Block B - Cell Killing

Question 1

How do neutrophils kill cells? (1 mark)

Answer 1

contains granules and enzyme pathways that assist in the elimination of pathogenic cells

Question 2

How do immune cells recognise pathogens, through what pattern?

Answer 2

PAMPs by PRRs

Question 3

Name 2 receptors that bind PAMPs and can induce phagocytosis

Answer 3

glucan receptors (dectin-1) and mannose receptor

Question 4

what are opsonins?

Answer 4

proteins that bind to foreign cells, making it easier for immune cells to recognise and destroy them. opsonins also act as a bridge

Question 5

Name 2 antibodies that act as opsonins?

Answer 5

IgM, IgA and IgG

Question 6

Name the complement fragment that acts as an opsonin?

Answer 6

C3b

Question 7

Name 2 of the best characterized opsonic receptors

Answer 7

Fc receptors (FcR) and the complement receptors (CR)

Question 8

What molecules do FcRs bind to?

Answer 8

the Fc portion of Antibodies, particularly IgG and IgA (since they are opsonins)

Question 9

Whats a phagolysosome and how does it help with the killing of cells? (3 marks)

Answer 9

its when a phagosome and lysosome fuse during the process of phagocytosis. lysosomes contain digestive enzymes which is how it destroys using oxygen-independant killing. oxygen-dependant killing is through reactive oxygen species (ROS)

Question 10

Briefly explain the process of an oxidative burst which lead to reactive oxygen species (ROS) being produced (2 marks)

Answer 10

-when a phagocyte engulfs a pathogen, it triggers an oxidative burst. there is then rapid production of ROS, primarily through the activation of the NADPH oxidase complex located in the phagocyte’s membrane

Question 11

How does the reactive oxygen species produce different types of ROS? (3 marks)

Answer 11

The NADPH oxidase complex consists of multiple subunits that come together upon activation. It converts molecular oxygen into superoxide anion. The superoxide can then be converted into hydrogen peroxide by superoxide dismutase.

Question 12

How does ROS help eliminate pathogens? Give 2 examples of some potent ROS types (5 marks)

Answer 12

-Superoxide and hydrogen peroxide, are potent antimicrobial agents in the ROS types.
-ROS can oxidize lipids in microbial membranes, increasing permeability and causing lysis.
-ROS can modify amino acids in proteins, leading to dysfunction of essential proteins in pathogens.
-ROS can induce mutations of microbial DNA, impairing their ability to replicate and function.

Question 13

What is Myeloperoxidase (MPO)? ( 2 marks)

Answer 13

It is an enzyme that is primarily found in neutrophils, a type of white blood cell. It plays a critical role in the immune response, particularly during the inflammatory process.

Question 14

What is the role of MPO? (2 marks)

Answer 14

MPO catalyzes the reaction of hydrogen peroxide with chloride ions to produce hypochlorous acid, a powerful antimicrobial agent. This reaction occurs during the oxidative burst in neutrophils.

Question 15

Whats the role of inducible nitric oxide synthase (iNOS)? (4 marks)

Answer 15

-Inducible nitric oxide synthase (iNOS) is an enzyme that produces nitric oxide (NO) in response to pro-inflammatory stimuli.
-NO is a potent antimicrobial agent. It can directly kill pathogens by damaging their DNA, proteins, and lipids.
-NO faciltates the activation and recruitment of other immune cells.
-iNOS promotes expression of pro-inflammatory cytokines

Question 16

Whats the role of hydrolytic enzymes? (3 marks)

Answer 16

-stored in lysosomes
-degrade proteins and polysaccharides in the cell wall of the bacteria
-also help modulate inflammation by degrading pro-inflammatory mediators

Question 17

Name the primary granules in Neutrophils and their role? (2 marks)

Answer 17

-Azurophils are released early during the immune response and play a crucial role in pathogen destruction.
-They release MPO which generates reactive oxygen species (ROS) that help kill microbes, and defensins which disrupt microbial membranes

Question 18

How do Neutrophil Granules help eliminate pathogens? (4 marks)

Answer 18

-the enzymes and proteins released during the degranulation process contribute to the destruction of bacteria and fungi.
-MPO plays a vital role in generating hypochlorous acid, contributing to the oxidative burst that helps kill engulfed pathogens
-neutrophil granules release cytokines and chemokines that recruit and activate other immune cells, amplifying the inflammatory response
-the tertiary granules contain MMPs and are involved in breaking down extracellular matrix components, facilitating neutrophil migration to sites of infection and contributing to the healing process.

Question 19

Describe 2 ways pathogens evade the immune response with examples (2 marks)

Answer 19

-Shigella flexneri destroys the phagosome before it fuses with lysosomes and escape the cytosol
-Legionella halts phagosome maturation into phagolysosomes

Question 20

CD4 and MHC II relates to which type of T-cell

Answer 20

T helper Cell

Question 21

CD8 and MHC I relates to which type of T-cell

Answer 21

cytotoxic T cell

Question 22

How does MHC-II recognition determine T cell lineage and function (3 marks)

Answer 22

when a double positive (DP) thymocyte expresses a TCR that interacts with MHC-II on a cortical thymic epithelial cell (cTEC), a CD4 co-receptor assists this interaction. this leads to loss of expression for the uninvolved CD8 co-receptor

Question 23

What specific type of pathogens do cytotoxic T cell target and why is this important?

