ICL 1.2: Function of Immune System

Question 1

which cells are the most important in the immune system?

Answer 1

phagocytes

Question 2

what is phagocytosis?

Answer 2

intracellular killing, inflammation and tissue damage

is carried out by several cell types, including the neutrophils, monocytes/ macrophages

Question 3

what is the CD marker for neutrophils?

Answer 3

CD66

Question 4

what are neutrophils?

Answer 4

neutrophils contain the enzyme-rich lysosomes, which can facilitate destruction of infectious microorganisms

they’re the most abundant WBC

short-lived phagocytic cells, they die within a few hours after entry, and form the pus at infected tissue

Question 5

is phagocytosis extra or intracellular?

Answer 5

it can be both!!

macrophages can kill bacteria inside and outside of them

Question 6

what are the three functions of monocytes/macrophages?

Answer 6

1. engulf: removal of bacteria and parasites, lysosomal granules break down materials into simple amino acids, and sugars
2. cytokine producing cells: TNFα, IL-1, IL-8
3. antigen-presenting cells: take up antigens, process them by denaturation or partial digestion and present them to T cells

Question 7

what are SOS signals?

Answer 7

how does our body know that bacteria has entered the body?

SOS signals are induced by N-formal methionine-containing peptides that are released by bacteria (stupid bacteria lol)

this peptide induces neutrophil and macrophage migration to the site of infection; it’s a chemoattractant factor

Question 8

which chemicals induce SOS signals?

Answer 8

N-formyl methionine-containing peptides

clotting system peptides

complement products

cytokines released by tissue macrophages

Question 9

which receptors do phagocytes have?

Answer 9

phagocytes bear different receptors that recognize microbial components and induce phagocytosis

these include:

• TLR4 (LPS Receptor)
• TLR2 (LTA receptor)
• FPR (fMLP receptor)
• Mannose Receptor

Question 10

what do the receptors on phagocytes do?

Answer 10

phagocytes bear different receptors that recognize microbial components and induce phagocytosis

binding of bacteria to these innate receptors causes activation of the phagocyte

this results in the synthesis and release of cytokines and the induction of lipid mediators of inflammation

the binding to the receptors also enhances phagocytosis and promotes killing of the bacteria

Question 11

what happens during phagocytosis?

Answer 11

Microbes are ingested into phagosomes, which fuse with lysosomes, and the microbes are killed by enzymes and ROI and NO = intracellular killing of microbes

the same substances may be released from the phagocytes and kill extracellular microbes

Question 12

what are the steps to phagocytosis?

Answer 12

1. microbes bind to phagocyte receptors
2. phagocyte membrane zips up around microbe
3. microbe ingested in phagosome
4. lysosome fuses with phagosome, killing microbe

Question 13

how do phagocytes kill bacteria?

Answer 13

phagocyte first forms pseudopods that engulf the bacterium, and this vesicle called the phagosome

fusion of a lysosome granule with the phagosome to form the phagolysosome releases the lysosomal proteins into the phagolysosome

Question 14

what are the lysosomal proteins?

Answer 14

1. proteases and lysozyme
2. defensins
3. production of reactive forms of oxygen

Question 15

what are defensins?

Answer 15

small cysteine-rich cationic proteins (18-45 amino acids).
They insert into membranes, creating pores that cause
components of bacteria to leak out

Question 16

what do ROS do to bacteria?

Answer 16

production of reactive forms of oxygen that are toxic to many bacteria, such as superoxide oxidizes disulfide linkages and inactivates essential bacterial surface
proteins

Question 17

what do lysozymes do?

Answer 17

hydrolyses mucopeptides in the cell wall

Question 18

what does lactoferrin do?

Answer 18

deprives pathogens of iron

Question 19

which molecules are involved in phagocyte oxygen-independent killing of bacteria?

Answer 19

1. lysozyme
2. lactoferrin
3. hydrolytic enzymes (proteases)

Question 20

how does oxygen-dependent killing of bacteria in phagocytes work?

Answer 20

NAPHD oxidase

intracellular bacteria in phagolysosomes are susceptible to reactive oxygen species, which damage cell wall components and fragment genomic DNA

Reactive Oxygen Intermediate (ROI) production is initiated by membrane-bound NADPH oxidase, which is activated by IFN-γ

O2 + NADPH –> NADP + superoxide radical via NADPH oxidase

O2- is further metabolized by superoxide dismutase (SOD) into peroxide

O2- + H+ –> O2 + H2O2

Question 21

when do granulomas form?

Answer 21

they may form when the macrophage cannot kill intracellular bacteria

a granuloma consists of a central core of infected macrophages, which can include multinucleated giant cells formed by macrophage fusions, surrounded by large single macrophages often called epithelioid cells

mycobacteria can persist in the cells of the granuloma

the central core is surrounded by T cells

Question 22

which cells kill foreign and altered self targets?

Answer 22

NK and LAK cells

ADCC cells

activated macrophages

eosinophils

CD8 T cells

Question 23

what are NK cells?

