IMMUNO Flashcards
(110 cards)
1
Q
In Mature, Naive Tcells at rest
What Cds do they express/are associated with?
What MHC/HLA class?
What TCR complex molecules are associated?
What are the main adhesion molecules?
and the main chemokine receptor?
A
CD4+, 8+, 28+ Class 1 CD3 and zeta LFA-1 and VLA-4 CCR7
2
Q
Where do MN Tcells habit and where are they activated?
and What activates them
A
Blood and lymph organs
Inflammation, DCs, and Bcells+ Macros (+Tmemory)
- CD4+ can in turn + Bs and Macros
3
Q
What are DCs when they are activated?
What adhesive marker becomes up regulated?
What CD expression is increased?
Where do they then go after +?
A
In the periphery, then they travel to the secondary lymph tissue as they mature via the High endotheliuim venules HEV
- CCR7–to bind and travel
- CD80 (B7)
4
Q
Tcell Receptors bind to which ligand? and cause what? L selectin LFA-1 CCR7 E and P selectin (+) LFA1 (beta2) and VLA4 (beta1 integrin) CXCR3
A
L-secectin ligand: weak adhesion of N Tcells in high endothelial venule in lymph node
- ICAM1: arrest on HEV
- CCL19 or CCL21: activate integrins and chemotaxis
- E or P selectin
- ICAM1 or VCAM1: arrest on endothelium
- CXCL10
5
Q
Where do B and Tcells proliferate?
A
Lymph Nodes (why they swell)
6
Q
Surface molecules: What function and what ligand if any? Cd3 zeta Cd4 8 28 LFA1 CTLA4 PD
A
none: signal transduction
none: signal transduction
MHC II: st
MHC I: st
B7: st on Ag presenters
ICAM1: adhesion/st
B7: inhibition on Ag presenters (such as T reg cells)
PD-L1 /2: Inhibition on Ag presenters, tissue cells, and tumor cells
7
Q
What type of Tcells do CD 4 and 8 work on
A
Helpers (produce cytokines) and cytotoxic Ts
8
Q
When a Tcell recognizes an Ag, what happens?
A
Integrin (ICAM) changes conformation increasing affinity and causing clustering
9
Q
What is the first signal for Tcell Activation, and what gets increased expression?
A
MHC/peptide complex binds to TCR
- CD40L in Tcells–> CD40 constitutively on APCs
- B7 on APCs–> CD28 constitutively on T
10
Q
CD80 is the same as
A
B7
11
Q
Intracellular signaling involving what two key things, leads to protein synthesis and the production of what major cytokines?
A
ITAM and ZAP70
-NF kappa B, and AP1
12
Q
What is it called when a non-activated Tcell becomes unresponsive?
A
Anergy (Anergic)
13
Q
What is the principle action and cell source for each cytokine? -IL2 IFN gamma -IL4 -IL5 -IL17 -IL22 -TGF beta/ IL10 -IL12
A
-Tcell proliferation and Tregulatory survival in +Tcells
-Macro activation in CD4 and 8+ Ts, and in NKs
Also stimulates HLAII and B7 expression
-Bcell switching to IgE, on CD4+ Ts and Mast cells
secreted by Th2
-+ of Eosinophils in CD4+ Ts, Mast, and innate lymphoid cells
secreted by Th2
- Stimulate acute inflammation in CD4 Ts and others
- Maintain Epithelial barrier function in CD4 Ts, NKs, and innate lymph cells
- Inhibit Tcell + and aid the differentiation of reg Ts in CD4/many other types
- Thelper proliferation
14
Q
What is the IL2 alpha chain equivalent to, and what does it promote when it binds to IL2 (autocrine signal)?
A
CD25
-Tcell proliferation and differentiation
15
Q
What binds to S1PR and what happens in result?
A
CD69 (short term) and the binding impairs migration of the Tcell from node–>periphery till about day 5
16
Q
Once a Tcell is +, CCR7 decreases inversely to what? and where does the Tcell travel to? to meet what?
