Humoral Immunity I (Lecture 3) Flashcards

1
Q

Effector Functions of Antibodies

Interactions with Accessory Molecules

A

LETS RIDE

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2
Q

The Complement System

3 types of events that result from activation of complement cascade, can be activated via of ____ different pathways

only talking about one pathway

A

three

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3
Q

The Complement System

  1. Plays a role in both ____ and ____ immunity.
  2. Involves a large number of ____ proteins and cell membrane receptors including the nine complement components that are designated C1 through C9.
  3. C1 through C9 are ____ proteins normally found in an ____ state.
  4. Activation of the system involves the sequential ____ of the individual components to generate proteolytic fragments that act on the subsequent component in the cascade.
  5. The products of this enzymatic cascade become ____ bound to the surface of a ____ or an ____ molecule attached to the microbe.
A

innate
acquired (humoral)

soluble

plasma
inactive
cleavage

covalently
microbe
antibody

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4
Q

The Complement System

  1. The system is tightly ____ by a number of molecules to prevent uncontrolled complement activation including proteins that are found on normal ____ but absent from ____ surfaces.
  2. There are three major pathways of complement activation:
    - the ____ pathway,
    - the ____ pathway,
    - the ____ pathway.
A

regulated
host cells
microbial

classical
alternative
lectin

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5
Q

The Complement System

even though ____ is different in each scenario, they all ultimately lead to the same three events: recruitment of ____, ____ of pathogens and the killing of the actual ____

be most familiar with is the classical pathway, bc it requires the presence of ____ molecules in order for it to be activated

A

activation
inflammatory
opsonization
pathogens

antibody

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6
Q

The Complement System

complement activated via alternative or lectin mediated pathway > acting as a form of ____ immunity, certain bacterial molecules that can bind to certain components of the pathway and activate it in the absence of ____ (____ is an example and ____ that are on surface of microbes that have capacity to activate the pathway)

A

innate
antibody
LPS
lectins

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7
Q

The Classical Pathway

The Classical Pathway
1. The classical pathway can be activated by the binding of ____ to the Fc regions of ____ and ____ when the antibodies are bound to antigen (the surface of a microbe or as part of an immune complex).

(1) binding of IgG or IgM to surface of microbe > (2) Ab molecules can then interact with the first component of the cascade: C1; each arm is capable of interacting with Fc portion of IgM pentamer, or two IgG molecules (a single IgG will ____ activate the process)

there is an alteration in the conformation of the C1 molecule > enzymatic activity on ____

A

C1
IgG
IgM

not
C4

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8
Q

The Classical Pathway
2. This event induces a conformational change in C1 which allows it to act on the next component, ____, cleaving it into two fragments.

C4 cleaved into two fragments: ____ and ____

C4A acts on next component: ____ > C2 acts on ____, follow the numbers below

  1. The cascade subsequently proceeds in the sequence of C2, C3, C5, C6, C7, C8, and C9.
A
C4
C4A
C4B
C2
C3
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9
Q

The Classical Pathway
4. Individual proteolytic fragments are biologically active:
- C3a, C4a and C5a are potent ____ of inflammation.
- C3b acts as ____ via binding to specific receptors
on the surfaces of certain types of phagocytic cells.

C3A, C4A, C5A > enhance inflammation, induce changes in structure of endothelial cells thereby increasing ____, the contents of blood in that environment will enter the EC space; can also act as ____ > bring WBC into the space where the complement has been activated

C3B > act as an opsonin > mediates opsonization; bacterial cell, C3B fragments accumulating on surface of cell, in addition to innate and Fc receptors, ____ also have complement receptors on surfaces; C3B provides the highest interaction bt phagocytic cell and bacterial cell > highest level of ____ at which microbe can be phagocytosed and eliminated

opsonization involved antibodies, complements, Fc receptors, etc.

A

inducers
opsonin

vascular permeability
chemoattractant

macrophages
efficiency

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10
Q

The Classical Pathway
5. The terminal complement proteins (C5, C6, C7, C8 and C9) polymerize to form the ____. This generates ____ in the plasma membrane of the cell on which the cascade was activated that can lead to ____.

release of substances from cells can have a ____ effect on your own tissue; complement rids cells, but can also contribute to ____ because of release of molecules from bacterial cells

there is often ____ damage via this pathway

A

membrane-attack complex
pores
osmotic lysis

deletrious
tissue damage

collateral

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11
Q

The Complement System

presence of IgG, IgM to ____

C1 > ____
generation of cleavage fragments recruiting cells (C3A)
C3B involved in ____

and then generation of the membrane attack complex > pores > lysis

important in immunity against pathogens

what happens first? phagocytosis or complement pore? if not phagotosed via C3B, the cell will be eliminated via one pathway or another

A

C1
C4
opsoninization

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12
Q

Functions of Complement

  • ____ of microbe
  • recruitment and activation of ____ by C5A, C3A
  • destruction of ____ by leukocytes
  • ____ of microbe

important against ____ but not effective against something within your ____

A

phagocytosis
leukocytes
microbes
osmotic lysis

extracellular pathogens
cells

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13
Q

Maternal Transfer of Antibody (The “Good” Side)

