Exam II Flashcards
(150 cards)
1
Q
What cells arise from the myeloid progenitor?
A
myeloid cells bb!
2
Q
What are erythrocytes?
A
-found in the blood
-no nucleus
-carry oxygen
3
Q
What is a megakaryocyte? Where found and what do
A
-found in bone marrow
-form platelets
-participate in clotting events
-no nucleus (anuclear)
4
Q
What are granulocytic cells and from which lineage do they arise?
A
-Possess granules containing enzymes and
pharmacologically active chemicals that are
released in response to infection
-myeloid cells
5
Q
What are the four types of granulocytic cells?
A
- Neutrophils
- Eosinophils
- Basophils
- Mast cells
6
Q
Some basics on neutrophils-
A
Found in blood, lymph and tissues
* Circulate in blood
* Migrate to tissues in response to infection
* Primary responders to infection
* Increased levels -> leukocytosis
* Professional phagocytes
looks-wise, multilobed nucleus
7
Q
What do neutrophil granules contain?
A
lytic enzymes and
antimicrobial proteins
(Exhibit an extensive respiratory burst)
8
Q
What receptor do neutrophils employ?
A
CD16, bind to antibody which triggers phagocytosis of bacterial cell
9
Q
Describe the 2 ways of neutrophil expression-
A
Expression
* PRRs
* Binds PAMPs
* Triggers phagocytosis
AND
* Class II MHC
-Expressed by all phagocytes
* Presents antigen to TH cells
10
Q
Some basics on an Eosinophil? Where found and what granules contain
A
Found in blood and lymph -> Tissues around GI tract
* Granules contain histamine and other
pharmacologically-active compounds
11
Q
What is the role of Eosinophils and how do they go about this?
A
-parasite killers
-Cluster around parasites
* Release contents of granules via exocytosis
* Histamine, etc., is toxic to helminths
* Histamine plays a role in triggering asthma/allergies
12
Q
How do Eosinophils bind to parasites?
A
Bind those coated in IgG antibodies, using FceR1 receptor
13
Q
Some basics on a basophil? Where found and what granules contain
A
Found in blood and lymph
* Granulocytic cells
* Granules contain—
* Histamine, heparin, proteases
* Cytokines that recruit other immune cells
14
Q
What is the role of Basophils and how do they go about this?
A
Parasite killers
- FcεRI/IgE binds multicellular parasite
- Cross-linking receptors triggers degranulation
- Release contents of granules via exocytosis
15
Q
How do Basophils bind to parasites?
A
Express FcεRI (High Affinity IgE Receptors)
* Binds free IgE
Bound IgE serves as an acquired antigen receptor
16
Q
What do primary neutrophil granules do?
A
Release enzymes into phagolysosomes to kill engulfed pathogens-
-defensins (antimicrobial peptide) , proteases, myeloperoxidase (H2O2)
17
Q
What do secondary neutrophil granules do?
A
Secreted extracellularly to help degrade microbial cell walls
18
Q
What do tertiary neutrophil granules do?
A
- enzymes secreted to break down extracelluar matric allowing movement to sites of infection
19
Q
What is NETosis ?
A
cells voluntarily die, secreting their DNA along with granule content to form neutrophil extracellular traps (NETs) to trap and kill pathogens
“they’re giving up their lives for you!”
20
Q
What are mast cells? Main purpose and what makes them different from most granulocytic cells?
(hint where they’re found)
A
Granulocytic myeloid cells, parasite killers
Similar to Basophils but found in tissues (skin, mucous
membranes, organs)
- Release contents of granules via exocytosis
- Play role in triggering allergies (esp. hives)
21
Q
Professional antigen-presenting cells have what characteristics?
A
- Phagocytic
- Process and display antigen on Class II MHC
- Upregulate costimulatory molecules to help activate TH cells
22
Q
What are the 3 main professional antigen-presenting cells?
A
Monocytes
Macrophages
Dendritic cells
23
Q
What is an opsonin?
A
a molecule that binds to an antigen and enhances its recognition and ingestion by phagocytes
24
Q
Monocytes! What are the 2 types, where found and what do?
A
Found in blood
-
Inflammatory monocytes
Enter tissues quickly in response to infection
Differentiate into macrophages -
Patrolling monocytes
Crawl slowly along blood vessels
Monitor repair processes
25
Macrophages arise (differentiate) from what?
Monocytes
26
Macrophages! What are 2 main types, where found and what do?
Found in tissues
Two main populations:
* Circulating macrophages
* Tissue-specific macrophages
27
Do tissue-specific macrophages tend to arise from circulating monocytes?
