Unit 1-5 Flashcards
(152 cards)
1
Q
Discuss how complement plays roles in both innate and adaptive immunity
A
Adaptive via classical pathway: IgG or IgM trigger complement
Innate via lectin and alternative pathway:
Alternative-specific epitopes on bacterial cell wall structures that activates the complement pathway
Lectin- mediated by mannose (carb of bacteria) binding protein (MBP/MBL)
2
Q
They are chemotactic for phagocytic WBCS- which flow in from distant areas
A
chemokines
3
Q
kidney bean shaped nucleus
A
monocyte
4
Q
Describe the sequence of appearance of cytoplasmic and surface immunoglobulins in developing B cells
A
Pro-B cells (mu chain only)–> pre-B cells (mu chain + kappa or lambda L chain= cytoplasmic IgM)–> immature B cell (cIgM + sIgM)–> mature B cell (sIgM + sIgD)
5
Q
The response to T-independent antigens is almost all ___
A
IgM
6
Q
involvement in allergic diseases
A
IgE adheres to histamine containing mast cells and basophils leading to the immediate hypersensitivity of allergic reactions
7
Q
Antigens are____ b/c they have multiple, different antigenic determinants or epitopes–> therefore multiple Ab can react to different determinants on same pathogen
A
MULTIVALENT
8
Q
what complement components which are:
lytic
A
C5b
C8
C9
9
Q
what do Th2 secrete
A
IL-4–> attracts and activates M2
10
Q
___ cell is important for protecting against autoimmunity
A
immature B cells
*if it binds in this stage, it is signaled for apoptosis
11
Q
at birth a babys IgG level is ___ compared to an adults level
A
100% of adults level but all maternal IgG
12
Q
undifferentiated cells, which give rise to stem cell and a daughter committed to differentiation (never run out); vary in their potential
A
stem cell
13
Q
how is complement activated by IgM and IgG
A
*C1q must interact w/ 2 Fcs simultaneously to be activated
- 2 IgGs close together (most abundant in blood)
- 1 IgM (always has 5 adjacent)
-Classical pathway when 1 IgM or 2 IgG bind to antigens –> confirmation change of Fc portion shape –> bind C1q
14
Q
List the components of complement in the order in which they become activated in the classical pathway
A
- C1q becomes activated upon binding of 2 IgGs or 1 IgM (must interact w/ 2 Fcs simultaneously)
1-4-2-3-5-6-7-8-9
15
Q
what cells interact w/:
MHC I
MHC II
A
MHC I: CTL
MHC II: Thelper cells
from outside the cell
16
Q
Cells who nucleus is LOBULATED
A
PMN cells aka granulocytes
ex. eosinophils, basophils, neutrophils, mast cells
17
Q
MHC class 2 receptors are expressed on the surface of what cells
A
DC
macrophage-type cells
B cells
*all of which are involved in some way in presenting antigenic peptides to Th cells
18
Q
short-range mediators made by lymphocytes that affect behavior of same or another cell
ex?
