Immuno 12: Acquired Immune Review

Question 1

T/F: The immune system will respond to a minimal amount of antigen (small antigen burden) with full force .

Answer 1

False. A minimum threshold of antigen must be met before the immune system will respond. Once the threshold is met, the innate response initiates inflammatory responses that control the pathogen replication while promoting antigen presentation to naive T cells and flow of antigen that can be recognized by B cells in the secondary lymphoid tissues.

Question 2

Immunological memory take this form:

Answer 2

Clonally expanded memory B cells and T cells. The host is left with long lived B cell and T cell-mediated immunity to reinfection with that particular pathogen.

Question 3

If the _________ immune response is unable to clear the infection by around day 4 of the infection, _______ immune responses are primed and ultimately, these responses will clear the infection from the body. Unless the person has full-blown AIDS.

Answer 3

innate; acquired

Question 4

Describe the barrier functions that inhibit infectious disease from 0-4 hrs (Immediate)

Answer 4

Skin, epithelia

Question 5

Describe the barrier functions that inhibit infectious disease from 4-96 hrs (Early)

Answer 5

Local inflammation C5a

Local TNF-alpha

Question 6

Describe the barrier functions that inhibit infectious disease from 96-100 hrs (Late)

Answer 6

IgA in luminal spaces
IgE on mast cells
Local inflammation

Question 7

Describe the general immune response to extracellular pathogens from 0-4 hrs (Immediate)

Answer 7

Phagocytes

Alternative and MBL complement pathways

Question 8

Describe the general immune response to extracellular pathogens from 4-96 hrs (Early)

Answer 8

MBL
C-reactive protein
T-independent B-cell antibody
Complement

Question 9

Describe the general immune response to extracellular pathogens from 96-100 hrs (Late)

Answer 9

IgG antibody and Fc receptor bearing cells

IgG, IgM antibody and classical complement pathway

Question 10

Describe the general immune response to intracellular bacteria from 0-4 hrs (Immediate)

Answer 10

Macrophages

Question 11

Describe the general immune response to intracellular bacteria from 4-96 hrs (Early)

Answer 11

Activated NK-dependent macrophage activation

IL-1, IL-6, TNF-alpha, IL-12

Question 12

Describe the general immune response to intracellular bacteria from 96-100 hrs (Late)

Answer 12

T-cell activation of macrophages by IFN-gamma

Question 13

Describe the general immune response to virus-infected cells from 0-4 hrs (Immediate)

Answer 13

NK cells

Question 14

Describe the general immune response to virus-infected cells from 4-96 hrs (Early)

Answer 14

IFN-alpha & IFN-beta

IL-12 activated NK cells

Question 15

Describe the general immune response to virus-infected cells from 96-100 hrs (Late)

Answer 15

Cytotoxic T cells

IFN-gamma

Question 16

Recognition of a PAMP by dendritic cells and other APCs, causes them to express this receptor (aka CD80) on their surface that binds to CD28 on T cells for activating T cells and in the case of APC B-cells, serves as their 2nd signal of activation.

Answer 16

receptor B7 (aka CD80)

Question 17

________ cells underlying mucosal surfaces can extend between epithelial cells to sample antigen in the gut lumen. (similarly to M cells)

Answer 17

Dendritic cells

Question 18

Well over 50% of the lymphocytes in our bodies reside in the _______.

Answer 18

MALT (mucosa-associated lymphoid tissue)

Question 19

CD4 T cells recognize their cognate peptides (antigen) bound to MHC class _____ molecules.

Answer 19

MHC class II

Question 20

CD4 effector cells have two primary effector functions:

Answer 20

1- supply the second signal of activation to B cells

2- activation of macrophages

Question 21

MHC class II molecules are only expressed on these 3 immune cells:

Answer 21

Macrophages
Dendritic cells
B cells

Question 22

CD8 T cells must recognize their cognate peptide determinant bound to MHC class _____ molecules.

Answer 22

MHC class I

Question 23

Which cells express MHC class I molecules?

Answer 23

ALL NUCLEATED cells in the body EXCEPT RBCs (notable non-nucleated cell) and neurons!

Question 24

CD8-mediated immune responses are typically most important for clearing intracellular or extracellular infections?

Answer 24

Intracellular

Question 25

Why is it critical that some extracellularly derived antigens be presented on MHC class I molecules and some intracellularly derived antigens be presented on MHC class II molecules? (cross-presentation)

Answer 25

If not for cross presentation, there would be no way to produce Th1 type effector CD4 T cells that have specificity for determinants of intracellular pathogens. It would also be impossible to produce an acquired antibody response to an intracellular pathogen.

Question 26

Briefly describe the two signals of activation of a naive T cell and why they are needed.

