Immunology Exam 3

_________ cells bind antigen at an infection site and then travel through lymphatic vessels to the draining secondary lymphoid tissue.

dendritic cells bind antigen at an infection site and then travel through lymphatic vessels to the draining secondary lymphoid tissue.

how are t-cell antigens brought from an infection site to a lymph node (or other secondary lymphoid tissue)?

For a non-mucosal tissue, antigens are transported from an infection site to secondary lymphoid tissue in lymphatic vessels (or via blood for the spleen). Extracellular fluid surrounding tissues forms lymph, which is drained by the lymphatics to secondary lymphoid tissues. Following activation by an antigen, dendritic cells travel in the lymphatics to a secondary lymphoid tissue to present antigen to T-cells. Free antigen (i.e., that has not been taken up by a dendritic cell) also enters the lymphatics and is transported to secondary lymphoid tissues where it can be taken up by dendritic cells resident in the secondary lymphoid tissue. (We will discuss how things are different in mucosal tissues and mucosal secondary lymphoid tissues in chapter 10).

How can un-activated/ immature dendritic cells become activated/ mature?

dendritic cells have many differnet pattern recognition receptors (PRRs). they become activated when a pathogen associated molecular pattern (PAMP) activates a PRR or when a danger/ damage associated molecular pattern (DAMP) activated a PRR (DAMPs are conserved molecules that signal cell stress).

Which 3 molecules does an immature dendritic cell upregulate on its surface following activation to become a mature dendritic cell?

upregulates
- the co-stimulatory molecule B7, which is required for T-cell activation
- peptide/ MHC complexes (i.e., peptide is presented to T-cells on MHC class I and MHC class II)
- chemokine receptor 7 (CCR7), which directs the dendritic cell toward a chemokine produced in secondary lymphoid tissues

Which molecules does an immature dendritic cell downregulate on its surface following activation to become a mature dendritic cell?

downregulates
- PRRs. the dendritic cell is no longer functioning to bind PAMPs. once activated, it is now funcitoning to present antigen to T-cells.

Dendritic cells take up antigens specifically (via PRRs binding to PAMPs) or non-specifically by macropinocytosis (non-specifically engulfs material and brings it into the cell in an endosome). What normally prevents dendritic cells being activated by self-antigens if they take up self-antigens via macropinocytosis?

self-antigens do not activate PRRs, so they should not cause an immature dendritic cell to become mature.

(it is possible that a dendritic cell could take up a self-antigen and simultaneously bind a microbial PAMP and become mature. The dendritic cell would then have the potential to activate a self-reactive T-cell that had escaped negative selection, and the result could be an autoimmune disorder (we will discuss autoimmunity in chapter 16)).

in which part of the lymph node do T-cells sample the antigens presented by dendritic cells?

T-cell areas

which 3 signals are needed for T-cell activation and proliferation?

1. T-cell receptor binds a peptide:MHC complex presented by a dendritic cell.
2. CD28 on the T-cell binds to the B7 co-stimulatory signal provided by a mature dendritic cell.
3. Cytokines
- IL-2 is required for T-cell proliferation following activation. the T-cell itself is the source of the IL-2. After the T cell receives the first 2 signals, it starts to produce Il-2 and a high affinity IL-2 receptor.
- cytokines delivered to the T-cell upon activation are the major factor that determines which effector subset a naiive CD4 T-cell will differentiate into.

Define anergy (i.e., to become anergic)

the T-cell (or B-cell) becomes permanently unresponsive. if the T-cell encounters an antigen again in the future, it will be unresponsive to it and cannot become activated.

