Adaptive Immunity

Question 1

What are some examples of antigen presenting cells?

Answer 1

Macrophages, B cells, dendritic cells, Langerhans’ cells

Question 2

What are some features of antigen presenting cells?

Answer 2

Strategically located (SALT, GALT, NALT, BALT, lymph nodes, spleen etc)

Pathogen capture (phagocytosis, macropinocytosis)

Diverse pathogen sensors (PRRS)

Question 3

What are pathogen regonition receptors?

Answer 3

They are proteins expressed by cells of the innate immune system to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with cell components that are released during cell damage or death.

Question 4

Where are dendritic cells located?

Answer 4

Lymph nodes, mucous membranes, blood

Question 5

What do dendritic cells present to?

Answer 5

Naive T cells

Question 6

Where are Langerhans’ cells located?

Answer 6

Skin

Question 7

What do Langerhans’ cells present to?

Answer 7

Naive T cells

Question 8

Where are B cells located?

Answer 8

Lymphoid tissues

Question 9

What do macrophages present to?

Answer 9

Effector T cells

Question 10

What do B cells present to?

Answer 10

Both naive and effector T cells

Question 11

What does MHC stand for?

Answer 11

Major Histocompatibility Complex

Question 12

What are PAMPs?

Answer 12

Pathogen-associated molecular patterns are molecules associated with groups of pathogens, that are recognized by cells of the innate immune system

Question 13

Where are class I molecules found?

Answer 13

On all nucleated cells

Question 14

What is the function of class I molecules?

Answer 14

To display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein.

Question 15

Where are class II molecules found?

Answer 15

On dendritic cells, macrophages, B cells

Question 16

What are the HLAs corresponding to class I molecules?

Answer 16

HLA-A, B, C

Question 17

What are the HLAs corresponding to class II molecules?

Answer 17

HLA-DR, DQ, DP

Question 18

Give a difference between class I and II molecules

Answer 18

The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I)

Question 19

What are some key features of MHC class I and II molecules

Answer 19

1) Co-dominant expression (greater number of different MHC molecules)
2) Polymorphic genes (presentation of different antigens/microbes)

3) Class I - present peptides from intracellular microbes
Class II - present peptides from extracellular microbes

Question 20

On which chromosome are the genes for MHC molecules coded?

Answer 20

6 (short arm)

Question 21

What is the peptide binding cleft?

Answer 21

Variable region with highly polymorphic residues

Question 22

Between which chains are the peptides presented in MHC class I molecules?

Answer 22

Between alpha 1 and 2

Question 23

What is the difference in the sizes of peptides that MHC class I and II can present?

Answer 23

Class I - between 9-10 amino acids

Class II - between 13-20 amino acids

Question 24

Where are the peptides presented in MHC class II molecules?

Answer 24

Between alpha 1 and beta 1

Question 25

True or False: An MHC molecule can only present one type of peptide

Answer 25

False Many peptides can be presented by the same MHC molecule

Question 26

What does MHC class I activate?

Answer 26

CD8+ T cells

Question 27

What does MHC class II activate?

Answer 27

CD4+ T cells

Question 28

True or False: The viral proteins on the airway epithelial cells are presented by MHC molecules called HLA-DP, HLA-DQ, HLA-DR

Answer 28

False These are class II molecules Should be presented by class I - HLA-A, HLA-B, HLA-C

Question 29

True or False: All peptides from the same microbe are presented by different MHC molecules

Answer 29

True

Question 30

Are both self and non-self peptides presented?

Answer 30

Yes

Question 31

What are long-tern nonprogressors?

Answer 31

Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load.

Question 32

What can determine whether a HIV-infected individual is a slow progressor or rapid progressor?

Answer 32

Slow progressors [HLA-B27, HLA-B51, HLA-B57] MHC molecules able to present key peptides for the survival of the virus (unmutated) so effective T cell response Rapid progressors [HLA-B35] MHC molecules present mutated peptides (less crucial peptides for the virus) - poor recognition by T cells, poor T cell response

Question 33

What are some clinical problems associated with MHC molecules?

Answer 33

Organ transplant rejection, Graft-Versus-Host reaction, association with autoimmune disease

Question 34

What is the association between HLA molecules and autoimmune disease?