No, many tissue-specific macrophages arise from embryonic
cells early in development rather than from circulating
monocytes
28
Describe phagocytosis as carried out by a macrophage: what triggers it, and what happens
Phagocytosis triggered when PAMPs engage PRRs
* Cells activate
* Phagocytic capacity increases
* Ability to destroy pathogens increases
* Lysosomal digestion
* Oxidative burst
29
Phagocytosis enhanced in response to what?
opsonins
30
What are Dendritic cells? What lineage from, what do, where found?
Arise from both Lymphoid and Myeloid pathways
* Found in tissues
* Phagocytic cells
* Captures antigen in tissues
* Migrate to lymph nodes, present antigen to TH cells
* Initiate adaptive immune response
basically snatch and show
31
What 3 ways might a dendritic cell internalize an antigen?
* Engulf by phagocytosis
* Internalize by receptor-mediated endocytosis
* Imbibe by pinocytosis (drink?) just taking a sample
32
Upon internalizing an antigen a Dendritic cell will:
-lose capacity for phagocytosis
-improved ability to present antigen
-expression of costimulatory molecules
-> activation of naiive T cells
33
What happens in the Primary Lymphoid organs?
place of maturation, where lymphocytes mature and become committed to a particular antigenic specificity
34
What are the 2 primary lymphoid organs
Thymus
Bone marrow
35
Secondary Lymphoid organs
specific tissues in locations where antigens and lymphocytes likely to come together, organs specialized for leukocyte and antigen interactions
36
What happens within the bone marrow?
-hematopoiesis
-promote random gene recombination in Ab genes (antibody/Ig) (ag- antigen)
-generate b cells with effective antibodies
-interact with antigen
-screen for who works best and doesn't self react
37
Screen B-cell receptors
Random recombination of BCR genes possible outcomes:
1) properly interact with foreign antigens
2) inappropriately respond to self-antigens
3) fail to form correctly
>90% B cells die during screening
Negative selection- eliminates B cells that react with self-Ag
38
What is the Thymus?
-bi-lobed structure, surrounded by capsule
-divided into little lobules
39
Function of the thymus?
Promotes random gene recombination in TCR genes
-generate T cells with ability to protect from infection
-interact with MHC
-read presented peptide
-respond appropriately
40
Screen recombination of TCR genes: possible outcomes
1) property interact with MHC, have potential to recognize foreign antigens
2) properly inteact with MH, recognize self-antigens
3) fail to interact with MHC
-bind too strongly to MHC
41
95% of thymocytes die in the thymus, undergo positive and negative selection. What are the results of these?
Positive selection: survival of t cells able to bind MHC (given growth factor, positive)
Negative selection- elimination of t-cells responding to self-Ag
42
Initially are all thymocytes double negative (no cd4/cd8) ?
Yes
43
TCR testing phase: testing signal transduction
What does this look like, and what determines who a T cell will become?
-CD3 cluster around t cell receptor
-Lack CD4, CD8
-unable to interact with MHC
-Double positive thymocyte-
Begins expressing C4 and CD8 at same time
-Have potential to become either Tc or Th cells hypothesis: first to interact determines fate
44
Lymph nodes, what they do?
Serve as filters for lymph
* Collect antigen from
local tissues
* Designed to optimize
interactions between
leukocytes and antigen
45
Lymph Nodes main locations
* Neck
* Chest
* Armpits
* Around the GI
* Groin
46
Spleen, what it do?
-main filtration system for blood
-collects antigen from blood
-designed to optimize interactions between leukocytes and antigen
47
What is the MALT, and what it do?
o Mucosal-associated Lymphoid Tissue (MALT)
-capturing antigen coming through mucosal tissue
-designed to optimize interactions of leukocytes and antigens
48
Two MALTs we discussed:
Peyer’s patches (small intestine)
Tonsils
49
Peyer’s patches (small intestine)
Capture antigen
coming through
mucosal
membranes
* Designed to
optimize
interactions
between leukocytes
and antigen
50
Tonsils
Capture antigen
coming through
mucosal
membranes
* Designed to
optimize
interactions
between leukocytes
and antigen
51
Appendix
-capture antigen coming through mucosal membranes
-storage site for intestinal flora, used to repopulate gut microbiome when necessary
52
Primary follicles-
* Primary follicles
-loose collection of a few cells, in active infection
53
General organization of 2 deg lymphoid tissues consists of:
* Primary follicles
* Secondary follicles
* Germinal centers
54
Secondary follicles
-b cells rounds of replication and testing
55
Germinal centers
Tissue is actively responding to infection
56
Tertiary Lymphoid Tissue
* Same function as secondary lymphoid tissue, but consist of a more loose association of cells (Found in tissues throughout the body)
* Generally contain fewer lymphoid cells
* Can rapidly import leukocytes to respond to localized
inflammation
57
(in context of the thymus)
Who is at the cortex?