What happens if a T-cell receptor binds to a peptide:MHC complex in the absence of a co-stimulatory signal? why does this happen?

the T cell becomes anergic. this happens as a protective mechanism to minimize the chances of a T-cell becoming activated by a self-antigen. self-antigens should not activate dendritic cells to produce the co-stimulatory B7 molecule because self-antigens do not usually contain PAMPs. therefore, if a dendritic cell presents antigen in the absence of a co-stimulatory B7 signal, it could be a self-antigen.

define naiive T cell

a naiive T cell is one that has not yet become activated

define effector T cell

an effector T-cell is one that has become activated by an antigen and how has effector function
- if a naiive T cell receptor binds the antigen/ MHC complex presented by a dendritic cell, it becomes activated to produce an effector T cell

What type of effector T-cell do naiive CD8 T-cells turn into following activation, and what is the function of that type of effector cell?

cytotoxic T cells, which function to destroy host cells infected with an intracellular pathogen (i.e., a pathogen that is replicating inside the cell as opposed to outside the cell).

how do cytotoxic T-cells identify a target cell to destory?

infected cells display pathogen peptides on MHC Class I molecules on the cell surface. if a cytotoxic T-cell receptor binds to its peptide:MHC complex on a cell surface (i.e., the same complex that ctivated the T-cell), then it will kill the target cell. once activated, a T-cell does not need a co-stimulatory signal, it only need to bind to the same peptide:MHC complex that activated it.

what are the 2 classes of cytotoxins stored in the granules of cytotoxic T cells? what is the purpose of each class of cytotoxin?

perforin disrupts the target cell membrane

granzymes are then delivered into the target cell, and they are proteases that activate the caspase proteins that induce apoptosis.

what is a cognate (or conjugate) pair, and why do CD8 T cells form a cognate (or conjugate) pair with their target cell?

a cognate pair includes a T cell and its target cell (also known as a conjugate pair). A cytotoxic T cell forms a cognate pair with one target cell at a time because its activity must be directed only towards the specific target cell and not bystander cell.

upon activation, a CD4 T cell can differentiate into one of several effector subsets (we focused on five, but an additional two subsets have also more recently been characterized). Name the 5 best characterized subsets of CD4 T cells.

The subsets are T helper 1 (TH1) cells, T helper 2 (TH2) cells, T follicular helper (TFH) cells, T helper 17 (TH17) cells, T regulatory (Treg) cells. (TH22 cells and TH9 subsets have also been recently characterized)

what determines the CD4 T-cell subset that a naiive T-cell will differentiate into?

combination and balance of lineage-specifying cytokines that are present during activation (which in turn largely depends on the type of infection present because the specific PRRs activated influence the cytokines that are subsequently released.

major function of TH1 cells?

they upregulate macrophages to become effective at phagocytosis. macrophages initially circulate in tissues in a downregulated state in the absence of infection (in this state they do not produce the potent reactive oxygen species). in the presence of infection, they can be upregulated to become more effective at phagocytosis.

During which type of infection are TH1 cells the CD4 T-cell subset that predominates (i.e., infection with an intracellular pathogen, a helminth pathogen, or extracellular pathogen)?

The TH1 response is important in defense against intracellular pathogens. Some pathogens (such as M. tuberculosis, P. jeroveccii, and Toxoplasma), have evolved to replicate inside macrophage endosomes, so macrophages must be upregulated more effectively combat such infections. Macrophages are also important and often upregulated during intracellular infection with a viral or bacterial pathogen that is replicating in the cytosol; they clear cellular debris resulting from the action of CD8 T-cells, and macrophages can also take-up the pathogen during phagocytosis when it is moving from cell to cell.

Why aren't macrophages constantly maintained in an activated state?

Macrophages produce potent antimicrobial substances to destroy the contents of endosomes/ phagosomes, and the antimicrobial substances can also damage host bystander cells. macrophages increase production of potent antimicrobial substance after activation. therefore, macrophages kept at ground state in the absence of infection to limit unnecessary production of antimicrobial substances that could potentially harm host cells. additionally, it takes more energy for the macrophage to be maintained in an activated state, so the macrophage doesnt need to unnecessarily waste energy.

which 2 signals does a macrophage need to become upregulated?

