Chapter 17- Adaptive Immunity- Specific Defenses of the Host

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Which of the following statements is NOT true of the IgA antibody class?

A. It can trigger the complement cascade.
B. It is the most abundant antibody class in body secretions.
C. It is a dimer in its most effective form.
D. It prevents pathogens from attaching to mucosal surfaces.
E. It can be found as a monomer in serum.

It can trigger the complement cascade.

Which of the following is the least abundant Ig?

IgE

Which of these statements is NOT true of antibody molecules?

A. Antibody molecules can directly destroy antigens.
B. Antibody molecules can enhance phagocytosis of the antigen.
C. Cell-bound antibody molecules can initiate a process that results in cell lysis.
D. Cell-bound antibody molecules can bind complement, triggering the complement cascade.
E. Cell-bound antibody molecules can bind cells that in turn release chemical compounds that damage parasitic worms.

Antibody molecules can directly destroy antigens.

Which of these processes is in the proper sequence?

IgE is formed; IgE binds to mast cells and basophils; antigen binds IgE; histamine is released.

Antigenic stimulation of a particular B cell that results in the production of a large number of plasma and memory cells, all capable of responding to that antigen, is referred to as __________.

Clonal selection

A new chemical messenger has been discovered that enhances the chemotaxis of macrophages and neutrophils toward sites of infection. It would be specifically classified as a(n) __________.

Chemokine

Which of the following is a correct match?

IgA: found in secretions such as colostrum, tears, and mucus

Which of these answers is a potential concern of using T-independent antigens as vaccines?

These antigens will be ineffective in producing an immune response in infants.

Each antibody has __________ antigen binding sites.

Two

Which of these lists is in the correct order of differentiation?

Stem cells to B cells to plasma cells

Which of the following is NOT an effect an antibody might have on a target cell?

Lysis

The most abundant Ig in the blood serum is __________.

G

Which of these pathogens would most likely be attacked by antibody-dependent cell-mediated cytotoxicity?

Blood flukes (schistosomes)

Which of the following statements about T-dependent antigens is true?

Activation of a B cell by a T-dependent antigen requires cytokines secreted by a TH cell.

Which of the following T cell is a component of both the cellular and humoral immune response?

T helper cells

Which of the following statements is NOT true of antigens?

A. They often have a molecular weight of less than 10,000.
B. They are often surface molecules on microbes.
C. They are often proteins or polysaccharides.
D. They are typically nonself molecules.
E. They can include nonmicrobial molecules, such as pollen, egg white, and blood cell surface molecules.

They often have a molecular weight of less than 10,000.

Which of the following is a reaction of the adaptive immune response?

Production of antibodies

What is a plasma cell?

A cell that produces antibodies

Which of the following is a true statement about the major histocompatibility complex (MHC)?

A. All of the answers are correct.
B. The MHC is a collection of genes that encode molecules of genetically diverse glycoproteins.
C. Class I MHC are found on the plasma membranes of mammalian nucleated cells.
D. Class II MHC molecules exist only on the surface of antigen-presenting molecules (APCs).
E. Thymic selection will rid the body of T cells that will not recognize MHC molecules of the host.

All of the answers are correct.

You get the following antibody titers against West Nile virus in three patients. Which patient probably has a current infection?

Patient A: 128 IgG, 0 IgM
Patient B: 128 IgG, 256 IgM
Patient C: 0 IgG, 0 IgM

Patient B

Cytokines that induce migration of leukocytes into areas of infection or tissue damage are known as __________.

Chemokines

The number of regions on an antibody molecule that can bind to an antigen is referred to as the __________ of that antibody.

Valence

The resistance to reinfection with measles virus following recovery from measles infection is called __________.

Adaptive immunity

In humans, where do B cells mature?

In the bone marrow

Which of the following statements concerning adaptive immunity is FALSE?

A. It is always present and instantly protects against infection.
B. It can form memory responses.
C. It can be stimulated by vaccination.
D. It requires specific recognition of microbes and antigens.

It is always present and instantly protects against infection.

The specificity of an antibody is due to

The variable portions of the H and L chains.