Answer 23

large granular lymphocytes (10%)

develop in bone marrow

circulate in blood, part of the innate immune system

no specific antigen recognition

Question 24

what’s the function of NK cells?

Answer 24

cell killing

the secretion of IFN-γ

Question 25

when are NK cells activated?

Answer 25

NK cells are an early component of host defense against infections they control the initial infection until adaptive immune system can eliminate the virus NK cells are activated by TNF, IFNα and IFNβ made by infected cells and macrophages

Question 26

how does positive feedback work with NK cells?

Answer 26

NK cells release IFN-γ IFN-γ activates macrophages macrophages release TNFα and IL 12 which activate NK cells

Question 27

what type of cells do NK cells recognize and target?

Answer 27

1. antibody-covered target cells FcγIII receptor (CD16) 2. "altered self" cells altered MHC I molecules

Question 28

how does antibody dependent cytotoxicity of NK cells work?

Answer 28

NK cells have FcγRlll receptors (CD16) on their surface. when these cells encounter cells coated with antibody, they rapidly kill the target cell 1. antibody binds to antigens on the surface of target cells 2. FcγRIII (CD16) receptors on NK cells recognize bound antibody on the target cell 3. cross-linking of Fc receptors signals the NK cell to kill the target cell 4. target cell dies by apoptosis

Question 29

why are normal cells not killed by NK cells?

Answer 29

``` NK cells express non-TCR-related receptors, called killer-cell inhibitory receptors (KIR), which bind to MHC class I molecules ``` when ligated, KIRs protect the cell from being killed by NK cells MHC class I on normal cells is recognized by KIRs so the NK cell doesn't kill the normal cell

Question 30

how are cancer cells killed by NK cells?

Answer 30

infected or tumor cells have reduced MHC class I on their surfaces so when such cells encounter NK cells, they fail to engage these killer-cell inhibitory receptors (cannot stimulate a negative signal) and therefore activated NK cell releases granule contents to kill the target cells altered or absent MHC class I cannot stimulate a negative signal so the NK cell is triggered by signals from activating and release granule contents inducing apoptosis in target cell

Question 31

how do inhibitory receptors of NK cells work?

Answer 31

the inhibitory receptors of NK cells recognize self class l MHC molecules, thus ensuring that NK cells do not attack normal host cells

Question 32

what does ADCC stand for?

Answer 32

Antibody-dependent Cellular Cytotoxicity

Question 33

what is ADCC?

Answer 33

a mechanism by which antibodies enhance innate immunity neutrophils, eosinophils, macrophages, and especially natural killer (NK) cells show enhanced killing of target cells that are precoated with specific IgG antibody the lytic process is called antibody dependent cellular cytotoxicity (ADCC) recognition of bound antibody occurs through a low affinity receptor on the leukocyte called FcγRIII or CD16

Question 34

what are the over-arching steps in ADCC?

Answer 34

ADCC = antibody dependent cellular cytotoxicity the way it works is that there are antigens on the surface of the target cell there are specific IgG antibodies that recognize the surface antigen, bind to it and coat the target cell the antibody-coated target cell is then recognized by effector cells like NK cells and the target cell is destroyed

Question 35

what are LAK cells?

Answer 35

LAK - lymphokine activated killer cell if IFN and IL2 cytokines both bind to LAK cells, they will induce the cell to release granules and kill transformed and malignant cells LAK cells are great for treating cancer!

Question 36

what percent of lymphocytes are B vs. T cells?

Answer 36

B cells = 10-15% T-cells = 75-80%

Question 37

what do T cells do?

Answer 37

they help activate B lymphocytes they're part of cell-mediated immunity

Question 38

what are null cells?

Answer 38

include specialized lymphocytes lack T or B cell surface (NK cells) that kill certain tumors markers and virus-infected cells

Question 39

what are cytotoxic T cells?

Answer 39

Cytotoxic CD8 T cells release granules that contain perforin and granulysin these enzymes make pores in the target-cell membrane through which the granzymes can enter and cleave certain cell proteins that initiate apoptosis

Question 40

how do cytotoxic T cells work?

Answer 40

activated cytotoxic T cells express the cell-surface cytokine Fas ligand, which binds to Fas molecules on the target-cell surface T cell releases granules at site of cell contact this interaction sends signals to the target cell to undergo apoptosis through capsase family

Question 41

what does CTL stand for?

Answer 41

Tk-Ly T-lymphocyte cytotoxic T lymphocyte

Question 42

what are the characteristics of NK cells?

Answer 42

Large granular lymphocytes no specific antigen recognition do not express T-cell receptor do not express Ig genes circulate in blood, part of the innate immune system

Question 43

what are the three ways phagocytes can kill microbes?

Answer 43

1. Oxygen-independent killing (proteases, lysozyme and defensins) 2. O2-dependent killing Reactive Oxygen Intermediate (ROI) 3. Nitric Oxide mediated killing

Question 44

which cells are cytotoxic cells?

Answer 44

NK LAK ADCC CD8T