Microbiology Exam 4 (not complete)

The term "humoral" means

"related to the bodily fluids"

A cytotoxic T cell with a TCR specific to virus X antigen is present in a person infected with virus X. What must occur for the cytotoxic T cell to help resolve the infection in this person? Place the steps in the correct order.

1. An APC from an infected site presents virus X antigen on MHC 1 2. Tc cell CD8 binds MHC I and the TCR binds virus X antigen 3. Tc cell receives IL-2 from activated TH1 cell 4. Tc cell is activated 5. Tc cell travels to site of infection

Breakdown of antigens, epitopes, and immunogens

1. Bacterial cells are made of many antigens. Every surface or cytoplasmic structure is an antigen 2. Each antigen can have one or more epitopes 3. Released from a cell, most epitopes are immunogens but some are haptens 4. Immunogens can generate an immune response

A primary antibody response is initiated following exposure to a pathogen for the first time. Order the primary antibody response below.

1. Foreign antigen binds B cell with appropriate antibody 2. B cells become activated and differentiate into plasma and memory cell 3. Low-affinity IgM is produced and secreted into serum 4. Isotype switching occurs 5. Large quantities of IgG are produced and secreted into serum 6. Plasma cell dies

Antigen-presenting cell interactions involved in making antibodies (humoral immunity)

1. In the periphery, an APC (dendritic cell) engulfs antigen and presents it on its surface 2. The APC travels to a lymph node to present the antigen to a helper T cell 3. The activated T cell the links to and activates a B cell bound to the same antigen (still in the lymph node) 4. The B cell the clonally expands to many B cells. Some become antibody-producing plasma cells, whereas others become long-lived memory B cells that can rapidly respond to a future encounter with the antigen

IgM can also be found in monomeric form on the surface of

B cells, where it forms part of the B-cell antigen receptor

Exceedingly high doses of antigen can cause

B-cell tolerance (anergy), a state in which B cells have been overstimulated to the point at which they do not repsond to subsequenct antigen exposures and make antibody

Helper T cell

a T cell that expresses CD4 on its self surface and secretes cytokines that modulate B cell isotype, or class switching

Cytotoxic T cells (Tc cells)

a T cell that expresses CD8 on its cells surface binds MHC I-presented epitopes, and can secrete toxic proteins such as perforin and granzymes

Which is most likely to be a potential antigen?

a bacterial exotoxin

Isotype switching

a change in the predominant antibody isotype produced by a B cell

Antigen

a compound, recognized as foreign by the cell, that elicits an adaptive immune response. Also called an immunogen derived from the term "antibody generating" describes anything that can elicit an immune response

Idiotype

a difference in amino acid sequence, usually in the antigen-binding site of an antibody, that distinguishes different antibodies within any isotype class of antibodies in an individual types of antibodies found within one individual

Even disntict three-dimensional shapes within a protein can be called

antigenic determinants (or three-dimensional epitopes) if they produce a specific response. this happens when two or more amino acids that are far removed from one another in a protein's primary sequence become aligned side by side in three-dimensional space by protein folding. such a three-dimensional structure may be recognized by the immune system as a single antigen

The immune system must become "blind" to its own

antigens, as a result, the host will often be blind to forgein antigens the resemble epitopes of its own cells

Regulatory T cells (Tregs)

are T cells that block activation of harmful self-reactive lymphocytes Prevent autoimmune disease

Antibodies made during this primary response, though specific for the immunogen

are actually not of the highest affinity (the "tightness" by which the antibody binds to its antigen)

T-cell receptors (TCRs)

are antigen-specific T-cell surface proteins

Immunodeficiency diseases (IDDs)

are disorders in which part of the immune system is missing or defective

Class I MHC molecules

are found on all nucleated cells (not red blood cells)

Primary immunodeficiencies

are genetic and present in early childhood

Antibodies, or immunoglobulins

are members of the immunoglobulin superfamily

Memory B cells do not secrete antibodies themselves but

are primed to quickly become antibody-secreting plasma cells if the host is reinfected with the same pathogens at a later date after the intitial infection

Antibodies, also called immunoglobulins

are the keys to immunological specificity

Antibodies bind to antigens by using

noncovalent interactions, which allows for reversible antigen-antibody interactions

Adaptive immune response to one antigen is generally

not effective against a different antigen (that is, one immune response "key" fits only one antigen "door lock")

The Fc tail region of an antibody is

not involved in antigen recognition but is very important for anchoring antibodies to the surface of certain host cells and for binding components of the complement system

Weakest antigens

nucleic acids and lipids they are made of relatively uniform repeating units and are very flexible Don't easily interact with antibodies

The secondary antibody response

occurs during subsequent exposures to an antigen and arises because memory B cells are activated. IgG is the predominant antibody made

Isotype switching

occurs late during primary response when a subclass of B cells switches from making IgM to making other antibody isotypes (for instance, IgM)

The Fc portion

of an antibody can bind to specific receptors on host cells. this binding is antigen independent

IgG provides the majority

of antibody-based immunity against invading microbes

MHC II Deficiency (Bare Lymphocyte Syndrome)

rare genetic disease in which MHC II molecules are absent on antigen-presenting cells, resulting in greatly increased susceptibility to may kinds of infection

A single B cell has approximately 50,000 B-cell receptors. How many distinct epitopes is this cell capable of recognizing?

1 epitope

Is not an antigen-specific response

so many different T cells can be activated

IgG is also the only

antibody capable of crossing the placenta to give passive immunity to the fetus

Following exposure to a pathogen, antibodies are produced as a part of the adaptive immune response. Place the steps of this response in the order that they generally occur.

1. Pathogens enter the body 2. Antigen-presenting cell engulfs the pathogen 3. Antigen-presenting cell presents antigen to helper T cell 4. Helper T cell becomes activated 5. Helper T cell activates B cell which has previously bound the same antigen 6. B cell clonally expands 7. Plasma B cells produce antibody

Place the given steps in order to create the natural course of type I hypersensitivity to cat dander.