Answer 34

Ankylosing spondylitis -> HLA-B27 in 90% of patients | Insulin dependent diabetes mellitus -> HLADQ2 in 50-75% of patients

Question 35

Summarise how extracellular microbes are processed and presented

Answer 35

Sensed by APC via the exogenous pathway (inside vesicles) Presented by MHC class II Activates CD4+ T cells Activates humoral response (antibodies, complement)

Question 36

Summarise how intracellular microbes are processed and presented

Answer 36

Sensed by APC via the exogenous AND endogenous pathway (in cytoplasmic compartment) Presented by MHC class II and MHC class I (cross presentation) Activates CD8+ and CD4+ T cells (need CD4+ to become cytotoxic T cell) Cell-mediated response and cytotoxic T cells activated

Question 37

Why is cross presentation required?

Answer 37

Need to activate CD4+ as well as CD8+ in order to get cytotoxic T cells (need the T helper cells too)

Question 38

Where do T cells mature?

Answer 38

Thymus

Question 39

What is the antigen receptor on the T cell called?

Answer 39

T cell receptor (TCR)

Question 40

How is TCR diversity generated?

Answer 40

Gene rearrangement

Question 41

Which kind of T cells are CD4+?

Answer 41

Helper

Question 42

Which kind of T cells are CD8+?

Answer 42

Cytotoxic

Question 43

What cytokines are produced by TH1 cells?

Answer 43

TNFalpha, IFNgamma

Question 44

What cytokines are produced by TH2 cells?

Answer 44

IL-4, IL-5, IL-10

Question 45

What cytokines are produced by TH17 cells?

Answer 45

IL-17

Question 46

What cytokines are produced by Treg cells?

Answer 46

IL-10, IL-35, TGFb

Question 47

How many signals do T cells require to become fully activated?

Answer 47

2 (costimulation)

Question 48

What are the signals required to fully activate a T cell?

Answer 48

A first signal, which is antigen-specific, is provided through the TCR which interacts with peptide-MHC molecules on the membrane of APCs. A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of APC and the T cell.

Question 49

What is an example of a costimulatory molecule?

Answer 49

CD28

Question 50

Which T helper cells are activated in response to extracellular microbes?

Answer 50

TH2, TH17

Question 51

Which T helper cells are activated in response to intracellular microbes?

Answer 51

TH1

Question 52

What is the action of TH1?

Answer 52

Activate CD8+ cytotoxic T cells | Produce IFNg which activates B cells (IgG) and macrophages

Question 53

How do cytotoxic T cells kill cells?

Answer 53

Perforin makes holes in cell membrane | Granzyme enters through holes and initiates apoptotic processs

Question 54

What is the main antibody that regulates allergies?

Answer 54

IgE

Question 55

What is the first antibody to appear in response to initial exposure to an antigen?

Answer 55

IgM

Question 56

Which pathway of the complement system does IgG activate?

Answer 56

Classical

Question 57

Describe the ratio of IgM to IgG upon first encounter of an antigen

Answer 57

High ratio

Question 58

What is the main antibody produced upon second encounter of an antigen?

Answer 58

IgG

Question 59

What is isotype switching?

Answer 59

Biological mechanism that changes a B cell's production of immunoglobulin (antibodies) from one type to another, such as from the isotype IgM to the isotype IgG

Question 60

What are the immune functions of IgG?

Answer 60

Enhanced phagocytosis, complement activation, neonatal immunity, toxin/virus neutralisation

Question 61

What is the main antibody found in breast milk?

Answer 61

IgA

Question 62

What is the function of IgA?

Answer 62

Mucosal immunity

Question 63

What are the functions of IgE?

Answer 63

Immunity against helminths | Mast cell degranulation (allergies)

Question 64

What is the function of IgM?

Answer 64

Complement activation

Question 65

In a case of chicken pox, which MHC molecules are expressing the viral peptides? Which cells?

Answer 65

MHC class I - all infected cells including APC

Question 66

In a case of chicken pox, which factors from the adaptive immunity will be used against the virus?

Answer 66

Antibodies, TH1, Cytotoxic T lymphocytes (NK cells used in innate immunity)

Question 67

How could you tell whether someone has had chickenpox before?

Answer 67

Blood test to look for VZV IgG (+/ IgM)