A
CXCR5 increases
travels to the folicular area from the medulla to meet a Bcell
17
Q
In T regulatory cells, what cytokines are they influenced by mainly? What do they secrete? and What is their novel transcription factor?
A
IL2 and TGF beta
-IL10 and TGF beta
-FOXp3
(act to suppress immune response and maintain homeostasis)
18
Q
What kind of Tcell is found mostly in the gut (small number) and must have a Ag while not recognizing many peptides?
A
Gamma Delta Tcells
19
Q
An effector T cell can bind to an Ag without need of co-stim by what interaction?
A
B7(CD80)—CD28
20
Q
What do Thelper-1 (bact and viruses) cells respond to? what do they secrete? and what is their novel Transcription factor?
A
IL12 and IFN gamma
- IL2 and IFN gamma
- T bet
21
Q
What do Thelper-2 (helminths/extracell parasites) cells respond to? what do they secrete? and what is their novel Transcription factor?
A
IL4
- IL4, IL5, IL13
- GATA3
22
Q
Key functions of Th2’s?
A
Stimulate IgE (Ab), mast cells, and eosinophils vs helminths Also IgA and aboves for atopic disease and mucus production
23
Q
What Interleukins activate inflammation in Macrophage 1s and which are anti-inflamm in alternatively activated Macro 2s
A
IL1, 12, 23
vs
Il-10, TGF beta
24
Q
What stimulates proliferation of Th 17, what does it do? What’s its novel TF? what does it secrete?
A
bacteria and fungus/ IL1 and IL6
- Induces inflamm and leukocytes (neutrophils)
- ROR gamma t
- IL-17, and 22
25
Why won't every effector T that enteres an area be specific for that Ag?
Selectins and Integrins get Tcells interested in an Ag but are not specific
26
What are the two cytotoxic T ways of killing?
1: deliver Granular proteins (granzymes-that +caspases and Perforin) to the surface of infected cell
2: Use FasL-on T and Fas- on target (CD95) induction of apoptosis
27
What type of cells produce IFN alpha and beta (associated with apoptosis)
Type 1 IFNs: NKs and DCs
| viruses
28
```
NKs
What kinds of cells do they try and kill? Using What?
What are they enhanced by?
What inhibits them?
What are their surface markers?
```
Tumor and viral infected using granzymes and perforin
- IFN alpha and beta, and IL12
- MHC class I
- CD 56 and 16
29
What are the two types of Mature, Naive Bcells?
B1: in Mucosa- have limited Ag specifity
B2:
Follicular: re-circulating (the majority)
Marginal: in the spleen: blood-borne polysacc Ags
30
What BCRs are present on M,N Bcells?
Which HLA class?
Other important CDs
IgM, D, Alpha, and Beta
CD: 19, 81, 21(CR2)
Class II and I (nucleated)
CD 40 and 20
31
What presents Ags to the B cells in the Follicle?
follicular Dendritic cells
| -without an Ag, B cell will die in weeks
32
How many signals does a B cell need to activate (or a T)?
2 signals
33
During the First Bcell activation signal, what gets phosphorylated? and what is the whole process similar to?
SyK (would be zeta in T)
Similar to T cell activation
34
What triggers the biochemical signals that are converted by receptor-associated signal moleucles by cross linking 2 or more BCRs
Ag-induced clustering of membrane bound Ig receptors
--Which have an alpha and beta proteins linked to ITAM (immunoreceptor tyrosine activation motif) that actually signals
(1st is not sufficient to activate fully)
35
What complement protein binds to ... receptor that is attached to CD 19 and 81 that help deliver activation signals to the B cell?
C3-d
| the CR2 receptor (this provides cross linkage for signaling)
36
The first B cell act signal:
What is secreted?
What are the consequences?
