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PHRM 100 – APPP > APPP 10 and 12: Body Defense System > Flashcards

APPP 10 and 12: Body Defense System Flashcards

1
Q

What are the 5 properties of the immune system?

A
  • mobility
  • replication
  • specificity
  • memory
  • diversity
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2
Q

Properties of the Immune System

Mobility

A

systemic protection against localized insults through rapid cell migration to infected area

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3
Q

Properties of the Immune System

Replication

A

immune response is amplified through clonal expansion and signaling cascade

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4
Q

Properties of the Immune System

Specificity

A

prevent recognition of non-cross-reacting antigens and identify self vs. non-self

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5
Q

Properties of the Immune System

Memory

A

faster and stronger response to (similar) subsequent infection

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6
Q

Properties of the Immune System

Diversity

A

combinatorial library of antigen receptors to recognize innumerable pathogens

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7
Q

What are the primary lymphoid organs of the immune system?

A
  • thymus
  • bone marrow
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8
Q

What are the mucosal lymphatic tissues of the immune system?

A
  • tonsils and adenoids
  • appendix
  • Peyer’s patches
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9
Q

What are the other organs of the immune system?

A
  • lymph nodes
  • spleen (gigantic lymph node)
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10
Q

What is the lymphatic system?

A

circulation system of lymphatic vessels

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11
Q

How does the immune system monitor all parts of the human body?

A

through the circulation system and the system of lymphatic vessels

  • cells and fluids are exchanged between blood and lymphatic vessels, enabling the lymphatic system to monitor the body for invading microbes
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12
Q

Where are lymph nodes located?

A
  • sit along the lymphatic vessels, with clusters in the neck, armpits, abdomen, and groin
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13
Q

What does each lymph node contain?

A

each node contains specialized compartments where immune cells congregate and encounter antigens

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14
Q

How many lymph nodes are in the human body?

A

500-600

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15
Q

What are the 4 functional areas of lymph nodes?

A
  • cortex
  • germinal centre
  • para-cortex
  • medulla
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16
Q

What does the cortex of lymph nodes do?

A

contains unactivated mature T cells

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17
Q

What does the germinal centre of lymph nodes do?

A

contains activated B cells → plasma cell development and antibody affinity maturation

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18
Q

What does the para-cortex of lymph nodes do?

A

contains a mix of unactivated and activated mature T cells

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19
Q

What does the medulla of lymph nodes do?

A

funnels to collect mature immune cells and antibodies for distribution to lymphatic/blood circulation

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20
Q

What is innate immunity?

A

first, rapid, short-term responses to a broad range of microbes – direct pathogen identification

  • external defenses
  • internal defenses
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21
Q

What are the external defenses of innate immunity?

A
  • skin
  • mucous membranes
  • secretions
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22
Q

What are the internal defenses of innate immunity?

A
  • phagocytic cells
  • antimicrobial proteins
  • inflammatory response
  • natural killer cells
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23
Q

What is adaptive/acquired immunity?

A

slower responses to specific microbes (activated by, and responds to, innate immunity) – specialized and adaptable to a single type of invader, recognize invaders inside host cells, and able to recall encounters

  • humoral response (antibodies)
  • cell-mediated response (cytotoxic lymphocytes), with help from APC
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24
Q

Innate vs. Adaptive Immunity

Specificity

A
  • innate: limited and fixed
  • adaptive: extensive
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25
Q

Innate vs. Adaptive Immunity

Memory

A
  • innate: none
  • adaptive: yes
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26
Q

Innate vs. Adaptive Immunity

Time to Response

A
  • innate: hours
  • adaptive: days
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27
Q

Innate vs. Adaptive Immunity

Soluble Factors

A
  • innate: lysozymes, complement, C-reactive protein, interferons, mannose-binding lectin, antimicrobial peptides
  • adaptive: antibodies, cytokines
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28
Q

Innate vs. Adaptive Immunity

Cells

A
  • innate: neutrophils, monocytes, macrophages, natural killer cells, eosinophils
  • adaptive: B lymphocytes, T lymphocytes
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29
Q

Describe the specificity of innate immunity.

A

non-antigen specific

  • uses pre-existing limited library of receptors (pattern recognition receptor) – ie. toll-like receptors (TLRs)
  • recognition of highly conserved structures (pathogen-associated molecular patterns or PAMPs) – those essential to microorganism survival or pathogenicity (such as LPS and mannose)
  • equal response to a range of organisms
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30
Q

What are the cellular mediators of innate immunity? (8)

A

blood:

  • neutrophils
  • eosinophils
  • monocyte
  • natural killer cells
  • basophils

peripheral tissues:

  • macrophage
  • dendritic cells
  • mast cells
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31
Q

What do neutrophils do?

A

ingest (phagocytotic) and destroy

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32
Q

What do eosinophils do?

