Unit 4 - Immune System PART C-E

Question 1

List the Innate Immunity – Physical Barriers

Answer 1

1. Skin
2. Hairs in Nasal Passageway / Eyelashes
3. Mucous Membranes

Question 2

Innate Immunity – Physical Barriers

Skin:

Answer 2

• tough protective layer outer layer (cells are KERATINIZED)
• sweat from sweat glands contains BACTERIOCIDAL CHEMICALS
• SEBUM (oil) from sebaceous glands blocks pores and reduces cracking of skin

Question 3

Innate Immunity – Physical Barriers

Hairs in Nasal Passageway / Eyelashes:

Answer 3

filter larger airborne particles

Question 4

Innate Immunity – Physical Barriers

Mucous Membranes:

Answer 4

• lines all body cavities/tracts that open to the outside of the
  body including the respiratory, gastrointestinal, urinary, and
  reproductive, tracts.
• mucus produced by Goblet cells in mucus membranes traps pathogens and other particles

Question 5

Innate Immunity – Mechanical Barriers

Answer 5

Involves flushing mechanisms (cilia that move creating fluid flow)

Question 6

Innate Immunity – Mechanical Barriers

Examples:

Answer 6

1. Mucociliary escalator
2. Flow of tears
3. Flow of urine
4. Coughing and Sneezing

Question 7

Innate Immunity – Mechanical Barriers

Mucociliary escalator:

Answer 7

• Involves the mucus membrane of the respiratory tract which is composed of a ciliated pseudostratified epithelium. The mucus produced by the goblet cells in this membrane traps microbes/debris.
• The beating (movement) of the cilia lining the bronchi and trachea then pushes the mucus along with its trapped microbes/debris from the lungs towards the pharynx (throat).

Question 8

Innate Immunity – Mechanical Barriers

Flow of tears:

Answer 8

Tears produced by the lachrymal gland flow over the surface of the eye diagonally, removing microbes and debris.

Question 9

Innate Immunity – Mechanical Barriers

Flow of urine:

Answer 9

Removes microbes and debris from the urinary tract.

Question 10

Innate Immunity – Mechanical Barriers

Coughing and Sneezing:

Answer 10

Blows out irritants (at speeds ≥ 160 km per hour)

Question 11

Innate Immunity – Chemical Barriers

Answer 11

1. pH
2. Enzymes
3. Antibodies
4. Complement System
5. Interferons (& innate defense against viruses)

Question 12

Innate Immunity – Chemical Barriers

pH:

Answer 12

acidity creates inhospitable environment for microbes

a. Skin
b. Stomach
c. Mucous Membranes

Question 13

Innate Immunity – Chemical Barriers

pH in SKIN:

Answer 13

Skin = pH 4.5 – 6 (referred to as the “acid mantle”)

Question 14

Innate Immunity – Chemical Barriers

pH in STOMACH:

Answer 14

Stomach = hydrochloric acid, pH = 1 – 2

Question 15

Innate Immunity – Chemical Barriers

pH in MUCOUS MEMBRANE:

Answer 15

Mucous Membranes = e.g. nasal cavity mucus has pH of 5.5-6.5

Question 16

Innate Immunity – Chemical Barriers

Enzymes:

Answer 16

damage microbes (especially bacteria)

a. Lysozyme
b. Proteases

Question 17

Innate Immunity – Chemical Barriers

Enzymes

Lysozyme:

Answer 17

damage bacterial cells walls of unencapsulated bacteria.

Found in many body fluids including tears, sweat, saliva, intestinal and bronchial mucus, breast milk).

Question 18

Innate Immunity – Chemical Barriers

Enzymes

Proteases:

Answer 18

(e..g. pepsin = digestive enzymes associated with

gastrointestinal tract) – antibacterial activity.

Question 19

Innate Immunity – Chemical Barriers

Antibodies

gA (Immunoglobulin A) antibodies:

Answer 19

bind to pathogens, clump them together and mark them for phagocytosis in case they cross into the internal environment.

Found in many body fluids including tears, sweat, saliva, intestinal and bronchial mucus, breast milk.