IgM in low levels
Increased survival/proliferation (mitosis and clonal expansion
interaction with helper Ts (if Ag is a protein);
responsiveness to cytokines;
migrations from follicle to T cell areas (edge of follicular zone where they meet the Ts- the pheripheral lymph organs)
37
What are the two ways the second B cell activation signal can happen?
By Ag independence
or Ag Dependence: Ag is presented on B cell surface and binds to Tcell receptor...
B7 and CD40 on B- associate with CD28 and CD40L on the Helper T----all 3 must occur before the cytokine signals released by T (activation of B)--> proliferation
38
After activation of B cell--> what do the cytokines from Ts modulate? what enzyme becomes expressed? and what is induced?
They modulate class switching (Abs of different heavy chain isotypes)
- enzyme AID (act induced deaminase)-makes nucleotides susceptible to cleavage/recombination
- ->CD40 signal induced AID... so VDJ moves to a C region and a new heavy chain is produced
-Affinity maturation aka: somatic hypermutation-a cellular mechanism by which the immune system adapts to the new foreign elements that confront it
SH and switching happen at the same time
39
What cytokines produce what immunoglobins in the germinal center after Bcell Activation (class switch)
IgM forms without anything--activates the complement system
IgG subclasses can form from INF gamma and others-- tagging and phagocytosis, complement activation, and neonatal immunity
IgE and IgG4 form from the cytokine IL4----immunity against helminths and mast cell degranulation
IgA from mucosal cytokines (TGF beta etc)--mucosal immunity
40
Which type of T Ags do we see class switching/ switch recombination?
only T-dependent
41
What is Affinity Maturation?
Where does it occur?
What does it result from?
Why is Ig mutation called somatic hypermutation?
- the process where affinity of Abs production increases in response to prolonged or repeated exposure to an Ag
- occurs in the germinal centers of lymphoid follicles
- somatic hypermutation of Ig genes in dividing Bcells followed by the selection of high aff Bs by an Ag
-Very high frequency in Ig mutations
AID turns random Cs to Us
42
What is cut out of the Naive Bcell chain during class switching?
the mu and delta segments
43
What kind of Tcell is a T Follicular Helper?
What holds the Activated Bcell and Tfh together and is important for the germ center reaction?
What is secreted by the TFh and what cytokines are released (common)
- CD4+ with low levels of CD25
- the associated btw ICOS-S (tfh) and ICOS-L (bcell)
IL21 is secreted--faciliates differentiation
IFNgamma and IL4
44
Plasma cells
-the markers: which are decreased and increased
Where do they migrate from the germ center?
Increased: CD27
Decreased: CD19, 20, and HLA Class II
to the bone marrow
45
B1 (Ag independent) cells respond to what kinds of Ags?
| Where are the Bcells located that contribute to T-independent Ab responses to ... ?
Non-proteins...lipids, polysaccharides, etc
the Marginal zone in spleen
respond to blood-borne Ags (polysaccharides)
46
What do Memory Bs express that contributes to their long life span?
What are the surface markers for mBs
anti-apoptotic protein Bcl-2
CD27 and CD45r
47
What is antibody feedback?
process where Ab being bound to an Ag inhibits further Ab production
-The Fc 'tail' on IgG is recognized by Fc receptor on Bcells (FcgammaRII)
Uses ITIMs
-a control mech dealing only with IgG
48
What is humoral immunity?
Branch of adaptive immunity mediated by Abs made by Bs and Plasmas. Main defense vs extracellular pathogens
49
All Ab effector functions are mediated by what region and what are it's two functions?
All the functions are triggered by the binding of the Ag to what region?
Fc'
1. Delivers Abs to inaccessible anatomical sites
2. Links bound Ag to molecules that effect destruction
Fab' (variable region)
50
```
What is the function of the main Ab isotypes?
