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Human Physiology 2 > Unit 4 - Immune System PART C-E > Flashcards

Unit 4 - Immune System PART C-E Flashcards

1
Q

List the Innate Immunity – Physical Barriers

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

Innate Immunity – Physical Barriers

Skin:

A
  • 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
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3
Q

Innate Immunity – Physical Barriers

Hairs in Nasal Passageway / Eyelashes:

A

filter larger airborne particles

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4
Q

Innate Immunity – Physical Barriers

Mucous Membranes:

A
  • 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
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5
Q

Innate Immunity – Mechanical Barriers

A

Involves flushing mechanisms (cilia that move creating fluid flow)

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6
Q

Innate Immunity – Mechanical Barriers

Examples:

A
  1. Mucociliary escalator
  2. Flow of tears
  3. Flow of urine
  4. Coughing and Sneezing
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7
Q

Innate Immunity – Mechanical Barriers

Mucociliary escalator:

A
  • 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).
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8
Q

Innate Immunity – Mechanical Barriers

Flow of tears:

A

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

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9
Q

Innate Immunity – Mechanical Barriers

Flow of urine:

A

Removes microbes and debris from the urinary tract.

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10
Q

Innate Immunity – Mechanical Barriers

Coughing and Sneezing:

A

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

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11
Q

Innate Immunity – Chemical Barriers

A
  1. pH
  2. Enzymes
  3. Antibodies
  4. Complement System
  5. Interferons (& innate defense against viruses)
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12
Q

Innate Immunity – Chemical Barriers

pH:

A

acidity creates inhospitable environment for microbes

a. Skin
b. Stomach
c. Mucous Membranes

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13
Q

Innate Immunity – Chemical Barriers

pH in SKIN:

A

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

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14
Q

Innate Immunity – Chemical Barriers

pH in STOMACH:

A

Stomach = hydrochloric acid, pH = 1 – 2

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15
Q

Innate Immunity – Chemical Barriers

pH in MUCOUS MEMBRANE:

A

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

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16
Q

Innate Immunity – Chemical Barriers

Enzymes:

A

damage microbes (especially bacteria)

a. Lysozyme
b. Proteases

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17
Q

Innate Immunity – Chemical Barriers

Enzymes

Lysozyme:

A

damage bacterial cells walls of unencapsulated bacteria.

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

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18
Q

Innate Immunity – Chemical Barriers

Enzymes

Proteases:

A

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

gastrointestinal tract) – antibacterial activity.

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19
Q

Innate Immunity – Chemical Barriers

Antibodies

gA (Immunoglobulin A) antibodies:

A

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.

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20
Q

Physical, mechanical & chemical barriers

A
  • Epithelium
  • Glandular Secretions
  • Stomach Acidity
  • Mechanical Removal
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21
Q

Epithelium

A

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

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22
Q

Glandular Secretions

A 
secretions include:
- mucous
- antibodies
- enzymes
to trap & disable pathogens
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23
Q

Stomach Acidity

A

the low pH of the stomach helps destroy swallowed pathogens

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24
Q

Mechanical Removal

A

pathogens can be physically removed

  • mucociliary escalator
  • tears
  • coughing, sneezing
  • GI motility
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25
Q

Innate Immunity – Chemical Barriers

Complement System:

A

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
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26
Q

The most important protein of the complement system is…

A

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

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27
Q

Other functions of the complement system include:

A

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.

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28
Q

Opsonins

A

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

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29
Q

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

A

pyrogens

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30
Q

Chemotaxins

A

chemicals that attract cells

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

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31
Q

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

A
  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
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32
Q

Innate Immunity – Chemical Barriers

Complement Activation:

A

a. Classical Pathway
b. Alternative Pathway

Fig 24.6

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33
Q

Innate Immunity – Chemical Barriers

Complement Activation:

a. Classical Pathway

A

(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.

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34
Q

Innate Immunity – Chemical Barriers

Complement Activation:

b. Alternative Pathway

A

(completely innate)

  • Carbohydrates on pathogen surface directly activate formation of C3 and C3b.
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35
Q

Innate Immunity – Chemical Barriers

Complement Activation:

c. Result of both pathways:

A

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)

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36
Q

Membrane Attack Complexes (MAC)

A

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)

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37
Q

Innate Immunity – Chemical Barriers

Interferons (& innate defense against viruses):

A

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.

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38
Q

Innate Immunity – Chemical Barriers

Interferons (& innate defense against viruses) also reinforce other immune activities:

A

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

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39
Q

Innate Immunity – Chemical Barriers

Interferons (& innate defense against viruses)

Mechanism of Interferon action:

A

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.

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40
Q

Innate Immunity – Chemical Barriers:

Interferons (& innate defense against viruses)

AVPs are _____ if host cell is not infected.

41
Q

There is evidence that _________ is associated with

more severe COVID-19 symptoms as a result of SARS-CoV-2 infection.

A

deficiency in interferon α & β

42
Q

Innate Immunity – Normal Flora

A
  1. Skin Microbiome

2. Gut microbiome

43
Q

Innate Immunity – Normal Flora

Skin Microbiome:

A

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.

44
Q

Innate Immunity – Normal Flora

Gut microbiome:

A

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).

45
Q

Innate Immunity either…

A

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

46
Q

Innate Immunity

Includes all…

A

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

47
Q

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

A

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.

48
Q

Note – NOT all phagocytes are ________

A

antigen presenting cells.