Question 20

Physical, mechanical & chemical barriers

Answer 20

• Epithelium
• Glandular Secretions
• Stomach Acidity
• Mechanical Removal

Question 21

Epithelium

Answer 21

the protective barrier of skin & mucous membranes is the body’s 1st line of defense

Question 22

Glandular Secretions

Answer 22

secretions include:
- mucous
- antibodies
- enzymes
to trap & disable pathogens

Question 23

Stomach Acidity

Answer 23

the low pH of the stomach helps destroy swallowed pathogens

Question 24

Mechanical Removal

Answer 24

pathogens can be physically removed

• mucociliary escalator
• tears
• coughing, sneezing
• GI motility

Question 25

Innate Immunity – Chemical Barriers Complement System:

Answer 25

Part of initial response to bacterial invasion. Cascade of over 30 proteins (found in extracellular fluids) that results in phagocytosis or lysis of foreign cells. - the complement proteins are secreted in inactive forms that are activated as the cascade proceeds - the cascade ends with the formation of MEMBRANE ATTACK COMPLEX, a group of lipid proteins that insert themselves into the cell membrane of pathogens & virus-infected cells & form giant pores (allow water & ions to enter the pathogen cells) - result: cells swell & lyse

Question 26

The most important protein of the complement system is...

Answer 26

complement protein C3 and specifically the C3b portion of this protein.

Question 27

Other functions of the complement system include:

Answer 27

a. Activation of inflammation via mast cells b. Opsonization (marking/flagging) of bacteria (via C3b). c. Complement proteins acting as chemotaxins (chemicals that attract cells) which helps to direct phagocytes towards invading pathogens like bacterial cells.

Question 28

Opsonins

Answer 28

are molecules that coat foreign particles to make them visible "food" for phagocytic leukocytes

Question 29

Some cytokines act as _____ that raise body temp by altering the hypothalamic set-poit

Answer 29

pyrogens

Question 30

Chemotaxins

Answer 30

chemicals that attract cells | - (signal molecules that attract leukocytes to help fight the infection)

Question 31

Describe the 3 steps in the immune responses to extracellular bacteria - bacterial infections cause inflammation & trigger immune responses

Answer 31

1. ACTIVATION OF THE COMPLEMENT SYSTEM - formation of membrane attack complex - activation of mast cells, with production of chemotaxins & histamine - complement proteins act as opsonins to enhance phagocytosis 2. ACTIVITY OF PHAGOCYTES - complement, antibodies, & other proteins act as opsonins to enhance phagocytosis 3. ADAPTIVE IMMUNE RESPONSE - antigen-presenting cells stimulate other lymphoid cells to produce antibodies & cytokines

Question 32

Innate Immunity – Chemical Barriers Complement Activation:

Answer 32

a. Classical Pathway b. Alternative Pathway Fig 24.6

Question 33

Innate Immunity – Chemical Barriers Complement Activation: a. Classical Pathway

Answer 33

(requires that adaptive immune response has occurred) C1 complement proteins are activated by binding to antibodies (IgG, IgM) that are already bound to pathogen (e.g. bacteria). Cascade produces C3 and C3b.

Question 34

Innate Immunity – Chemical Barriers Complement Activation: b. Alternative Pathway

Answer 34

(completely innate) - Carbohydrates on pathogen surface directly activate formation of C3 and C3b.

Question 35

Innate Immunity – Chemical Barriers Complement Activation: c. Result of both pathways:

Answer 35

i. C3b acts as opsonin that flags/marks pathogens for PHAGOCYTOSIS (phagocytes have C3b receptors) ii. C3b helps to form MEMBRANE ATTACK COMPLEXES (MAC) - Is converted to C5b, which punctures holes (pores) in microbe cell membranes, allowing Na+ and water to enter the cell – result = LYSIS (rupture of cell membrane iii. Byproducts C3a and C5a activate leukocytes involved in inflammatory response (mast cells, basophils)

Question 36

Membrane Attack Complexes (MAC)

Answer 36

Is converted to C5b, which PUNCTURES holes (pores) in microbe cell membranes, allowing Na+ and water to enter the cell – result = LYSIS (rupture of cell membrane)

Question 37

Innate Immunity – Chemical Barriers Interferons (& innate defense against viruses):

Answer 37

Interferons play an important role in short term innate immune defense against viruses. Also reinforces other immune activities: 1) enhances macrophage phagocytic activity; 2) stimulates antibody production; 3) enhances action of Natural Killer Cells.

