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Immunity Week 1 > ICL 1.0: Introduction to Innate Immunity > Flashcards

ICL 1.0: Introduction to Innate Immunity Flashcards

1
Q

what are the beneficial effects of the immune system?

A
  1. protection from invaders (extracellular and intracellular)
  2. elimination of altered self (tumors)
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2
Q

what are examples of intracellular invaders?

A

viruses

some bacteria and parasites

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3
Q

what are examples of extracellular invaders?

A

most bacteria, fungi and parasites)

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4
Q

what are some of the detrimental effects of the immune system?

A
  1. inflammation = discomfort

2. autoimmunity = damage to self

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5
Q

what did the smallpox vaccine do?

A

vaccination was first used against smallpox, a viral infection.

in 1979, after 3 years in which no case of smallpox was recorded, WHO announced that the virus has been eradicated

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6
Q

what is a pathogen?

A

any organism with the potential to cause disease

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7
Q

what is an opportunistic pathogen?

A

any organism that causes disease if the body’s defenses are weakened

in a normal, healthy situation, they wouldn’t cause disease

ex. HIV patients will be a lot more effected by viruses because HIV has lowered the number of T-cells in their body whereas normally, these viruses wouldn’t have done anything

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8
Q

what are the four kinds of pathogens?

A
  1. bacteria
  2. virus
  3. fungi
  4. parasites
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9
Q

what are some examples of bacteria? what diseases are they associated with?

A
  1. salmonella enteritidis = food poisoning

2. mycobacterium tuberculosis = tuberculosis

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10
Q

what are some examples of viruses? what diseases are they associated with?

A
  1. variola = smallpox
  2. influenza = flu
  3. HIV = AIDS
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11
Q

what are some examples of fungi? what diseases are they associated with?

A
  1. epidermophyton floccosum = ringworm

2. candida albicans = thrush, systemic candidiasis

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12
Q

what are some examples of parasites? what diseases are they associated with?

A
  1. trypanosoma brucei = sleeping sickness

2. plasmodium falciparum = malaria

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13
Q

what does a virus, bacteria, fungi and parasite look like?

A

slide 7

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14
Q

what is the 1st line of defense against a microbe?

A

innate immune system

block entry of pathogen into body

  • skin
  • mucous membranes (GI tract and airway)
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15
Q

what is the 2nd line of defense against a microbe?

A

innate immune system

if the microbe enters the body, internal defenses like phagocytes and complement kick in

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16
Q

which cells are phagocytes?

A
  1. neutrophils
  2. monocytes
  3. macrophages
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17
Q

what is the 3rd line of defense against a microbe?

A

adaptive immune system

specific immune defense like B cells and T cells

B cells = antibodies

T cells = cytotoxic T cells, helper T cells

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18
Q

what happens during the immediate stage of your immune defense response?

A

0-4 hours after exposed to microbe

mediated by the innate immune system

key molecules = complement, histamine, etc.

key cells = macrophages, mast cells, neutrophils

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19
Q

what are mast cells?

A

basophils in the tissue

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20
Q

what is the complement system?

A

part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane

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21
Q

what happens during the early stage of your immune defense response?

A

4-96 hours after exposed to microbe

mediated by the innate immune system

key molecules = complement, IL-1, TNFα, IL12, IFNα/β, MBP, CRP

key cells = macrophages, neutrophils, NK cells

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22
Q

what happens during the late stage of your immune defense response?

A

> 96 hours after exposed to microbe

mediated by the specific immune system

key molecules = IgM, IgG, IL2, IL4, IL12, IFNγ

key cells = T cells, B cells, macrophages

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23
Q

what are the three types of innate host defenses against infection?

A
  1. anatomical barriers
  2. humoral components
  3. cellular components
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24
Q

what are the anatomical barriers?

A
  1. mechanical factors
  2. chemical factors =
  3. biological factors
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25
Q

what are the humoral components of the immune system?

A
  1. Complement
  2. Coagulation system
  3. Cytokines
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26
Q

what are the cellular components of the immune system?

A
  1. Neutrophils
  2. Monocytes and macrophages
  3. NK cells
  4. Eosinophils
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27
Q

what parts of your body make up the “skin” part of the physical barrier against microbes?

A
  • hair
  • skin
  • nails
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28
Q

what parts of your body make up the mucosal surfaces of the physical barrier against microbes?

A
  • sinuses
  • trachea
  • lungs
  • kidney
  • bladder
  • vagina
  • stomach
  • intestines
  • eyes

aka the GI tract and respiratory tract

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29
Q

what are some of the mechanical factors that act as anatomical barriers?

