Immunology - Block 1

Front 1

Name two different types of dendritic cells?

What are their functions?

Back 1

Interdigitating (activates T cells in lymph node via MHC) AND Follicular (helps mature B cells - does not have MHC).

Front 2

Interdigitating cells are found in....

Follicular cells are found in...

Back 2

Present in most organs (they migrate to lymph node and activate T cells in the paracortex region)

Lymph node and spleen

Front 3

Addressins are found....

Back 3

on HEVs of secondary lymphoid tissues and inflammed endothelium.

Front 4

Last stage of immune response....

For Extracellular Pathogens

For Intracellular Pathogens

Back 4

For Extracellular Pathogens -- (1) CD4-Th1 -> Activate macrophage to kill pathogens (2) Ab molecules bind to pathogens and activate complement system for their destruction

For Intracellular Pathogens
(1) CD8-Cytotoxic T cells -> Kill the host cell via perforin and granzyme enzymes
(2) NK Cells

Front 5

Which enzymes are released by Cytotoxic T cells?

Back 5

Perforin and Granzyme

Front 6

How is the mode of action different for Helper and Cytotoxic T cells?

Back 6

Helper T cells - Activate Macrophage. Use MHCII to recognize Ag.

Cytotoxic T Cells - Kill host cell directly and recognize Ag via MHCI.

Front 7

Which organ is important for systemic infection?

Back 7

Spleen - it removes damaged RBCs.

Front 8

List the cells that come from lymphoid lineage and erythroid lineage?

Back 8

Lymphoid...T cells, B cells and NK cells

Erythroid - RBC, Megakaryocytes (Platelets)

Front 9

List the cells that are from myeloid lineage and where are they found?

Back 9

Neutrophil (blood)
Basophil (blood)
Eosinophil (blood)
Mast Cells (tissues, CT)
Macrophages (tissues, CT)
Dendritic cells (tissues, CT)

Front 10

List three unique characteristics of NK cells?

Back 10

(1) Do not have TCR or product Ig.
(2) Secrete IFNy
(3) Destroy cells with intracellular pathogen (just like cytotoxic T cells)

Front 11

Which granylocytes are....

Phagocytic?
Attach to IgE?
Release histamine?

Back 11

Neutrophils

Eosinophil, Basophil (and Mast cells)

Basophil (and mast cells)

Front 12

Which cells are primary players in allergic response?

Back 12

Mast cells (also involved are Basophils, Eosinophils)

Front 13

Which cells are considered to be circulating counterpart of Mast cells?

Explain?

Back 13

Basophils

because they both bind to IgE and release histamine as part of the allergic response.

Front 14

List the APC for innate and acquired immune response.

Back 14

Innate - Macrophages

Acquired - Macrophages, Dendritic (Interdigitating and Follicular)

Front 15

List the two types of Dendritic cells?

Where are they found?

Their function and What kind of receptor are found on their surface?

Back 15

Interdigitating - in most organs. Pick up Ag, travel to lymph node and present Ag to T cells via MHC II (in the paracortex of the lymph node).

Follicular - In follicles of lymph node and spleen. Present Ag to B cells (do not have MHC II, instead have Fc receptors to trap Ag:Ab complement).

Front 16

Name the specialized epithelial cells that deliver pathogens across mucosa?

Back 16

M cells

Front 17

What is the structure of integrin?

What is their function?

Back 17

heterodimeric molecules consist of alpha and beta chain.

Leukocyte adhesion to endothelium or other immune cells.

Front 18

What is the function of following integrin types? Examples?

B1
B2
B3

Back 18

B1 - Binding cells to extracellular matrix (VLA1-6)

B2 - Leukocyte to endothelium (LFA1, CR3, CR4)

B3 - Interactions of platlets and neutrophils at inflammatory site or sites of vascular damage

Front 19

What is the function of Addresin?

Back 19

Bind to circulating T cells at HEVs and direct them to lymphoid tissues.

Help direct T cells to various locations (distinct adhesion molecules on HEVs of different tissues).

Front 20

Strongest Immunogen

Back 20

Protein > Polysaccharides > Lipids > Nucleic acids

Front 21

A substance that nonspecifically enhances the immune response to an Antigen

Back 21

Adjuvant

Front 22

What are Haptens? Give an example.

Back 22

Small molecules that do not provoke antibodies by themselves; covalent attachment to a protein carrier makes these molecules immunogenic.

Poison Ivy Catechol

Front 23

Ig splits...

Papain vs. Pepsin

Back 23

Papain - yields two Fab and one Fc fragments.

Pepsin - yields 1 Fab' (containing two Ag binding site) and degrades Fc region.