Question 38

Innate Immunity – Chemical Barriers Interferons (& innate defense against viruses) also reinforce other immune activities:

Answer 38

1) enhances macrophage phagocytic activity; 2) stimulates antibody production; 3) enhances action of Natural Killer Cells.

Question 39

Innate Immunity – Chemical Barriers Interferons (& innate defense against viruses) Mechanism of Interferon action:

Answer 39

a. Viral RNA enters cell (e.g. COVID-19, Influenza, West Nile Virus, etc.) b. Virus uses host cell for replication. c. Virus causes host cell to produce Interferon α & β d. Interferon α & β are released from infected host cell and bind to cell membrane receptors on healthy neighboring cells. Triggers production of antiviral proteins (AVPs) in healthy cells. e. When virus tries to infect cells with AVPs, viral replication is blocked.

Question 40

Innate Immunity – Chemical Barriers: Interferons (& innate defense against viruses) AVPs are _____ if host cell is not infected.

Answer 40

INACTIVE

Question 41

There is evidence that _________ is associated with | more severe COVID-19 symptoms as a result of SARS-CoV-2 infection.

Answer 41

deficiency in interferon α & β

Question 42

Innate Immunity – Normal Flora

Answer 42

1. Skin Microbiome | 2. Gut microbiome

Question 43

Innate Immunity – Normal Flora Skin Microbiome:

Answer 43

commensal (“friendly”) bacteria on skin surface act to: a. BREAKDOWN SEBUM (oil and protein mixture released from sebaceous/oil glands in the skin), which releases fatty acids that contribute to low pH of skin surface. b. OUTCOMPLETE HARMFUL MICROBES.

Question 44

Innate Immunity – Normal Flora Gut microbiome:

Answer 44

commensal “friendly” bacteria in gastrointestinal tract act to: a. OUTCOMPETE HARMFUL MICROBES b. PROMOTE production of ANTIMICROBIAL PEPTIDES by intestinal epithelial cells. In the presence of a pathogen they signal to innate lymphoid cells in the gut lining causing these cells to release interleukin-22 (a cytokine). IL-22 stimulates production and secretion of antimicrobial proteins by the epithelial cells. c. REINFORCE TIGHT JUNCTIONS between epithelial cells in the gut (protect and maintain physical barrier).

Question 45

Innate Immunity either...

Answer 45

clears the infection or contains it until the adaptive immune response is active - key element is its broad specificity

Question 46

Innate Immunity Includes all...

Answer 46

immune cells except T and B lymphocytes which are involved in the adaptive immune response only.

Question 47

Several of the cells involved in the innate immune response have...

Answer 47

actions that impact adaptive immunity (i.e. they connect the two processes). These cells are the phagocytes (macrophages and dendritic cells) that act as antigen presenting cells (APCs). Note – not all phagocytes are antigen presenting cells.

Question 48

Note – NOT all phagocytes are ________

Answer 48

antigen presenting cells.

Question 49

Phagocytes

Answer 49

ingest material from the ECF using a large vesicle & include neutrophils, macrophages, dendritic cells

Question 50

Antigen-presenting cells (APCs)

Answer 50

have the ability to display bits of antigen on their surface as a signal to other immune cells

Question 51

The primary Antigen-presenting cells (APCs) are the...

Answer 51

macrophages & dendritic cells

Question 52

Innate Immunity includes:

Answer 52

1. The Phagocytes a. Macrophages b. Dendritic cells c. Microglia d. Neutrophils 2. Mast Cells & Basophils 3. Eosinophils 4. Natural Killer Cells (NKCs)

Question 53

Innate Immunity The phagocytes:

Answer 53

a. Macrophages b. Dendritic cells c. Microglia d. Neutrophils

Question 54

Innate Immunity The phagocytes: a. Macrophages

Answer 54

formed from monocytes --> precursor cells of tissue macrophages - not very common in blood (1-6% of all WBC's) - spend only ~8 hours in transit from bone marrow --> permanent position in the tissues - once in the tissues, monocytes enlarge & differentiate into phagocytotic MACROPHAGES

Question 55

Innate Immunity The phagocytes: a. Macrophages i. Professional phagocytes in tissues.