Answer 26

1st: recognition of cognate peptide:MHC complex on surface of APC thru the TCR. 2nd: Interaction between CD28 on T cell with B7 on APC 2nd signal of activation helps prevent activation of T-cells when there is no infection...if T cells recognize their cognate determinant when there is no infection ongoing, their cognate determinant is most likely a self determinant and the T cell will become anergic and die. (that is how peripheral tolerance works)

Question 27

Once the T-cell is activated by the 2nd signal of activation, it produces what cytokine that induces proliferation and differentiation into effector cells?

Answer 27

IL-2

Question 28

Once a T cell becomes activated and begins to proliferate, initially most of the daughter cells will differentiate into short-lived effector cells, while some of the daughter cells will differentiate into ________ cells that represent a clonally expanded population of cells that are specific for a determinant of a pathogen and will live for a very long time in the secondary lymphoid tissues.

Answer 28

Memory T cells

Question 29

Due to the elevated presence (10-100 fold) of these cells after a primary infection or immunization (compared to before), upon subsequent infections, re-exposure to the same pathogen (antigen) will result in much more rapid and effective T cell responses.

Answer 29

Memory T cells

Question 30

Do effector T cells require costimulatory (B7) signaling?

Answer 30

Nope.

Question 31

What are effector T cells gonna do when they recognize their cognate peptide antigen bound to an MHC molecule?

Answer 31

"perform their effector function" aka FUCK SHIT UP

Question 32

How is it that effector T cells access the tissues in which they will "perform their function", aka raise hell bitches.

Answer 32

They have an adhesion molecule array (VLA-4 & LFA-1) on their surface that allows them access. It's kind of like a battering ram for kicking down doors to FUCK SHIT UP

Question 33

If Effector T cells where a division of local law enforcement, what would they be?

Answer 33

The SWAT team. They got the call from the regular police (APCs via MHC and B7), got suited up (IL-2, proliferation, differentiation) and have their battering rams, door breech shotguns, and flash-bangs (adhesion molecule array: VLA-4 & LFA-1) for FUCKING SHIT UP

Question 34

How do naive T cells get into the secondary lymphoid tissues so they can get a taste of what's going on infection-wise in the rest of the body?

Answer 34

They express L-selectin that binds to addressins on high epithelial venules. Once they enter the 2ndary lymphoid tissues, their ability to express LFA-1 allows them to interact closely enough with APCs to sample their MHC:peptide complexes

Question 35

Let's say a Cytotoxic T cell aka CD8 aka Badass mofo arrives at a site of intracellular infection. BA mofo diapedeses over to a pissed off looking enterocyte he suspects may be infected with a Salmonella sp. (that the CTL happens to be specific for). What does he need for confirmation before he initiates programmed cell death in the enterocyte aka SHUTS THAT SHIT DOWN.