Front 24

Which Ig...

Crosses placenta?
Is first one to be produced?
Has secretory component?
Marker for naive, mature B cells?
Present at highest levels in serum?

Back 24

IgG
IgM
IgA
IgD
IgG

Front 25

How do Abs work?

Back 25

(1) Neutralization - Tightly bind to pathogen; inhibiting growth, replication etc..

(2) Opsonization - Phagocytosis of a pathogen when coated with IgG or complement. (Macrophages phagocytosed a pathogen MUCH more efficiently when it is bound to Ab or complement).

Front 26

Which Ab are good for...

Opsonization?
Activation of complement system?
Neutralization?
Binding to Mast cells?

Back 26

Opsonization - IgG

Complement System - IgG and IgM

Neutralization - IgG, IgM

Mast Cell Binding - IgE

Front 27

List the ways Ab changes after exposure to Ag?

Back 27

(1) Differential RNA Splicing - (secreted versus membrane bound Ab)

(2) Isotype switching - Heavy Chain Class switching

(3) Hypermutation (increase affinity)

Front 28

Which cell in B-cell development first shows surface Ig?

Back 28

Pre-B cell (It has BCR and surrogate light chain)

Front 29

Which cells express MHC Class I and Class II molecules?

Back 29

MHC I - All cell except RBC
MHC II - APC; Macrophages, B cells and Dendritic cells and endothelial cells can be induced to express Class II

Front 30

How are proteins transported from cytosol into the ER?

Back 30

Using TAP (its gene is contained within MHC gene)

Front 31

How does Ag get loaded onto Class I?

Back 31

(1) Calnexin stabilizes ClassI heavy chain until B2m binds.
(2) Calnexin is released as B2m binds.
(3) ClassI heterodimer, Tapasin and Calreticulin bind to TAP. (UNTIL Ag binds)
(4) Ag is transported into ER by TAP.
(5) Ag is presented and ClassI molecule dissociates from Calreticulin, Tapasin and TAP.

Front 32

What is CLIP?

Back 32

Fragmented invariant chain on the HLA-ClassII. Invariant chain is digested in the exocytic vesicle and CLIP is what's left on the HLA-II complex.

Front 33

How is CLIP released from HLAII complex?

Back 33

Via HLA-DM

Front 34

CD1

Back 34

MHC like protein that presents lipids.

CD1a-c - Presents to CD4/CD8 T cells

CD1d - Presents to NK cells

Front 35

List three differences between Ig and TCR?

Back 35

Ig has (1) Affinity maturation (2) Subtype switching (3) Membrane bound and secreted

Front 36

Two types of TCR are...

Back 36

alpha/beta and gamma/delta

(T cells contain one or other but NOT both)

Front 37

gamma/delta TCR is found in...

Back 37

mucosal tissues

Front 38

Variable region of TCR is encoded by which gene (for alpha and beta chain)

Compare this to Ig.

Back 38

Alpha variable chain - VJ
Beta variable chain - VDJ

(Constant region is Ca, Cb, Cd, Cg)

Ig - Variable heavy chain - VDJ; variable light chain is VJ

Front 39

How does TCR commit to gamma/delta?

Back 39

gamma/delta TCR signals Tcell to cease gene rearragement and so TCR remains as gamma/delta.

Front 40

How does TCR commit to alpha/beta receptor?

Back 40

If beta chain rearranges before gamma/delta it stops rearragement and forms Pre-TCR (beta chain with surrogate alpha chain). Proliferation begins. Then, gene rearranges to get alpha chain (and delta is deleted).

Front 41

What is Pre-TCR?

Back 41

Beta chain with surrogate alpha chain. (Proliferation and alpha chain rearrangement follows)

Front 42

Which molecule is responsible for signal transduction for TCR?

Back 42

CD3 (TCR can't leave the surface).

CD3 has intracellular domain with ITAMS.

Front 43

Which are peptide binding regions in MHC I and MHC II?

Back 43

MHC I - alpha1 and alpha 2

MHC II - alpha 1 and beta 1

Front 44

What is superantigen?

Back 44

A molecule that binds to external portion of MHC and activates TCR without an antigen on the MHC.

Front 45

Which CD markers are present on T cell during beta chain rearrangement?

Back 45

CD25 and CD44low

Front 46

When the a double negative Tcell become double positive T cell? What does double negative mean?

Back 46

Double negative means CD4-, CD8-.

After beta chain is generated and transferred to the surface (PRE-T CELL stage), T cell becomes double positive.

Front 47

What is unique about gamma/delta T cells?

Back 47

(1) They are usually found around mucosal surfaces.
(2) They do not undergo positive or negative selection.