Answer 55

- Some move around and patrol tissues, waiting to be recruited to a particular area as part of the innate immune response. These migratory macrophages are particularly associated with mucous membranes. - Some are resident macrophages in a single tissue. These are typically sessile (little movement, or movement contained to a small area). For example alveolar macrophages in the lungs. (in either case, macrophages are the primary scavengers within the tissues) - All are larger and more effective phagocytes than neutrophils. They ingest up to 100 bacteria during their life span (long lived).

Question 56

Innate Immunity The phagocytes: a. Macrophages All are...

Answer 56

All are larger and more effective phagocytes than neutrophils. They ingest up to 100 bacteria during their life span (long lived).

Question 57

Innate Immunity The phagocytes: a. Macrophages ii. Role/Function in Innate Immunity

Answer 57

remove dead/dying cells, cellular debris, old RBCs, dead neutrophils; and ingest and digest pathogens

Question 58

Innate Immunity The phagocytes: a. Macrophages ii. Role/Function in Adaptive Immunity

Answer 58

act as ANTIGEN PRESENTING CELLS (APCs) - present antigens (pieces of digested pathogens) to T-cells

Question 59

Antigen-presenting macrophage displays...

Answer 59

antigen fragments on MHC-II surface receptors

Question 60

Innate Immunity – Cellular Barriers The Phagocytes: b. Dendritic Cells

Answer 60

are macrophage relatives characterized by long, thin processes that resemble the dendrite neurons

Question 61

Innate Immunity – Cellular Barriers The Phagocytes: b. Dendritic Cells i. Also professional phagocytes in tissues.

Answer 61

- Found IN SKIN (Langerhans cells) and other tissues, - Cells have LONG THIN PROCESSES. - Upon activation, they MIGRATE to lymphoid tissues (lymph nodes, and spleen)

Question 62

Innate Immunity – Cellular Barriers The Phagocytes: b. Dendritic Cells ii. Role/Function in Innate Immunity

Answer 62

NON-specific pathogen recognition; ingest and digest pathogens

Question 63

Innate Immunity – Cellular Barriers The Phagocytes: b. Dendritic Cells ii. Role/Function in Adaptive Immunity

Answer 63

act as ANTIGEN PRESENTING CELLS (APCs) - present antigens (proteins/carbohydrates from the pathogen cell surface) to T-cells in the lymph nodes and spleen.

Question 64

Innate Immunity – Cellular Barriers The Phagocytes: b. Dendritic Cells Have a key role in...

Answer 64

linking innate & adaptive immune responses by displaying bits of foreign antigen that they have ingested & processed

Question 65

Innate Immunity 1. The Phagocytes: c. Microglia i. Also professional phagocytes in tissues.

Answer 65

- Found in central nervous system (CNS) - Blood brain barrier blocks entry of other leukocytes and antibodies from the blood, so microglia function as the resident macrophages of CNS.

Question 66

Innate Immunity 1. The Phagocytes: c. Microglia ii. Role/Function in Innate Immunity

Answer 66

remove dead/dying cells, cellular debris; and ingest and digest pathogens

Question 67

Innate Immunity 1. The Phagocytes: c. Microglia ii. Role/Function in Adaptive Immunity

Answer 67

In healthy/homeostatic CNS – none.

Question 68

Innate Immunity 1. The Phagocytes: d. Neutrophils i. Important phagocytic immune cells.

Answer 68

- most abundant WBC (50-70% of total). - Short-lived: 1-2 day lifespan, during which it consumes only 5-20 bacteria. - Segmented nucleus with 3-5 lobes so also called POLYMORPHONUCLEAR CELLS

Question 69

Segmented nucleus with 3-5 lobes so also called...

Answer 69

POLYMORPHONUCLEAR CELLS

Question 70

Innate Immunity 1. The Phagocytes: d. Neutrophils ii. Role/Function in Innate Immunity

Answer 70

- First cell recruited to site of infection, attracted by chemotaxins produced as a result of complement activation. - removes invading microorganism (non-selective) - Releases pyrogens (fever causing cytokines)

Question 71

Innate Immunity 1. The Phagocytes: d. Neutrophils ii. Role/Function in Adaptive Immunity

Answer 71

None. NOT antigen-presenting.

Question 72

Innate Immunity 1. The Phagocytes: d. Neutrophils ONLY move into...