the cytokine IFN-gamma and the CD40 ligand (CD40L), which binds to the CD40 receptor on the surface of the macrophage. the macrophage presents material derived from its vesicles on MHC class II molecules. when an activated TH1 cell binds to an antigen / MHC compelx being presented (the same complex that activated the TH1 cell), then the TH1 cell forms a conjugate pair with the macrophage and delivers the 2 signals.

what is a granuloma and why does it form?

granuloma forms when activated macrophages cannot eliminate a pathogen. it is a collection of macrophages and TH1 cells that chronically cooperate to wall off the pathogen and prevent pathogen dissemination. For example, M. tuberculosis results in formation of a granuloma in the lungs. in latent infection, the bacteria go into a latent/ dormant state in the lung granuloma.

What is the function of TFH cells?

they provide one of the activating signals needed to activate B-2 cells, and the same signals are also required for somatic hypermutation and class switching of B-2 cells in the germinal center

what is the function of TH2 cells?

promote defense against helminth parasites, they function by releasing cytokines that act on other cells.

name 3 outcomes of the cytokines released by TH2 cells?

i) promote immune responses by mast cells, eosinophils, and basophils
ii) promote class switching to the IgE antibody class
iii) promote body responses intended to flush out the parasite, such as increased epithelial cell turnover, increased mucus production, and smooth muscle contraction together with increased permeability of blood vessels (which causes vomiting and/ or diarrhea)

what is function of TH17 cells? and what are the effects of cytokines released?

they enhance the response to infection with extracellular pathogens, which is most often extracellular bacteria and fungi.

release cytokines

i) increase neutrophil production and recruitment to the infection site

ii) act on muscosal epithelial cells to increase turnover rate and increase production of antimicrobial molecules (to limit colonization of the mucosal surface)

Match the T-cell type (I-V) with the innate lymphoid cell (ILC) type (A-D) that performs a parallel function during the innate immune response.
A. TH17 B. TH1 C. TH2 D. CD8 T-cell
I. Natural killer cell II. ILC1 III. ILC2 IV. ILC3

A. TH17 - IV. ILC3
B. TH1 - II. ILC1
C. TH2 - III. ILC2
D. CD8 T-cell - I. Natural killer cell

what is function of Treg cells?

They are anti-inflammatory and function to suppress the activity of other T cell subsets to prevent immune responses against self-antigens and other harmless antigens. The anti- inflammatory cytokines they secrete can also promote repair of damaged tissue after an immune response.

what is the difference between natural Tregs and induced Tregs regarding when they are produced?

natural Tregs are produced in the thymus during T cell development; some cells that bind strongly to a self-peptide/ MHC complex during negative selection may become natural Tregs instead of undergoing apoptosis. Natural Tregs play an important role in preventing activation of self-reactive T-cells that escaped negative selection

Induced (adaptive) Tregs differentiate from naiive CD4 T cells following activation in a secondary lymphoid tissue in the presence of anti-inflammatory cytokines. induced Tregs are primarily produced in the mucosal immune system (discuss in ch 10) is response to innocuous antigens like commensal microbes and food antigens.

Tregs _____ - regulate inflammatory immune responses

Tregs suppress/ inhibit/ down - regulate inflammatory immune responses

what is the function of γ:δ T-cells (gamma:delta T-cells)?

they detect and destroy stressed/ damaged cells and promote tissue repair
- account for most T cells in tissues (only 5% in blood)
- do not interact with MHC molecules

what type of antigen do γ:δ T-cells recognize? do they interact with MHC molecules?

they have a much more limited receptor repertoire than α:β T-cells. rather than directly binding to pathogen antigens, they bind to antigens that are produced when a cell is under stress, which is often caused by infections. γ:δ T-cells bind to antigen directly, they do not interact with MHC molecules.

why are γ:δ T-cells described as 'innate-like' immune cells?

like other cells that function during the innate response, γ:δ T-cells bind to conserved antigens (associated with cell stress) rather than antigens that are microbe specific (like α:β T-cells B-2 cells) and they act early during an immune response (function immediately after binding to antigen unlike α:β T-cells, which take several days to become activated.)

what is severe combined immunodeficiency disorder, SCID (i.e., which leukocytes/ white blood cells are deficient)?