1. Person encounters cat for the first time 2. B cell with high-affinity match to dander is activated by T helper cell 3. Large amounts of cat dander-specific IgE are produced and bind mast cells 4. Person encounters cat a second time 5. Cat dander binds to multiple mast-cell-bound IgE, causing degranulation 6. Person experiences symptoms such as sneezing and itching

Adaptive immunity develops over

3 or 4 days after you have been exposed to an invading microbe

Which of the following are B-cell neoplasms?

A B cell that is matched to a low-affinity antigen has lost the ability to undergo apoptosis. A cell proliferation gene is expressed at the same rate as an immunoglobulin gene.

What starts the clonal selection process?

A naive B cell (those that have not previously encountered antigen) can produce only IgM and IgD both of which have identical antigen specificities. These two antibody classes are displayed like tiny satellite dishes on the B-cell surface, anchored by their Fc regions.These surface antibodies are the keys to stimulating proliferation. Upon binding to its correspinding antigen via these surface antibodies, the B cell is said to become activated and begins to multiply

MHC II Deficiency (Bare Lymphocyte Syndrome)

A rare disease caused by lack of MHC II expression on APCs Caused by genetic mutation in regulators of MHC II gene Results in lack of cell-mediated immunity as T cells cannot be properly activated

Humoral immunity

A type of adaptive immunity mediated by antibodies

A patient with A, Rh- blood needs a transfusion. Which of the following blood types can be used without risk of a type II hypersensitivity response?

A, Rh- O, Rh-

Pathogens that get engulfed are digested within endocytic compartments into smaller pieces

After digestion, the antigens are presented on MHC II

Activated TC cells bind to and kill the target cell by inducing apoptosis

All cells have MHC I, and therefore any cell can be killed by TC cells

Determining the Cause of Type 1:

Allergens are delivered locally to the skin to determine if there is an inflammatory reaction This skin test is useful in identifying the antigen to which a patient is allergic

Fill in the blanks below to create a correct statement regarding antibody diversity.

Amino acid sequence differences distinguish five classes of antibodies in humans: IgG, IgA, IgM, IgE and IgD, each of which represents a distinct ISOTYPE. While all humans possess IgD, your IgD ALLOTYPE differs in several small ways from those of others, including members of your own family. Within your own body, you make many IgD monomers that are specific to antigens from many foreign sources; these IgD immunoglobulins differ at the IDIOTYPE level.

Severe Combined Immunodeficiency (SCIDs)

An immune deficiency in which T cell responses are absent. there are multiple genetic causes, but it is invariably fatal unless T-cell immunity can be restored by transplantation or gene therapy

Rheumatoid Arthritis

Antibodies form immune complexes to connective tissue in joints and cause inflammation

Immunological specificity

Antibodies generated are specific for a single antigen

B cells also need two signals to become activated:

Antigen cross-links the BCRs on the membrane During the early phase of primary response, the second signal is binding of complement factor C3 bound to pathogen During the late phase of primary response, the second signal is binding to TH cell ===> CD40 binds to CD40L on the surface of the TH cell

Which of the following statements regarding adaptive immunity are true?

Antigens elicit the formation of specific antibodies. Microbial pathogens are composed of many antigens.

CD4 T cells arebassociated mainly with

antibody-mediated immunity

Myasthenia Gravis

Autoantibodies bind and block the muscle receptors for acetylcholine

Hashimoto's Disease

Autoantibodies bind and damage the thyroid causing hypothyroidism

Grave's Disease

Autoantibodies bind to the thyroid-stimulating hormone receptor causing hyperthyroidism

Once activated

B cells can also produce memory B cells that remember the exposure and stand ready to quickly generate plasma cell, should the antigen be encountered months or years later

Only one isotype is made per

B cell clone

Antigens stimulate

B cells (B lymphocytes) to differentiate into antibody-producing plasma cells

T cells are activated only by

antigen bound to another cell's surface that is by antigen-presenting cells (APCs)

Activation of oncogenes can cause proliferation of B cells and plasma cells leading to a number of cancers:

Burkitt's lymphoma: a B cell cancer associated with Epstein-Barr virus infection Chronic lymphocytic leukemia: The most common type of leukemia, it's a B-cell cancer often associated with an abnormality in specific microRNA production Hodgkin's lymphoma: a cancer of the lymphocytes sometimes associated with prior infectious mononucleosis caused by Epstein-Barr virus and characterized by the presence of Reed-Sternberg cells Non-Hodgkin's lymphoma: any lymphoma that does not contain Reed-Sternberg cells and hence is not a Hodgkin's lymphoma

The body must regulate the immune system carefully

so that a response is not leveled against itself

The TCR is associated with the

CD3 complex that helps it signal

Cytotoxic T cells display

CD8

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Each light chains also has a constant region designated

CL

Two ways to activate a B cell to make antibody:

Capping the receptors on a B-cell with a large repeating epitope Single epitopes cannot cause capping; therefore the helper T cells bind and activate B cells

DiGeorge Syndrome

Caused by mutations in several genes Results in incomplete development or absence of thymus and parathyroid glands Immunodeficiency includes T cell deficiency and hypoparathyroidism Treatment involves thymus transplant

Type IV hypersensitivity

Does not involve antibodies, involves T cells

Memory cells are created upon exposure to antigen:

Exposure through natural infection process Exposure through vaccination with a harmless antigen

Different immune responses are more appropriate than others to provide protection from particular pathogen types. Fill in the blanks to accurately describe this regulation.

Extracellular pathogens are most effectively targeted by HUMORAL immunity and the production of antibodies, while intracellular pathogens cannot be reached by antibodies and must therefore be targeted by the CELLULAR immune response. Direction of this response to a particular pathogen is largely governed by the ratio of T-cell types produced and the CYTOKINES these cells secrete locally. More subtle control of this response may also be achieved. For example, TH2 cells directly stimulate B cells to class switch, producing immunoglobulin isotype IgE, which is useful in targeting PARASITIC WORMS.