The antibodies found in mucus, saliva, and tears are

IgA

The antibodies that can bind to large parasites are

IgE

The most abundant class of antibodies in serum is

IgG

Which of the following best characterizes clonal selection?

The production of identical B cells producing the same antibody

What is produced by the process of clonal expansion?

Plasma cells and memory B cells

An antigen that is potent enough to activate a B cell on its own is known as

T-independent antigens.

Based on the animation, T cells recognized the antigen displayed by what protein of the B cell?

MHC

How can a sufficient humoral immune response occur if a plasma cell only lives for a few days?

Each plasma cell can produce up to 2000 antibodies every second.

Antigen processing and presentation

Is a way for a cell to give information about its activities.

Why would a body cell that is not a phagocyte need to present antigens?

Non-phagocytic body cells can become infected with a virus.

How do phagocytes communicate to other cells what they have captured?

They present antigens from engulfed foreign cells.

Plasma cells are activated by a(n)

Antigen

What makes agglutination by antibodies possible?

Each antibody has at least two antigen-binding sites.

What is the role of plasma cells in humoral immunity?

Plasma cells produce antibodies.

How might a pathogenic bacterium be affected by antibodies?

The antibodies may block proteins necessary for binding the pathogen to the host, may opsonize the bacterium, or may agglutinate bacteria.

What is apoptosis?

The process of programmed cell death.

What is the function of the CD8 receptor?

Bind to MHC molecules

What is the fate of activated cytotoxic T-cells?

They proliferate into a clone of cells specific to the same antigen; some of these cells then differentiate into long-lived memory T-cells, while others mature to attack infected cells.

Which molecule triggers apoptosis?

Granzyme

Which event happens first during cytotoxic T-cell activation?

CD8 binds to MHC molecules of infected cells

Which receptor on the helper T-cell recognizes the specific antigen from an antigen-presenting cell?

TCR

TH2 cells produce cytokines that activate

B cells

Which proteins on the antigen-presenting cell are recognized by the helper T-cell?

MHC proteins

When do helper T-cells develop into TH1 or TH2 cells?

After proliferation into a clonal population

Natural killer cells are activated by

TH1 cells.

Which type of cell directly attacks infected cells?

Cytotoxic T-cells

Immune cells that secrete cytokines and activate other immune cells are:

Helper T-cells

HIV directly infects T-cells. Why is this problematic for cell-mediated immunity?

Cytotoxic T-cells begin to attack the virally infected T-cells, reducing the number of T-cells in the body.

How do helper T-cells and cytotoxic T-cells work together?

Helper T-cells produce cytokines to activate other cells of the immune system.

What type of immunity results from vaccination?

Artificially acquired active immunity

What type of immunity results from recovery from mumps?

Naturally acquired active immunity

What type of immunity results from transfer of antibodies from one individual to a susceptible individual by means of injection?

Artificially acquired passive immunity

Newborns’ immunity due to the transfer of antibodies across the placenta is an example of

Naturally acquired passive immunity

An individual may be exposed to a pathogen and become infected without actually getting sick. This is known as a subclinical infection. Even in subclinical infections, the individual’s adaptive immune system can generate memory for the pathogen. What type of adaptive immunity is this?

Naturally acquired active immunity

Which cells are involved in a secondary response?

Memory B cells and plasma cells

How is the secondary response different from the primary response in terms of antibody concentration in the blood?

The secondary response is faster and produces more antibodies than the primary response.

According to the animation, on which day does the production of IgG occur in the secondary response?

Day 5

An anamnestic response is

Another name for secondary response.

Adaptive immunity

Range of antimicrobial defenses that target specific pathogens. Defenses are acquired through infection or vaccination and are highly specific. Comes into play only when innate defenses fail.

Immunization or vaccination

Method where adaptive immunity to disease is mimicked by deliberate exposure to harmless versions of pathogens that caused certain diseases, thus rendering them immune.

Primary response

First time the adaptive immune system meets and combats a particular foreign substance

Secondary response

Later interactions with the same cell or substance, which will be faster and more effective as a result of a "memory" of the first infection. Exclusive to the adaptive immune system.