SCID is an immunodeficiency disoder characterized by T-cell deficiency. it can have multiple causes: IL-2R mutation (X-linked SCID), RAG protein mutation (Omenn syndrome), abnormal thymic development
- no functional T-cells

What causes AIDS? in AIDS, which leukocytes/ white blood cell is deficient?

Acquired immunodeficiency syndrome (AIDS)

is caused by the HIV virus. it infects CD4 T cells and results, over time, in CD4 T-cell deficiency

what symptoms are experienced by patients with a severe T-cell deficiency, such as SCID or AIDS?

without T cells, the body effectively does not have an adaptive immune system as T-cells function in all aspects of adaptive immunity. patients without functional T cells are extremely susceptible to all types of infection, including infections that dont typically cause symtpoms in an immunocompetent individual, but can be life-threatening in patients with defective T cell function (e.g., P. jirovici and cytomegalovirus)

where do B-2 cells sample antigens?

in the B-cell areas in secondary lymphoid tissue. in the lymph nodes, the B-cell areas are called lymphoid follicles. in non-mucosal tissues, antigen arrive in secondary lymphoid tissues via lymphatics

where are follicular dendritic cells (FDCs) located, and what is their role during B-cell activation?

follicular dendritic cells are found in the B-cell areas in secondary lymphid tissues. they are not blood cells and are not derived from hematopoietic stem cells in the bone marrow (like conventional dendritic cells, they are named dendritic cells bc of their branched processes called dendrites.
FDCs present antigen to B-cells

in what form do FDCs present antigen to B cells? (i.e., intact antigen or degraded?

They are not phagocytic, so they do not internalize antigen. They display intact antigen to B-cells because we need to activate B-cells that will produce antibodies against antigens that are accessible on the surface of microbes.

what is a naiive B cell? What type of cell do naiive B-cells turn into following activation?

a naiive B-cell is one that has not yet been activated. following activation, a naiive B-cell differentiates into a plasma cell that secrete antibody (or as we learn later, some naiive B-cells can instead differentiate into memory B-cells, which functions during a memory response.)

what are the 3 signals needed for B-cell activation in response to a thymus-dependent antigen?

1. binding of antigen to B-cell receptor
2. binding of complement fragment C3d to the B-cell co-receptor
3. signals delivered by a conjugate T follicular helper cell (TFH):
i) binding of CD40 ligand (CD40L) on the T-cell to the B-cell receptor CD40 receptor (promotes class switching and somatic hypermutation in the germinal center)
ii) binding of cytokines secreted by the TFH cell to B-cell cytokine receptors.
these signals from a TFH cell are required for naiive B-cell activation and proliferation (rapid cell division to produce many clones), and, also for somatic hypermutation and class switchingterm-42

The requirement for T-cell help serves as a mechanism of B-cell ______ _________.

The requirement for T-cell help serves as a mechanism of B-cell negative selection.

- if a B-cell receptor binds self-antigen, there is unlikely to be a conjugate (partner) T-cell present

what T-cell subset provides activating signals to a B-cell during B-cell activation?

T follicular helper (TFH) cells

B cells and T cells are activated in ____?

B cells and T cells are activated in secondary lymphoid tissues

Define linked recognition regarding the antigen recognized by a B-cell receptor and the conjugate TFH cell receptor?

The B-cell receptor and the conjugate TFH cell receptor do NOT recognize the same antigen, but the antigens must be a part of the same overall structure.
for example, in the case of a pathogen, a B-cell receptor will be activated by a surface antigen. it will then internalize the whole pathogen and break it down. the proteins will be processed into small peptide fragments and presented on the surface of MHC class II to TFH cells. therefore, the peptide antigens that are being presented on MHC II to TFH cells are different from the antigen that activated the B-cell receptor, but the antigens are a part of the same pathogen.

how does the B-cell requirement for T-cell help serve as a negative selection mechanism that protects the body from self-reactive B-cells that escaped negative selection? (i.e., B cells with a receptor that binds to self-antigen)?