-got b cells in primary follicles
58
(in context of the thymus)
Who is at the paracortex?
-t-cell zone
*
59
(in context of the thymus)
Who is at the medulla?
-macrophages and plasma cells, activated b cells go
60
(in context of the thymus)
Subcapsular sinus
-antigens travel from infected tissues to the cortex (enter through afferic vesicles, fill these sinuse spaces)
61
Why are there fewer thymocytes in the medulla?
Selection processes: eliminate thymocytes that–
a. Fail to interact with MHC molecules
b. Recognize/bind self-antigens
62
For function of the thymus see slides
08 Organs of the immune system A slide 23
63
For function of bone marrow, see slides
08 Organs of the immune system A slide 30
64
Cortex of lymph node-
“B-cell Zone”
* Outermost layer of the lymph node
* Rich in B cells, macrophages, follicular dendritic cells
* Cells arranged in primary follicles
* After antigenic challenge, enlarge to form secondary follicles
65
Paracortex of lymph node
“T-cell Zone”
* Lies beneath the cortex
* Contains mostly T cells and dendritic cells
66
Medulla of lymph node
* Innermost layer of the lymph node
* Primarily contains active plasma cells
* Actively secrete antibodies for distribution
throughout the body
67
Lymph node process:
1. Antigen travels from infected tissue to the cortex
a. Enters through afferent vessels
b. Empties into the subcapsular sinus
Afferent
vessels
2. Antigen travels from infected tissue to the cortex
a. May enter in particulate form (cells or proteins)
b. May have been processed and presented as peptides by migrating antigen-presenting cells
68
High Endothelial Venules (HEV)
-most naïve lymphocytes enter the cortex through extravasation through high endothelial venules (HEV)
69
What do naive T cells do in lymph node paracortex? (hint shoppinggg)
Naïve TH cells spend 16-24 hours browsing all the MHC-peptide complexes in the paracortex
70
Fibroblastic reticular cells (FRC)
create
a network of fibers, APCs wrap themselves around the fibers, T cells follow chemokines and adhesion molecules around the network
71
What does following the FRCC (follicular reticular cell conduit system) enhance for naïve Th cells?
the probability that Th cells
will meet their specific MHC-peptide combination
72
If Naïve TH cells do not find their MHC-peptide match (in a lymph node,)
they will-
exit via the efferent lymphatic vessels
73
f Naïve TH cells do find their MHC-peptide match (in a lymph node,) they will-
activate, proliferate, then seek out B cells, TC cells, and macrophages
74
Central memory cells reside in
secondary
lymphoid organs
75
B cells enter via what anf follow what to enter the lymph node
HEV and follow chemokine signals to the follicles in the cortex.
76
B cells follow tracks (through lymph node) through the follicle generated by
follicular dendritic cells (not macrophages)
77
If a B cell binds its antigen, what then occurs?
the B cell becomes partially
activated; engulfs the antigen, processes it, and presents it as a peptide-MHC complex
78
A partially activated B cell (presenting a peptide MHC complex) moves to the paracortex, then
seeks out a TH cell to activate and is fully activated in turn (maintain contact for several hours)
79
An activated B cell proliferates and differentiates, if directly into plasma cells, where go and what secrete?
migrate to medulla and secrete IgM (Primary response)
80
Activated B cells may remain in the follicle, which develops a germinal center, what 3 things can happen from there?
a. Clonal expansion
b. Somatic hypermutation
c. Clonal selection
81
What does Somatic hypermutation alter in activated B cells?
Somatic hypermutation alters the CDR regions
May change amino acid sequence
* May shorten/lengthen each CDR
82
Only B cell clones with the highest affinity antibodies survive (positive selection.) What things can happen to them after this point?
a. Some differentiate into plasma cells
i. Some take up residence in the medulla
ii. Some migrate back to bone marrow
b. Some differentiate into memory cells
i. Central memory cells: Reside in secondary lymphoid organs
ii. Circulatory memory cells: Circulate between blood, tissues and lymph
iii. Tissue-resident memory cells: settle in peripheral tissues
83
In the spleen the sinusoids are where____
red blood cells go to DIE
84
In the spleen, white pulp consists of what two guys?