In addition to the two "arms" that bind antigen, called the

F(ab)2 region, every antibody contains a "tail", called the Fc region

Each B cell is capable of recognizing and producing antibody to multiple antigens of a single pathogen

False

Killing of infected cells by cytotoxic T cells is beneficial and not harmful to the host.

False

The constant region of antibodies' heavy chains has the same amino acid sequence in all classes of immunoglobulin.

False

The exact chromosomal locations of all primary immunodeficiencies are known. For example, chronic granulomatous disease is caused by a defect in the CYBB gene.

False

sotype switching occurs only from IgM to IgG.

False

Complement Deficiencies

Genetic mutations that can occur in either early complement components (C1-C4) or late complement components (C5-C9) Patients are more susceptible to infections such as S. pneumoniae, S. pyogenes, H. influenzae, and N. meningitidis Treatment involves plasma that contains complement and antibiotics Other aspects of humoral and cell mediated immunity are intact

This highly survivable cancer is characterized by groups of multinucleated, B-cell-derived Reed-Sternberg cells and often occurs following certain viral infections.

Hodgkin's lymphoma

TH1 Cells Activate Cytotoxic T Cells

IL-2, produced by TH1 cells, must bind to TC cell

Alpha heavy chain is called

IgA

Mothers can naturally, passively provide protection against pathogens to their infants by giving them pre-formed antibodies that are able to prevent some pathogens from adhering to the infant's intestinal cells and infecting. Which antibody type would be associated with this protection?

IgA

Plasma cells within mucosal membranes synthesize the

IgA dimer

Delta heavy chain is called

IgD

Epsilon heavy chain is called

IgE

Which statements accurately describe the treatment of a type I (anaphylactic) hypersensitivity response?

IgE may be neutralized prior to mast cell binding, preventing sensitization. Benadryl mimics histamine, competing for binding sites. Inhaled steroids minimize inflammation . IgG antibodies may be induced to neutralize antigens before those antigens can bind mast cells.

Gamma heavy chain is called

IgG

Mu heavy chain is called

IgM

During the early stages of an immune response

IgM is the first antibody isotype detected

Match the characteristic to the class of antibody with which it is primarily associated. More than one characteristic may be associated with an antibody class.

IgM: commonly found as five monomers joined by a J-chain. first antibody produced in the initial adaptive immune response IgG: transmitted across the placenta from mother to fetus. most abundant antibody in blood IgE: associated with the degranulation of mast cells and allergy IgA: commonly found as a dimer secreted across mucosal surfaces IgD: found at low levels in blood but is abundant on the surface of B cells

Immunodeficiencies leave their sufferers more susceptible to a variety of microbially caused diseases, though these deficiencies vary in both origin and outcome.

Immunodeficiencies, which have a genetic basis and generally manifest in early childhood, are known as primary immunodeficiencies, whereas secondary or acquired immunodeficiencies occur as a result of exposures such as to infection or radiation. Immunodeficiencies may affect either the adaptive branch of the immune system, if T cells or B cells have defects, or the innate branch of the immune system, if the defect exists in the complement system

B cells must be activated in order to begin clonal expansion into populations of plasma cells that produce antibody. This process may be T-cell independent or T-cell dependent.

In T-cell-dependent activation, B cells must first bind to an antigen that matches their existing B-cell receptors' VARIABLE regions. The B-cell receptor is a structure composed of an ANTIBODY and two additional membrane proteins. The bound antigen is ENDOCYTOSED by the B cell and then processed and attached to MHC II, which is re-displayed on the cell surface. This process makes the B cell its own ANTIGEN-PRESENTING CELL. A HELPER T CELL is then able to bind the antigen display complex and activate the B cell, allowing clonal proliferation.

Vaccination is an artificial process that can increase the protective effects of the immune system

In active immunization, antigens are deliberately administered to a person, prior to exposure to the matching live pathogen capable of causing illness. The type of antigen administered may vary. In some vaccines, inactive toxins, or toxoids, are administered to prevent disease. This is a type of subunit vaccine, in which only antigenic potions of a microbe are purified.

Four Basic Types of Vaccines

Killed, whole cells or inactivated viruses Live, attenuated (weakened) bacteria or viruses Antigen molecules purified from the pathogen DNA vaccines (not commercially available)

Requirements of an Effective Vaccine

It should not harm the person being vaccinated It should stimulate B-cell and T-cell responses It should result in long-term memory It should not require many boosters It should protect against the natural pathogen

TCR binds peptides only if bound by

MHC

Intracellular pathogens that are found in the cytoplasm of the cell degrade and are presented on

MHC I

Associate the following items with either major histocompatibility complex class I or major histocompatibility complex class II.

MHC I: presents antigen produced within APCs recognized by CD8 T cells found on all nucleated body cells MHC II: presents antigen phagocytosed by APCs found only on APCs (dendritic, macrophage, and B cell) recognized by CD4 T cells

Transplant Rejection

MHC recognition is an important part of self-recognition When transplanted tissue has a different MHC, rejection can occur

How may autoimmunity be induced?

Microbial antigen similar to self antigen is presented. Self-reactive B cells are activated without a self-reactive specific T cell.

Selective IgA Deficiency

Most common primary immunodeficiency Although patients lack IgA they have normal levels of other isotypes Cause is largely unknown Patients suffer from recurrent mucosal infections Incidence of autoimmune disease is more common in patients with this condition

B-Cell Disorders X-linked Agammaglobulinemia (Bruton's Disease)

Mutations in Bruton tyrosine kinase gene on X chromosome results in lack of B cell development and maturation No or little immunoglobulin is made Treatment includes IVIG and antibiotics

Hyper IgM Syndrome

Mutations in X chromosome on genes encoding CD40 ligand Without CD40 ligand, B cells can not be activated by T helper cells to class switch from IgM For unknown reasons, patients also lack neutrophils Monthly IVIG is used as treatment as well as bone marrow transplant if an identical MHC donor is available

The killing of infected cells by cytotoxic T cells resembles the process of killing by natural killer cells. How do the two processes differ?

