Term
TNF
Definition
Source: macrophages, T cells Target: recruit neutrophils Synthesize acute phase proteins in liver cause inflammation & coagulation in endothelial cells (upregulate selectins integrins) increase muscle & fat catabolism -> cachexia
Term
IL-1
Definition
Source: macrophages, endothelial cells
Target:
recruit neutrophils
upregulation of selectins & integrins in endothelial cells
Term
Chemokines
Definition
source: macrophages & dendritic cells
Target: Increase integrin affinity of leukocytes for endothelial binding
Term
IL-12
Definition
Source: macrophages, dendritic cells
Target: NK cells, T cells
-Increase IFN-y production
Term
IFN-y
Definition
Source: NK cells, T cells
Target: activates macrophages
Term
IL-10
Definition
Source: Macrophages, dendritic cells, T cells
Target: inhibits IL-12 production & reduces expression of MHCII's (Suppresses inflammation)
Term
IFN-a & IFN-B
Definition
Source: alpha - dendritic & macrophages; beta - fibroblasts
Target: increase MHC I expression & activate NK cells
Term
IL-6
Definition
Source: Macrophages, endothelial cells ,T cells
Target: synthesis acute phase proteins in liver
Term
IL-15
Definition
Source: Macrophages
Target: NK cell & T cell proliferation
Term
IL-18
Definition
Source: macrophages
Target: Increase IFN-y production (From NK & T cells)
Term
TGF-B
Definition
Inhibits inflammation & promotes T-regs
Term
IL-8
Definition
chemotactic for neutrophils
Term
Acute phase response
Definition
Mannose binding lectin (MBL) - binds carbs to target them for phagocytosis
CRP - binds phosphocholine & targets for phagocytosis
Term
'Second signal' mechanism
Definition
T cells: Signal 1 = antigen
signal 2 = macrophages that encounter microbe express B7, which binds to CD28 receptor on naive T cell. IL-12 also produced to stimulate T cell differentiation & proliferation

B-cells: Microbe activates complement system - C3d becomes bound to microbe. B cells recognize antigen + C3d --> proliferation
Term
CCR7
Definition
Promotes entry into T cell zones of lymph nodes
-Expressed by immature dendritic cells after microbe capture, so that MHC can present to T cells
-Expressed by naive T cells so that they concentrate in one location as they circulate
-expressed by B cells after encountering antigen to move to margins & encounter Th cells
Term
Cross-presentation (cross-priming)
Definition
dendritic cells ingest other infected cells & present antigen to CD4 & CD8 T cells
Term
RAG
Definition
responsible for the recombination & cuts out all the unneeded sequences in VDJ / VJ recombination
Term
TdT
Definition
inserts new nucleotide sequences into sites of V(D)J recombination
Term
Ig alpha & Ig beta
Definition
proteins associated w membrane Ig that mediate signaling functions
Term
CD3 & zeta
Definition
Associated w TCRs to mediate signaling functions
Term
5 things that generate diversity in Ig & TCRs
Definition
1. Multiple VH(β) and VL(α) genes in the germline
2. Combinatorial association - VDJ and VJ
3. Random assortment of heavy and light chains
4. Junctional diversity – CDR3, RAG enzyme, TdT
5. Somatic mutation – B cells only (after Ag exposure)
Term
hyper IgM immunodeficiency
Definition
x-linked recessive
-lack CD40L, so can't activate B cells to switch classes; only get IgM production
Term
C1, C4, C2, C3 deficiency
Definition
Immune complex diseases, increased bacteria susceptibility
Term
C-5 deficiency
Definition
Neisseria meningitides
Term
C1 inhibitor deficiency
Definition
hereditary angioneurotic edema
Term
DAF / CD59 deficiency
Definition
paroxysmal noctural hemoglobinuria
Term
Treg gene & function
Definition
FoxP3
Produce IL-10 & TGF-Beta to inhibit Th1 & Th2
Term
IPEX
Definition
mutation in FoxP3 gene --> autoimmune disease in multiple organs
Term
Secretory eosinophil products
Definition
ROIs, collagenase, antigen presentation, cytokines, lipid mediators
Term
Mast Cells
Definition
Have FCeRI receptors (200,000) & need 10% bound for degranulation of heparin / histamine
Term
Allergy cytokine players
Definition
IL-4 --> B cell activation & switching to IgE
IL-5 --> Eosinophil growth
IL-13 --> affects lung smooth muscle directly
Term
Memory T cell receptors
Definition
IL-7R & CD45 (need IL-7 & IL-15 to stay alive)
Effector: CCR7 low
Central: CCR7 high
Term
Herd immunity
Definition
60-90% (depending on pathogen) of population needs to be vaccinated for whole population to receive benefit
Term
Features of an effective vaccine
Definition
Safe, perceived as safe, protective for at least a few years, low cost, stable, easy to administer
Term
Attenuated virus
Definition
ex: MMR, Sabin polio vaccine, varicella zoster
Live virus that mimics real thing but lacks some central component.
Produces long-lasting immunity
Term
Inactivated Virus
Definition
Virus is dead. Not as effective
ex: Salk polio vaccine; tDAP
Term
Conjugated vaccine
Definition
Ex: H influenza
bacterial polysaccharide is attached to a protein toxin so that both antibodies & CD8 memory cells are made. And children can't make t-independent antibodies well, so need T cell involvement
Term
Subunit vaccine
Definition
composed of capsid / envelope protein of a virus
Ex: Hep B, HPV
Term
Antiserum vaccine
Definition
Antivenom is given as an antibody in an emergency since you don't have time to spare to mount immune response. Passive immunity
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