Dual system

Adaptive immunity contains humoral and cellular components

Humors

Blood, phlegm, black bile, and yellow bile; old science that believed health depended on these body fluids

Humoral immunity

Describes immunity brought about by protective molecules (antibodies). Involves B lymphocytes (B cells). Responses are directed at antigens that are extracellular (such as in blood or other body fluids). Efforts tend to focus on bacteria and their toxins, as well as viruses before they penetrate the target cells.

Antibodies or immunoglobulins (Ig)

Combat foreign molecules called antigens and capable of combining specifically with that antigen. Globulin proteins, which are compact and relatively soluble. Made in response to antigens and can recognize and bind to that antigen.

B lymphocytes or B cells

Involved in humoral immunity; remove viruses, bacteria, and toxins from body tissue fluids and blood by recognizing antigens and making antibodies against them

B cell receptors

Recognition of different antigens depends on these receptors for antigens that coat the surface of the B cell

Where are B cells produced?

Initially produced in fetal liver, but by the third month of life, they are produced by stem cells in red bone marrow.

T lymphocytes or T cells

Basis of cellular immunity. Do not bind to antigens directly, but recognize antigenic peptides after they have been processed by phagocytic cells, such as macrophages.

Cellular immunity or cell-mediated immunity

An immune response that involves T cells binding to antigens presented in antigen-presenting cells; T cells then differentiate into several types of effector T cells. Centers on attacking antigens that make their way inside cells. Generally best at fighting viruses that have infected a cell, as well as some fungal and parasitic infections, which generally involve pathogens much larger than bacteria or viruses.

Where are T cells produced?

By stem cells in red bone marrow.

Where do T cells mature?

Under the influence of the thymus.

Where are T cells and B cells primarily found?

Blood and lymphoid organs.

T cell receptors (TCRs)

T cells respond to antigens by means of receptors on their surface. Contact with an antigen complementary to a TCR can cause certain types of T cells to proliferate and secrete cytokines rather than antibodies.

Cytokines

Chemical messengers facilitating communication required for the immune response; soluble proteins or glycoproteins that are produced by practically all cells of the immune system in response to a stimulus

Interleukins

Cytokines that serve as communicators between leukocytes. Role in stimulating the immune system has suggested their use as therapeutic agents.

Chemokines

Small cytokines that induces the migration of leukocytes into areas of infection or tissue damage; from chemotaxis

Interferons (INFs)

Cytokines named for their function of interfering with viral infections in host cells. INF-y stimulates the immune system.

Tumor necrosis factor (TNF)

Cytokine family named because tumor cells were observed to be one of its targets. Strong factor in inflammatory reactions of autoimmune diseases.

Hematopoietic cytokines

Cytokines functioning in controlling the pathways by which stem cells develop into different red or white blood cells. Some are interleukins, others are colony stimulating factors (CSF).

Colony stimulating factor (CSF)

Glycoproteins that promote production of white blood cells (mainly granulocytes such as neutrophils), in response to infection.

Cytokine storm

Cytokines, among other things, may stimulate cells to produce more cytokines. When this feedback loop gets out of hand, it results in a harmful production of cytokines. This can do significant damage to tissues, which appears to be a factor in the pathology of certain diseases and conditions.

Antigens or immunogens

Substances that cause the production of antibodies. Most are either proteins or large polysaccharides. Lipids and nucleic acids are usually antigenic only when combined with proteins and polysaccharides. Play key roles in the response of the immune system. Provoke a highly specific immune response in humoral immunity that results in the production of antibodies that are capable of recognizing the antigen that gave rise to them. Generally have a molecular weight of 10,000 or higher.

What are some antigenic compounds? What are some non-microbial antigens?

-Antigenic compounds are often components of invading microbes, such as capsules, cell walls, flagella, fimbriae, and toxins of bacteria. -Non-microbial antigens include pollen, egg white, blood cell surface molecules, serum proteins from individuals or species, and surface molecules of transplanted tissues and organs.

Epitopes or antigenic determinants

Antigens recognize and interact with specific regions on antigens. The nature of this interaction depends on the size, shape, and chemical structure of the binding site on the antibody molecule

What are pathogen associated molecular patterns (PAMPs)?

Pathogenetic bacteria generally possess a number of recognizable antigens; they serve as warning flags of an invading organism that the host can recognize by means of receptors, such as TLRs.