A

release toxic molecules and destroy

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33
Q

What do monocytes do?

A

ingest, destroy, and antigen presentation

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34
Q

What do natural killer cells do?

A

kill cancer or viral-infected host cells

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35
Q

What do basophils do?

A

release first chemicals that start inflammation

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36
Q

What do macrophages do?

A

ingest, destroy, and antigen presentation

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37
Q

What do dendritic cells do?

A

ingest, recruit others, and antigen presentation

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38
Q

What do mast cells do?

A

release first chemicals that start inflammation

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39
Q

Tissue-Specific Types of Monocytes

Brain

A

microglial cells

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40
Q

Tissue-Specific Types of Monocytes

Lung

A

alveolar macrophages

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41
Q

Tissue-Specific Types of Monocytes

Liver

A

Kupffer cells

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42
Q

Tissue-Specific Types of Monocytes

Kidney

A

mesangial phagocytes

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43
Q

Tissue-Specific Types of Monocytes

Lymph Node

A

resident and recirculating macrophages

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44
Q

Tissue-Specific Types of Monocytes

Spleen

A

macrophages

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45
Q

Tissue-Specific Types of Monocytes

Blood

A

monocytes

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46
Q

Tissue-Specific Types of Monocytes

Bone Marrow

A

precursors

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47
Q

Tissue-Specific Types of Monocytes

Joint

A

synovial A cells

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48
Q

Where are macrophages located?

A

in every tissue

  • some macrophages circulate in the blood and migrate with rapid response to insults in tissues
49
Q

Describe the structure and lifespan of macrophages.

A
  • morphology is amoeboid-like
  • inactive lifespan: months to years
  • active lifespan: days to weeks
50
Q

What are the functions of macrophages (3)

A
  • phagocytosis
  • antigen presentation (APC)
  • initiation of tissue repair
51
Q

Where are dendritic cells located?

A
  • immature: in blood and tissues – generally located in tissues interfacing with the outside (ie. skin, nose, lungs, stomach)
  • mature: activated cells move to lymph nodes – interact with T cells and B cells
52
Q

What are the functions of dendritic cells? (4)

A
  • phagocytes
  • antigen-presenting cells
  • activate adaptive immune response
  • regulate T-cell activation
53
Q

What are the specific functions of adaptive/acquired immunity? (5)

A
  • recognizes ‘non-self’ when ‘self’ is present
  • antigen-specific and clonal
  • each clonal population recognizes only one type of antigen
  • eliminates pathogens and infected cells
  • generates immunological memory
54
Q

Describe the development of B cells.

A
  • form and mature in bone marrow
  • classes: memory B cell, plasma cell
55
Q

Describe the development of T cells.

A
  • produced in bone marrow
  • mature in thymus
  • classes: helper, cytotoxic, memory, regulatory
56
Q

Helper T Cell

A
  • assist other immune cells with maturation/activation
  • enhance or suppress immune cell actions
  • recognize signal from antigen-presenting cells (binds to MHC II)
  • CD4+ co-receptor – activates cytotoxic T cells and B cells
  • 70% of all T cells
57
Q

Memory T Cell

A
  • coordinate rapid response to re-infection with same agent
  • proliferate when reintroduced to antigen
  • CD4+ or CD8+ co-receptor
58
Q

Cytotoxic T Cell

A
  • kill altered or infected cells
  • recognized infected cells (binds to MHC I)
  • CD8+ co-receptor – activation induces release of cytotoxic molecules
  • around 25% of all T cells
59
Q

T Regulatory Cell

A
  • suppress and regulate auto-reactive T cells
  • T cell receptor
  • CD4+
  • CD25
60
Q

What do T cells do?

A

activity against infected host cells (inaccessible to antibodies)

  • bacteria, viruses, fungus, parasites, cancer, transplants
  • no antigen-presenting property
61
Q

Memory B Cell

A

initiate rapid response to re-infection with same agent

  • allow for a stronger and faster immune response next encounter
62
Q

Plasma B Cell

A

neutralize toxins and viruses, opsonize bacteria

  • antibody production
63
Q

Describe the receptors of B lymphocytes.

A

each B lymphocyte produces only one type of antigen receptor

64
Q

What can activated B cells do?

A

can act as APC to activate helper T in the classical B cell activation pathway

65
Q

Interplay Between Innate and Acquired Immunity

A
  • co-activation of B cells through BCR and TLR
  • antigen presentation by macrophage
  • complement proteins
  • cytokines (ie. interferons, TNF, IL1
66
Q

Severe COVID

What does a reduction or dysfunction in the adaptive immune response lead to? (4)

A
  • over-activity of the innate system
  • exaggerated cytokine response
  • compromised normal immune functions
  • coagulation dysfunctions and other organ system failures
67
Q

What is inflammation?