If a B cell receptor binds to a self-antigen it will not likely be activated because there will not likely be a TFH cell that recognizes a linked antigen. (That would require a T-cell that had also escaped negative selection for the same self-antigen. Also, as we will learn in chapter 8, T-cells that bind self-antigen in the absence of a costimulatory signal become anergic rather than activated). B-cells undergo apoptosis if they bind antigen, but do not encounter a conjugate T-cell

following activation of the B-cell receptor and B-cell co-receptor (
first two signals), which area does a B-cell go to encounter its conjugate TFH cell?

to the boundary region between the B cell/ Tcell areas to present antigen on MHC class II to newly activated TFH cells.
following T cell activation in the T-cell area, activated TFH cells also move to teh boundary region to meet the B-cells.

when and where (in a lymph node) does a primary focus form?

following activation, B-cells and conjugate TFH cells move to the medullary cords and form a primary focus.

what is produced in the primary focus, and which antibody class is secreted from plasma cells formed in a primary focus?

In the primary focus, B-cells and conjugate T-cells undergo proliferation. Some B-cells in the primary focus differentiate to plasma cells that secrete low affinity IgM antibody (because the B-cells have not undergone somatic hypermutation and class switching).

when and where is a germinal center formed?

Following initial proliferation in the primary focus, most B cells and conjugate TFH cells move back to the lymphoid follicles (B-cell area) to form a germinal center

activated B-cells differentiate into plasma cells in __ waves.

2 waves
1. the B-cell T-cell cognate pair moves to the medullary cords to form primary focus
2. remaining B-cells move back to the lymphoid follicles to form a germinal center

which two events take place in the germinal center?

The gene encoding the AID enzyme is expressed in the germinal center, so somatic hypermutation (resulting in affinity maturation) and class switching occur in the germinal center as B-cells continue to proliferate

describe how affinity maturation takes place in the germinal center including:
a) what happens in the dark zone
b) what happens in the light zone
c) what happens to B-cells that have high affinity receptors and bind antigen in the light zone
d) what happens to B cells that do not have high affinity receptors and do not bind antigen in the light zone

a. B-cells in the dark zone are referred to as centroblasts; they undergo proliferation, and DNA encoding the receptor undergoes somatic hypermutation and class switching. b. B-cells in the light zone are referred to as centrocytes; they have undergone somatic hypermutation and now display the mutated receptor on the surface to see if it can bind antigen. c. Centrocytes with a high affinity receptor will successfully compete for antigen displayed by follicular dendritic cells and will continue to receive signals from conjugate TFH cells (CD40L and cytokines- the same signals that activated the B-cell). High affinity centrocytes will then undergo further rounds of somatic hypermutation and selection. The centrocytes that remain after several rounds will differentiate into plasma cells that secrete high affinity, class-switched antibody. d. Centrocytes that do not have a high affinity receptor will not be able to compete for antigen in the light zone, so they will not continue to receive signals from conjugate TFH cells and will die by apoptosis.

which molecules determine the antibody class that will be produced during class switching?

class switching is largely determined by the cytokines received by the B-cell

which properties distinguish a plasma cell from a naiive B cell?

A plasma cell is a terminally differentiated B cell that secretes antibody. Plasma cells no longer express the B cell receptor on the surface, and they do not express MHC class II molecules because they have already been activated (and therefore do not need to display the B-cell receptor or interact with T cells). They are terminally differentiated, so they do not have the capability of any further proliferation, affinity maturation, or class switching.

regarding the need for TFH cell help during activation, what is the difference between a thymus dependent antigen response and a thymus independent antigen response? What is the primary antibody class produced during a thymus-independent response?