49
Q

Phagocytes

A

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

50
Q

Antigen-presenting cells (APCs)

A

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

51
Q

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

A

macrophages & dendritic cells

52
Q

Innate Immunity includes:

A
  1. The Phagocytes
    a. Macrophages
    b. Dendritic cells
    c. Microglia
    d. Neutrophils
  2. Mast Cells & Basophils
  3. Eosinophils
  4. Natural Killer Cells (NKCs)
53
Q

Innate Immunity

The phagocytes:

A

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

54
Q

Innate Immunity

The phagocytes:

a. Macrophages

A

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
55
Q

Innate Immunity

The phagocytes:

a. Macrophages
i. Professional phagocytes in tissues.

A
  • 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).
56
Q

Innate Immunity

The phagocytes:

a. Macrophages

All are…

A

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

57
Q

Innate Immunity

The phagocytes:

a. Macrophages
ii. Role/Function in Innate Immunity

A

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

58
Q

Innate Immunity

The phagocytes:

a. Macrophages
ii. Role/Function in Adaptive Immunity

A

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

59
Q

Antigen-presenting macrophage displays…

A

antigen fragments on MHC-II surface receptors

60
Q

Innate Immunity – Cellular Barriers

The Phagocytes:

b. Dendritic Cells

A

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

61
Q

Innate Immunity – Cellular Barriers

The Phagocytes:

b. Dendritic Cells
i. Also professional phagocytes in tissues.

A
  • Found IN SKIN (Langerhans cells) and other tissues,
  • Cells have LONG THIN PROCESSES.
  • Upon activation, they MIGRATE to lymphoid tissues (lymph nodes, and spleen)
62
Q

Innate Immunity – Cellular Barriers

The Phagocytes:

b. Dendritic Cells
ii. Role/Function in Innate Immunity

A

NON-specific pathogen recognition; ingest and digest pathogens

63
Q

Innate Immunity – Cellular Barriers

The Phagocytes:

b. Dendritic Cells
ii. Role/Function in Adaptive Immunity

A

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

64
Q

Innate Immunity – Cellular Barriers

The Phagocytes:

b. Dendritic Cells

Have a key role in…

A

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

65
Q

Innate Immunity

  1. The Phagocytes:
    c. Microglia
    i. Also professional phagocytes in tissues.
A
  • 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.
66
Q

Innate Immunity

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

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

67
Q

Innate Immunity

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

In healthy/homeostatic CNS – none.

68
Q

Innate Immunity

  1. The Phagocytes:
    d. Neutrophils
    i. Important phagocytic immune cells.
A
  • 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
69
Q

Segmented nucleus with 3-5 lobes so also called…

A

POLYMORPHONUCLEAR CELLS

70
Q

Innate Immunity

  1. The Phagocytes:
    d. Neutrophils
    ii. Role/Function in Innate Immunity
A
  • 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)
71
Q

Innate Immunity

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

None. NOT antigen-presenting.

72
Q

Innate Immunity

  1. The Phagocytes:
    d. Neutrophils

ONLY move into…

A

to tissues in response to infection (otherwise remain in blood)

  • found in bone marrow too & released into the circulation
73
Q

Phagocytosis

A
  • 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
74
Q

Innate Immunity

  1. The Phagocytes:

Process of Phagocytosis:

A

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:

75
Q

Digestion by pathogens by phagocytosis is a critical step that…

A

links the nonspecific innate response to antigen-specific adaptive responses

76
Q

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

A

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

77
Q

Innate Immunity

The Phagocytes:

Process of Phagocytosis:

v. In phagolysosome microbes are killed by:

O2 DEPENDENT PHAGOCYTOSIS involves:

A

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

78
Q

Innate Immunity

The Phagocytes:

Process of Phagocytosis:

v. In phagolysosome microbes are killed by:

O2 INDEPENDENT PHAGOCYTOSIS involves:

A
  • 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.
79
Q

Lysoszyme

A

damages bacterial cell membrane

80
Q

Defensins

A

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

81
Q

Phagocytes can also ingest…

A

inorganic particles like asbestos and carbon.

These cannot be digested/broken down enzymatically, so they stay in the cells.

82
Q

Innate Immunity

Mast Cells and Basophils:

A

A type of non-phagocytic granulocyte

- 1 morphological group of leukocytes is the GRANULOCYTES, WBC’s whose cytoplasm contains prominent granules

83
Q

Innate Immunity

Mast Cells and Basophils:

a. A type of non-phagocytic granulocyte.

A
  • 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.
84
Q

Basophils are precursor to _____.

A

MAST CELLS

85
Q

Degranulation

A

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

86
Q

Innate Immunity

Mast Cells and Basophils:

b. Role/Function in Innate Immunity

A

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)

87
Q

Histamine

A

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
88
Q

Heparin

A

Anticoagulant

89
Q

Chemotaxins

A

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

90
Q

Innate Immunity

Mast Cells and Basophils:

b. Role/Function in Adaptive Immunity

A

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

91
Q

Innate Immunity

Eosinophils:

a. Cytotoxic cells related to neutrophils..

A
  • ~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)

92
Q

Innate Immunity

Eosinophils:

b. Role/Function in Innate Immunity

A

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

93
Q

Innate Immunity

Eosinophils:

c. Role/Function in Adaptive Immunity

A

some roles in coordinating responses of T cells.

94
Q

Natural Killer Cells (NKCs):

A

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
95
Q

Innate Immunity

  1. Natural Killer Cells (NKCs):
A

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)

96
Q

nnate Immunity

  1. Natural Killer Cells (NKCs):
    b. Activated by
A

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).

97
Q

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

A

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).

98
Q

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

A

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

99
Q

Without MCH protein, the host cell…

A

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

Human Physiology 2 (37 decks)

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