NK cells do not recognize specific antigen

T-Cell Disorders Severe Combined Immunodeficiency (SCIDs)

No T cells are made By 6 months of age, most SCID infants develop recurrent infections Treatment is bone marrow transplant or IVIG IVIG: antibodies pooled from 1000's of donors

Different antigens interact with the adaptive immune system in different ways, with several features influencing how great the immune response will be to a given antigen.

Nucleic acids and lipids are weaker antigens than PROTEINS in part because they are made of relatively uniform repeating units and are flexible. Size is also a factor, with LARGER antigens being more readily presented on MHC than SMALLER antigens. Each antigen has a different THRESHOLD dose that will produce the optimal immune response. A lower dose will activate few B cells, while an excessive dose produces a tolerance response called ANERGY in which antibodies are not produced following subsequent exposures. This response helps prevent the body from recognizing its own "self" antigens, which are generally abundant.

Herd Immunity

Only possible for diseases that are contagious and transmitted between humans Estimates are 3/4th of a population or more must be immunized to reduce disease through herd immunity *This varies with each pathogen

Which are true of complement system deficiencies?

Patients with complement defects may be treated with complement-containing plasma. Complement-deficient patients have normal T-cell responses. Complement-deficient patients should receive normal vaccinations.

Pieces of evidence that support the hygiene hypothesis include which of the following?

Reducing gut flora in young children is associated with asthma. Bacterial infections that increase TH1 responses may inhibit IgE formation.

T-cell education occurs in the thymus:

Positive selection: T cells that weakly recognize self MHC are allowed to live Negative selection: T cells that bind to self MHC too strongly are destroyed

Common Variable Immunodeficiency (CVID)

Predominantly adult onset and relatively common; the molecular cause is unknown Results in B cells that are unable to effectively class switch and therefore very low levels of antibody are made Treatment requires IVIG

How does this happen?

Rearrangement of antibody genes Random introduction of mutations Generation of different codons during rearrangements

Hemolytic disease of the newborn can result under these conditions.

Rh- mother/Rh+ fetus, second pregnancy

Examples of how pathogens escape immune action include

Some viruses down-regulate MHC I or utilize a decoy MHC receptor Many pathogens alter their surface proteins through antigenic variation Some pathogens cause cell death of T cells Some block pro-inflammatory cytokines

Self tolerance: B and T cells learn not to react with self antigens

T cells that are self-reactive are deleted in the thymus B cells that bind self antigen in bone marrow undergo apoptosis Some self-reactive lymphocytes may escape selection Infection can trigger the formation of autoimmune reactions

For cytotoxic T cells (TC) to be activated:

TC cells must bind to antigen presented on MHC I TCR is specific for antigen CD8 on the TC cell binds to self MHC I on target cell

The adaptive immune response allows the body to recognize specific pathogens it has encountered previously, thereby providing an efficient and targeted response to that pathogen when it is encountered again.

The adaptive immune response is divided into two branches. The first is HUMORAL immunity, in which antibodies are produced that bind to ANTIGENS associated with the foreign cell. In the second branch, CELLULAR immunity, T CELLS recognize foreign cell structures and may either destroy infected HOST cells or help activate B CELLS, which can then generate plasma cells that produce ANTIBODIES.

The immune system is responsible for the recognition of microbial pathogens, but that is not its only role in protecting us.

The immune system is also responsible for the process of immune surveillance, which allows it to detect neoplasms or cancer as these growths of abnormal cells arise. Masses of cells that form in tissue, called tumors, are not always malignant, that is, characterized by rapid, uncontrolled growth that may spread throughout the body. Instead, they may be benign and self-contained, posing no risk of spreading. Like microbial invaders, cancerous cells display antigens not present on normal body cells that allow the immune system to recognize and target them.

The power of adaptive immunity can be used to prevent disease. By exposing people to certain antigens before they come into contact with the associated pathogens, the adaptive immune response can respond fully before the pathogen has a chance to replicate and cause illness.

The process of exposing a person to ANTIGENS in order to allow an adaptive immune response that prevents disease is VACCINATION. Most VACCINES, the materials administered to the person in this process, are currently composed of weakened or ATTENUATED microorganisms, killed pathogens, or inactivated protein TOXINS.

T cells must be educated in the thymus to avoid damaging self-recognition. In this process, what is the fate of T cells that weakly recognize self MHC?

These cells leave the thymus and move to secondary lymphoid tissues

Antigenicity of an epitope is dependent on its shape. Denaturing proteins generally removes the conformational epitope.

True

Autoimmune diseases can be correctly thought of as hypersensitivity reactions that occur in response to self, rather than foreign, antigens.

True

More than 200 separate primary immunodeficiencies are known, with B-cell defects being the most common subtype.

True

Suppose that a B cell is activated by two signals. The first signal is capping. The second signal is a TLR on the B cell interacting with a PAMP. Given these two signals, the B cell will produce only IgM and no further class switching will occur.

True

The absence of some immune components, or defects in those components, increases a person's chances of infection and cancer.

True

Though each antibody is specific to one antigen, highly similar antigens may be recognized by the same antibody. Because of this, some foreign antigens that resemble self antigens are "ignored" by the immune system in order to prevent damage to the body's own cells.

True

Diabetes

Type I occurs in childhood when T cells attack the islet cells of the pancreas

Type III hypersensitivity reactions, like those of types I and II, involve antibody-antigen binding. Type III hypersensitivity reactions are unique from these type I and II reactions in the formation of antigen-antibody complexes, which can become trapped in tissues.

Unlike type II reactions, in which antibodies bind to antigens on cells, in type III reactions, antibodies bind soluble antigen. Low levels of these complexes will be engulfed by macrophages, but higher levels may remain in circulation and become embedded in the walls of blood vessels. Bound antibody initiates complement via the classical pathway, which, in turn, attracts polymorphonuclear leukocytes, which further stimulate local inflammation and associated symptoms. An example of a type III reaction induced by the administration of animal-derived immunoglobulin is serum sickness.

The variable regions are referred to as the

VL and VH regions

We can synthesize 10^11 different antibodies!

Which means 10^11 different B cells!