In a thymus-dependent antigen response, the B-cell requires T-cell help to become activated and then to undergo somatic hypermutation and class switching in the germinal center. In a thymus-independent antigen response, a B-cell can be activated in the absence of T-cell help. The primary antibody class secreted during a thymus-independent response is low affinity IgM, as it occurs outside of the germinal center

what type of antigens can activate a TI-1 response, and what is the benefit of having B-cells that are able to be activated by TI-1 antigens?

TI-1 antigens include common bacterial PAMPs, such as LPS and bacterial DNA, that may reach a high concentration during an infection. At high concentration, they can activate B-cells non-specifically (i.e., regardless of B-cell receptor specificity) without T-cell help. B-cells are activated by binding of the PAMP to a B-cell PRR. Some of the B-cells that were activated non-specifically will produce antibodies that can bind to other antigens on the pathogen. Thymus-dependent B-cell responses are also activated, but the thymus-independent response arises earlier and provides quick initial protection while the body waits for the thymus-dependent response to develop

what type of antigen can activate a TI-2 response, and what type of B-cells are activated by TI-2 antigens?

TI-2 antigens are highly repetitive polysaccharide (carbohydrate) antigens in bacterial capsules. The highly repetitive structures can cross-link many B-cell receptors and send a strong signal to activate the B-cell without T-cell help. B-1 cells (and another subset called marginal zone B cells in the spleen) produce TI-2 antigen responses.

what is the benefit of having B-cells able to be activated by TI-2 antigens?

Bacteria with a capsule are more resistant to phagocytosis, so their antigens do not get processed efficiently by dendritic cells for presentation to T-cells. Therefore, T-cell dependent (i.e., thymus dependent) B-cell activation can difficult in the absence of an initial TI-2 response. Once the initial TI-2 response has been produced, the antibodies may aid in the activation of B-2 cell responses (e.g., by resulting in the microbe being tagged by opsonins).

what are the 5 antibody classes?

IgA, IgG, IgM, IgD, and IgE

what is the first antibody class to be secreted?

IgM, during immune response (from primary focus), relatively low affinity

what is the most abundant antibody class in a) the body and b) blood serum?

a) IgA - due to large amount of IgA that is produced to protect mucosal surfaces
b) IgG

During fetal development, which antibody class is transferred across the placenta?

IgG

what is the primary (most abundant) antibody class present in breast milk that protects the infant's mucosal surfaces?

IgA - it is passively transferred to the digestive tract mucosal surfaces of an infant following ingestion of breast milk (and some mucosal surfaces of the upper respiratory tract)

which antibody class is typically the first class to be secreted during a primary infection (i.e., first encounter with an antigen)?

igM - it is produced from plasma cells that differentiate in the primary focus

which antibody classes are most effective at moving out of blood and protecting extravascular tissues?

IgG and monomeric IgA (IgM can also move out of blood to protect vascular tissues, but it is bulkier, so it doesn't move into the tissues as readily. IgM is also a lower affinity antibody)

which antibody class is the primary class that protects mucosal surfaces (i.e., most abundant and most effective)?

dimeric IgA. (IgM also provides protection at mucosal surfaces, but it is present at a lower concentration; also, IgM is a lower affinity antibody, so it is not as effective as IgA at neutralization).

which antibody class binds to Fc receptors on the surface of mast cells to 'sensitize' masts cells?

IgE

Why are young infants vulnerable to infections in the first year (think about the level of antibodies)?

Regarding antibody levels, an infant is building up its antibody levels during the first year. IgM levels gradually rise during the first year, but it takes approximately a year to develop high levels. IgG that came from the mother steadily declines after birth; an infant starts to produce an appreciable level of its own IgG at approximately 3 months, but the level is relatively low until ~1 year of age (IgG levels continues to increase up to ~5 years old). IgA level also starts to steadily rise from about 3 months but is relatively low until ~ 1 year of age (and IgA levels continue to increase after the first year). However, an infant can be supplied with maternal IgA from breast milk to help protect mucosal surfaces while IgA levels are increasing.