IgG
IgM
IgA
IgE
```
```
G: neutralize microbes and toxins
Opsonize Ags for phago by Macros and NPhils
Classical Comp activation
Ab-dependent cytotoxicity by NK cells
Neonatal immunity (Ab across placenta)
Feedback - of Bcell Activation
```
M: +classical complement path
A: Mucosal immunity: secreted into GI lumens and respiratory tract
Neutralize microbes and toxins
E: Helminth defense
Mast cell degranulation
51
Which Abs bound to Ags can activate the complement system?
| What component of complement binds to the Fc region of the Ab/Ag complex?
IgM or 2x IgG
the C1 component (q associates to two r's and s's
52
What are the effector functions of the Ig Abs?
- Activate complement
- Neutralize infectivity of microbes and the toxin interaction w/ host cells
-Opsonize for phagocytosis
-plays role of waste manager
CR1 on erythocytes binds with C3b and C4b to transport to liver and spleen
```
Using Fcgamma (CD16), NK (and other leuks) cells are activated to Ab-coated cells for killing
"Ab Dependent cellular cytotoxicity" ADCC
```
Therapeutics: ie IV-IG after exposure for rapid protection
- inflamm diseases/autoimmune
- uses inhibitory FcR on Bcells to suppress immune response
- Use IgM and IgG to cross-react with blood alloAgs
- Use IgE for Eosinophil/Mast cells reactions vs Helminths and Allergies
Use IgA and IgM for mucosal immunity
53
Which Abs are found in the placental fetus and in the breastmilk
IgG
IgA
54
What transports IgG from maternal circulation across the placental barrier, and across the intestine?
Where is it found?
FcRn found on the surface of endothelial cells, Macros, and other cell types
55
When is a baby most vunerable to immune compromise?
between about months 3-12 when maternal IgG decreases and new IgG, IgA is still being formed
56
What is passive immunization and what are examples?
- Uses preformed Abs...short term but immediate
| - snake bites, mother to child Ig, Ebola?
57
Active Immunization
vaccine and natural pathogen exposure
-long term (memory) but delayed in working
Can have combined immunizations with both passive and active
-tetanus and rabies
58
Evasion of Humoral Immunity
By Antigenic variations
Inhibition of complement activation
and
Blocking hyaluronic acid capsule
--viruses and bact (HIV...Neisseria Gonorrhae)
--Many bact like N Gono
--Streptococcus
59
What is the epitope?
The part of an Ag that is recognized--contains Ag binding site of Ab
60
What is the difference between T-dependent and non-dependent Ags?
D: proteins---need Th and Bs to stimulate Ab response
N: non proteins (lipids, polysaccs)
61
What is a haptin?
a small molecule that cannot induce an immune response alone
62
Which Tcells do MHC class 1 and 2s present to?
1: CD8+ cytotoxic Ts
2: CD4+ helper Ts
63
HLA-DM is associated with which MHC class?
| and what does it do?
Class II
| Faciliates the removal of CLIP (from Ii) and the addition of peptides
64
HLA Class II: Ii chain enters with the protein Ag in vesicles and combines with what cell component?
What does Ii do?
What important molecule is formed from the degradation of Ii?
Lysosomes/endosomes
stabilizes and blocks peptides from binding groove
CLIP
65
```
What MHC class pathway is TAP associated with?
What does it do and where does it do it?
```
HLA Class I
| Transports peptides from cytosol to interior ER where it is trimmed and loaded onto Class I molecule
66
In class I HLA path, how is the protein Ag broken down (whether viral or in phagosome)?
It is ubiquinated, then peptides are chopped by proteosome--> then enters the TAP (using tapasin) into the ER
67
What allele is expressed in most Ankylosing Spondylitis cases?
HLA-B27
68
What do BCRs contain?
Immunoglobin with alpha and beta (making invarient chain) =ITAM on bottom
69
What structures are involved with TCR signaling?
CD3 complex and zeta
70
What is allelic Exclusion?