Answer 23

targets intracellular pathogens, important because antibodies cannot access intracellular pathogens

Question 24

MHC class I molecules are found on _____

Answer 24

all nucleated cells

Question 25

MHC class II molecules are found on _____

Answer 25

APCs only

Question 26

Describe how cytotoxic T cells specifically target cells with lytic granules? (3 marks)

Answer 26

-after forming a immunological synapse, the cytotoxic T cell recognizes the infected target cell through specific binding of the TCR to the antigen-MHC class I complex on the target cell
-Upon activation, the cytotoxic T cell undergoes signaling that triggers the exocytosis of lytic granules
-these granules, perforin and granzymes, are released into the synaptic cleft which specifically induces apoptosis in infected or abnormal cells while sparing healthy cells that do not present the specific antigen

Question 27

How specifically does perforin trigger apoptosis? (3 marks)

Answer 27

-perforin is released when cytotoxicity is triggered
-creates holes in the target cell membrane
-which allows granzymes into the cell to cleave important substrates in the cell

Question 28

Describe how granzyme B works to induce apoptosis?

Answer 28

-Once inside the cytoplasm, Granzyme B can directly activate caspase-3, which is a crucial executioner caspase in the apoptosis pathway and can lead to the cleavage of proteins involved in DNA repair
-caspase-3 can also cleave structural proteins, disrupting the integrity of the membrane and can lead to necrosis
-promotes the release of cytochrome c which binds to Apaf-1, forming the apoptosome, which activates initiator caspase-9, which is an imporant enzyme in the apoptosis pathway.

Question 29

Which cytokine regulates perforin and granzyme expression?

Answer 29

IL-2

Question 30

Name a factor that protects Tc from being killed by its own granules?

Answer 30

perforin is inactive at the acidic PH found inside the cytolytic granules, its only once its in neutral PH when its released from the cell that it activates

Question 31

Which cytokine do NK cells require for proliferation?

Answer 31

IL-15

Question 32

Where do NK cells originate from in the body? (1 mark)

Answer 32

NK cells originate from hematopoietic stem cells in the bone marrow

Question 33

As NK cells mature, precursors start expressing markers such as _____ and loss of _____

Answer 33

CD56, CD16

Question 34

Describe the characteristics of NK cells with high CD56bright surface markers? (2 marks)

Answer 34

more proliferative and produce high levels of cytokines like IL-2 and IFN-γ, but they have lower cytotoxic activity.

Question 35

Describe the characteristics of NK cells with high CD56dim surface markers? (3 marks)

Answer 35

These are more cytotoxic and are typically the dominant subset in peripheral blood. They express CD16, which allows them to mediate antibody-dependent cellular cytotoxicity (ADCC).

Question 36

After maturation in the bone marrow, NK cells migrate to where?

Answer 36

peripheral tissues such as the spleen, liver, and lymph nodes and can also circulate in the bloodstream

Question 37

Compare NK cells to cytotoxic T cells. (5 marks)

Answer 37

-they both secrete cytokines and chemokines, like perforin and granzymes influencing the immune response
-they both kill infected cells
-the cytoplasm of NK cells have granules in it while Tc cells need to be activated before the produce granules
-NK cells dont require prior exposure to the antigen like Tc cells do. they instead rely on a balance of signals from activating and inhibitory receptors to detect infected cells
-Tc cells can also develop into T memory cells, providing lost lasting protection while NK cells do not

Question 38

EQ. Discuss the mechanisms of target recognition employed by Natural Killer (NK) cells (4 marks)

Answer 38

-NK cells assess the overall signal balance from activating and inhibitory receptors. If the activating signals outweigh the inhibitory ones, the NK cell will be activated and initiate cytotoxic responses.
-they recognize cells that lack normal MHC class I expression, which is a common feature used by many virus-infected and cancerous cells to evade Tc cell recognition, this promotes activation
-NKG2D recognizes ligands that are often upregulated on infected or tumor cells which lead to activation signals
-KIR (Killer Immunoglobulin-like Receptors) and NKG2A, bind to MHC class I molecules on healthy cells. When NK cells encounter a healthy cell expressing MHC class I, these inhibitory signals prevail, preventing activation.

Question 39

Describe what role CD16 plays in the activation of Natural Killer (NK) cells (4 marks)

Answer 39

-CD16 is a receptor on NK cells primarily involved in ADCC, a process where NK cells target and kill antibody-coated cells (such as infected or tumor cells)
-When antibodies bind to antigens on the surface of these target cells, the Fc region of the antibodies is exposed.
-CD16 binds to the Fc region of IgG antibodies attached to the target cell.
-this engagement activates NK cells, leading to their degranulation and the release of cytotoxic factors

Question 40

Describe how nectins promote NK cell activation (4 marks)

Answer 40

-highly expressed on tumour cells
-becomes accessible when the structure of epithelium is disrupted
-stabilises binding to NK cells during immunological synapse formation
-if the signal is strong it results in cell cytotoxicity