Haptens

A molecule too small to stimulate antibody formation itself; usually not antigenic unless attached to a carrier molecule.

What happens once an antibody forms against the hapten?

Antibody will react with the hapten independent of the carrier molecule. Ex. is penicillin, which is not antigenic itself but some people develop an allergic reaction to it. When penicillin combines with host proteins, the resulting combined molecule initiates an immune response.

Valence

Each antibody has at least two identical antigen-binding sites that bind to epitopes’ number of antigen binding sites on an antibody. Human antibodies have two bindings sites (bivalent).

Monomer

Bivalent antibodies have the simplest molecular structure. Typical antibody monomer has four protein chains: two identical light chains and two identical heavy chains, in reference to their molecular weight. Chains are joined by disulfide links and other bonds to form a Y-shaped molecule. Flexible and can assume a T shape.

Variable (V) regions

Two sections located at the ends of the Y arms; these bind to the epitopes. Amino acid sequences and 3D structure of the variable regions are identical on any one antibody.

Constant (C) regions

Stem of the antibody monomer and lower parts of the arms. The same for a particular class of immunoglobin. Five major types of C regions, which account for the five major classes of immunoglobins.

Fc region

Stem of the Y-shaped antibody monomer; so named because it was a fragment that crystallized in cold storage. Important in immunological reactions. If left exposed after both antigen-binding sites attach to an antigen such as a bacterium, Fc regions of adjacent antibodies can bind complement, leading to the destruction of the bacterium. Conversely, Fc region can bind to a cell leaving the antigen binding sites of adjacent antibodies free to react with antigens.

What are the five classes of immunoglobulins and what are their structures?

-IgG, IgD, and IgE molecules are Y-shaped -IgA and IgM are aggregates of two or five monomers, respectively, that are joined together.

IgG

-Name is derived from the blood fraction gamma globulin. -Accounts for about 80% of all antibodies in serum. -In regions of inflammation, these monomer antibodies readily cross the walls of blood vessels and enter tissue fluids (ex. maternal IgG antibodies can cross the placenta and confer passive immunity to the fetus). -Protect against circulating bacteria and viruses, neutralize bacterial toxins, trigger the complement system, and when bound to antigens, enhance the effectiveness of phagocytic cells. -Detection of IgG, which is relatively long-lived, may indicate that immunity against a particular pathogen was acquired in the more distant past.

IgM

-M refers to macro, reflecting their large size, which prevents them from moving about as freely as IgG -Make up 6% of antibodies in serum. -Pentamer structure consisting of five monomers held together by a joining (J) chain. -Generally remain in blood vessels without entering the surrounding tissues. -Predominant type of antibody involved in response to the ABO blood group antigens on the surface of red blood cells. -Much more effective than IgG in causing the clumping of cells and viruses and in reactions involving the activation of complement. -Appears first in response to a primary infection and is relatively short-lived , making it uniquely valuable in diagnosing disease. High concentrations against a certain pathogen indicate the disease is caused by that pathogen.

Joining (J) chain

Polypeptide that holds the five monomers of the IgM molecule together

IgA

-Accounts for only 13% of antibodies found in serum, but the most common form in mucous membranes and body secretions (milk, mucus, saliva, tears). Taking this into consideration makes it the most abundant in the body. -The form circulating in serum (serum IgA) is usually in the form of a monomer. The most effective form consists of two connected monomers that form secretory IgA. -Immunity is relatively short-lived, length of immunity to many respiratory infections is correspondingly short. -Presence in milk helps protect infants from GI infections.

Secretory IgA

-The two connected monomers form a dimer. -IgA is produced in this form by plasma cells in the mucous membranes (15 g/day mostly by intestinal epithelial cells). -Each dimer enters and passes through a mucosal cell, where it acquires a secretory component. -Main function is probably to prevent attachment of microbial pathogens to mucosal surfaces, which is especially important in resistance to respiratory and intestinal pathogens.

Secretory component of secretory IgA

Polypeptide that protects secretory IgA from enzymatic degradation

IgD

-Make up about 0.02% of total serum antibodies. -Structure resembles that of IgG molecules. -Found in blood, lymph, and particularly on the surfaces of B cells. -Serum IgD has no well-defined function; on B cells, it assists in the immune response.