A
  1. skin = squamous epithelium
  2. mucous membranes
    - non-ciliated epithelium like in the GI tract; does peristalsis
    - ciliated epithelium like in the respiratory tract; it’s a mucociliary elevator
    - epithelium like in the nasopharynx; flushing activates tears, saliva, mucus and urine
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30
Q

what are some of the chemical factors that act as anatomical barriers?

A
  1. skin
    - sweat = anti-microbial fatty acids
  2. mucous membranes
    - HCl = low pH
  • tears and saliva = lysozyme and phospholipase A
  • defensins in the respiratory and GI tract = antimicrobial
  • sufactants in lungs = opsonin
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31
Q

what are some of the biological factors that act as anatomical barriers?

A

normal flora in skin and mucous membranes

they have antimicrobial substances and compete for nutrients and colonization

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32
Q

what does the complement system do?

A

It’s a very important part of the innate immune system!

  • lysis of bacteria and some viruses
  • opsonin
  • increase in vascular permeability
  • recruitment and activation of phagocytic cells

Complement proteins are produced by the liver; the most important is C3

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33
Q

what does the coagulation system do?

A
  • increase vascular permeability
  • recruitment of phagocytic cells
  • Β-lysin from platelets; a cationic detergent
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34
Q

how do lactoferrin and transferrin work?

A

compete with bacteria for iron

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35
Q

how do lysozyme work?

A

they break down bacterial walls

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36
Q

what do neutrophils do?

A
  1. phagocytosis and intracellular killing

2. inflammation and tissue damage

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37
Q

what do macrophages do?

A
  1. Phagocytosis and intracellular killing
  2. Extracellular killing of infected or altered self targets
  3. Tissue repair
  4. Antigen presentation for specific immune response
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38
Q

what do NK and LAK cells do?

A

killing of virus-infected and altered self targets

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39
Q

what do eosinophils do?

A

kill certain parasites

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40
Q

what are the components of the immune system

A
  1. nonspecific = innate immune system which is made up of humoral and cellular parts

humoral = complement, interferone, TNF, etc.

cellular = macrophages, neutrophils

  1. specific = adaptive immune system which is made up humoral and cellular parts

humoral = antibodies

cellular = T cells and other effector cells

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41
Q

how can one single cell divide into such large array of

physically and functionally different type of cells?

A

different locations and different environments and different growth factors make the stem cell turn into different things!

42
Q

which cells are antigen independent cells?

A
  1. RBCs
  2. platelets
  3. neutrophils
  4. macrophages
  5. NK cells
  6. CD8
  7. CD4

don’t need to be activated

43
Q

which cells are antigen-dependent cells?

A
  1. cytotoxic T-cell
  2. TH1
  3. TH2

a bacteria or virus or some other antigen has to induce the change into these types of cells

without antigens, CTL, TH2, and TH1 cells won’t develop

44
Q

what do a T cell, B cell, NK cell, macrophages, dendritic cell, and neutrophil look like?

A

slide 23

slide 25-27

45
Q

what do lymphocytes do?

A

production of antibodies (B cells) or cytotoxic and helper functions (T cells)

46
Q

what do NK cells do?

A
  1. kill cells infected with certain viruses

2. Produce INFγ to activate macrophages

47
Q

what do plasma cells do?

A

they’re full differentiated form of B cells that secrete antibodies

48
Q

what do neutrophils do?

A

phagocytosis and killing of microorganisms

They are the backups for macrophages!

But they do NOT present antigens to T-cells

49
Q

what do dendritic cells do?

A

macrophages in the skin

they activate T cells and initiate the adaptive immune response

50
Q

what do mast cells do?

A

expulsion of parasites from body through release of granules containing histamine and other active agents

51
Q

what do macrophages do?

A

phagocytosis and killing of microorganisms

activation of T cells and initiation of immune responses

52
Q

what is innate immunity?

A

keeps most people healthy for most of the time

however, some infections outrun the innate immune response

53
Q

what is adaptive immunity?

A

the adaptive immune response adds to an ongoing innate immune response

increases the power and focus of the immune response, which provides a highly specialized defense against one pathogen

54
Q

what are the differences between the innate and adaptive immune system?

A
  1. innate immune system
    - self vs. non-self germline encoded
  • antigen independent
  • no memory response and no changes after 1st exposure
  • immediate response; within minutes
  1. adaptive immune system
    - self vs. non-self somatically selected
  • antigen specific
  • memory response
  • latent response; days
55
Q

which parts of the immune system involve innate immunity?