In utero, maternal ____ is passed across the placenta via FcRn. After birth, maternal ____ and ____ can be passed via breast milk.

maternal IgG passed against ____ and into fetal circulation; continues all the way into birth and then disappears in ____ months

this antibody acts as an initial form of ____ immunity for the newborn infant;
begin producing ____ during utero, the only source is what has been passaged from maternal circulation

this antibody is not being reproduced, passed from mother to the infant > at 9 mo: producing only IgG and IgA; mediated via another FcRn (neonatal Fc receptor) > expressed in synctiotrophoblast cells

IgG taken up via Rm ____ > in endosome interacts with the receptor, protects from degradation and transfers it into fetal circulation

provides neonate with a source of IgG molecules; after birth, in mice, IgG and IgA can be transferred to newborn via breatmilk; but in humans ____ is transferred over

the secretory IgA that is taken up, is not taken into circulation, will only act against pathogens found within the ____ (exposed to often during first few months of birth; can survive without, however)

A
IgG
IgG
IgA
synctiotrophoblast
9

adaptive
IgM

endocytosis

secretory IgA

GI tract

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14
Q

Maternal Transfer of Antibody (The “Bad” Side)

if mother has autoimmune disease involving IgG molecules > ____ DISEASE (____ antibodies); these antibodies can cross and enter the fetal circulation, and the infant can be born with grave’s disease

not a lifetime problem, as decay of maternal antibody takes place, the baby will recover (over ____ months the baby will ultimately recover)

A

Graves
anti-TSHR
9

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15
Q

Relative Role of Antibody Classes in Antimicrobial Immunity

❖ Now put this into context of the different kinds of pathogens- extracellular (EC) and intracellular (IC)
❖ Most antibody-mediated approaches are for ____
❖ If pathogen gets into cell, hard for antibodies to get at it
❖ Cell-mediated approaches are more for ____

A

extracellular pathogens

intracellular pathogens

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16
Q

Relative Role of Antibody Classes in Antimicrobial Immunity

antibody mediated immunity is important; in the case of influenza > can enter the mucosa > ____ is a mucosal antibody

once viruses are within our cells > evading humoral detection > ____ forms become important

A

IgA

cell-mediated

17
Q

for bacteria; ____ is more important, cell-mediate immunity not as important

organisms on top are ____ pathogens; bottom of the list: spend most of time within cells

A

antibody-mediated

extracellular

18
Q

Humoral Immunity

  • B Cell Biology

Let’s talk about the cells responsible for producing antibodies

19
Q

Lymphocyte Differentiation

hematopoietic SC will differentiate into a ____ > can differentiate into NK cells, B cells, T cells

when lymphoid progenitor cells instructed to form B cells, all of this occurs within the ____ (when they differentiate into mature B lymphocytes)

A

common lymphoid progenitor cell

bone marrow

20
Q

Cell Surface Markers

cannot differentiate between B and T cells ____

A

microscopically/morphologically

21
Q

CD (Cluster of Differentiation) Molecules

Cell surface molecules expressed on
various types of immune cells:
• To date, approximately ____ different CD
molecules have been identified.
• Many have important functional roles in
immune reactions.
• They can be used as ____ markers
to differentiate between distinct types of cells (cell surface markers).

A

250

phenotypic

22
Q

CD Molecules

____ on b cells, ____ on b cells

____, ____, ____ on t cells

____ - found on surface of NK cells; mediating ADCC

A

CD19
CD21

CD3
CD4
CD8

CD16

23
Q

Cell Surface Markers

❖ Many companies cell antibodies against these cell surface molecules like CD3, 4, 8, 16, 19, 21

❖ Can take sample of ____ cells and incubate them with antibody molecules (often conjugated to fluorescent molecule)

❖ Mixture of ____ and ____ positive T cells

❖ Antibody against CD4 will bind to CD4 will bind to left, antibodies
against CD4 and CD8 will bind to middle, antibodies against CD8 will bind to right

A

human
CD4
CD8

24
Q

Flow Cytometry

counts the number of cells that exerts certain ____

cells that fluoresce both = ____ color

allows you determine numbers of different subsets of immune cells

can purify diff ____ of cells based on cell surface markers, and add them back in to determine which are required for immunoloigc activites