The four polypeptides combine to form a

Y-shaped, tetrameric (four subunit) structure held together by disulfide (-S-S-) bonds

X-linked Agammaglobulinemia (Bruton's Disease)

a disease in which the body fails to make B cells owing to mutation in the x-linked BTK gene; gene product, Btk, is a protein tyrosine kinase essential for normal B-cell development

Primary immunodeficiency

a disease or disorder of the immune system that is the result of a genetic or developmental error

The bivalency enables antibodies to cross-link identical antigens

a feature critical to antibody function

Plasma cell

a fully differentiated antibody-producing cell

Memory B cell

a long-lived type of lymphocyte preprogrammed to produce a specific antibody. after encountering their activating antigen, memory B cells differenitate into antibody-producing plasma cells

Immunoglobulin

a member of a family of proteins that includes antibodies and B-cell receptors

Secondary antibody response

a memory B cell-mediated rapid increase in the production of antibodies in response to a repeat exposure to a particular antigen

How can DNA vaccines be described?

a method of producing antigen presentation similar to natural infection nucleic acid sequences placed directly into muscle cells

Superantigen

a molecule that directly stimulates T cells without undergoing antigen-presenting cell processing and surface presentation

What is the name for an antigen that causes the immune system to react more strongly than is warranted by the antigen itself, or that mimics host structures?

allergen

DiGeorge Syndrome

a recessive genetic immunodeficiency disorder causing undevelopment of some facial features, and twitching of extremities

IgA containing the alpha heavy chain is called

a secretory antibody because it is secreted across mucosal surfaces

Hapten

a small compound that must be conjugated to a larger carrier antigen in order to elicit an antibody response generally less than 1,000 daltons (molecular mass) cannot elicit an immune response unless they are attached to a larger carrier protein Ex.: penicillin, the tiny molecules must bind to another protein before the immune system can recognize it

Epitope (antigenic determinant)

a small segment of an antigen that can elicit an immune response. An antigen can have many epitopes a specific binding site on an antigen antigens can have more than one epitope

Lymphoma

a solid mass in a lymphoid organ

Isotype

a species-specific antibody class, defined by the structure of the constant region of the heavy chain. IgG, IgA, IgM, IgD, and IgE are the five isotypes types of antibodies found in all different individuals in related species

Cell-mediated immunity

a type of adaptive immunity employing mainly T-cell lymphocytes Some T cells help B cells become plasma cells; other T cells destroy host cells infected by the microbe possessing the antigen T cells determine whether antibody-or cell-mediated mechanisms predominate in response to a specifc antigen

Lower doses

activate only a few B cells

Specific T cells in the node then link to the antigen presented on the APC and become

activated T cells

What term describes the strength of the binding between an antibody and its epitope?

affinity

Humoral immunity

against infection is the result of antibody production orginaited by B cells

We actually produce five classes of antibodies, defined by five different types of heavy chains

alpha mu gamma delta epsilon

The differences in these amino acid sequences in different antibodies

alter the shape of the antigen-binding site and allow each antibody to bind a different antigen

Each subclass varies in its

amino acid composition and by the number of interchain cross-links

The antigen-binding sites form at the

aminoterminal (NH3) ends of the light and heavy chains

The deposition of clumps of secreted antibody light chains in organs, particularly the kidney, can cause damage. What are these clumps of secreted antibody light chains called?

amyloid

Allotype

an amino acid difference in the antibody constant region that distinguishes individuals within a species types of antibodies found within one species

During the primary antibody response

an antigen binds to B cells that are only able to make antibodies against that antigen

Type II hypersensitivity occurs when:

antibody binds to antigen on a cell surface

Type III hypersensitivity occurs when:

antibody binds to soluble antigen

Antigen-presenting cells (APCs)

an immune cell that can process antigens into epitopes and display those epitopes on the cell surface for recognition by naive T cells

The cytotoxic T cell recongizes

an infected cell that places antigens from the invading microbe on its host cell surface

T cells are subdivided into many types, each of which has a particular function in the response to a pathogen. Match the T-cell type to its primary role.

anti-inflammatory: Treg B-cell activation: TH2 pro-inflammatory: TH17 activate cytotoxic T cells: TH1 destroy infected or cancerous body cells: TC

In humoral immunity

antibodies are produced that directly target microbial invaders

Which is an example of cross-protection?

antibodies to cowpox can provide some protection against smallpox

Adaptive immunity, in contrast develops

as the need arises Ex.: adaptive immunity against malaria develops only after the individual has encountered the plasmodial parasite for the disease; that is, the immune response adapts to the presence of the new organism

Phagocytes possess surface Fc regions that can

attach to the Fc region to gain a firmer "grip" on the microbe, facilitaing phagocytosis

One light chain is then

attached near its carboxyl (COO-) end to the middle of each heavy chain by a single disulfide bond

Opsonizing IgG antibodies coat the microbe by

attaching to microbe surface antigens

Match the common approved vaccine to its type.

attenuated virus: influenza chickenpox measles inactivated virus: influenza hepatitis A rabies toxoid: tetanus pertussis

All antibody isotypes have the same

basic structure

The humoral immune response

begins with an infection somewhere in the body

Cytokines alter the balance

between cell-mediated (TH1) and antibody-mediated (TH2) immune responses

Superantigens

bind outside of the MHC binding site and cause a massive "cytokine storm" to be released

IgG can also directly neutralize viruses by

binding to virus attachment sites and is one of only two antibody types that can activiate complement by the classical pathway

T-cell receptor (TCR)

binds antigen on the surface of T cells

Innate immune mechanisms are present from

birth

Other classes circulate only in

blood

How are T-cell receptors similar to B-cell receptors?

both bind specific antigens

Secondary immunodeficiencies

can be acquired at any age Caused by infection, immunosuppressive drugs, or radiation therapy

Multiple myeloma

cancerous plasma cells at multiple sites, mainly throughout the bone

T-cell-independent activation of B cells is associated with which of the following?