1)follicles (b cells)
2) periarticular lymphatic tissue (T cells)
85
Marginal zone (in spleen) is what?
first line of defense against blood-borne pathogens
86
How the process for encountering an antigen differ in the spleen vs lymph node?
The overall process for encountering antigen and responding is essentially the same as for lymph node *hehe trick Q*
87
In association with the MALT, gonna be what antibody? (mucous membranes,)
IgA
88
IgG
in spleen, best for blood (can also cross placenta)
89
IgE
skin
90
IgM
produced as soon as B cells activated (main antibody of primary response)
91
IgD
in all vertebrates, probably og
92
What are M cells? What do they do? (hint, fringe of the MALT)
“Microfold cells”
* Capture antigen in lumen
* Release in pocket with B cells, TH cells, Macrophages
* Antigen is processed, presented, used to activate lymphocyte
93
Macrophages and T cells in the MALT somehow can
*Differentiate between
pathogens and commensal
bacteria*
* If pathogenic –
* Activate B cells -> Plasma cells
* If communalistic –
* Silence B cells
(induce tolerance)
Withhold Signal 2
94
Plasma cells produce IgA, then IgA crosses the epithelium (slgA.) What does sIgA do?
* sIgA binds antigen in lumen
* Protects intestinal wall from inflammation and invasion
* Entraps antigen
* Prevents Ag binding
* Ensures flushing from
body
95
What do plasma cells produce?
IgA
96
Why is the MALT Often considered as a
separate immune system:
“Mucosal Immune System”
* Different objectives:
* Distinguish between
commensal and
pathogenic bacteria
* Prevent entry into the
body
* No killing involved
97
Antigenicity
Ability of a molecule to specifically bind to
antibodies and/or T cell receptors (TCRs)
98
Immunogenicity
Ability of a molecule to induce a humoral and/or cell-mediated immune response
99
Antigen:
any molecule the immune system can recognize as being foreign
-antigens may or may not illicit an immune response
100
Hapten:
a small compound that can be bound by antibodies but cannot, themselves, elicit an immune response (only way to get immune response to specific DNA I think)
101
Chemical complexity contributes to
immunogenicity. Are hetero or homo polymers usually more immunogenic?
* Homopolymers (chains of the same amino acids or sugars) tend to lack immunogenicity
* Heteropolymers of different amino acids or a mixture of sugars are usually more immunogenic
102
Large insoluble macromolecules are more
immunogenic because
they can be more
readily phagocytosed and processed
* Peptides constructed of D-amino acids tend to be non-immunogenic (our proteases cannot hydrolyze them)
103
What must molecules be able to be in order to activate the immune system?
*Processed,* before they can be used to active the immune system; if they can’t be presented to TH cells, there will be no immune response
104
Genetic variability of an individual will affect
the immunogenicity of any given macromolecule
105
What main 2 things affect how Immunogen exposure will be processed by the body?
(think for preventative vaccine purposes)
* Inoculation route makes a big difference in how the body will respond
* Dose also has a big impact
106
What other factors affect how Immunogen exposure will be processed by the body?
(think for preventative vaccine purposes)
* Insufficient doses and excessive doses may induce tolerance
* Multiple medium-sized exposures (boosters) can help increase clonal proliferation
107
What is the purpose of a route?
What are the possible routes of entry for Immunogen exposure that will be processed by the body?
Route: activates specific groups of cells
i. Oral/inhaled vaccines mucosal systems
ii. IV (intravenous) into a vein (blood)
iii. IM (intramuscular)
108
Problem: your antigen is not eliciting an immune
response when you inject 10 μg into muscle; what
might you do?
Another route of giving or altering the dose, or altering the location of injection
109
Adjuvants are chemicals injected along with an antigen; why?
they help create a stronger immune response, by coagulating antigens and causing irritation eliciting further immune response
110
Example of an adjuvant?
aluminum potassium sulfate
1. Precipitates proteins
2. Increases effective exposure times to
several weeks (vs. a few days)
ii. Water-in-oil emulsions
* Antigen is released more slowly from site
111
Factors that influence immunogenicity? (causing immune response)
prep there are 7
1. Foreignness
2. Molecular size
3. Chemical composition & heterogeneity
4. Ability to be processed and presented
5. Genotype of recipient
6. Immunogen dosage and exposure route
7. Co-injection of adjuvants
112
Epitopes
Antigen Recognition
* Discrete sites on an
antigen that
physically bind with
effector molecules
(TCR or BCR)
113
are B cell epitopes
distinctly different
than T cell epitopes?
yes
114
What do B cell epitopes do with antibodies?