A
Lympokine
ex. IL-2, IFNgamma, IL-4, IL-5, IL-10
19
Q
The fertilized ovum is the ___ cell
A
totipotential stem cell
20
Q
describe the H chain
A
- 1 variable domain (VH) and 1-4 constant domains (CH1, CH2, CH3, CH4)
- each Ab has 2 identical H chains
21
Q
Secretes IFNγ (lymphokine)→ Proinflammatory, chemotactic for monocytes and macrophages
A
Th1 (delayed hypersensitivity T cells)
22
Q
where are T cells found in the lymph node
A
Para- or Deep Cortex- less dense than cortex, but still has HUGE number of lymphocytes, mostly T cells
23
Q
describe pre-b cells
A
cell w/ cytoplasmic IgM but no surface IgM
-develop from CLP
24
Q
immature B cell has ___
mature B cell has___
A
*first detectable is mu chain
Immature B cell has sIgM only
Mature B cell has sIgM and sIgD
25
what cells can activate DC
activated at wound site by cytokines and chemockins
26
CTL require help from ___
- activated in lymph nodes after contact w/ APC, DC
| - Th1 in the form of IL-2
27
calculate absolute counts for the different cell types (as cells of that type /μL)
Absolute (Abs) ___ = WBC count x percent ___ (expressed as a decimal)
*Allows you to determine the absolute count per mcL of each type of cell
Ex. % lymphs = 30% and WBC = 2.5 x 103/mcL (2500 cells/mcL)
2.5 x1000 x 0.30 = 750 lymphs/mcL
28
- A domain that is different in sequence between antibodies of different specificities
- On the N-terminal
Variable domain
29
protect the extracellular spaces of the body—the tissue fluids, blood, secretions—by releasing antibody into these fluids
B cells
30
what cells are APCs
DCs, macrophages, B cells
*only DCs can activate naive T cells
31
Discuss the mechanism by which T cells help B cells
1. B cell endocytosis antigen→ presents on MHC II→ detected by Tfh→ head to follicels→ help B cells that have recognized antigen become activated and differentiate into Ab-secreting plasma cells
2. Th cells help is needed to switch over to IgG (spleen), IgA (gut), or IgE
3. For protein antigens, neither IgM nor IgG is made w/o T cell help
32
Lectin pathway
Mannose binding protein (MBP)-4-2-3-5-6-7-8-9
*Mannose binding protein (MBP) is functionally similar to C1q
33
where do the peyers patch drain
drain to a large collection of mesenteric lymph node
34
what are these examples of?
| IL-1, TNF β, IL-12
cytokines
35
-T-helpers in gut and lung preferentially drive what immunoglobulin class switch to occur
IgM to IgA switch
36
Distinguish between negative and positive selection in the thymus.
1) if CDR 1s and 2s engage MHC→ T cell is POSITIVELY selected
2) if CDR 1s, 2s and 3s engage→ T cell is NEGATIVELY selected→ Apoptosis OR becomes Treg
37
part of blood W/ FIBRINOGEN (clotting factor) and serum, mostly water
plasma
38
describe the L chain
- 1 variable domain (VL) and 1 constant domain (CL)
| - each Ab has 2 identical L chains
39
helps get rid of parasites
IgE
40
Describe markers that Th1, Th2, and killer T cell subpopulations in humans have on their surfaces
Th1- CD3, CD4
Th2- CD3, CD4
CTL- CD3, CD8
41
- 21 peptides (10L, 10H, 1 J chain)
- 19 disulfide bonds
- Decavalent
- in blood as pentamer of a basic unit (2L, 2H)
IgM
42
where uncommitted helper T cells (Th0) can get stimulated and become the aggressive Th1, the slightly more peaceful
Th2, or the sophisticated Treg, which tells its siblings to calm down
The Peyer patch
43
describe the electrophoretic separation of human serum and ID albumin, alpha-1, alpha-2, beta, and gamma peaks
- Origin is Cathode (-)
- moves to anode (+)
Peaks:
- highest/most dense/furthest from origin= albumin
- next peak, smallest= alpha-1
- next peak (middle)= alpha2
- next peak = Beta 1
- next peak, moves least = gamma
44
when is the the most antibody in precipitate
when antigen and antibody are equivalent in presence
45
C1q must interact w/ ___ simultaneously to become activate
2 Fcs simultaneously
46
what is the constant domain made of
-Made up of 1 (in L chain) to 4 (in epsilon and mu) compact, structurally-similar domains
47
Proinflammatory, chemotactic for monocytes and macrophages
IFNgamma (lymphokine)
48
- 4 peptides (2L, 2H)
- 3 disulfide bonds
- divalent
- extra long hinge region
IgD
49
identify the family of bacteria for which lysis is a very important pathway.