Answer 35

``` An infected enterocyte would be expressing MHC class I on its surface bearing a peptide that the CTL would recognize, at which point he would initiate apoptosis in the enterocyte aka SHOOT HIM IN THE FACE WITH HIS OWN GUN. Note: no secondary activation required ```

Question 36

Regarding the effector T cell types: | What do CTLs do, basically?

Answer 36

Kill infected host cells Via: Cytotoxins--> perforin, granzymes, granulysin Cytokines--> IFN-gamma, LT, *Fas ligand*

Question 37

Regarding the effector T cell types: | What do Th1 cells do, basically?

Answer 37

1- *they activate macrophages* (primary signal of activation) 2- supply second signals of activation to naive B cells to make antibodies (become a plasma cell) 3- Production of opsonizing antibodies such as IgG1What Via: Cytokines--> *IFN-gamma*, expression of CD40 ligand to bind CD40 receptor on macrophages for 2ndary activation, GM-CSF, TNF-alpha

Question 38

Regarding the effector T cell types: | What do Th2 cells do, basically?

Answer 38

1- supply second signals of activation to naive B cells to make antibodies (become a plasma cell) Via: Cytokines: *IL-4, IL-5*, IL-10

Question 39

What do CD4 Th17 cells do again?

Answer 39

Enhance neutrophil response

Question 40

What do CD4 Treg cells do again?

Answer 40

Suppress T-cell responses

Question 41

Let's say an activated CD4 Th1 cell diapedeses up to a macrophage bearing his cognate antigen on an MHC class I molecule. What's gonna happen next? a) they take it to the HOTEL MOTEL HOLIDAY INN b) Macrophage signaled to get his shit together and start breaking down the intracellular pathogens he's been hosting in his phagosomes

Answer 41

Tehe

Question 42

Let's say a CD4 Th1 or Th2 cell diapedeses up to a B cell that has his cognate antigen on an MHC class II molecule on it's surface. What's gonna happen next? a) they go on a couple more dates until the B cell realizes the CD4 cell is just using it to get closer to its SISTER. b) The Th1/2 cell gives the B cell its second signal of activation which stimulates it to differentiate into a plasma cell and start secreting antibodies.

Answer 42

Hey, her sister was cuter...

Question 43

CD4 Th17 cells recruit neutrophils with these cytokines:

Answer 43

IL-17A IL-17F IL-6

Question 44

CD4 Treg cells tell T-cells to CHILL OUT with these suppressive cytokines:

Answer 44

IL-10 | TGF-beta

Question 45

CD4 Th0 cells activated in the presence of ______ and _______ will become Th1 cells.

Answer 45

IL-12 and IFN-gamma

Question 46

CD4 Th0 cells activated in the presence of ____ and ____ will become Th2 cells.

Answer 46

IL-4 and IL-6

Question 47

If the infection is caused by an extracellular pathogen, it is likely that a CD4 Th0 cell will be activated to a Th1 or Th2 cell?

Answer 47

Th2

Question 48

If the infection is caused by an intracellular pathogen, it is likely that a CD4 Th0 cell will be activated to a Th1 or Th2 cell?

Answer 48

Th1

Question 49

CD4 Th1 cells have 3 primary effector functions:

Answer 49

1- Macrophage activation 2- Production of IL-2 that can help drive proliferation of activated T cells 3- Production of cytokines and chemokines that promote production of macrophages and neutrophils and migration of those cells to the inflammatory site.

Question 50

In a T-cell activation of a B-cell, what are the reciprocal receptors on their surfaces that bind for activation?

Answer 50

1- MHC complex (B cell) with TCR (T cell) | 2- CD40 (B cell) with CD40 (T cell)

Question 51

Plasma and memory cells are derived from what immune cell type?

Answer 51

Activated B cells

Question 52

What happens during a germinal center reaction?

Answer 52

1- B cell proliferation 2- Somatic HYPERMUTATION 3- Affinity maturation 4- Isotype switching

Question 53

In the acute phase serum, higher levels of IgM or IgG will be seen?

Answer 53

IgM

Question 54

In the convalescent serum (2 months after first exposure to antigen), higher levels of IgM or IgG will be seen?

Answer 54

WAY higher levels of IgG

Question 55

List the Ab isotype(s) most associated with: | Neutralization

Answer 55

* ** IgG1,2,3,4 | * ** IgA

Question 56

List the Ab isotype(s) most associated with: | Opsonization:

Answer 56

* **IgG1 | * *IgG3

Question 57

List the Ab isotype(s) most associated with: | Sensitization for killing by NK cells

Answer 57

* *IgG1 | * *IgG3

Question 58

List the Ab isotype(s) most associated with: | Sensitization of mast cells

Answer 58

***IgE

Question 59

List the Ab isotype(s) most associated with: | Activation of complement system

Answer 59

* **IgM * **IgG3 * *IgG1

Question 60

List the Ab isotype(s) most associated with this property: | Transport across epithelium

Answer 60

***IgA dimer

Question 61

List the Ab isotype(s) most associated with this property: | Transport across placenta

Answer 61

* **IgG1 * *IgG3 * *IgG4

Question 62

List the Ab isotype(s) most associated with this property: | Diffusion into extravascular sites

Answer 62

* **IgG1,2,3,4 | * *IgA monomer

Question 63

Which Ab has the highest serum levels?

Answer 63

IgG1 (300% higher than 2nd highest)

Question 64

Can all isotypes of Abs that neutralize toxins/pathogens also serve as opsonins?

Answer 64

No.

Question 65

List the 3 basic functions of IgA as a neutralizer of toxins or pathogens.

Answer 65

1- Export toxins/pathogens from lamina propria, across epithelium (inside cells via Poly-Ig receptor) to lumen of gut. Can also bind toxins/pathogens on its way across epithelium while bound to Poly-Ig receptor. 2- Bind and neutralize toxins/pathogens on mucosal surface in gut. 3- Bind toxin/pathogen on M cell surface and take it to lymphoid tissue/dendritic cell for presentation to T cells.

Question 66

_______ (Ig) and ______ (Ig) can initiate antibody-dependent cell-mediated cytotoxicity (ADCC).

Answer 66

IgG1 and IgG3

Question 67

What cell type is the effector cell of Antibody-dependent cell-mediated cytotoxicity (ADCC)?

Answer 67

NK cells

Question 68

What are the events of ADCC that lead to the killing of the target cell?

Answer 68

1- Ab binds to target cell surface 2- Fc receptors of NK cell recognize/bind Ab on target cell 3- Cross-linking of Fc receptors signals NK cell to kill target cell 4- Target cell dies by apoptosis

Question 69

Mast cells express high-affinity receptors on their surface for this Ab to use as their antigen specific receptors:

Answer 69

IgE

Question 70

What cell type's granules contain the most inflammatory mediators of any immune cell?

Answer 70

Mast cell

Question 71

Why do repeated exposures to the same pathogen, several months after Effector T cells have already dropped after the first infection, not yield disease?

Answer 71

Antibody levels are still very high (long half-life of plasma cells and IgG) and thus the acquired immune response swiftly aborts the infection before it escalates to disease.