Immuno Pre-Midterm Flashcards
RAG 1,2
Somatic recombination (V,D,J recombination)
Tdt
Joins V,D,J at junctions
A pan B cell marker
CD19
CD79a CD79b also called
Igalpha, Igbeta
CD79a CD79b
Associate with membrane Ig to initiate intracellular signaling with B cells
Which CD’s are associated with the BCR complex?
CD19, 21, 81
B7-CD28
CD40-CD40L
When is CD20 first expressed?
Pre-B cells
Disruption of IL-4
Prevents isotype switching to IgE
BLyS
Cell surface protein on monocyte, macro, dendritic; an overexperssion of BLyS –> survival of autoreactive B cells
BtK kinase
Pro B cell stage –> Pre B cell stage
XL-Agammaglobinemia
X linked-Agammaglobinemia
Mutation in BtK kinase
S protein, also called
Vitronectin
Prevent MAC (C5b, 6, 7
Function of S protein
Prevent MAC (C5b, 6, 7)
Function of vitronectin
Prevent MAC (C5b, 6, 7)
CD59
Prevents C8 in MAC
Regulators of alternative complement pathway
Factor H (C3b)
DAF (C3 convertase)
Factor I (C3b inactivate)
AI
Regulators of classic complement pathway
C1 INH (C1 / kallekrein) DAF (C3 convertase) Factor I (C4b inactivate) AI C4Bp
Common regulators of classic and alternative complement pathways
DAF (CD 55)
Factor I
Another name for CD55
DAF
What is properdein? What is another name for it?
Also called Factor P; stabalizes C3 convertase (alternate)
A deficiency in C1 esterase inhibitor leads to…
Hereditary angioedema
Which complement factor is a chemotactic factor and an anaphylatoxin?
C5a
Activates alternative complement pathway
IgA
Ab in breast milk
IgA
Ab of mast cells/basophils
IgE
Ab called reaginic Ab
IgE
Ab on immature B cells
IgM
Ab’s that activate classical complement pathway
IgM*, IgG
Difference between papain & pepsin
Papain: 2Fab
Pepsin: Fab2
Who has a FC-gamma-receptor?
Monocyte, macrophage, neutrophil, B cell
Which Ab’s have a J chain?
IgA, IgM
IgA is generally: mono/di/trimer
Dimer
IgM in plasma is…
Pentamet (Membrane = monomer)
Ab with longest 1/2 life
IgG
Ab associated with isohemagluttins
IgM
Dendritic cells express… (CD’s, etc.)
B7-1; B7-2 (CD80, 86, 28)
Differentiate between unique features of Class 2 and Class 2 MHC
Class 2: invariant chain
Class 1: beta-2-microglobulin
CR1
phagocytes, RBC’s
CR2
B cells; EBV!!!
C3a-C4aR
Mast cells, basophils
C5aR
Mast, basophils, endothelial cells
MHC is on what chromosome?
6
The 3 opsonins for phagocytosis
- CRP
- IgG
- C3b
Differentiate between somatic recombination, somatic mutation, switch recombination
Somatic recombination: V,D,J
Somatic mutation: affinity maturation (non-genomic)
Switch recombination: genomic isotype switching
ICAMI/LFA1; LF3/CD2
Stabalize B-cell - T-cell receptor complex
What keeps memory B-cells in recirculation?
Down regulation of L-selectin; no HEV entry
Downregulation of iNOS
TGFB, IL-4, IL-10
Increased secretion of IFN-gamma by NK cells
IL-12
CRP
IL-6
NK –> LAC
IL-2
Murine/mouse
Class I
CD3
5 invariant polypeptides on T cell surface; link the Ag binding site with signaling pathways
CD79a/b is to B cells, as _____ is to T cells
CD3
Differentiate the variable regions of B & T cells.
B: heavy + light (h = VDJ, l = VJ)
T: alpha/beta (a=VJ; b=VDJ) or gamma/delta
CD19 is to B-cells as CD__ is to T cells
CD2
What is a double positive T cell?
CD4 and CD8 expressed
What is allelic exclusion?
If a VJ or VDJ recombination is successful on one of the alleles (e.g, father‟s allele), then recombination will not occur on the other allele (mother‟s allele). If, however, the attempted recombination is unsuccessful on the first attempted allele, then recombination will be attempted on the second allele. If the recombination is unsuccessful on both alleles, the cell dies
When does tolerance induction take place for T cells?
After TCR-CD3-DP stage
Differentiate between positive and negative T cell selection.