capping or cross-linking of multiple B cell receptors

Medium antigens

carbohydrates

Two classes of MHC molecules are found on

cell surfaces

CD8 T cells carry out

cell-mediated immunity

In a process called

clonal selection, the antigen selects which B cell clone proliferates and differentiates into antibody-producing plasma cells or memory B cells

The antibody response to each indiviual epitope is

clonal; that is a single B cell that makes an antibody to a single epitope will upon "seeing" that epitope replicate to produce a large population (a clone) of B cells, all of which make antibodies to that epitope

Match each clinical example to the deficient immune component.

complement: C3 deficiency B cells: hyper IgM syndrome phagocytes: chronic granulomatous disease T cells: DiGeorge syndrome severe combined immunodeficiency (SCID)

Besides proteins, other structures in the cell, such as

complex polysaccharides can have linear and three-dimensional epitopes

As a whole, the adaptive immune response is a

complex, interconnected, and cross-regulated defense network and it has a memory

A B cell receptor

consists of a membrane-bound antibody on a B cell in association with the Igalpha and Igbeta proteins. Binding of antigen to the B-cell receptor triggers B-cell proliferation and differention

The MHC

consists of membrane proteins with variable regions that can bind antigens. Class I MHC molecules are on all nucleated cells, whereas antigen-presenting cells contain both class I and class II MHC molecules

The heavy chains in each class differ one from another at a specifc region in their amino acid sequence called the

constant region, denoted CH

Cellular immunity, in general, is

critical for dealing with intracellular pathogens such as viruses

Another type of T cell, called

cytotoxic T cells (Tc cells) can also bind to microbial antigens presented on an APCC and become activatavied

Besides directly killing infected cells

cytotoxic T cells also can synthesize and secrete growth factors called cytokines that incite nearby macrophages to indiscriminately attack cells in the local area

Vaccination

describes the technique of exposing indiviudals to "tame" microbes to protect to person against the more dangerous, pathogenic strains

IgA is most commonly found as a

dimer whose monomeric parts are held together by a protein called the J chain

The route to antibody production requires antigens with multiple repeating epitopes to

directly cross-link B cell receptors to trigger B cell proliferation and differentaition into a plasma cell

The various heavy-chain constant regions impart

distinct purposes to each class of antibody

Soluble proteins (proteins not attached to a microbe)

do not usually contain multiple repeating units

There are five classes (isotypes) of heavy chains

each antibody isotype is defined by the sequence of the heavy chain

Each antibody molecule contains two antigen-binding sites

each binding site is formed by the hypervariable ends of a heavy and light chain pair

"Unprofessional" APCs

endothelial cells fibroblasts

A patient with type B, Rh+ blood is concerned about hemolytic disease in her newborn because her husband has type AB, Rh+ blood and her first child had type A, Rh+ blood. Her concerns are warranted because anti-A antibodies can cross the placenta.

false

In commonly administered TB skin tests, a small amount of antigen associated with the Gram-positive bacillus that causes tuberculosis is injected under the skin. Approximately 48 hours later, the person is examined for the occurrence of a type IV hypersensitivity reaction at the injection site. A positive result would indicate that the person has a current tuberculosis infection.

false

Individuals with a genetic predisposition to allergy commonly experience an anaphylactic reaction to bee stings the first time they are stung.

false

The secreted molecule, now called secretory IgA (sIgA) is

found in tears, breast milk, and saliva and on other mucosal surfaces

An IgA dimer can bind

four molecules of antigen

An antibody consists of

four polypeptide chains

T cells do not bind

free-floating antigen

Dendritic cells and macrophages patrolling the area

gather up the forgein antigens and present them on their cells surface

Clonal

giving rise to a population of genetically identical cells, all descendants of a single cell

Immunoglobulins are

glycoproteins made by the body in response to an antigen

Class II MHC molecules

have a more limited distribution. Are expressed only by antigen-presenting dendritic cells, macrophages, and B cells. Are critical to the immune system because the T cell, to be activated must first recognize a foreign antigen attached to an MHC receptors have a degree of antigen specificty and are formed from DNA rearrangements similar to those used to make antibody bonding sites

Antibody classes are named according to their

heavy chains

There are two long

heavy chains that are colored green

B cell responses to these types of antigens require assistance from

helper T cells (TH cells)

About 90% of the US population is vaccinated against the measles virus, which leaves approximately 31 million unvaccinated individuals. The rate of infection in those 31 million people, however, is not the normal background rate but is instead much lower, because transmission does not occur through the vaccinated population. What is this phenomenon called?

herd immunity

The activated B cells the proliferates and differentiates into

high-output antibody-secreting plasma cells and memory B cells

When mast cells degranulate, they can release a compound that mediates allergic symptoms. This compound binds to receptors on multiple cell types, leading to itching, smooth muscle contraction, and increased vascular permeability. What is this compound?

histamine

Which best describes the mechanism of transplant rejection?

host T cells react to foreign MHC molecules

Circulating IgM, containing the mu heavy chain is a

huge ferris wheel-shaped molecule formed from five monomeric immunoglobulins tethered together by the J-chain protein

There are two types of adaptive immunity:

humoral and cell -mediated

Two disulfide bonds connect the two

identical heavy chains to each other

An antibody circulates through blood and lymph

ignoring all antigens except for its specific target antigen

Immune surveillance

immune system functions to detect and eliminate cancer cells as they arise

The molecule sIgA is important for

immunity against pathogens that use mucosal membranes as portals of entry

Secondary antibody response is the basis for

immunization

Secondary immunodeficiency

immunodeficiency acquired as a result of infection, radiation treatment or use of immunosuppressive drugs

What term describes the degree of immune-response induction that an antigen can produce?

immunogenicity

Both classes belong to the

immunoglobulin family of proteins, but they are not immunoglobulins

Antibodies belong to the

immunoglobulin superfamily of proteins and the B-cell and T-cell receptors

Epstein-Barr virus (EBV) is associated with which of these immune disorders?

infection of B cells leading to neoplasms

Which of these techniques might microbes use to successfully evade an immune response mounted against them?