Where one allele is silenced (only one antigenic epitope)
71
The production of the Heavy chain Bcell correlates to which Tcell chain?
Light chain B?
What does not happen in Tcr's that does in BCRs?
Heavy B=== Beta T
Light B=== Alpha T
Somatic hypermutation (adapting to viruses etc... class switching)
72
Which genes lead to junctional diversity in Chains?
What inserts nucleotides randomly after the cutting?
Which nucleotide adding type is not in light chains?
RAG 1 and 2
TdT
N is not in light chains. P is in both (templated)
--all leads to diversity in the hypervariable region
73
Which cytokine acts on B and Ts altering the protein express requirements?
IL-7
74
What adhesion molecules are used in B-cells/stem cells initially?
VCAM1 and VLA4
75
The Pre-BCR contains a surrogate light chain that allows the Pre-BCR to signal what?
Proliferation (largest expansion during Bcell development)
| Irreversible inhibition of Lg Heavy chain--leading to allelic exclusion, maintaining clonal specificity
76
What stage of Bcell development has the heavy chain recombined?
Where is Rag and Tdt expressed?
Pre-B stage
Between Pro and Pre-B stages
77
Which stage does the Bcell move from the Bone Marrow to the pheriphery (and spleen)?
Immature B phase (where is undergoes negative selection and receptor editing)
IgM is shown as a surface marker
78
Where are surface markers IgM, IgD, and Cd19 all expressed? (what Bcell stage)
Mature Naive B
| where it gets activated (prolif and differentiate)
79
Does the self-reactive rescue mechanism happen in Tcells?
| How does it work?
NO! just Bs
RAG proteins stay and keep rearranging for a second round, if the new light chain is not reactive, then it will mature and migrate to periphery, if it is recognized after the receptor editing, then it dies.
80
How does a mature T lymph leave the Thymus?
The blood
81
What stage of Tcell maturation does it leave the bone marrow and enter the Cortex of thymus?
When does it enter the medulla?
When does it go to the periphery?
Stem cell--> proT
PreT-->Double Positive T
Single positive (immature) --> Mature Naive T
82
T regs are a small population of which T lymphs?
What is their function?
What surface markers?
What unique transcription factor is present?
self-reactive CD4+s that undergo differentiation
To inhibit self-reactive Thelper1s in the periphery (suppression)
CD4 and CD25**-from IL2
FoxP3
83
Defensins definition:
```
small, cysteine-rich cationic proteins which active vs bact. fungi, and enveloped/nonenv viruses
In granules (neurtrophils)
```
84
Left shift is seen when?
acute infection-- bone marrow dishing out WBCs and releasing before they are mature**
85
What makes up a neutrophil NET?
core DNA element which histones, proteins (cathepsins) and enzymes are released from granules
They continue functioning/chemotaxis after it's release
86
```
What is a macrophage called in the
Bone
CNS
Lung
Liver
Connective tissue
Spleen
```
```
Osteoclast
Microglial
Alveolar
Kupffer cell
Histiocyte
White/Red pulp; marginal zone; metallophilic
```
87
What kind of cell is a Langerhans, and where is it?
DC (fetal stage development)
| in the epidermis
88
Major difference btw Mast and Basophiles?
Mast: tissue fixed
Baso: circulating
parasites and allergies
granules w/ hist, sero, heparin, cytokines/chemos
89
What makes up the Sentinel cells?
DCs, tissue Macros, Mast cells
90
What is unique about Eosinophils?
Large secondary granules w/ 4 basic proteins
Small granules have Major Basic Protein
anti-parasitic, exfoliation, brochospasm
91
Bcells can develop where?
Bone marrow
| Spleen
92
Cell Mediated Im is comprised of what?
Tcells in concert many times w/ Ag presenters and Phagocytes
viruses and bact that aren't accessible to circulating Abs
93
What is sebum consisted of?
lactic acid and fatty acids
| -reduce skin pH
94
What are the pyrogenic cytokines?
| What do they activate?