Positive: low affinity interaction / allowed to survive
Negative: high affinity interaction T cell-MHC / killed
Negative selection is more finely tuned in the thymic cortex or medulla.
Medulla (APC’s are bone marrow derived; not just thymic epithelial cells)
APECED
Mutation in the AIRE gene, which primarily affects endocrine organs
Describe how naive lymphocytes make their way to lymph nodes.
Through HEV’s
- L-selectin
- Integrins / LFA-1
- Metalloproteinases / degrade collagen
Why don’t memory B cells reside in lymph nodes?
No L-selectin!
What are the two nTregs & transcription factor?
CD4, 25
FOX P-3
Depletion of nTregs can lead to…
Enhanced immune responses to pathogens, tumor rejection
Differentiate between central and peripheral tolerance
Central: BM/T
Peripheral: Tregs
IPEX Syndrome
Multiorgan autoimmune inflamm disease; Mutation of FOX-P3 (tReg)
immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. This disorder presents as watery diarrhea, eczema, and Type I diabetes (or other endocrine pathology). Bone marrow transplantation or large doses of immunosuppression are required; otherwise infected males typically die within first two years of life.
The AIRE gene
Enables synthesis of all different types of cells in the thymic medulla to test for autoreactivity (i.e. insulin secreting cells)
What are the 3 chatacteristic features of an innate response?
Complement, phagocytosis, cell-mediated toxicity
Who are the anaphylatoxins?
C3a, 4a, 5a
Lysosomes have these enzymes
Lactoferrin (iron)
Lysozyme (muramic acid)
Defensins
MPO (myeloperoxidase) – generate hypochlorite
The battlefield inside of a phagosome includes:
- Lysosomal enzymes
- ROS
- RNS
Myeloperoxidase, though a lysosomal enzyme…
requires hydroxyl from NADPH oxidase
The most prominent down regulator of RNS/ROS
TGFbeta (IL-4, 10)
A genetic defect in NADPH oxidase
CGD
How do natural killer cells know who to kill?
FC-gamma-receptor
Differentiate between direct and indirect recognition of pathogens.
Direct - PPRR’s, TLR, NOD
Indirect - IgG, C3b, CRP
Natural killer cells are enhanced by…
IL-12, 2
Who has FC-epsilon-receptor, Major Basic protein?
Eosinophils
Dendritic cells in the skin are called…
Langerhan’s cells
The 2 modes of entry of HIV into a cell..
CCR5, CXCR4
T/F Dendritic cells are in the brain
False
Differentiate between MHC 1 & 2
1: A, B, C (CD8) – beta-2-microglobulin
2: DP, DQ, DR (CD4) – invariant chain
HSV
Sabotaging expression of Class I MHC; sequestered inside neurons for life
Neurons already have little MHC1
How are HLA expressed in humans?
Co-dominant
EBV
Latent infection in B cells; inhibits activity of proteasome
CMV
redirects MHC1 to be degraded by proteasome
* Symptoms in immunocompromised patients (encephalitis, pneumonia, hepatitis, retinitis, blindness)
Who is the most effective APC?
Dendritic cell; everywhere but brain; B7-1,2, Cd80,86
From which CD are dendritic cells derived?
34
Define avidity
Overall binding energy
What co-stimulatory signals influence B cells?
B7/CD28; CD40/40L (isotype switching)
Describe T-cell maturation stages
CD2 –> pre-TCR-CD3 (transient) –> pre-TCR-CD3-DP –> TCR-CD3-DP (tolerance induction) –> TCR-CD3-SP (lineage selection)
Another name for IL-8
CXCL8 (Macrophages + endothelial cells) * Neutrophils
Another name for MCP-1
CCL2 (Macrophages + endothelial cells) * monocytes
Another name for CCL11
Eotaxin (Epithelial cells + fibroblasts)
Major chemokines
IL8/CXCL8, CCL2/MCP-1, CCL11/Eotaxin
CD28
On T cells; binds to B7-1 (CD-80) & B7-2 (CD-86)
CD19, 20, 21
On B cells
CD54
Another name for ICAM-1 (which binds LFA-1-integrin)
ICAM-1
Also called CD-54; binds LFA-1 (integrin)
* On endothelial cells
LFA-3
Also called CD58; binds CD2
CD55
DAF (complement)
CD59
Inhibits; C8/Membrane Attack Complex
IgA is a monmer/dimer/pentamer
Dimer
Factor P
Properdein (stabalizes C3 convertase/alternative)
In order for a pCTL to develop into a CTL over the course of 1 week, there is a requirement for these cytokines from ____ cells.