Front 48

How does dbl-positive Tcell get to be single positive (CD4 or CD8)?

Back 48

During positive selection, if TCR recognizes MHC I, it becomes CD8+ cell and if it recognizes MHC II, it becomes CD4+ cell.

Front 49

List three exit markers on the HEV in the lymph node? Which molecule on T cell binds these markers?

Back 49

GlyCAM1, MadCAM1, CD34

L-Selectin binds these markers to exit endothelial cells.

Front 50

Which molecules are involved in holding Tcell close to the APC during the screening process?

Back 50

LFA1-ICAM3
LFA1-ICAM1
CD2-LFA3

Front 51

Which molecules are responsible for co-stimulation during the activation of naive T cell?

Back 51

CD28 (on T cell) and B7 (on APC)

Front 52

List the following for T cells...

Coreceptors molecules
Co-stimulatory molecules
Signal transduction molecule

Back 52

Coreceptors molecules - CD4/CD8
Co-stimulatory molecules-CD28
Signal transduction molecule-CD3

Front 53

Signaling cascade for T cell.

Back 53

(1) MHC-Ag-TCR complex binding leads to ITAM phosphorylation.
(2) CD4/CD8 co-receptors binds to stabilize the connection
(3) ZAP70 binds to ITAM
(4) Lck phosphorylates and activates ZAP70

Front 54

Activated ZAP70 activates...

Back 54

PLCy -> DAG/IP3 formation -> IP3 activates Calcineurin leading to NFAT activation. AND DAG+Ca activate PKC activating NF-kB.

ZAP 70 also activates GEF -> Induction of MAP kinase -> Fos and Jun induction and AP-1 formation and activation.

Leads to gene transcription.

Front 55

What is unique about naive CD8 T cell activation?

Back 55

It requires stronger signal. Only DC can provide this signal by themselves.

Macrophages required IL2 from CD4 to have higher expression of B7 to bind to CD8 T cells.

Front 56

What are the homing receptor in on T cells for lymphoid organs versus activated endothelium?

Back 56

Lymphoid Organ - L-selectin
Activated (inflammed) endothelium - VLA4

(these molecules are on the T cells)

Front 57

CD45RO

Back 57

Product of splicing of CD45RA.

Associates with CD4 and TCR. Resulting in increased sensitivity to stimulation thus requiring lower concentraion of MHC:Peptide molecules.

Front 58

Mechanism of action of Cytotoxic T cell.

Back 58

(1) Release of cytotoxins - Perforin (creates pores) and Granzyme B (enters through pores and cleaves proteins)

(2) FasL on T cell binds to Fas receptor resulting in capsase activation and apoptosis.

Front 59

Which molecules are important in Th1 differentiation?

Back 59

IL27, IL12, STAT4 (phosphorylated), T-bet transcription factor

Front 60

Which molecules are important in Th1 differentiation?

Back 60

IL27, IL12, STAT4 (phosphorylated), T-bet transcription factor

Front 61

Mechanism of action of Th1 cell.

Back 61

Th1 activates macrophages via CD40L and IFNy.

(1) Increase phagocytosis
(2) Synthesizes microbicidal molecules
(3) Increase B7 expression

Front 62

Which molecule is vital for Th2 differentiation

Back 62

IL4, Transcription factor GATA3 and STAT6

Front 63

Which ILs are produced by effector TH2?

Back 63

IL4 - B cell proliferation
IL5, IL6 - B cell differentiation

Front 64

Foxp3

Back 64

Essential for developemtn/fucntion of Tregs.

Front 65

Function of Tregs?

Back 65

Involved in peripheral tolerance, prevention of autoimmunity.

Front 66

Treg is highly dependent on which IL?

Treg produces...

Back 66

IL2

IL10/TGFbeta

Front 67

Signal transducers for Bcell and T cell?

Back 67

B cell - Iga and Igb
T cell - CD3

Front 68

Coreceptors for Bcell and Tcell?

Back 68

B cell - CD21, CD81, CD19

T cell - CD4, CD8

Front 69

What type of Ig are produced by TI Antigens? What are some other characteristics of TI Antigens?

Back 69

IgM; No class switching, No affinity maturation, No immunological memory

Front 70

What are signals 1 and 2 for the primary response of B cel activation for TD Ag?

Back 70

Signal 1 - Ag binding to B cell

Signal 2 - CD40-CD40L contact and cytokines released by CD4 T cell.

Front 71

List the steps of primary response of B cell immunity.