A
  1. epithelial barriers
  2. phagocytes
  3. complement
  4. nK cells
56
Q

which parts of the immune system involve adaptive immunity?

A
  1. antibodies

2. effector T cells

57
Q

what are the two parts of the innate immune response?

A
  1. recognition that a pathogen is present

2. kill and eliminate it

58
Q

what are the steps involved in the innate immune response?

A
  1. healthy skin is not inflamed
  2. surface wound introduces bacteria which activates resident effector cells to secrete cytokines
  3. vasodilation and increased vascular permeability allow fluid, protein and inflammatory cells to leave blood and enter tissue
  4. the infected tissue becomes inflamed, causing redness, heat, swelling and pain
59
Q

what are the signs of inflammation?

A
  • heat
  • pain
  • redness
  • swelling
60
Q

what are some of the things that can develop as a side effect of the immune response?

A
  1. allergies
  2. contact dermatitis
  3. Celiac disease
  4. Graft-versus-host disease
  5. rejection of organ transplant
  6. autoimmune diseases
61
Q

what is contact dermatitis?

A

a red, itchy rash caused by direct contact with a substance or an allergic reaction to it

many substances can cause such reactions, including soaps, cosmetics, fragrances, jewelry and plants

62
Q

what is Celiac disease?

A

disruption of the gut because of hypersensitivity to wheat gluten

63
Q

what is graft-versus-host disease?

A

when MHC-disparate transplanted BM attacks the skin, liver and intestines of the recipient

usually only happens with BM transplants

64
Q

what are PAMPs?

A

PAMP = Pathogen-Associate Molecular Patterns

they are bacterial components or products that induce a host innate immune-response

65
Q

what are some examples of PAMPs?

A

lipopolysaccharide (LPS), Gram -

peptidoglycan (PGN), Gram +

lipoteichoic acid (LTA), Gram +

N-formylated peptides (fMLP), both Gram - and Gram +

lipoarabinomannan (LAM), mycobacteria

66
Q

what are PRRs?

A

PRR = Pattern Recognition Receptors

recognition of PAMPs by PRRs results in the activation of different Intracellular
signaling molecules which mediate inflammatory responses & drive T cell development which leads to activation of adaptive immunity

67
Q

How does antigen presentation work in the innate vs. adaptive immune system?

A

the innate immune system can be activated by free antigens = pathogenic molecules detected freely in blood and tissue

the adaptive immune system requires antigen presentation = the pathogens must be engulfed by cells, broken down and the pieces of the protein are transported to the surface and the antigen is “presented” to T-cells for activation

68
Q

What are cytokines?

A

Cell signaling proteins

They’re often released by immune cells and stimulate inflammatory response

69
Q

What are the types of cytokines?

A
  1. Chemokines
  2. Interleukins
  3. TNF
  4. TGF
  5. Interferons
70
Q

What are chemokines?

A

A cytokines that attracts immune cells = chemotaxis

71
Q

What do interferons do?

A

Cytokines that interfere with viral replication

72
Q

What is chemotaxis?

A

The process of attracting immune system cells

73
Q

What are cluster of differentiation structures of the cell?

A

Cellular surface molecules found on many immune cells and are used to identify cell types

Some are used as receptor/cell binding sites

74
Q

Which cells are in the innate immune system?

A
  1. Phagocytes = macrophages and neutrophils
  2. Complement
  3. NK cells
  4. Eosinophils
  5. Mast cells and basophils
75
Q

How do the cells of the innate immune system recognize molecules that are foreign?

A

By looking for structures on pathogens called PAMPs = pathogen associated molecular patterns

PAMPs are patterns of molecules found on many microbes but not many human cells

Innate immune system cells recognize PAMPs by using pattern recognition receptors like toll-like receptors (TLRs)

76
Q

Where are TLRs found?

A

TLR = toll-like receptors —> a type of pattern recognition receptor that recognizes PAMPs

They’re found on macrophages, dendritic cells and mast cells

77
Q

What do TLRs do?

A

They’re PRRs that recognize PAMPs and then secrete cytokines which trigger an inflammatory response

78
Q

What are some of the PAMPs that the innate immune system responds to?

A
  1. Endotoxin (LPS)
  2. Peptidoglycan cell wall
  3. Mannose
  4. Lipoteichoic acid on gram-positive bacteria
  5. Double stranded RNA
  6. Unmethylated DNA
79
Q

What are endotoxins?