IgE

-Slightly larger than IgG molecules -Constitute 0.002% of total serum antibodies -Bind tightly by their Fc stem regions to receptors on mast cells and basophils (specialized cells that participate in allergic reactions) -When an antigen, such as pollen, links with IgE antibodies attached to a mast cell or basophil, that cell releases histamine and other chemical mediators, provoking a response (allergic reaction) -Can have protective response by attractive complement and phagocytic cells. Especially useful when binding to parasitic worms. -Concentration of IgE is increased during allergic reactions and parasitic infections, which is useful in diagnosis.

How does the process of antibody production begin?

When B cells are exposed to free or extracellular antigens.

T/F: The majority of the B cell’s surface immunoglobulins are IgM and IgD.

True; all of which are specific for the recognition of the same epitope.

Clonal expansion or proliferation

When a B cell’s immunoglobulins bind to the epitope for which they become specific, the B cell is activated. The activated B cell undergoes this process.

T helper cell (Th)

B cells usually require the assistance of a Th.

T-dependent antigen

An antigen that requires a Th cell for antibody production. Mainly proteins, such as those found in viruses, bacteria, foreign RBCs, and haptens with their carrier molecules.

How are antibodies produced in response to a T-dependent antigen?

It is necessary both T and B cells are activated and interact. This process is initiated when the B cell contacts an antigen. The antigen contacts the surface immunoglobulins on the B cell and fragments are combined with the major histocompatibility complex (MHC).

Major histocompatibility complex (MHC)

Collection of genes that encode molecules of genetically diverse glycoproteins (part carbohydrate, part protein). -Class I MHC are found on the plasma membranes of mammalian nucleated cells. They identify as "self," preventing the immune system from making antibodies that would be harmful to the host. -Class II MHC molecules exist only on the surface of antigen-presenting molecules (APCs), including B cells.

What is the process of clonal selection?

When an inactive B cell meets an antigen that can bind to its particular surface receptor, it will engulf and process it, displaying antigen fragments bound to its MHC class II molecules. This attracts T helper cells to the B cells. T helper cells in contact with the antigenic fragment presented on the surface of the B cell begins production of cytokines that activate the B cell. The B cell proliferates into a large clone of cells, some of which differentiate into antibody-producing plasma cells. Other clones become long-lived memory cells that are responsible for the enhanced secondary response to an antigen.

Class switching

IgM is the first antibody B cells make during the primary response to an antigen, but an individual B cell is also capable of making different classes of antibody, such as IgG, IgE, or IgA, all with unchanged specificity. This is observed especially in the case of the primary and secondary immune response. When IgG begins to be produced in the secondary response, the production of IgM will decrease or be sharply curtailed.

Clonal deletion

Pool of B cells does not contain many that are harmfully reactive against host tissue, or self. These are usually eliminated at the immature lymphocyte stage by clonal deletion.

T-independent antigens

Antigens that stimulate B cells directly without the help of T cells. Such antigens are characterized by repeating subunits such as are found in polysaccharides or lipopolysaccharides. Bacteria capsules are good examples. Repeating subunits can bind to multiple B cell receptors, which is probably why they do not require T cell assistance. These antigens generally provoke a weaker immune response than T-dependent antigens. Response composed primarily of IgM and no memory cells are generated. Immune response of infants may not be stimulated by T-independent antigens until about age 2.

Antigen-antibody complex

Forms when an antibody encounters an antigen for which it is specific. Antibody binds to an antigen, such as a bacterium, at the epitope or antigenic determinant. The binding of an antibody to an antigen protects the host by tagging foreign cells and molecules for destruction by phagocytosis and complement. The antibody itself is not damaging to the antigen.

Affinity

The strength of the bond between an antigen and an antibody. The closer the fit, the higher the affinity.

What are the mechanisms by which foreign organisms and toxins are rendered harmless?

Agglutination, opsonization, neutralization, antibody-dependent cell-mediated cytotoxicity, and the activation of complement leading to opsonization, inflammation, and cell lysis.