Answer 72

to tissues in response to infection (otherwise remain in blood) - found in bone marrow too & released into the circulation

Question 73

Phagocytosis

Answer 73

- a receptor-mediated event, which ensures that only unwanted particles are ingested - phagocyte receptors recognize many diff. types of foreign particles, both organic & inorganic, leading the cells to ingest everything

Question 74

Innate Immunity 1. The Phagocytes: Process of Phagocytosis:

Answer 74

i. Phagocytes identify microbes and other foreign particles by their PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPs) which bind to PATTERN RECOGNITION RECEPTORS (PRRs) on the phagocyte. Example of PRRs include Toll-like receptors. ii. Extensions of phagocyte cell membrane wrap around pathogen (with PAMPs on the pathogen binding to PRRs on the phagocyte along the way). As a result, the phagocyte engulfs the pathogen. iii. Ingestion of pathogen forms a cytoplasmic vesicle called a PHAGOSOME. iv. PHAGOSOME fuses with a lysosome that contains digestive enzymes and oxidizing agents. Fusion of the phagosome and lysosome forms a PHAGOLYSOSOME. v. In phagolysosome microbes are killed by: - O2 dependent phagocytosis involves: - O2 independent phagocytosis involves:

Question 75

Digestion by pathogens by phagocytosis is a critical step that...

Answer 75

links the nonspecific innate response to antigen-specific adaptive responses

Question 76

Phagocytes CANNOT instantly recognize all foreign substances, b/c some pathogens...

Answer 76

LACK markers that react with pattern recognition receptors ex: certain bacteria have evolved a polysaccharide capsule that masks their surface markers from the host immune system - these encapsulated bacteria are not as quickly recognized by phagocytes & consequently are more pathogenic b/c they can grow unchecked until the immune system finally recognizes them & makes antibodies against them

Question 77

Innate Immunity The Phagocytes: Process of Phagocytosis: v. In phagolysosome microbes are killed by: O2 DEPENDENT PHAGOCYTOSIS involves:

Answer 77

oxidizing agents (e.g. HYDROGEN PEROXIDE, SUPEROXIDE ANION, NITRIC OXIDE) produced in the phagolysosome are harmful to most cells/pathogens.

Question 78

Innate Immunity The Phagocytes: Process of Phagocytosis: v. In phagolysosome microbes are killed by: O2 INDEPENDENT PHAGOCYTOSIS involves:

Answer 78

- Enzymatic breakdown of microbe by LYSOSZYME (damages bacterial cell membrane), PROTEASES, or HYDROLYTIC ENZYMES. - Lysis by Antimicrobial peptides – e.g. DEFENSINS – bind to cell membrane and form pores (similar to MACs); effective against bacteria, fungi, viruses.

Question 79

Lysoszyme

Answer 79

damages bacterial cell membrane

Question 80

Defensins

Answer 80

bind to cell membrane and form pores (similar to MACs); effective against bacteria, fungi, viruses.

Question 81

Phagocytes can also ingest...

Answer 81

inorganic particles like asbestos and carbon. These cannot be digested/broken down enzymatically, so they stay in the cells.

Question 82

Innate Immunity Mast Cells and Basophils:

Answer 82

A type of non-phagocytic granulocyte | - 1 morphological group of leukocytes is the GRANULOCYTES, WBC's whose cytoplasm contains prominent granules

Question 83

Innate Immunity Mast Cells and Basophils: a. A type of non-phagocytic granulocyte.

Answer 83

- Mast cells present in tissues, basophils in circulation. Basophils are precursor to mast cells. - concentrated in connective tissue of skin, lungs and gastrointestinal tract (places where they are most likely to encounter pathogens). - covered with receptors for IgE, and often bound to IgE which triggers degranulation of mast cell and release of chemical mediators (contribute to inflammation) of the innate immune response.

Question 84

Basophils are precursor to _____.