A

acute (immediate) response to tissue injury and immune activation

  • mediated by the innate immune system
  • cross-talk and signaling through the release of cytokines and inflammatory chemicals/hormones
68
Q

Mediators of the Inflammatory Response

Pre-formed vs. Newly Synthesized Mediators (Slide 36)

69
Q

Protein Mediators of the Immune Response

Proteins and Polypeptides (Slide 37)

70
Q

Protein Mediators of the Immune Response

What are cytokines?

A

protein signaling molecules

71
Q

Protein Mediators of the Immune Response

What are the 5 types of cytokines?

A
  • interferons
  • chemokines
  • interleukins
  • TNF 𝛼
  • growth factors
72
Q

Protein Mediators of the Immune Response

What is the function of interferons?

A

involved in innate antiviral response

  • type I (𝛼, 𝛽)
  • type II (𝛾)
73
Q

Protein Mediators of the Immune Response

What is the function of chemokines?

A

chemotaxis proinflammatory – mediate chemoattraction/chemotaxis between cells

  • MCP-I
  • IL-8
  • etc.
74
Q

Protein Mediators of the Immune Response

What is the function of interleukins?

A

leukocyte development – acts on leukocytes, various functions

  • IL-6
  • IL-10
  • etc.
75
Q

Protein Mediators of the Immune Response

What is the function of TNF 𝛼 (tumour necrosis factor family)?

A

regulate immune and inflammation response

  • acute phase response
  • coagulation
76
Q

Protein Mediators of the Immune Response

What is the function of growth factors?

A

growth differentiation – blood cell production,

  • VEGF
  • GM-CSF
  • TGF 𝛽 – regulation of immunity and wound healing
  • etc.
77
Q

Protein Mediators of the Immune Response

Describe the composition of cytokines.

A
  • soluble proteins, peptides, or glycoproteins
  • picomolar (10^-12) or 0.000,000,000,000,1 mol/L
  • significant roles in inflammatory response – function as both pro- and anti-inflammatory molecules
78
Q

Chemical and Hormonal Mediators of the Immune Response

Amino Acids and Lipids (Slide 40)

79
Q

Chemical and Hormonal Mediators of the Immune Response

Describe these mediators.

A
  • signaling molecules activated or released by immune cells as well as injured cells
  • mediate inflammatory responses
80
Q

Chemical and Hormonal Mediators of the Immune Response

What are the 3 types of mediators?

A
  • amino acid derivatives: histamine, serotonin
  • lipid derivatives: prostaglandins, leukotrienes (both are eicosanoids)
  • hormones and other neurotransmitters: bradykinin, substance P
81
Q

Chemical and Hormonal Mediators of the Immune Response

What is histamine derived from and what is its main source?

A
  • derived from amino acid histidine
  • produce, store, and release mainly from mast cells
  • also from basophils
82
Q

Chemical and Hormonal Mediators of the Immune Response

What is the function of histamine?

A

vasodilation and increase permeability

  • serves important roles in immune responses and inflammation process
  • binds to and activates GPCRs (H1 to H4 tissue-specific subtypes)
83
Q

Chemical and Hormonal Mediators of the Immune Response

What is serotonin derived from and what is the main source?

A
  • derived from amino acid tryptophan
  • produced by enterochromaffin cells and stored mainly in platelets
84
Q

Chemical and Hormonal Mediators of the Immune Response

What is the function of serotonin?

A

vasodilation, increase permeability, pain, fever

  • neurotransmitter serves multiple functions in homeostasis (GI, CNS, and body defence)
  • binds to and activates GPCRs (5HT1 to 7 tissue- and function-specific subtypes
85
Q

Lipid Mediators of the Humoral Immune Response

How are eicosanoids synthesized?

A

synthesized with arachidonic acids (diet + cell/nuclear membrane

86
Q

Lipid Mediators of the Humoral Immune Response

What are eicosanoids?

A

lipid mediators

87
Q

Lipid Mediators of the Humoral Immune Response

Describe the structure of eicosanoids.

A
  • made by oxidation of omega-6 fatty acids
  • 20 carbons, 4 double bonds
  • biosynthesis by cyclo-oxygenase (prostagalndins) or lipo-oxygenase (leukotrienes)
88
Q

Lipid Mediators of the Humoral Immune Response

What are the 3 main mediators?

A
  • prostaglandins
  • leukotrienes
  • platelet activating factor
89
Q

Lipid Mediators of the Humoral Immune Response

What is the main source of prostaglandins?

A

mast cells, leukocytes

90
Q

Lipid Mediators of the Humoral Immune Response

What is the function of prostaglandins?

A

vasodilation, pain, fever

91
Q

Lipid Mediators of the Humoral Immune Response

What is the main source of leukotrienes?