Define neutralization.

antibodies bind to an antigen and prevent attachment of microbes, toxins, and venoms to host cells (e.g., a bacterium is unable to attach to and colonize a surface, a microbe is unable to cross an epithelial layer, a virus or toxin is unable to bind to a cell receptor to enter a cell)

which antibody classes are most effective at neutralization and why?

IgG and IgA, bc they are high affinity antibodies that have undergone affinity maturation. IgG is the primary neutralizing antibody class in systemic tissues, and dimeric IgA is the primary neutralizing antibody class at mucosal surfaces. (IgM can also function in neutralization, but it is a lower affinity antibody, so it is less effective)

which antibody classes are the biggest contributors to activating the classical complement pathway?

IgM and IgG

(Monomeric IgA can activate the classical complement pathway too, but most IgA is dimeric IgA found at mucosal surfaces where complement proteins are not present. Therefore, for our purposes, we will say that it is not a major function of the IgA antibody class as a whole).

IgM and IgG bind to the pathogen surface and recruit ____, which activates the classical complement pathway.

IgM and IgG bind to the pathogen surface and recruit C1, which activates the classical complement pathway.

they do not interact with C1 when not bound to the pathogen surface

what is an Fc receptor?

a receptor that binds the Fc portion (heavy chain constant region) of an antibody.

which anitbody class functions in defense against helminth parasites?'
which cells does the antibody class interact with as part of that response?

IgE
mast cells, basophils, and eosinophils have a receptor for binding IgE. We will discuss IgE mediated responses to parasites and allergens a lot more in the fourth unit of the course.

define antibody dependent mediated cytotoxicity (ADCC). Which antibody class functions in ADCC, and which white blood cell/ leukocyte does it interact with?

binding of IgG to Fcγ receptors on NK cells promote ADCC

Infected host cells display pathogen antigens on the surface on MHC class I. IgG antibodies (that were generated against the antigens when the pathogen was outside the cell) bind to their antigen when the antigen is presented on the host cell surface. Natural killer cells have an Fcγ receptor that binds to IgG when IgG is attached to a host cell surface. Binding to IgG through its Fc receptor causes the natural killer cell to destroy the infected host cell. ADCC complements the function of cytotoxic T cells during the adaptive immune response.

define opsonization. which antibody classes are the most effective opsonizing antibodies and why? which white blood cells/ leukocytes do opsonizing antibodies interact with?

The coating of an antigen with a molecule (e.g., antibody and/or complement) that facilitates uptake of the antigen by phagocytes. IgG is the most important class that functions in opsonization. (Monomeric IgA can also be an opsonizing antibody, but most IgA is dimeric IgA found at mucosal surfaces where there are no macrophages or neutrophils present. Therefore, for our purposes, we will say it is not a major function of the IgA antibody class as a whole). The phagocytes that ingest opsonized pathogens are macrophages and neutrophils.

what type of infections would you expect a patient with a deficient antibody response to be particularly susceptible to?

Particularly infections with extracellular bacteria and fungi.

However, antibodies are also involved in combating viral infections; antibodies are generated against viral antigens during the extracellular phase of viral infection, and the antibodies function in neutralization, activation of the classical complement pathway, opsonization, and ADCC, which all help combat the infection. Therefore, individuals with deficient antibody responses can also be more susceptible to some viral infections. Although there are other mechanisms for dealing with viral infection (cytotoxic T cells, NK cells), the infections may not be dealt with as quickly and efficiently in the absence of antibodies

first antibody class to be secreted following B-cell activation?

IgM

antibody protects extravascular tissues?

IgA and IgG (and IgM but lower affinity)

antibody class that binds to the surface of mast cells?

IgE

antibody that is transferred across placenta?

IgG

primary class transferred to an infant in breast milk?

IgA

primary class that protects mucosal surfaces (i.e., most abundant and effective)

IgA

class functions in opsonization?