Agglutination

Antibodies cause antigens to clump together. IgG antibody can combine with epitopes on two different foreign cells, aggregating the cells into clumps that are more easily phagocytized. IgM is more effective at cross-linking and aggregating due to having more bonding sites. IgG requires 100-1000 times as many molecules for the same results.

Opsonization

The antigen, such as a bacterium, is coated with antibodies, or complement proteins, that enhance its ingestion and lysis by phagocytic cells

Antibody-dependent cell-mediated toxicity

Resembles opsonization in that the target organism becomes coated with antibodies. However, the target cell is destroyed by immune system cells that remain external to their target cell.

Neutralization

IgG antibodies inactivate microbes by blocking their attachment to host cells, and they neutralize toxins in a similar manner.

Activation of the complement system

Either IgG or IgM antibodies may trigger this activation. Inflammation is caused by infection or tissue injury. One aspect of inflammation is that it will often cause microbes in the inflamed area to become coated with certain proteins. This, in turn, leads to the attachment to the microbe of an antibody-complement complex. This complex lyses the microbe, which then attracts phagocytes and other defensive immune system cells to the area.

What is a theory as to why T cells developed?

Some bacteria live within cells. Humoral antibodies are effective against freely circulating viruses and bacteria. T cells evolved in response to the need to combat intracellular pathogens. They are also the way in which the immune system recognizes cells that are abnormal, especially cancer cells.

T/F: Like B cells, T cells are specific for only a certain antigen. Rather than coating of immunoglobulins that provide specificity for B cells, T cells have T cell receptors (TCRs).

True

Thymic selection

Most immature T cells (98%) are eliminated into the thymus, which is analogous to clonal deletion in B cells. This reflects a weeding-out process of T cells that will not recognize MHC molecules of the host and T cells that will attack host cells. This is important in preventing the body from attacking its own tissues. Mature T cells migrate from the thymus by way of the blood and lymphatic system to various lymphoid tissues.

Microfold cells or M cells

Most pathogens of the type that enter the cellular immune system is designed to combat first enter the GI tract or lungs, where they encounter a barrier of epithelial cells. Normally, they pass this barrier in the GI tract only by way of a scattered array of gateway cells. M cells are located on Peyer’s patches. M cells are well adapted to take up antigens from the intestinal tract and allow their transfer to the lymphocytes and antigen presenting cells of the immune system found throughout the intestinal tract, just under the epithelial cell layer, but especially in the Peyer’s patches. It is also here that antibodies, mostly IgA essential for mucosal immunity, are formed and migrate to the mucosal lining.

Peyer’s patches

Secondary lymphoid organs located on the intestinal wall

Dendritic cells (DCs)

Characterized by long extensions called dendrites because they resemble the dendrites of nerve cells. Principal antigen-presenting cells (APCs) to induce immune responses by T cells. Act as sentinels in these tissues by engulfing invading microbes, degrading them, and transferring them to lymph nodes for display to T cells located there.

Langerhans cells or Langerhans DCs

Dendritic cells in the skin and genital tract

Macrophages

Cells usually found in a resting state. Important for innate immunity and for ridding the body of worn0out blood cells and other debris. Phagocytic capabilities are greatly increased when they are stimulated to become activated macrophages.

Activated microphages

Activation is initiated by ingestion of antigenic material. Other stimuli, such as cytokines produced by an activated helper T cell, can further enhance the capabilities of macrophages. Once activated, macrophages are more effective as phagocytes and as APCs. Important factors in the control of cancer cells, virus-infected cells, and intracellular pathogens. They are larger and more ruffled.

What happens to APCs after taking up an antigen?

APCs tend to migrate from their locations in virtually all tissues to lymph nodes or other lymphoid centers on the mucosa, where they present the antigen to T cells located there. T cells carrying receptors that are capable of binding with any specific antigen are present in relatively limited numbers. Migration of APCs increases the opportunity for these particular T cells to encounter the antigen for which they are specific.

T helper cells (Th)

Cooperate with B cells in the production of antibodies, mainly through cytokine signaling. Important part of humoral immunity and even more essential element of cellular immunity, helping T cells interact more directly with antigens.

precursor T cytotoxic cells (CTLp)

Can differentiate into an effector cell called cytotoxic T lymphocyte (CTL).