Answer 84

MAST CELLS

Question 85

Degranulation

Answer 85

in all 3 types of granulocytes, the activated leukocyte releases its granule contents by exocytes, the activated leukocyte releases its granule contents by exocytosis, a process called DEGRANULATION

Question 86

Innate Immunity Mast Cells and Basophils: b. Role/Function in Innate Immunity

Answer 86

signaling (cytokine release and inflammatory response). i. Releases Histamine – mediates inflammation and is sensitized in allergy ii. Releases Heparin – Anticoagulant iii. Releases Chemotaxins – recruitment of other immune cells (e.g. neutrophils)

Question 87

Histamine

Answer 87

mediates inflammation and is sensitized in allergy - found primarily in granules of mast cells & basophils - active molecule that initiates the inflammatory response when mast cells degranulate - brings more leukocytes to the injury site to kill bacteria & remove cellular debris by dilating BV's, which increase BF to the area, & by opening pores in capillaries which allows plasma proteins to go into interstitial space, pulling water with them & leading to tissue edema - result of their release is a hot, red, swollen, area around a wound or infection site

Question 88

Heparin

Answer 88

Anticoagulant

Question 89

Chemotaxins

Answer 89

recruitment of other immune cells (e.g. neutrophils)

Question 90

Innate Immunity Mast Cells and Basophils: b. Role/Function in Adaptive Immunity

Answer 90

Same as above, but in response to antibodies IgE, IgG

Question 91

Innate Immunity Eosinophils: a. Cytotoxic cells related to neutrophils..

Answer 91

- ~1-3% of WBCs, short lived 6-12 hours. - concentrated in found in GI tract, lungs, urinary and genital eptithelia; connective tissue of skin (therefore, few found in peripheral circulation) - these locations reflect their role in defense against parasitic invaders (also participate in allergic rxns, where they contribute to inflammation & tissue damage by releasing toxic enzymes & oxidative substances)

Question 92

Innate Immunity Eosinophils: b. Role/Function in Innate Immunity

Answer 92

i. Specialized for ATTACKING LARGE PARASITES (antibody coated) ii. EXOCYTOSIS of GRANZYMES (hydrolytic enzymes) and Perforin onto parasite cell surface – creates a pore in cell membrane which will kill the parasite. - i.e. release substances from their granules that damage or kill the parasites

Question 93

Innate Immunity Eosinophils: c. Role/Function in Adaptive Immunity

Answer 93

some roles in coordinating responses of T cells.

Question 94

Natural Killer Cells (NKCs):

Answer 94

kill virus-infected cells - form a 3rd category of lymphocytes - dev. in bone marrow as well as in other tissues - participate in innate response against viral infections - act more rapidly (within hours of a primary viral infection) than other lymphocytes - programmed to recog. virus-infected cells & induce them to commit suicide by APOPTOSIS before the virus can replicate

Question 95

Innate Immunity 4. Natural Killer Cells (NKCs):

Answer 95

a. INNATE (NON-SPECIFIC) LYMPHOCYTES. (unlike B and T cells which have specificity). - Major Histocompatibility Complex I receptors have an INHIBITORY EFFECT on the action of NKCs, so can only kill any cell that LACKS MHC I proteins in their membranes. Healthy cells will have intact MHC 1. (NK cells target virus-infected cells by looking for cells without MHC cells I proteins on their surface - some viruses try to evade the human immune system by blocking the host cell's synthesis of MHC proteins)

Question 96

nnate Immunity 4. Natural Killer Cells (NKCs): b. Activated by

Answer 96

b. Activated by INTERFERONS (IFs – interfere with viral replication) or macrophage released cytokines to kill altered self cells : e.g. VIRUS infected cells, cancerous cells . - Altered self cells/tumor cells lack MHC I molecules and virus infected cells down-regulate MHC I expression. - When MHC I is missing/downregulated, activated NKCs can attack, and will: i. Release perforin in proximity to target cell – forms hydrophilic pore in membrane (similar to action of MACs on bacterial cells) ii. Release granzyme B – a cytotoxic enzyme that initiates apoptosis (cell death).

Question 97

When MHC I is missing/downregulated, activated NKCs can attack, and will:

Answer 97

i. Release perforin in proximity to target cell – forms hydrophilic pore in membrane (similar to action of MACs on bacterial cells) ii. Release granzyme B – a cytotoxic enzyme that initiates apoptosis (cell death).

Question 98

Natural Killer Cells (NKCs) secrete multiple antiviral cytokines, including...

Answer 98

INTERFERONS - ability to interfere with viral replication by promoting syn. of antiviral proteins

Question 99

Without MCH protein, the host cell...

Answer 99

CANNOT display viral antigen on its surface, which allows the virus to hide undetected inside the cell - but NK cells don't need viral antigen to activate them - instead they are programmed to find & attack cells displaying low [ ]'s of MCH I