IL2, IFN-gamma
Th1 cells
Delivery of the “lethal hit” by CTL’s can be one of two methods. What is the molecule required?
Osmotic lysis – perforin
Apoptosis
- Ca dependent or independent
T/F The CTL lives after delivering the lethal hit
True
Who requires LESS co-stimulation for activation: CD4 or CD8 T cells?
CD8
Among the T cells, who Secretes cytokines that enhance macrophage cytotoxicity
Th1 cells
Superantigens present to …
CD4 at a site outside the normal TCR site
B or T: LPS
B
B or T: Pokeweed
B & T!
B or T: Concav A
T
B or T: Phytohemagglutin
T
Which two cytokines promote the differentiation of a Thp cell into a Th17
IL-6, TGFB
Th17 cells are most effective at fighting these types of infections…
Fungal
What is the role of IL-23?
It is a stabilization factor for the dendritic cell-Thp cell interaction
This cytokine promotes the division of Th0 cells into a/i Tregs
TGFBeta
Where do CD8+ responses occur?
Anywhere in the body
Which cytokine is responsible for amplifying the response of IL-17?
IL-21
T/F Th17 cells are chemotactic for neutrophils
True
Describe CTLA-4
Also called CD152; binds to B-7-1 and B-7-2 with greater affinity than CD 28
* Negative T cell activator
Describe the CD200/CD200R interaction
Down-regulates the T cell response
This cytokine promotes the Th0 –>Th1 pathway
IFN-gamma
This cytokine promotes the Th0 –>Th2 pathway
IL-4
Another name for CD40L
CD154
Who are the two co-stimulatory molecules in the APC-T cell interaction?
CD80 (B-7-1) & CD86 (B7-2) —bind to—-CD28 (CD-28 has a higher affinity for CTLA 4, which downregulates the T cell response)
What is special about superantigens?
They bind to allosteric sites
What are the characteristics of inflammation?
Redness, heat, pain, edema
Classically, an inflammatory response is caused by 4 major events:
- Complement
- Mast cell degranulation
- Coagulation cascade
- Macrophages/neutrophils
The intrinsic coagulation plays an important role in tissue damage. What factor is attracted to damaged collagen & what are the downstream effects?
Factor 12 –> Factor 11
(Pre-kallekrien –> kallekrin)
Kallekrein cleaves HMW kininogen to bradykinin - a vasodilator
Kallekrein also cleaves C5 to C5a (histamine release)
Three molecules promote vasodilation in infection.
- Bradykinin
- Histamine
- Leukotriene b4
Differentiate between the source of P & E selectin
P: from cytoplasmic stores
E: de novo synthesis (stim by IL-1, TNF)
Where is L-selectin expressed?
Circulating/non-inflammatory lymphocytes
Different families of integrins are based on what chain?
Beta (1,2,7)
What is one of the most important metalloproteinases?
Gelatinase B (Cleaved by elastase); secreted by many leukocytes
Transmigration of leukocytes through endothelial junctions is done by this interaction
PECAM-PECAM
What is responsible for hypotensive shock?
IL-1, TNF, IL-6 — systemic vasodilation
Who acts on the hypothalamus to induce fever?
IL-1, TNF
Adaptive immune responses to primary infections occur in…
Secondary lymphoid tissue
Adaptive immune responses to secondary infections occur in…
Primary site of infection
Differentiate between MMP2 MMP9
MMP2 = progelatinase A (inflammation)
MMP9 = progelatinase B (VIP, VLA-4 interaction)
* Secreted by T-cells as matrix metalloproteins
How do T cells know how to get to the site of infection?
Integrins LPAM, VLA4 — interaction with VCAM1
What is the role of type 1 cytokines at the site of primary infection?
IL-2, TNF, IFN-gamma – activate macrophages
CD40-CD40L interaction
What is the role of type 2 cytokines at the site of primary infections?
Down-regulation of Type 1 cytokines; elimination of microbes, tissue healing, shedding of adhesion molecules
What is the role of Th17 cells at the site of primary infection?
Autoimmune role
From whom is bradykinin derived?
High molecular weight kininogen
Which one of the following molecules is chemotactic for neutrophils and induces enhanced adhesiveness of Mac-1 and LFA-1? IL-2, 4, 6, 8, 10
IL-8
Which T cell/endothelium interactions may have a dual role in the steps leading to T cell diapedesis?
LPAM/VCAM-1
VLA-4/VCAM-1
What is another name for VLA-4?
CD49a