B cell epitopes must combine with antibodies
115
Roles of Antibodies (2 main points)
1. Specifically bind and mark Ag as foreign
2. Recruit other cells/molecules to destroy
These two roles are spatially separated on an antibody molecule
116
Antibodies bind their antigen only through
non-covalent interactions, must also maximize interactions to
ensure tight binding
117
Antibodies are created through random gene recombination BEFORE
the body ever encounters the antigen
118
Epitopes Recognized by B cells (lotta points here)
* Found on the surface of free antigen
(non-processed)
* Tend to consist of hydrophilic amino acids
* Hydrogen bonding
* Ionic bonds
* Typically consist of 5 – 8 amino acids
* Shape is crucial for recognition
119
T cell epitopes- Where presented?
* Presented in complex with MHC molecules
* T cell epitope size
120
Do T cell epitopes need the 3D shape?
No, ALWAYS sequential
(Native 3D shape is irrelevant)
121
Do T cell epitopes require processing?
Where in the protein do these sequences emerge?
* Processing is required to generate epitopes
* Can come from anywhere in the protein
* Most often internal
* Usually hydrophobic (anchor points)
122
mIg:
Present on Naïve and Memory B cell
membranes (B cell receptors, BCR)
123
sIg:
Secreted by plasma cells
124
Light chains ~how long?
~25,000 Da
125
How are the 2 main roles of an antibody physically orientated?
These two roles are spatially separated on an antibody molecule
126
antibody heavy chains ~how long?
~50,000 Da
127
Overall length of a given antibody (in Da)
~150,000
128
What is the role of
the antibody constant region?
* Effector functions
* Binding to Fc receptors
* Mediating transport
* Activating complement
-disulfide bond fomration
-glycosylation sites
129
Two types of light chains
* Kappa (κ)
* Lambda (λ)
130
Heavy chain isotopes:
“My dad gets every apple”
Mu (μ)
Delta (δ)
Gamma (γ)
Epsilon (ε)
Alpha (α)
IgM
IgD
IgG
IgE
IgA
131
Mu (μ)
Delta (δ)
Gamma (γ)
Epsilon (ε)
Alpha (α)
IgM
IgD
IgG
IgE
IgA
132
Immunoglobulin can be what?
* Antibody
* Individual heavy or light chain of an antibody
-Domain (110 amino acids)
133
Domain (antibodies)
110 amino acids
* Two antiparallel β-sheets
* Folded together
into sandwich
structure
* Anchored with a
disulfide bond
134
How many immunoglobulin domains does each light chain have?
2 immunoglobulin domains
135
γ, δ, and α heavy chains
generally describe shape, and how many sulfide bonds?
Disulfide bonded, shorter Y
136
μ and ε heavy chains, general shape and how many sulfide bonds?
Long Y, one disulfide bond
137
Which of the following heavy chains do NOT contain a disulfide bond?
γ, μ, δ, α, and ε
μ, ε
138
Which heavy chains contain the Hinge region?
γ, δ, and α heavy chains
139
Hinge region of an γ, δ, or α antibody composition?
What does this region allow for?
lots of prolines (no helices bc theyre breakin)
-antibodies binding together
-both arms together, angle 0, then 3 60 deg, then 4 90 deg
-hinge region has big range
-those with hinge region can bind greater # of antigens and form more flexi complexes (u and e one sulfide bond, no hinge region)
140
If an antibody is secreted, what is the pro or anti water status of the C terminus?
hydrophilic
141
If an antibody is membrane-bound, what is the pro or anti water status of the C terminus?
hydrophobic (makes sense bc phospholipids)
142
Where is the C terminus of an antibody?
Bottom of the Y
143
Immature B cell- what antibody excreted?
mIgM (membrane bound
144
Naïve B cell-
mIgM and mIgD
145
Plasma cell-
sIgM, sIgD, sIgG, sIgE, sIgA (only one of these, probably tissue location specific) sIgm first, then change to what’s needed
146
Memory B cell-
mIgM, mIgG, mIgE, or mIgA
147
Want what antibody secreted in MALT?
IgA
148
Spleen-
mainly IgG, best for blood
149
Tissues-
IgE, best for parasites
150
Why is IgA ideal for the MALT?
It’s optimized for transcytosis, secreted outside body to bind bacteria together in big complexes so easier to remove (not free to affect body)
basically makes all the bacs hold hands so it can yeet them out