inhibit production of pro-inflammatory cytokines trigger apoptosis of immune cells induce production of anti-inflammatory cytokines

Activiation of a B cell

into an antibody-producing plasma cell usually requires two signals. The first is antigen binding to a B-cell receptor. The second signal is binding to a TH cell activated by the same antigen. The TH signal is (1) the T-cell receptor binding to an MHC II molecule bearing antigen on the B cell and (2) the CD40 ligand on the T cell binding to CD40 on the B cell. Both interactions are required

Antigenicity (immunogenicity)

is a measure of how well an antigen elicits an immune response

The antigen-binding part of an antibody, regardless of the heavy-chain class

is formed by highly variable amino acid sequences at the amino-terminal ends of the light and heavy chains

Antibody diversity

is generated during B-cell development by recombining (mixing and splicing) about 1,000 DNA gene cassettes and introducing mutations within DNA segments corressponding to the antigen-binding site

One type of antibody (IgM)

is made quickly in response to an infection but binds to its target with only a moderately tight grip, only to be followed by another antibody type (IgG) that very tightly grips its target

Humoral immunity

is most effective against extracellular bacterial pathogens such as Streptococcus pneumoniae, one cause of pneumonia

The immune response to a microbe

is really a composite of responses to different epitopes by thousands of individual B cells, the cells responsible for producing antibodies

One class (IgA)

is secreted onto mucosal surfaces where pathogens try to sneak into our bodies

Threshold dose

is the amount of antigen needed to generate an optimal response

Serum

is the fluid that remains after your blood clots

Clonal selection

is the rapid proliferation of a subset of B cells during the primary or secondary antibody response

IgG

is the simplest and most abundant antibody in blood and tissue fluids

During a later stage of the primary response, a process known as

isotype switching (also called class switching) occurs in activated B cells in which the predominant antibody type produced becomes IgG rather than IgM

When an antibody finds its antigenic match

it binds to the antigen and initiates several events that destroy the target

What is true of type IV hypersensitivity reactions?

it includes contact dermatitis

Although immunological specificity is important

it is not absolute

Your immune system does not recongize the whole microbe

just innumerable tiny pieces of it

In contrast to the five heavy chains, there are only two classes of light chains

kappa and lambda

Two-thirds of all antibody molecules carry

kappa chains; the rest have lambda chains

Most vaccines the material used to vaccinate someone are

killed pathogens, live but crippled (attenuated) strains of the pathogen, or inactivated microbial toxins (for example, diphtheria toxin)

Match the cell type to its description

kills infected host cells displaying antigen: cytotoxic T cell activates other adaptive immune cells: helper T cell produces and secretes antibodies: plasma B cell rapidly produces new antibody-secreting cells following re-exposure to antigen: memory B cell

There are two short

light chains that are colored yellow

One type of activated T cell the finds, binds, and activates a

lymph node B cell that encountered the same antigen

Many memory B cells and most plasma cells leave the

lymph node and migrate to the bone marrow. other plasma cells remain in the lymph node

"Professional" APCs

macrophages (monocytes) mast cells dendritic cells B cells

The APC surface proteins that hold and present the antigen to T cells are know as

major histocompatibility complex (MHC) proteins

Leukemia

malignant lymphoid cells found in circulation or bone marrow

Immunological specificity

means that antibody made to one epitope will not bind to different epitopes (although some weak cross-binding can occur)

Class I MHC molecules

membrane surface protein found on all nucleated cells of the human body (absent from red blood cells and platelets); presents cytoplasmically synthesized foreign antigen epitopes to cytotoxic T cells

Class II MHC molecules

membrane surface protein found on antigen-presenting cells (dendritic cells, macrophages, and B cells); presents phagocytized foreign antigen epitopes to helper T cells

Antibodies are Y-shaped

molecules that contain two heavy chains and two light chains

IgG is made as a

monomer but has four subclasses in humans

During the secondary antibody response

most B cells switch from IgM production to IgG production as they become plasma cells

You are examining a patient's results from serum electrophoresis and note that the gamma-globulin band is abnormally narrow, indicating the overproduction of a monoclonal antibody. This result would likely lead you to consider a diagnosis of which type of neoplasm?

multiple myeloma

B cell activation can thus take place by one of two routes:

one that does not involve the use of T cells (the T cell independent route) and one that does

T cells are activated

only by binding to APC-presented antigens

IgG is able to bind to antigens on the surface of a pathogen. Once bound, the Fc region of the antibody is exposed and can interact with phagocytes, increasing the likelihood the pathogen will be engulfed and destroyed. What term describes the process of IgG binding to the pathogen?

opsonization

B-cell tolerance is

part of the reason your immune system does not attack your own antigens

Which of the following is an example of a hapten?

penicillin

IgM is so large that it cannot cross the

placenta

The interaction authorizes those B cells to generate

plasma cells able to pump out larger amounts of specific antibody (note that plasma cells are not B cells)

Which are true of regulatory T cells?

possess CD4 inhibit T cells that should have been eliminated in the thymus but were not

Each B cell is

preprogrammed to make antibody for one and only one epitope

T cells recognize antigen

presented only on "self" MHC-containing APCs

During this lag period, a series of molecular and cellular events known as the

primary antibody response take place

Vaccination has been used to

protect humans against many microbial and viral pathogens

Strongest antigens

proteins they form a variety of shapes they maintain their tertiary structure they are made of many different combinations these features provide stronger interaction with antibodies in the bloodstream and enable better recognition by lymphocytes

Antibodies are

proteins that circulate in the bloodstream and recognize foreign structures called antigens

Which steps contribute to the generation of antibody diversity?

rearrangement of genes in the genomes of B cells random mutations generation of different codons

Activation of a TH0 cell requires which of the following?

recognition of specific antigen by TCR APC presentation of antigen on MHC II CD28 binding to B7 on the surface of an APC

MHC help determine whether a given antigen is

recongized as coming from the host (a self-antigen) or from another source (a foreign antigen) in a phenomenon called histocompatibility