A

mast cells, leukocytes

92
Q

Lipid Mediators of the Humoral Immune Response

What is the function of leukotrienes?

A

increase permeability, leukocyte adhesion, chemotaxis

93
Q

Lipid Mediators of the Humoral Immune Response

What is the main source of platelet activating factor?

A

leukocyte, mast cells

94
Q

Lipid Mediators of the Humoral Immune Response

What is the function of platelet activating factors?

A

vasodilation, increase permeability, leukocyte adhesion, chemotaxis

95
Q

What are eicosanoids essential for?

A
  • essential for control of inflammation and immunity
  • synthesized upon activation signals
  • specific inhibition of the major biosynthesis enzymes is a major mechanism to control inflammation
96
Q

Eicosanoids

What is the function of prostacyclin?

A

vasodilation

97
Q

Eicosanoids

What is the function of prostaglandin D/E?

A

vasodilation

98
Q

Eicosanoids

What is the function of thromboxane A2?

A

vasoconstriction

99
Q

Eicosanoids

What is the function of leukotrienes C/D/E?

A

vasoconstriction

100
Q

Eicosanoids

What is the function of leukotrienes C/D/E?

A

vascular permeability

101
Q

Eicosanoids

What is the function of prostaglandin D?

A

vascular permeability

102
Q

Eicosanoids

What is the function of leukotriene B?

A

chemotaxis and leukocyte adhesion

103
Q

Eicosanoids

What is the function of HETE?

A

chemotaxis and leukocyte adhesion

104
Q

Eicosanoids

What is the function of leukotrienes C/D/E?

A

bronchoconstriction

105
Q

Eicosanoid Functions
(Slide 46)

106
Q

What are major histocompatibility compexes (MHCs)?

A

present as a peptide epitope on surface of cell

  • polymorphic – around 2000+ alleles
  • co-dominant – express both allele equally
  • polygenic – 6 major MHC loci plus minor loci
107
Q

What are the functions of major histocompatibility complexes (MHCs)?

A

play essential roles in immune system engagement

  • recognition of self from non-self
108
Q

What are the properties of MHC I?

A
  • present on all nucleated cells and platelets
  • display infectious epitopes from hijacked cells’ synthesis of infectious agent (non-self) that are recognized by cytotoxic T cells
109
Q

What are the properties of MHC II?

A
  • present on antigen-presenting immune cells – macrophages, dendritic cells, and B cells
  • display degraded/digested pathogen epitopes that are recognized by helper T cells
110
Q

What role do cytotoxic T cells play in antigen recognition?

A
  • cytotoxic T cell (CD8+) receptor recognizes MHC I markers
  • special breaks to ensure a regulated immune activation (CTLA4 and PD1 receptors)
111
Q

What role do helper T cells play in antigen recognition?

A
  • helper T cell (CD4+) receptor recognizes MHC II markers
  • special breaks to ensure a regulated immune activation (CTLA4 and PD1 receptors)
112
Q

T-Cells Antigen Recognition Diversity – Genetic Recombination of the T Cell Receptor (TCR)

(Slide 51)

113
Q

Describe the structure of T cell receptors.

A
  • T cell receptor consists of an alpha and a beta chain (subunits)
  • each subunit is generated through recombination of 1 segment each from the V and j loci (alpha) and V, D, and J loci (beta)
  • generates immunological diversity, as each mature T cell will have a different combination of subunits that recognize different antigens
114
Q

How does T cell specificity occur?

A

positive and negative selection in thymus during development/maturation

  • positive selection of affinity for MHC I or MHC II (antigen-presenting cell surface molecules) with either the CD4 or CD8 receptors – MHC not recognized, therefore apoptosis
  • negative selection of cells that recognize self antigens – cannot be autoreactive
  • 2% survival
115
Q

Describe the functional diversity of T cells.

A

same TCR (progeny of a single T cell), different functional role through cytokines-directed differentiation

116
Q

Describe the diversity of B cell receptors (BCR).

A
  • each mature B cell is covered with a single type of BCR
  • BCRs are predecessors of an antibody that recognized one antigen
  • two identical binding sites on each fork of the Y
  • BCR can bind antigen directly in the absence of co-receptors
  • B cells with BCR that recognizes self antigens are destroyed (central and peripheral tolerance)
117
Q

Antigen Recognition Diversity – VDJ Genetic Recombination

(Slide 58)

A
  • gene components scattered through one chromosome
  • rearranged gene components encoding a heavy chain
  • assembled BCR molecule
118
Q

Describe the steps of the T-cell dependent pathway of B-cell activation.

A
  • antigen binding to BCR
  • internalization and MHC II presentation to T helper cells
  • T helper cell release cytokines
  • activated B cell differentiates into plasma cells for antibody production and memory B cells

PHRM 100 – APPP (23 decks)

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