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
2
Q
Properties of the Immune System
Mobility
A
systemic protection against localized insults through rapid cell migration to infected area
3
Q
Properties of the Immune System
Replication
A
immune response is amplified through clonal expansion and signaling cascade
4
Q
Properties of the Immune System
Specificity
A
prevent recognition of non-cross-reacting antigens and identify self vs. non-self
5
Q
Properties of the Immune System
Memory
A
faster and stronger response to (similar) subsequent infection
6
Q
Properties of the Immune System
Diversity
A
combinatorial library of antigen receptors to recognize innumerable pathogens
7
Q
What are the primary lymphoid organs of the immune system?
A
- thymus
- bone marrow
8
Q
What are the mucosal lymphatic tissues of the immune system?
A
- tonsils and adenoids
- appendix
- Peyer’s patches
9
Q
What are the other organs of the immune system?
A
- lymph nodes
- spleen (gigantic lymph node)
10
Q
What is the lymphatic system?
A
circulation system of lymphatic vessels
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
12
Q
Where are lymph nodes located?
A
- sit along the lymphatic vessels, with clusters in the neck, armpits, abdomen, and groin
13
Q
What does each lymph node contain?
A
each node contains specialized compartments where immune cells congregate and encounter antigens
14
Q
How many lymph nodes are in the human body?
A
500-600
15
Q
What are the 4 functional areas of lymph nodes?
A
- cortex
- germinal centre
- para-cortex
- medulla
16
Q
What does the cortex of lymph nodes do?
A
contains unactivated mature T cells
17
Q
What does the germinal centre of lymph nodes do?
A
contains activated B cells → plasma cell development and antibody affinity maturation
18
Q
What does the para-cortex of lymph nodes do?
A
contains a mix of unactivated and activated mature T cells
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
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
21
Q
What are the external defenses of innate immunity?
A
- skin
- mucous membranes
- secretions
22
Q
What are the internal defenses of innate immunity?
A
- phagocytic cells
- antimicrobial proteins
- inflammatory response
- natural killer cells
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
24
Q
Innate vs. Adaptive Immunity
Specificity
A
- innate: limited and fixed
- adaptive: extensive
25
Innate vs. Adaptive Immunity
Memory
- innate: none
- adaptive: yes
26
Innate vs. Adaptive Immunity
Time to Response
- innate: hours
- adaptive: days
27
Innate vs. Adaptive Immunity
Soluble Factors
- innate: lysozymes, complement, C-reactive protein, interferons, mannose-binding lectin, antimicrobial peptides
- adaptive: antibodies, cytokines
28
Innate vs. Adaptive Immunity
Cells
- innate: neutrophils, monocytes, macrophages, natural killer cells, eosinophils
- adaptive: B lymphocytes, T lymphocytes
29
Describe the specificity of innate immunity.
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
30
What are the cellular mediators of innate immunity? (8)
blood:
- neutrophils
- eosinophils
- monocyte
- natural killer cells
- basophils
peripheral tissues:
- macrophage
- dendritic cells
- mast cells
31
What do neutrophils do?
ingest (phagocytotic) and destroy
32
What do eosinophils do?
release toxic molecules and destroy
33
What do monocytes do?
ingest, destroy, and antigen presentation
34
What do natural killer cells do?
kill cancer or viral-infected host cells
35
What do basophils do?
release first chemicals that start inflammation
36
What do macrophages do?
ingest, destroy, and antigen presentation
37
What do dendritic cells do?
ingest, recruit others, and antigen presentation
38
What do mast cells do?
release first chemicals that start inflammation
39
Tissue-Specific Types of Monocytes
Brain
microglial cells
40
Tissue-Specific Types of Monocytes
Lung
alveolar macrophages
41
Tissue-Specific Types of Monocytes
Liver
Kupffer cells
42
Tissue-Specific Types of Monocytes
Kidney
mesangial phagocytes
43
Tissue-Specific Types of Monocytes
Lymph Node
resident and recirculating macrophages
44
Tissue-Specific Types of Monocytes
Spleen
macrophages
45
Tissue-Specific Types of Monocytes
Blood
monocytes
46
Tissue-Specific Types of Monocytes
Bone Marrow
precursors
47
Tissue-Specific Types of Monocytes
Joint
synovial A cells
48
Where are macrophages located?
in every tissue
- some macrophages circulate in the blood and migrate with rapid response to insults in tissues
49
Describe the structure and lifespan of macrophages.