Neisseria (gonorrhea, meningitis)
* must go up to C9 for lysis to occur
- if C6 def. cannot lyse Neisseria
50
The functional structure of the Peyer patches includes ____, which are ___
specialized mucosal M cells
gatekeepers, ingesting proteins and particles as big as a viruses and transporting them to the
abluminal (away from the lumen) side
51
Capable of releasing histamine non-specficially from mast cells or basophils – increase in blood flow in the area of antigen deposition, and a better chance for inflammatory cells to get out of the blood into the tissues
C3a, C4a, C5a
* anaphylatoxic components of MAC
* Can cause hives if person has a lot of complement activation
52
where do B cells develop
bone marrow
*NOT bursa of Fabricius like in birds
53
what complement components which are:
| anaphylatoxic
C3a
C4a
C5a
*Capable of releasing histamine non-specficially from mast cells or basophils – increase in blood flow in the area of antigen deposition, and a better chance for inflammatory cells to get out of the blood into the tissues
54
Frequent, very dense areas w/ many dividing B cells in the cortex
germinal center
55
what is the bursa of fabricuis
- B cell progenitors leave the bone marrow and finish their development in a separate organ called the Bursa of Fabricius (in birds- where B cell development was first studied)
- Bursa is located in the hind end of the gut
*no human equivalent organ
56
__are uniquely effective at killing parasites
Eosinophils
57
wha tis the most important lymphokine secreted by Th1
IFN gamma
58
measures the strength of interaction between an epitope/antigen determinate and an antibody’s antigen binding site (aka variable region)
affinity
59
direct B cell switching from IgM to IgG, IgA, or IgE; the switching depends on the location of the lymph node
Tfh
60
what are the 4 actions of the complement
1. opsonizing
2. lytic
3. anaphylatoxic
4. chemotactic
61
what is the half life of IgG?
Half life of IgG is ~3 weeks
-so in 7 half lives= 21 weeks after birth there is less than 1% of starting amount of maternal IgG left→ Infant begins to make its own IgG at ~12 weeks
62
Discuss how complement is important in immunity to bacteria even if the bacteria are resistant to lysis by C9.
- Complement activates different ways to destroy bacteria aside from cell lysis.
- These include opsonization by C3b and IgG/FcR receptors, which attract PMNs and macrophages for phagocytosis.
- C5a attracts neutrophils to further help phagocytosis. C3a, C4a, and C5a all increase histamine release and inflammation to increase movement of inflammatory cells into the antigen area.
63
what are these examples of?
| IL-2, IFNγ, IL-4, IL-5, IL-10
lymphokines
64
- Activates “M1” – angry macrophages which avidly ingest and kill bacteria or other foreign invaders
- Macrophages release cytokines (TNFα and IL-1)→ intensify inflammation
Th1
65
Th2 gives rise to what type of cell
Tfh
66
when does a baby have the lowest amount of IgG?
between 1-6 months of age when maternal IgG levels drop off; highest risk for infection in baby
67
short-range mediators made by any cell that affect primarily cause inflammation
chemokine
ex. MIP-1, CCL28, CXCL16, Eotaxin, IL-8
68
single multi-lobed nucleus (2-5 lobes), colorless
neutrophils
69
what structures do Th cells recognize by TCR
Antigen + MHC II (on APC)
70
what are some foreign patterns recognized by TLR
TLR2- peptidoglycan (gram +)
TLR3- dsRNA
TLR4- lipolysaccharides (Gram -)
TLR 7/8- ssRNA
71
Stress or damage indicators expressed by body cells that our PRPs in our innate immune system detect
DAMP
| damage-associated molecular pattern
72
List the normal adult white cell count and differential percentages
Total WBC: 4,500-11,00 per uL of blood (4.5-11x10^9/L)
```
Neutrophils- 40-80%
Eosinophils- 0-6%
Basophils- 0-2%
Monocytes 2-11%
Lymphocytes 20--50%
```
*Young children (up to at least 2) have more lymphocytes than neutrophils (reverse for adults). Of lymphocytes in blood, 70% are T cells, 20% B cells, and the rest something else.
