32.3 Effector Mechanisms in Immunity to Infection

Question 1

How do antibodies aid in elimination of infection?

Answer 1

Opsonization and initiation of acute inflammation.

Question 2

What is opsonization?

Answer 2

Opsonins (e.g. Ab) are used to tag foreign pathogens for elimination by phagocytes.
*Antibody is bound to microorganisms and the Fc portion binds to the Fc receptors of phagocytes

Question 3

How can Abs initiate acute inflammation?

Answer 3

*Complement activation (IgM/G) –> inflammation
*Abs on phagocytes –? phagocytosis –> initiation of acute inflammation

Question 4

How do antibodies provide resistance against infection?

Answer 4

Prevent pathogen binding to and entering host cells

Question 5

What can antibodies neutralize?

Answer 5

Viruses and bacterial products, such as toxins.

Question 6

How do antibodies neutralize?

Answer 6

By binding to surface structures (antigens) and preventing it from interacting with other cells (e.g. host cells)

Question 7

What is the role of Fc in the immune response?

Answer 7

While Fab is bound to the target cell, Fc binds to FcRs on leukocytes
–> triggers signalling pathway and release of lytic enzymes, perforin, granzymes, TNF
–> destroys target cell

Question 8

Give examples of an Fc receptor-mediated Ab function.

Answer 8

*Antibody-dependent cell-mediated cytotoxicity (ADCC)
*Ab-dependent cellular phagocytosis (opsonise pathogen to tag for ingestion + destruction)
*Complement-dependent cytotoxicity

Question 9

What happens in Complement-dependent cytotoxicity?

Answer 9

Abs activate complement system –> lysis of the pathogen or infected system.

Question 10

What is antibody-dependent cellular cytotoxicity?

Answer 10

A mechanism of cell-mediated immune defense where an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies.

Question 11

Which cells are Fcreceptor-expressing?

Answer 11

monocytes, macrophages, NK cells.

Question 12

What is the mucosae in terms of pathogen entry?

Answer 12

It is the major site of pathogen entry

Question 13

How is mucosal immunity achieved?

Answer 13

Through MALT (mucous-associated lymphoid tissue) underlying mucosa
Throughout body, known as the common mucosal immune system.

Question 14

What are the Peyer’s patches?

Answer 14

MALT lining the small intestine. Here antigens are samples and it is a SLO able to initiation of the immune response begins with the activation of lymphocytes.

Question 15

What does MALT contain?

Answer 15

• T cells, B cells
• Plasma cells
• Macrophages
• Intestine: M cells, which sample antigen from the lumen

Question 16

What are the functions of IgA antibodies?

Answer 16

The first line of defence in the mucosae in the resistance against infection, via inhibiting bacterial and viral adhesion to epithelial cells and by neutralisation of bacterial toxins and virus, both extra- and intracellularly.

Question 17

Which MHC class do CD8+ T-cells recognise?

Answer 17

peptide-MHC class I complexes (recognised by CD8)

Question 18

What is required for CD8 activation?

Answer 18

MHC class I:peptide binding with TCR receptor and CD8 molecule
Costimulation with B7 (CD80) on APC interacting with CD28 on T cell
Cytokines IL-1 and IL-2

Question 19

What does IL-2 stimulate in T cells?

Answer 19

Stimulates T cell proliferation (clonal proliferation) of antigen specific T cells

Question 20

What is CD8+ T-cells cytotoxic role?

Answer 20

induction of apoptosis in target cell: killing the virally infected cells to abort the infection and potentially killing tumour cells.

Question 21

How do CTLs detect tumour cells in the body?

Answer 21

When malignant cells accumulate somatic mutations, they generate novel (non self) proteins which are expressed by MHC class I molecules
CTLs are activated by dendritic cells that present the neoantigens and infiltrate and kill the tumour cells

Question 22

Why do CD8+ T cells need to be highly regulated?

Answer 22

All nucelated cells express MHC class I so all cells are potential APCs
Require IL-2 for their activation produced by nearby Th CD4+ cells

Question 23

What are CD8+ T-cells mechanisms of lysis?

Answer 23

perforin/ granzyme and FasL killing.

Question 24

What is the perforin/ granzyme mechanism of lysis?