- morphology is amoeboid-like
- inactive lifespan: months to years
- active lifespan: days to weeks
50
What are the functions of macrophages (3)
- phagocytosis
- antigen presentation (APC)
- initiation of tissue repair
51
Where are dendritic cells located?
- 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
What are the functions of dendritic cells? (4)
- phagocytes
- antigen-presenting cells
- activate adaptive immune response
- regulate T-cell activation
53
What are the specific functions of adaptive/acquired immunity? (5)
- 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
Describe the development of B cells.
- form and mature in bone marrow
- classes: memory B cell, plasma cell
55
Describe the development of T cells.
- produced in bone marrow
- mature in thymus
- classes: helper, cytotoxic, memory, regulatory
56
Helper T Cell
- 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
Memory T Cell
- coordinate rapid response to re-infection with same agent
- proliferate when reintroduced to antigen
- CD4+ or CD8+ co-receptor
58
Cytotoxic T Cell
- 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
T Regulatory Cell
- suppress and regulate auto-reactive T cells
- T cell receptor
- CD4+
- CD25
60
What do T cells do?
activity against infected host cells (inaccessible to antibodies)
- bacteria, viruses, fungus, parasites, cancer, transplants
- no antigen-presenting property
61
Memory B Cell
initiate rapid response to re-infection with same agent
- allow for a stronger and faster immune response next encounter
62
Plasma B Cell
neutralize toxins and viruses, opsonize bacteria
- antibody production
63
Describe the receptors of B lymphocytes.
each B lymphocyte produces only one type of antigen receptor
64
What can activated B cells do?
can act as APC to activate helper T in the classical B cell activation pathway
65
Interplay Between Innate and Acquired Immunity
- co-activation of B cells through BCR and TLR
- antigen presentation by macrophage
- complement proteins
- cytokines (ie. interferons, TNF, IL1
66
Severe COVID
What does a reduction or dysfunction in the adaptive immune response lead to? (4)
- over-activity of the innate system
- exaggerated cytokine response
- compromised normal immune functions
- coagulation dysfunctions and other organ system failures
67
What is inflammation?
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
Mediators of the Inflammatory Response
Pre-formed vs. Newly Synthesized Mediators (Slide 36)
-
69
Protein Mediators of the Immune Response
Proteins and Polypeptides (Slide 37)
-
70
Protein Mediators of the Immune Response
What are cytokines?
protein signaling molecules
71
Protein Mediators of the Immune Response
What are the 5 types of cytokines?
- interferons
- chemokines
- interleukins
- TNF 𝛼
- growth factors
72
Protein Mediators of the Immune Response
What is the function of interferons?
involved in innate antiviral response
- type I (𝛼, 𝛽)
- type II (𝛾)
73
Protein Mediators of the Immune Response
What is the function of chemokines?
chemotaxis proinflammatory – mediate chemoattraction/chemotaxis between cells
- MCP-I
- IL-8
- etc.
74
Protein Mediators of the Immune Response
What is the function of interleukins?
leukocyte development – acts on leukocytes, various functions
- IL-6
- IL-10
- etc.
75
Protein Mediators of the Immune Response
What is the function of TNF 𝛼 (tumour necrosis factor family)?
regulate immune and inflammation response
- acute phase response
- coagulation
76
Protein Mediators of the Immune Response
What is the function of growth factors?
growth differentiation – blood cell production,
- VEGF
- GM-CSF
- TGF 𝛽 – regulation of immunity and wound healing
- etc.
77
Protein Mediators of the Immune Response
Describe the composition of cytokines.
- 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
Chemical and Hormonal Mediators of the Immune Response
Amino Acids and Lipids (Slide 40)
-
79
Chemical and Hormonal Mediators of the Immune Response
Describe these mediators.
- signaling molecules activated or released by immune cells as well as injured cells
- mediate inflammatory responses
80
Chemical and Hormonal Mediators of the Immune Response
What are the 3 types of mediators?
- amino acid derivatives: histamine, serotonin
- lipid derivatives: prostaglandins, leukotrienes (both are eicosanoids)
- hormones and other neurotransmitters: bradykinin, substance P
81
Chemical and Hormonal Mediators of the Immune Response
What is histamine derived from and what is its main source?