73
what does MHC restriction mean?
means that T cells can only recognize antigen that are complexed/presented by cells of their OWN body. If dendritic cells from another person presented an antigen to that same T cell, no dice
74
___ see antigen ONLY when it is complexed with cell surface MHC molecules; they do not interact with free antigen
T cells
75
what do Treg secrete
- TGFbeta
| - IL-10
76
what antibody classes have J chains
IgM
| IgA
77
what cells are found in Bone marrow
- HSC
- pre-T cells
- B-cells
78
fxns of M2
- aids in healing (debris removal, scar formation, walling off pathogen that M1 have killed)
- chemotactic for eosinophils (specialized for killing parasites)
79
Name the 5 antibody classes, and their characteristic heavy chains
1. IgG (2 gamma chains) + 2 light chains
2. IgA (2 alpha chains) + 2 light chains in a dimer with secretory component (attached through a J chain)
3. IgM (2 mu chains) + 2 light chains in a pentamer (closed by J chain)
4. IgE (2 epsilon chains) + 2 light chains
5. IgD (2 delta chains) + 2 light chains
80
Identities infected self-cells w/ MHC class I and signals apoptosis
CTL
81
____ is where antigens come into the body more frequently than anywhere else
The Peyer patch
82
passage across the placenta
IgG w/ active transport
83
- 10 peptides (4L, 4H, 1J chain, 1 secretory component)
- 6 disulfide bonds
- 6 CDR (ab binding sites)
- secreted form is dimer, basic unit is 2L, 2H, 1J chain, 1 secetory component)
IgA
84
describe clonal deletion/abortion
If an immature B cell (sIgM but no sIgD) binds antigen signals the cell it may be auto-reactive --> it activates its apoptosis suicide program and dies
*This is partially why we don’t make antibodies to ourselves
85
- a reaction in which a soluble antibody reacts w/ a soluble antigen to give an insoluble molecule (aka a precipitate)
- When a molecule-sized immune complex lattice of antigen and antibodies become insoluble and fall out of solution; easily destroyed by macrophages
precipitation
86
Lymph node-like structure that underline the mucosa, especially in the small intestine
GALT or MALT
* peyers patch
* There a rich content of dendritic cells acquire antigens and carry them to the adjacent B cell follicles and T cell zones of the Peyer patch
87
describe the process that occurs after TLR binding
TLR bind foreign pattern (DAMP/PAMP)--> signal a cascade-->expression of factors (Cytokines and chemokines) that cause inflammation--> increased BV diameter/stickiness/leakiness--> efflux of fluid and phagocytic WBC into tissues--> DC travels to lymph node--> activates adaptive immune
88
when can a baby start making its own IgG
3-4 months postnatally
*maternal IgG starts dropping as soon as birth --> reaches 0 around 7-8 months (~21 weeks)
89
Peripheral lymph organs
- lymph node
- spleen
- Peyer's patch
- Mesentric lymph nodes of gut
- tonsils
- adenoids
**Where most lymphocytes are found
90
what immunoglobulin is most resistant to enzymatic digestion
IgA
*has secretory component that helps reduce digestion in the gut
91
gives rise to all cells of the blood but no others
Hematopoietic stem cell (HSC)
| multipotential
92
large circular nucleus w/ little cytoplasm
small lymphocyte
93
They initiate inflammation by attracting and activating monocytes and macrophages, which are specialized for phagocytosis and destruction
cytokines
94
describe the antibody response to a typical antigen in a primary and secondary exposure/response
Primary Exposure- IgM first secreted, then T-helper cells get involved and there is a switch to IgG, or possibly IgA or IgE
-T-helpers in gut and lung preferentially drive IgM to IgA switch
Secondary Exposure- IgM response is about the same, IgG response (efficiently helped by T cells) is sooner, faster, higher, and more prolonged
95
central lymph organs
BW and thymus
*where lymphocyte devlop
96
where are there disulfide bonds on an antibody
- connecting L chain to H chain and
| - connecting H chain to H chain
97
part of blood w/ NO clotting factors, mostly water and dissolved proteins (albumin and globulins), hormones, minerals and CO2, good source of electrolytes
serum
98
Sketch the lattices obtained in antigen or antibody excess, and at equivalence
Ag excess- more antigen than Ab binding sites
Equivalence- equal antigens to binding sites
Ab excess- less antigen than binding sites
99
Nonspecific defense mechanism that occurs w/in hours of antigen appearance
-Fast to act
innate immune response
*recognized DAMPs and PAMPs
100