Answer 24

Secretion of perforin/ protease filled granules by CD8+ T-cells:
*Perforin monomers form transmembrane channels in target cells → leak.
*Proteases can enter cell cytosol (e.g. granzyme B → cleaves procaspases into caspases to initiate cell apoptosis).

Question 25

What is the FasL killing mechanism?

Answer 25

Fas-FasL interactions
Induce IC signalling → activate caspases → cell apoptosis
Secrete TNF-alpha → TNF Rs on target cells → apoptosis.

Question 26

What do Tfh cells express and secrete to aid CD8+ T cells?

Answer 26

Express CD40L which interacts with dendritic cells to increase the expression of costimulatory molecules (CD80/B7) to ensure activation of T cells
Secrete IL-2 needed for T cell clonal proliferation

Question 29

How do some viruses and tumours try to evade the adaptive immune system and how is this combatted?

Answer 29

• Some viruses and tumours avoid immune surveillance by down-regulating or inhibiting MHC class I expression and becoming invisible to CTL
• In order to avoid this scenario, natural killer (NK) cells are deployed which actively kill somatic cells devoid of MHC class I

Question 30

What is the lineage of natural killer (NK) cells?

Answer 30

• NK cells derive from the common lymphoid progenitor and are closely allied to T and B cells
• However, they are considered components of the innate immune system, so they are frequently called ‘innate lymphoid cells’, which seems like somewhat of an oxymoron

Question 31

Which immune system are natural killer (NK) cells part of?

Answer 31

They are part of the innate immune system, but they are activated by the adaptive immune system.

Question 32

Which cytokines activate NK cells?

Answer 32

IL-12
IL-2
IFN -gamma

Question 33

How do natural killer cells know whether to kill a cell?

Answer 33

• Natural killer cells lack either a TCR or surface Ig for antigen recognition
• Killing of target cells does not require prior priming
• The decision of whether to kill a target cell depends on the balance between activating and inhibitory receptor signaling
• Killing occurs only if the activating signal is dominant: dominant inhibitory signals pacify the cell

Question 34

Which receptor is found on NK cells that prevents apoptosis

Answer 34

Killer inhibitor receptor which normally binds to MHC class I to stop apoptosis of target cells

Question 35

Why is it important to kill cells not displaying MHC class I molecules?

Answer 35

Many cells loose their ability to synthesise MHC class I molecules after infection with a virus

Question 36

Why are NK cells generally thought of as being part of the innate immune system?

Answer 36

Despite being derived from common lymphoid progenitor cells, they do not recognise their target by detecting antigens presented by MHC, have no memory and are not enhanced upon exposure to pathogens
They are non specific

Question 37

Give an example of an activating and inhibitory stimulus for natural killer cells.

Answer 37

Activating:

• NK cells express CD16, which is a receptor for the Fc region of immunoglobulins.
• Therefore, although NK cells are part of the innate immune response, they are stimulated by the adaptive immune response.

Inhibitory:

• NK cells express KIRs (Killer Cell Immunoglobulin-like Receptors)
• They bind specifically to MHC class I, regardless of the peptide presented
• Stimulation of the KIRs inhibits the NK cell
• Failure to do so results in NK cell activation and killing of the target cell -> Thus this protects against certain virus infections or tumours that inhibit MHC class I expression

Question 38

What are some functions of natural killer cells?

Answer 38

• Killing virally-infected/tumour cells.
• Activation of macrophages early in response

Question 39

What do natural killer cells secrete to stimulate macrophages?

[IMPORTANT]

Answer 39

IFN-γ

Question 40

How do NK cells kill target cells?

Answer 40

Secrete cytotoxins (perforins and granzymes) which make a hole in the membrane to release the contents of the cells

Question 41

What is the function of macrophages in the innate immune response?

Answer 41

*Phagocytosis
*Antigen presentation (interplay with specific immune response)
*Secrete CKs that initiate/ regulate inflammation
*Wound healing + repair
*ROS secretion to kill phagocytosed bacteria.
*Granuloma formation (wall of infections body is unable to eliminate)

Question 42

How do macrophages aid the specific immune response?

Answer 42

Once they have phagocytosed and digested the pathogen, they will display peptides on MHC class II molecules for interaction with T helper cells