IgG, monomeric IgA (dimeric IgA is not an opsonizing antibody bc there are no phagocytes at mucosal surfaces)

class functions in neutraliztion?

IgG, IgM (just not as effective, lower affinity)

class functions with natural killer cells in ADCC?

IgG

primary class that functions in defense against parasites

IgE

class that functions in activation of classical complement pathway?

IgG, IgM, and monomeric IgA (dimeric IgA does not activate complement system bc there are no complement proteins at mucosal surfaces.)

class functions in sensitization of basophils in the upper respiratory tract?

IgD

what is mucus? what cells produce mucus and how does it protect mucosal surfaces?

mucus is a secretion that contains a high proportion of glycoproteins called mucins.
it is secreted by goblet cells in the epithelial layer of mucosal surface. Mucus lubricates and protects mucosal surfaces: it physically impedes microbes from reaching the epithelial layer, it serves to tether antibodies and antimicrobial substances in place at the mucosal surface, and it turns over (replaced) every couple of days.

where are mucosal surfaces located?

mucosal surfaces line the body's glands and internal tubes: respiratory tract, gastrointestinal tract, and urogenital tract

which secondary lymphoid tissues serve the small intestine?

the gut associated lymphoid tissues (GALT) and mesenteric lymph nodes

The GALT of the small intestine include the Peyer's patches and isolated lymphoid follicles, which are located directly under the epithelial layer. The Peyer's patches are larger and have characteristic B cell and T cell areas, whilst the isolated lymphoid follicles are smaller and contain only a single lymphoid follicle. (The appendix is also classed as a gut associated secondary lymphoid tissue, but its function is unclear, so we didn't focus on the appendix. It is not involved in 'typical' mucosal immune system responses like those produced in the Peyer's Patches and isolated lymphoid follicles

where are M cells (microfold cells) located, and what is their function?

M cells (microfold cells) are in teh epithelium directly overlying Peyer's patches and isolated lymphoid follicles. M cells transport antigens from the gut lumen into the underlying secondary lymphoid tissues to proactively activate immune responses.

Do non-mucosal tissues generate proactive immune responses?

no. non-mucosal tissues (underlying the skin) do not often encounter antigens (skin is tough and impermeable and not often breached). therefore, adaptive immune responses are only generated in response to an infection, and these reactive immune responses are inflammatory in nature. inflammatory immune responses also cause collateral damage to host tissue, which must be repaired afterwards. however, infections do not happen very often in systemic tissues, so occasional inflammation followed by tissue repair does not compromise the function of systemic tissues.

why must mucosal tissues be proactive in generating immune responses against microbial antigens at mucosal surfaces?

Compared to skin, mucosal surfaces are thin and permeable and more vulnerable to being breached by pathogens and commensal microbes. In the absence of a proactive immune response, frequent infections would result in chronic inflammation of mucosal tissue because the surfaces would be frequently breached. Inflammation also damages host tissues, so chronic inflammation would compromise the function of the mucosal tissue (e.g., absorption of food in the small intestine)

how is it that such proactive immune responses do not result in chronic inflammation?

Proactive immune responses produced against antigens in the lumen are non-inflammatory in nature, so they do not cause inflammatory damage to mucosal tissues. Plasma cells secrete neutralizing IgA antibody, which protects the mucosal surface. Antigen specific effector T cells are present in the lamina propria, but, in the absence of infection, they are kept in check by regulatory T cells. These proactive immune responses mean that if a microbe makes it across the epithelial layer, then there is already an adaptive response ready and waiting to deal with it very quickly, which minimizes inflammation.

how do macrophages in systemic tissues and mucosal tissues differ regarding the production of inflammatory cytokines?

systemic tissue macrophages are phagocytic, and they also secrete inflammatory cytokines in response to PAMPs to generate an inflammatory response (learned earlier).

mucosal tissue macrophages are only phagocytic, they do not secrete inflammatory cytokines in response to PAMPs, so they do not generate an inflammatory response.

mucosal tissue macrophages are _______?

non-inflammatory