describe the circulation of lymph through a lymph node
Lymph flows into subcapsular sinus→ percolates through substance of the node→ leaves in efferent lymphatics via the hilum
101
ability to activate complement by the classical pathway
IgM (best/most efficient)
IgG-Takes 2 IgGs close together to activate the first component of complement- only happen if the density of epitopes on the antigen is high enough for this to occur
*IgM is 500x more effective than IgG
102
Receptors that are on the cells surface or inner membranes that detect molecular “motifts” or chemical structures found in pathogens but not in humans
PRP
| pattern recognition pattern
103
foreign molecular structures that PRPs in our innate immune system detect
PAMP
| pathogen-associated molecular pattern
104
recognizes a foreign molecular structure that humans don’t have
TLR
105
Cell filled with basophil granules
mast cels
106
where do T cells originate and develop
originate- bone marrow
develop-in thymus
*(~1% continue to peripheral lymphoid organs)
107
Explains much of the inflammation in an Ab-mediated rxn, and why PMN are the hallmark of such a rxn
C5a is chemotatic for phagocytes, esp. neutrophils
108
what structures do CTL recognize by TCR
Antigen + MHC I (on any cell)
109
what is the fxn of IFN gamma
- Pro-inflammatory, chemotactic for monocytes and tissue macrophages
- Activates Th1 to become angry M1
110
Distinguish IgG, IgA, and IgM classes in terms of:
| size
smallest to largest
| G-->A-->M
111
what immunoglobulins does a fetus have?
low levels of IgM- its own (made before birth around 2-3 months conception)
IgG- maternals
112
what is the hinge region
Region in between Fab and Fc that allows flexibility
-mostly made of disulfide bonds
*When the antibody binds to an antigen, a conformational change occurs thanks to this Hinge region between the Fab and Fc components of the antibody to mark for phagocytosis, complement system etc.
113
what complement components which are:
| chemotatic
C5a- chemotactic for phagocytes, especially neutrophils.
114
describe the surface markers that can be used to distinguish between B and T cells in human
- ALL T cells: CD3
- T-helper cells: CD4
- CTLs- CD8
- B cell surface: MHC I, MHC II, IgM, IgD
*There are no reliable antibodies yet to distinguish Th1 from Th2 or Treg.
115
defines the class of antibody
H-Chain
alpha, gamma, mu, epsilon, delta
116
Only see antigen on the surface of another cell (ex. APC)
T cells
117
MHC class ___ is on all nucleated cells
MHC class I
*not on RBCs
118
Migrate into lymphoid follicles→ IL-4 push B cells w/ recognized antigen to become active and differentiated to switch from naïve IgM/IgD to IgG (spleen), IgA (gut), or IgE
Tfh
119
what type of cell helps with class switching?
T helper cells
*help switch IgM to IgG in primary and secondary exposure
120
what cells can phagocytose
neutrophils
macrophages
DC
B lymphocytes
121
Describe the structure of antibody combining sites.
Antibody combining sites are specific regions of the variable domains of the H and L chains, specifically called the CDR. A stretch of 10-20 amino acids on the antigen (called an epitope) bind with the antibody’s CDR to create a conformation change in the antibody that flags the complex for phagocytosis/complement etc.
122
what are these examples of?
| MIP-1→ -4, RANTES, CCL28, CXCL16, Eotaxin, IL-8
Chemokines
123
help B cells become activated and differentiate into antibody secreting plasma cells
Tfh
124
Undecided precursor, found in paracortex of lymph nodes
Th0
125
what is the Fc
constant domains of the Heavy chain only and is the handle of the fork
-interacts w/ cell surface receptors
126
leukocytes whose nucleus has a SMOOTH outline
mononuclear cells
| ex. monocytes, macrophages and lymphocytes
127
There is a change in the ___ portions of the antibodies after interaction with antigen, which allows the binding and activation of C1q
Fc
128
where do DCs loaded w/ antigen go on arrival to a lymph node
arrive in afferent lymph-- tend to gather at interface btwn cortex and paracortex
129
what immunoglobulin is the “First line of defense”
IgM-- first seen in blood
130
- 4 peptides (2L, 2H)
- 3 disulfide bonds
- divalent
- Extra long constant domain
IgE
131
the number of antigen binding site possessed by an antibody, two per immunoglobulin monomer, or the number of antigenic determinants possessed by an antigen, usually a large number
valence
ex. IgM= decavalent (10)
132
who would you immunize if there was a shortage of flu vaccines?