A

fluorescence
orange

populations

25
B Cell Differentiation For most antigens, B cell activation necessitates binding of the ____ to the cell’s antigen receptor and interaction between the B cell and a ____ cell. This requires ____ contact between the cells and expression of membrane and secreted molecules (____) by the T cell that bind to receptors on the B cell. cell's antigen receptor = ____ molecule (for B cells) interaction between B cell and T cells; they have ____ for one another ____ signals required for B cell activation in context of most types of antigens
antigen T physical (cytokines) antibody ligands two
26
B Cell Differentiation For most antigens, B cell activation is a ____-step process initiated by binding of antigen to the B cell antigen receptor (antibody). B cell has CD19, CD21 on surface > not involved in ____ process molecules that are involved = membrane bound antibody molecules; encoded within the ____ first thing that has to happen; Ab on cell surface must engage an interaction with unique epitopes on antigen molecule; requires crosslinking of ____ Ab molecules antigens that require this two-step process = ____ dependent antigens; cells derived from thymus are important are T cells once B cell interacts with ____ cell > interaction of green box > second signal that leads to activation
two inactivation MHC multiple thymus helper T
27
B Cell Differentiation Binding of antigen to membrane immunoglobulin results in the delivery of biochemical signals that initiate the activation process. amplification signals following engagement of receptor ultimately results in ____; enhance expression of ____ encoding proteins that are involved in activity of B cell
TF | genes
28
B cell Differentiation circulating throughout blood = ____ cells (never exposed to antigen before) on surfaces > large # of Ab molecules; resting B cells express ____ and ____ on cell surface*** (unique characteristic of resting phase of mature B cell); the antibodies all have the same antigen specificity, they're all ____ enter circulation, between blood and lymphatics; constantly through secondary lymphoid, looking for antigen if they don't bump into antigen, after a couple of days: ____; its to their advantage to encounter the antigen; then activated via interaction with T cell begin to proliferate > give rise to genetically ____ daughter cells (expressing the same antigen receptor); T cells also secrete cytokines that tell B cells to stop producing ____ and produce others > ____; absent of help > become ____ cells (secrete ____ pentamer) (thymus independent antigens) under influence of cytokines > plasma cells secreting ____, or ____, or ____; also results in generation of memory of cells vaccine induces ____; some into IgM, IgG plasma cells, and memory cells (long lifespan) > memory responsible for large amounts of antibodies produced (secondary immune response)
resting B IgD IgM identical ``` apoptosis identical IgD/IgM isotype switching plasma IgM ``` IgE IgG IgA (secretory) clonal expansion
29
B Cell Differentiation cont. ❖ In addition to making plasma cells, this also generates memory cells that act during second exposure to same antigen o Vaccines are trying to induce this o Plasma cells have ____ life span; memory cells have ____ life span o Memory cells produce rapid secondary immune response within a couple of hours upon second exposure ❖ Also, note that proteins are ____ antigens o This may be why they’re such ____ antigens
short long T-dependent potent
30
How Is The Antigen Specificity Of A B Cell Determined? side chain hypothesis; antigen that tells the cell what Ab to produce selective (clonal selection) hypothesis: each B cell is ____, only has one type of antigen receptor on surface; antigen has nothing to do with determining specificity of B cell; close to original inference, except he thought that cell can express multiple receptors
monospecfic
31
The Clonal Selection Hypothesis Antigen-Independent Stage of B Cell Differentiation ❖ In bone marrow, events give rise to resting B cells that express IgM and IgD on surface, all ____ of antigens ❖ We have monospecific cells being generated all the time with thousands of copies of receptor on surface
independent
32
The Clonal Selection Hypothesis Antigen-Dependent Stage of B Cell Differenttiation ❖ Clonal Selection Hypothesis argues that cells in peripheral circulation, especially secondary lymphoid organs, are exposed to antigens ❖ Antigen that binds to cell with appropriate receptor will provide signal 1 ❖ This usually occurs in conjunction with activation by T cells, signal 2 ❖ Within clone of cells, some differentiate into ____ cells and others differentiate into ____ cells that act in secondary, tertiary responses ❖ This is the accepted model today ❖ People who proposed this got a Nobel for coming up with better hypothesis than Erlisch in 1810 or 1820
plasma | memory B
33
The Clonal Selection Hypothesis ❖ Looking at diagram on right ❖ On top is IgM and IgD positive ____ ❖ With antigen and T cell help, becomes ____ ❖ T-cell derived cytokines instruct clones which ____ of antibody they will produce ❖ Not every microbe and body compartment is dealt with effectively with the same antibody ____ o Respiratory problems best dealt with ____ o If peripheral circulation problems, should make____ ❖ So T cells ____ response and fine tune it to make appropriate type of antibody for infection in body compartment
``` resting B cell activated B cell class response secretory IgA IgG quarterback ```
34
B Cell Differentiation interaction bt mature B cell that has engaged antigen; receiving secondary signals from T cell gives rise to genetically ____ daughter cells; under influence of cytokines will give rise to different ____ cells and ____ memory cells do not go through the ____ signalling (T-independent activation); certain antigens have charactristics that directly activate a B cell
identical class switching plasma two-step
35
T-Dependent Versus T-Independent Antigens t-independent: extremely repetitive types of structures > lipids, carbohydrates > activate b cells directly > only Ab that the b cells produce > ____ (does not have diverse capabilities that IgG has); in terms of protective function > you want ____; thymus indepedent > response is not ____ enough in protecting from infection, however, gets adaptive immune response ____
IgM thymus-independent potent started
36
B Cell Differentiation first response we see are production of ____ molecules; once interaction of B cells and T cells > production of ____ molecules (induce ____) > antibody molecules that have more diveristy function as antigen diminishes, these antigens fall off; but a production of ____ cells have been produced second time exposed > you have preformed population of cells that can recognize antigen (still ____ T cell help) > doesn't take as long for it to happen, and predominantnly the class of antibody one sees is ____, the response slowly falls off
IgM IgG class switching memory require IgG