Clusters of differentiation (CD)

T cells are classified by certain glycoproteins on their surface. These are membrane molecules that are especially important for adhesion to receptors. Most importantly: CD4 and CD8

CD4+

Cell carrying CD4 molecule. Th cells are classified as CD4+, which bind to MHC class II molecules on B cells and APCs.

CD8+

Cell carrying CD8 molecules. CTL cells are classified as CD8+, which bind to MHC class I molecules.

T/F: Th cells can recognize an antigen presented on the surface of a macrophage and activate the macrophage, making it more effective in both phagocytosis and in antigen presentation.

True

How does a CD4+ T cell become activated?

-Dendritic cells are especially important in the activation of CD4+ T cells and in developing their effector functions. -To become activated, its T cell receptor recognizes antigen fragments held in a complex with proteins of MHC class II on the surface of the APC. This is the initial signal for activation. -The second signal, costimulatory signal that comes from either the APC or T helper cell, is also required for activation. Activated Th cell begins to proliferate at the rate of two or three cell cycles a day and to secrete cytokines, which are essential for its effector functions. -Proliferating Th cells differentiate into populations of subsets (Th1, Th2, Th17). -They also form a population of long-lived memory cells. -The effector functions of these subsets are based on the cytokines produced by these Th cells, which act on different cells of the body’s defensive systems.

Th17

Named due to production of large quantities of cytokine IL-17.Excessive amounts of these cells contribute to the inflammation and injury to tissue found in certain autoimmune diseases (multiple sclerosis, psoriasis, Crohn’s disease, etc.). They are also associated with pathologic effects of diseases such as asthma and allergic dermatitis. Serve to helpfully combat microbial infections of the mucosa by the production of cytokines that produce antimicrobial proteins. A severe deficiency may make one more susceptible to opportunistic infections.

Th1 cells

Cytokines produced by these cells, especially IFN-y, activate mostly those cells related to important elements of cellular immunity, such as delayed hypersensitivity and are responsible for activation of macrophages. Stimulate the production of antibodies that promote phagocytosis and are especially effective in enhancing the activity of complement, such as opsonization and inflammation. Generation of cytotoxic T lymphocytes requires activation by a Th1 cell.

Th2 cells

Produce cytokines that are associated primarily with the production of antibodies, especially IgE, that are important in allergic reactions. They are also important in the activation of the eosinophils that defend against infections by extracellular parasites.

T regulatory cells (Treg) or T suppressor cells

Make up about 5-10% of the T cell population. Subset of the CD4+ T helper cells and are distinguished by carrying an additional CD25 molecule. Their primary function is to combat autoimmunity by suppressing T cells that escape deletion in the thymus without the necessary "education" to avoid reacting against the body’s self. Useful in protecting, from the immune system, the intestinal bacteria required for digestion and other useful functions. In pregnancy, they may play a role in protecting the fetus from rejection as non self.

Endogenous antigens

T cytotoxic cells are not capable of attacking any target cell as they emerge from the thymus, but quickly gain this capability. This differentiation requires sequential, and complex, activation of the precursor CTL by an antigen processed by a dendritic cell and interaction with a Th cell and costimulatory signals. Resulting CTL is an effector cell that has the ability to recognize and kill target cells that are considered non self. Primarily, these target cells are self-cells that have been altered by infection with a pathogen, especially viruses. On their surfaces they carry fragments of endogenous antigens that are generally synthesized within the cell and are mostly of viral or parasitic origin. Other important target cells are tumor cells and transplanted foreign tissues. Rather than reacting with antigenic fragments presented by an APC in complex with MHC class II molecules, the CD8+ T cell recognizes endogenous antigens on the target cell’s surface that are in combination with an MHC class I molecule. MHC class I molecules are found on nucleated cells, therefore a CT: can attack almost any cell of the host that has been altered.

Perforin

In its attack, a CTL attaches to the target cell and releases this pore-forming protein. Pore formation contributes to subsequent death of the cell and is similar to the action of the complement membrane attack complex. Enables granzymes to enter through the pores.