TNF
IL-1 and 6 in Macros
Potent fever inducers
Hypothalamus
95
What terminal glycan is not found in humans?
```
Mannose
Mannose Receptor (Pattern Recognition Receptor)
```
96
What TLRs are extracellular, which are intracellular
1-6, not 3
3, 7-9
ff: 2,4,9 for Neisseria meningitidis
97
Which Toll Like Receptor does not signal to MyD88?
TLR3
MyD88 stimulates IRAK--> MAPK--> NFkB
or Interferon Reg Factor IRF
98
What do many PAMPs activate?
| What do they do?
Inflammosomes containing NOD-like Receptors--
- Scaffolding proteins: assemble platforms that trigger NFkB and MAPK signaling paths
- Inflammosomes + protease caspase 1: process IL-1beta and IL-18----POTENT PROINFLAM cytokines
99
What is fMet and what is unique about it's location?
in Prokaryotes only
It's a PAMP: phagocytes use it to distinguish self from non-self
-initiates phago by Phag cells
100
Where are mast cells located? and why is it important?
Near sites exposed to external env- like skin....near blood vessels- to regulate vascular perm and recruitment of blood cells
Can be activated by IgE+Ag, cytokines, C3 and C5a's, temp/pressure change
101
What is special about activated C1 in classical complement path?
What is the classical C3 Convertase?
What is the role of C3b?
One can cleave many C2 and C4 molecules
C4bC2a
either Phagocytosis (opson) activation or formation of C5con
102
What are c-reactive protein and Mannose binding protein considered?
What do they do?
Which of those two is a marker along with Serum Amyloid P for diagnosis of ....?
Acute Phase Proteins
Fix complement, opsonization
CRP and SAA used for inflammation diagnosis (up to 100 fold increase w/in 24-48 hours)
103
Where do Neutros and Monocytes ender tissue?
Post-capillary venules----caps in parenchymal tissue (kidney, lungs, liver)
104
What are key activities helping neutrophils enter Endothelial cells ECs (after activation by TNFalpha and IL1 from Mast and Macros)?
Increased expression of adhesion molecules E and P selectin (PSGL1 and ESL1 on neutrophils)
LFA1 and VLA1 are on neutrophils and activated by chemokine signals, then bind to ICAM1 and VCAM1 before being brought in (diapedesis)
105
What is the difference between classically activated M1 Macros and Alternatively activated M2 Macros?
M1: induced by microb products binding to TLRs/cytokines (IFNgamma)-----proinflammatory
M2: induced by IL-4 and IL-13-----Anti-inflammatory; tissue repair and fibrosis
106
What is the order of the respiratory burst in Macros?
O2 consumption
Superoxide anion production
H2O2 production (potent ox agent--broken down by catalase)
Singlet Ox production
Hydorxyl radicals produced (react w/ most organics)
Myeloperoxidase can cat toxic peroxidation of hydroxy rad or Hypochlorite (very antimicrobial)
107
What are the two methods of Anti-viral innate immunity?
1. NK cells
2. Type 1 IFNs alpha/beta
- PKR blocks viral rna translation
- IFNs + ribonuclease --> rna degrade
- IFNs also + NKs
-NKs kill and release IFNgamma to stim Macros Phagocytosis
108
Important Receptors of NKs
Activating: KIR (killer Ig like rec)- recognize stress molecules MICA and B
--trigger PTK
Inhibitory: recognize class I MHC and activate PTP
If sufficient KIR binding to MHCI (PTP) occurs, cell walks away with its life
109
How might Neisseria Meningitidis and Steptococci resist innate immunity?
Blocking C3 and C5 convertases or C3b binding to complement receptors
110
What is the bridge between Innate and Adaptive Responses?
Pathogen recognition by PRRs---causing + of APCs---> Ag presentation to naive Ts---> secreted cytokines assist development and maturation