- derived from amino acid histidine
- produce, store, and release mainly from mast cells
- also from basophils
82
Chemical and Hormonal Mediators of the Immune Response
What is the function of histamine?
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
Chemical and Hormonal Mediators of the Immune Response
What is serotonin derived from and what is the main source?
- derived from amino acid tryptophan
- produced by enterochromaffin cells and stored mainly in platelets
84
Chemical and Hormonal Mediators of the Immune Response
What is the function of serotonin?
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
Lipid Mediators of the Humoral Immune Response
How are eicosanoids synthesized?
synthesized with arachidonic acids (diet + cell/nuclear membrane
86
Lipid Mediators of the Humoral Immune Response
What are eicosanoids?
lipid mediators
87
Lipid Mediators of the Humoral Immune Response
Describe the structure of eicosanoids.
- made by oxidation of omega-6 fatty acids
- 20 carbons, 4 double bonds
- biosynthesis by cyclo-oxygenase (prostagalndins) or lipo-oxygenase (leukotrienes)
88
Lipid Mediators of the Humoral Immune Response
What are the 3 main mediators?
- prostaglandins
- leukotrienes
- platelet activating factor
89
Lipid Mediators of the Humoral Immune Response
What is the main source of prostaglandins?
mast cells, leukocytes
90
Lipid Mediators of the Humoral Immune Response
What is the function of prostaglandins?
vasodilation, pain, fever
91
Lipid Mediators of the Humoral Immune Response
What is the main source of leukotrienes?
mast cells, leukocytes
92
Lipid Mediators of the Humoral Immune Response
What is the function of leukotrienes?
increase permeability, leukocyte adhesion, chemotaxis
93
Lipid Mediators of the Humoral Immune Response
What is the main source of platelet activating factor?
leukocyte, mast cells
94
Lipid Mediators of the Humoral Immune Response
What is the function of platelet activating factors?
vasodilation, increase permeability, leukocyte adhesion, chemotaxis
95
What are eicosanoids essential for?
- 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
Eicosanoids
What is the function of prostacyclin?
vasodilation
97
Eicosanoids
What is the function of prostaglandin D/E?
vasodilation
98
Eicosanoids
What is the function of thromboxane A2?
vasoconstriction
99
Eicosanoids
What is the function of leukotrienes C/D/E?
vasoconstriction
100
Eicosanoids
What is the function of leukotrienes C/D/E?
vascular permeability
101
Eicosanoids
What is the function of prostaglandin D?
vascular permeability
102
Eicosanoids
What is the function of leukotriene B?
chemotaxis and leukocyte adhesion
103
Eicosanoids
What is the function of HETE?
chemotaxis and leukocyte adhesion
104
Eicosanoids
What is the function of leukotrienes C/D/E?
bronchoconstriction
105
Eicosanoid Functions
(Slide 46)
-
106
What are major histocompatibility compexes (MHCs)?
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
What are the functions of major histocompatibility complexes (MHCs)?
play essential roles in immune system engagement
- recognition of self from non-self
108
What are the properties of MHC I?
- 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
What are the properties of MHC II?
- 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
What role do cytotoxic T cells play in antigen recognition?
- cytotoxic T cell (CD8+) receptor recognizes MHC I markers
- special breaks to ensure a regulated immune activation (CTLA4 and PD1 receptors)
111
What role do helper T cells play in antigen recognition?
- helper T cell (CD4+) receptor recognizes MHC II markers
- special breaks to ensure a regulated immune activation (CTLA4 and PD1 receptors)
112
T-Cells Antigen Recognition Diversity – Genetic Recombination of the T Cell Receptor (TCR)
(Slide 51)
-
113
Describe the structure of T cell receptors.
- 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
How does T cell specificity occur?
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
Describe the functional diversity of T cells.
same TCR (progeny of a single T cell), different functional role through cytokines-directed differentiation
116
Describe the diversity of B cell receptors (BCR).
- 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
Antigen Recognition Diversity – VDJ Genetic Recombination
(Slide 58)
- gene components scattered through one chromosome
- rearranged gene components encoding a heavy chain
- assembled BCR molecule
118
Describe the steps of the T-cell dependent pathway of B-cell activation.
- 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