- kids and elderly
| - immunes kids if still a shortage (immunize the vector)
133
short-range mediators made by any cell that affect behavior of same or another cell
ex?
Cytokine
ex. IL-1, TNFB, IL-12
134
Th0 divide and differentiate into other Th or Treg cells depending on ___
pattern recognition receptor, cytokines and chemokines present
135
- a reaction when a soluble antibody reacts w/ insoluble particles (such as bacteria), the antibodies link the bacterial cells together forming an agglutinate
- When cell or cell-sized immune complexes form and precipitate
agglutination
136
what is the Fab
- includes constant domains of both the heavy and light chains as well as the VARIABLE domains aka the tongs of the fork
- part of Ab that binds to antigen
137
the nodes outer region, full of tightly packed (but highly motile) lymphocytes arranged in follicles, mostly B cells (also Tfh)
Cortex
138
Given a newborn’s antibody titer, interpret its significance if the antibody is IgG, or IgM. If IgG, calculate what the titer will be at 4 months of age, and state the assumptions you made when you did the calculation
At 4 Months:
-IgG- likely end of maternal IgG PLUS some of baby’s own IgG (starts to form around 3 months)
- Half life of IgG is ~3 weeks, so in 7 half lives= 21 weeks after birth there is less than 1% of starting amount of maternal IgG left→ Infant begins to make its own IgG at ~12 weeks
- Therefore at 15 weeks= 5 half lives --> ~ 1.5% of maternal IgG remaining
- Neonate acquires capacity to make IgG at ~3 = 12 weeks postnatally
-IgM- higher than at birth, but still not to 100% of adult level, all baby’s own IgM
139
what do activated Thelper cells do
1. produce cytokines
| 2. activate B cells to proliferate
140
describe pre-t cells
- Do not have characteristic surface antigens to distinguish T cells from others --> go to thymus to diversify their receptor genes--> selected for their responsiveness to “self + antigen”
- arise from CLP
- found in bone marrow
141
- 4 peptides (2L, 2H)
- 3 disulfide bonds
- divalent
- lightest
IgG
142
where are DC predominately located
skin, lung, and mucous membranes (interface btwn body and outside world)
143
what is CDR
part of variable chains in Abs and T cell receptors that binds w/ antigen or HCM
144
what complement components which are:
| opsonizing
C3b**- Split product of activated C3- adheres to membranes. Phagocytic cells (PMNs, macrophages) have C3b receptors, and so can get a firm grip on an antigen if it is opsonized with C3b
IgG-Phagocytes have receptors for its Fc end called FcR
C4b
145
When DC brings matching antigen, they divide and differentiate into other Th or Treg cells depending on pattern recognition receptor, cytokines and chemokines present
Th0
146
single 2-lobed nucleus, red/pinkish
eosinphils
147
survey the surfaces of the body’s cells, looking for ones that have parasites within them or that are dangerously changed or mutated
T cells
148
compare the cellular repertoire of older and younger individuals
Young: FEW memory, MORE naive cells
Old (~40): MORE memory cells (higher baseline), FEW naive --> more prone to newer disease
- FEWER but LARGER clones than younger ppL
ex. SARS, flu shot, West nile fever
149
what does Th1 secrete?
IFNgamma--> proinflammatory and activates M1
| IL-2--> activates CTL cells
150
Makes judgement about severity of threat to increase or decrease activation and fxn of other Th
Treg
*if dysfunctional you will have an overactive immune system
151
what is Fab2
When the Fab region is digested BELOW the hinge so the 2 Fabs are still joined
152
Distinguish IgG, IgA, and IgM classes in terms of:
| approximate concentration in serum
least to most
| M-->A-->G