Back 71

(1) Ag recognition/binding via BCR (signal 1)
(2) Interaction with Ag specific Th2 (signal 2) driving proliferation/ differentiation
(3) IgM secretion
(4) Some migrate to GC undergo isotype switching, affinity maturation, competition for interaction with Th2s
(5) More proliferation/differentiation(6) non IgM secreting plasma cells and/or memory cells

Front 72

What are the differences between the primary and secondary response of B cell immunity?

Back 72

Time course - Secondary is much faster.

Ab titer - Many more Ab produced as part of secondary response

Ab class - Primary is mainly IgM, secondary can be any class.

Ab affinity - Abs produced as part of secondary Ig have higher affinity.

Front 73

List three important Fc receptors? Their function?

Back 73

FcyRI - Low affinity, Enhances neutrophil, macrophage ability to phagocytose

FcyRIII - Factilitates cytotoxicity by NK cells via binding to IgG.

FceRI - High affinity receptor, Binds to IgE, Found on mast cells, Basophils and Eosiniphils.

Front 74

Which receptor is involved in the transcytosis of IgA?

Back 74

poly-Ig receptor. (It is cleaved in the endocytic vesicle. Fragment that stays with IgA is the secretory component)

Front 75

Which receptor is involved in the transcytosis of IgG?

Back 75

Two Brambell receptor (FcRB)

Front 76

What is passive immunity? Its characteristics

Back 76

Passive immunity is when Ab from one individual is transferred into another individual. (Mom to fetus)

No immunologic memory is involved with passive immunity.

Front 77

C3b

Back 77

Intermediate in Completement cascades. This is where all three pathways merge.

C3b on a pathogen marks the pathogen for destruction.

Front 78

What are the components of C3 convertase and C5 convertase?

Back 78

C3 convertase - C4b and C2a (C4b2a)

C5 convertase - C4b, C2a, C3b (C4b2a3b)

Front 79

Steps of classical complement cascase...

Back 79

(1) C1q binds to IgM or IgG(2)
(2)C1r activates C1s
(3)C1s cleaves C4 and C2
(4)C4b and C2a come together forming C3 convertase
(5) C3b is formed and it binds to the pathogen surface marking it for destruction. (It MUST bind to the pathogen)

Front 80

What is analogous to C1r and C1s in the Lectin based completement cascade pathway

Back 80

MASP - Manose associated serine protease (it cleaves C4 and C2)

Front 81

In the alternative pathway, C3 is cleaved twice; which molecules are used for this cleavage? When does the cleavage happen?

Back 81

Cleavage 1 - During activation - iC3Bb is soluble and not pathogen bound. (hence it is not called C3 convertase).

Cleavage 2- Via C3 convertase (c3bBb). This happens after C3b has bound to pathogen and properdin has stabilized C3 convertase.

Front 82

Properdin

Back 82

Stabilizes Alt C3 convertase to allow for large deposition of C3b on pathogen surface.

Front 83

What is C5 convertase in the Alternative pathway

Back 83

C3b2Bb

Front 84

What is produced by NK cells when they recognize mycobacterial lipid?

Back 84

IL-4 and IFNy

Front 85

EBNA 1

Back 85

Responsible for maintaining Mono. Proteosome unable to degrade EBNA-1 for presentation to CD8s.

Front 86

What is DAF?

Back 86

Decay Accelerating factor - Dissociates C3b and Bb.

Stops complement cascade

Front 87

How does CR2 inhibit completement cascase?

Back 87

Dissociates C3b from Bb.

Front 88

What is MCP? And how does it regulate complement cascades?

Back 88

MCP - Membrane Cofactor protein.

Works three ways...(1) Dissociates C3b from Bb (2)Cofactor for Factor I (which inactivates C3b by cleaving it) (3) Binds to C4b, making it susceptible to attack from Factor I.

Front 89

What are HRF and CD59? Mechanism of action?

Back 89

Inhibit Membrane Attack complex.

Bind to C5b6-8 and prevent C9 polymerization

Front 90

How are immune complexes removed? (not bound to pathogen)

Back 90

Complement components C4b and C3b bind to CR1 on RBC, which carries it to spleen for removal.

(Note: When pathogen is bound....opsoniazation, activation of MAC, Inflammation remove pathogen).

Front 91

What is factor I?

Back 91

It stops complement pathway by inactivating C3b.

Front 92

Give an example of an organism that exploits split tolerance?

Back 92

Mycobacterium Leprae

Front 93

List the three chemokines that play a role inflammation response?

Back 93

CXCL8 (IL8) - Chemoattractant for neutrophils

MIP1 (CCL3) - Chemoattractant for CD8

RANTES (CCL5) - Chemoattractant for memory T cells and monocytes etc.. Binds HIV coreceptor.