Granzymes

Proteases that induce apoptosis

Apoptosis

Programmed cell death. Cell host has evolved to detect the death of cells and to determine whether the death is natural, in which case no threat is involved and the remnants of the course are simply removed. If the cell’s death is due to trauma or disease, the body’s defense mechanisms are mobilized. If a cell cannot clear a pathogen any other way, it clears it by dying.

What happens when a cell dies of apoptosis?

Cells first cut their genome into fragments, and the external membranes bulge outward in a manner called blabbing. Signals are displayed on the cell’s surface that attract circulating phagocytes to digest the remains before any significant leakage of contents occurs.

Natural killer (NK) cells

Large, granular leukocytes (10-15% of circulating leukocytes). they can attack parasites, which are much larger than bacteria. Not immunologically specific- they do not need to be stimulated by an antigen. Distinguish normal cells from cells infected with pathogens. NK cells first contact the target cell and determine whether it expresses MHC class I self antigens. If it does not, which is often the case in early stages of viral infection and with some infecting viruses that have developed a system of interfering with the usual presentation of antigens on APC, they kill the target cell by mechanisms similar to that of a CTL. Tumor cells also have a reduced number of MHC class I molecules on their surfaces. NK cells cause pores to form in the target cell, which either leads to lysis or apoptosis.

Antibody-dependent cell-mediated cytotoxicity (ADCC)

With the help of antibodies produced by the humoral immune system, the cell-mediated immune system can stimulate NK cells and cells of the innate defense system, such as macrophages, to kill targeted cells. An organism, such as a protozoan or helminth that is too large to be phagocytized can be attacked by immune system cells. The target cell is first coated with antibodies. A variety of cells from the immune system bind to the Fc regions of the antibodies and thus, to the target cell. Attacking cellos secrete substances that can then lyse the target cell.

Secondary response or memory (anamnestic) response

Antibody-mediated immune responses of the host intensify after a second exposure to an antigen. This response is comparatively more rapid, reading a peak in 2-7 days, lasts many days, and is considerably greater in magnitude. Some activated B cells do not become antibody-producing plasma cells but persist as long-lived but non proliferating memory cells. Is these cells are stimulated by the same antigen, they very rapidly differentiate into antibody-producing plasma cells.

Antibody titer

Intensity of the antibody-mediated humoral response can be reflected through an antibody titer, the relative amount of antibody in the serum. After initial contact with the antigen, the exposed person’s serum contains no detectable antibodies fro 4-7 days. Then, there is a slow rise in the antibody titer: first, IgM class antibodies are produced, following by IgG peaking in about 7-10 days, after which antibody titer gradually declines.

Active

Immunity acquired when a person is exposed to microorganisms or foreign substances and the immune system responds

Passive

When antibodies are transferred from one person to another. Lasts only as long as the antibodies are present- usually a few weeks.

Naturally acquired active immunity

Develops when a person is exposed to antigens through every day life, becomes ill, and then recovers. Once acquired, immunity is lifelong for some disease (measles). For others, immunity may only last for a few years (intestinal disease). -Subclinical infections or inapparent infections: those that produce no noticeable symptoms or signs of illness can also confer immunity

Naturally acquired passive immunity

Involves the natural transfer of antibodies from a mother to her infant. Antibodies in a pregnant woman cross the placenta to her fetus (transplacental transfer). Certain antibodies are transferred from the mother to her nursing infant in breast milk, especially in the first secretions called colostrum. Passive immunity generally only lasts for only a few weeks to a few months. Maternal antibodies are essential for providing immunity to the infant until its own immune system matures.

Artificially acquired active immunity

Result of vaccination (immunization); introduced vaccines into the body.

Vaccines

Antigens, such as killed or living microorganisms or inactivated bacterial toxins

Artificially acquired passive immunity

Involved injection of antibodies (rather than antigens) into the body. These antibodies come from an animal or human who is already immune to the disease.

Antiserum

Generic term for blood0derived fluids containing antibodies

Serology

The study of reactions between antibodies and antigens

Gamma globulin or immune globulin serum

Gamma fraction contains the most antibodies; it is often used to transfer passive immunity. When it is taken from an individual who is immune to a disease and it is injected into another individual, that individual now has immediate passive protection against the disease. Because it is immediate it is short-lived because antibodies are degraded by the recipient. The half life of an injected antibody is typically about 3 weeks.

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