A

a PAMP also known as LPS

LPS is found in gram negative bacteria and can bind to LPS-binding protein found in the plasma - then that complex can bind CD14 on macrophages

CD14 binds LPS*****

Once CD14 is found, it triggers TLR4 which leads to cytokine production = IL-1, IL6, IL-8, TNF

80
Q

What is the peptidoglycan cell wall?

A

a PAMP that the innate immune system recognizes

If bacteria get inside a macrophage, there are intracellular NOD receptors

Once peptidoglycan binds to NOD inside the macrophage, it induces the production of cytokines

81
Q

What is mannose?

A

a PAMP that is a polysaccharide on bacteria/yeast

MBL (mannose-binding lectin) from liver binds to mannose and activates the lectin pathway of the complement activation

82
Q

Why does the innate immune recognize double stranded RNA?

A

Human cells don’t have double stranded RNA but many RNA viruses have double stranded RNA

83
Q

Why does the innate immune system recognize methylated DNA?

A

Most human DNA is methylated; unmethylated DNA is more common in bacterial DNA

84
Q

How long do monocytes circulate in the blood?

A

3 days

When the monocytes enter tissue they become macrophages

85
Q

What are liver macrophages called?

A

Kupffer cells

86
Q

What are the three functions of macrophages?

A
  1. Phagocytosis
  2. Cytokine production = trigger inflammatory response
  3. Antigen presentation to adaptive immune system
87
Q

What is phagocytosis?

A

When macrophages engulf pathogens into a structure called a phagosome

Phagosome inside the macrophage then merges with a lysosome inside the macrophage

lysosome has deadly enzymes which kills the virus or bacteria

88
Q

What is inside macrophage lysosomes?

A
  1. Reactive oxygen species

NADPH oxidase produces superoxides and H2O2 which are toxic to pathogens

  1. Reactive nitrogen intermediates

NO + O2- —> ONOO- (peroxynitrite)

  1. Enzymes

Proteases, nucleases, lysozyme

89
Q

How does tuberculosis effect phagocytosis?

A

It blocks the process of the phagosome fusing with the lysosome by modifying the phagosome so that it’s unable to fuse with the lysosome

This allows TB to proliferate inside the macrophage AND it’s protected from antibodies outside the macrophage that can’t get in!!

90
Q

What is Chediak-Higashi Syndrome?

A

Rare immune deficiency syndrome

Results in failure of lysosomes to fuse with phagosomes during phagocytosis

People who have this have recurrent bacterial infections

91
Q

What things activate macrophages?

A
  1. LPS from bacteria
  2. Peptidoglycan
  3. Bacterial DNA
  4. IFN-gamma from T-cells and NKC
  5. C5a protein from complement
92
Q

What are some of the surface receptors on macrophages?

A

CD14 —> binds LPS on gram - bacteria

Fc receptor —> binds to Fc portion of antibodies

C3b receptor —> binds to C3b portion of complement proteins

93
Q

Which 3 molecules allow macrophages to interact with T-cells?

A

MHCII binds to CD4 on T cells

B7 binds to CD28 on T cells

CD40 binds to CD40L on T cells

94
Q

Which cytokines do macrophages release?

A

IL-1 and TNF-α

Both increase the synthesis of endothelial adhesion molecules which allows neutrophils to enter inflamed tissue

They also release IL-6, IL-8, and IL-12

95
Q

What is IL-1?

A

It’s an endogenous pyrogen released by macrophages = causes fever

Acts on the hypothalamus and raises the set point in the body

96
Q

What is TNF α?

A

It’s released by macrophages and can cause vascular leak and septic shock

It’s a cachetin because it inhibits lipoprotein lipase in fat tissue which reduces utilization of fatty acids and leads to cachexia - this is why people can become cachexic when they have an infection!

TNF α can cause DIC….

97
Q

What does IL-6 do?

A

Causes fever

Stimulates acute phase protein production in liver like C-reactive proteins

98
Q

What does IL-8 do?

A

Attracts neutrophils

99
Q

What is IL-12?

A

Promotes TH1 T-cell development

100
Q

Which cells are chemotaxins for neutrophils?

A

IL-8 from macrophages

C5a from complement system

101
Q

What are opsonins?

A

They bind to foreign invaders and increase the likelihood it’ll be taken up by phagocytosis

A major opsonin for neutrophils is IgG — neutrophils have receptors for Fc portion of IgG antibody

102
Q

Which surface molecules are on NK cells?

A

CD16
Binds Fc portion of IgG antibodies which enhances activity of NK cells

CD56
Also called NCAM and it’s commonly expressed on the surface of NK cells and aids in binding to other cells

Immunity Week 1 (14 decks)

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