Antibody isotype, allotype, and idiotype

refer to amino acid sequence differences found at the different levels of antibody diversity. Isotypic differences are found between species, allotypic differences are found within a single isotype (for instance IgG) between two individuals of the same species, and idiotypic differences are found within a single antibody allotype in a single individual (usually at the antigen-binding site)

Activation of a TH0 cell

requires two signals: T-cell receptor CD4 binding to an MHC II-antigen complex on an antigen-presenting cell, and CD28-B7 interaction

Activation of cytotoxic cells

requires two signals: T-cell receptor CD8 molecules that recognize MHC I antigen complexes on APCs and cytokines such as IL-2 made fom activated TH1 cells. The activated cytotoxic T cells in turn destory infected host cells

Antigen presentation also plays a

role in how immunogenic an antigen is

Secondary exposure to the antigen triggers an almost instantaneous

secondary antibody response

Memory B cells require an activation signal in addition to specific antigen binding in order to produce new plasma cells. What is the second, activating signal?

secreted IL-4 and IL-6 from activated helper T cells

Huge amounts of IgG antibody are

secreted from these plasma cells

The humoral and cellular immune responses are not

separate, but interwinded, each relying on some facet of the other to work effecintely

Match the term to its defining feature

single-site plasma cell neoplasm: plasmacytoma solid tumor in lymphoid tissue: lymphoma malignant lymphoid cells in circulation or bone marrow: leukemia plasma cell neoplasms with several locations: multiple myeloma

Soluble proteins possess many different

small, discrete, single epitopes, making it diffulct to cross-link two B cell receptors on the same cell

MHC proteins differ between

species and among individuals within a species

Superantigens

stimulate T cells by directly linking the T-cell receptor on a T cell with MHC on an APC without undergoing APC processing and surface presentation

APCs

such as dendritic cells, present antigens synthesized during an intracellular infection on their surface class I MHC molecules, but place antigens from engulfed microbes or allergens on their class II MHC molecules. T cells recognize antigens bound MHC

Antigen-presenting cells

such as phagocytes degrade microbial pathogens and present distinct pieces on their cell-surface MHC protiens

APCs

such as phagocytes, degrade microbial pathogens and present distinct pieces on their cell-surface MHC proteins

Release of cytokines from immune cells stimulates other cells to release these molecules as well, which can lead to an over-amplification of these signals known as a cytokine storm. Some proteins (including known bacterial toxins) can trigger this response by directly binding to the outside of T-cell receptors without being recognized or processed as antigens. What is the name of these proteins?

superantigens

Helper T cells display the

surface antigen CD4

IgG binds and opsonize microbes

that is they coat the microbe to make it more susceptible to phagocytes

Proteins are better immunogens

that nucleic acids and lipids because proteins have more diverse chemical forms

Once activated by TH cell

the B cell undergoes isotype switching from IgM to IgG or IgA

T-cell independent immunity

the activation of B cells without the help of helper T cells is possible when an antigen possesses multiple repeating epitopes that bind multiple B-cell receptors (capping)

By "variable" we mean that

the amino acid sequence of an antigen-binding site on an antibody that binds, say peptidoglycan, is very different from the antigen-binding site on an antibody that binds a different antigen

Variable region

the amino-terminal portions of antibody light and heavy chains that confer specificity to antigen binding and define the antibody idiotype

This binding "tags" the microbe and leaves

the antibody Fc regions protruding outward

The mechanism of clonal selection begins with

the antigen binding to a matching B cell (a B cell preprogrammed to bind to that antigen)

The better an antigen can bind to the MHC surface proteins

the better it can trigger an immune response (or the more immunogenic it is)

Capping

the clustering of B-cell receptor molecules at one pole of a B cell after receptors have been cross-linked by antigens or epitopes

A good example in which cross-protection doesn't work is

the common cold, caused by hundreds of closely related rhinovirus strains (rhinitis, a runny nose, is one of the symptoms of this viral disease)

After leaving the lymph node

the cytotoxic T cell can seek out and directly kill any host cell infected with the microbe

The net result of the primary antibody response is

the early synthesis and secretion of pentameric IgM molecules specifically directed against the antigen or immunogen

The stronger the binding

the easier it is for certain ,ymphocytes (T cells) to recognize the complex

The further away an antigen structure is from "self"

the greater its immunogenicity will be

Heavy chains

the larger of the two proteins types that make up an antibody. each antibody contains two heavy chains and two light chains

As the immunogen is cleared from the body

the levels of both IgG and IgM decline because the plasma cells that produced them die. Most plasma cells die within 3 months

The larger the antigen is

the more easily the APC can degrade it and present the epitopes on the APC's cell-surface MHC molecules, a necessary step before an immune response can occur

The larger the antigen

the more likely it is that antigen-presenting phagocytic cells such as macrophages and dendritic cells will "see" and engulf it

The more complex a foreign protein is

the more likely it will possess unique antigenic determinants that a lymphocyte can recognize as nonself

The autoimmune process involved in systemic lupus erythematosus, in which antibodies and antigens interact to form clusters that may be deposited in tissue, is similar to which type of allergic reaction?

type III hypersensitivity

However, each isotype has a

unique "super" structure and each is designed to carry out a different task

Opsonize

the process by which phagocytosis is aided by coating pathogens with IgG antibodies of complement

Primary antibody response

the production of antibodies upon first exposure to a particular antigen. B cells become activated and differentaitee into plasma cells and memory B cells

Clonal selection

the rapid proliferation of a subset of B cells during the primary or secondary antibody response

Fc region

the region of an antibody that binds to specific receptors on host cells in an antigen-independent manner. it is found in the carboxy-terminal "tail" region of the antibody

Constant region

the region of an antibody that defines the class of a heavy chain (isotype) or light chain

Memory B cells imitate

the secondary antibody response

Light chains

the smaller of the two protein subunits that make up an antibody. each antibody contains two heavy chains and two light chains

F(ab)2 region

the two linked antigen-binding arms of an antibody molecule

Memory B cells are maintained in the body because

they continue to divide

Each specific antigen has a different

threshold dose needed to generate an optimal response

T cells develop in the

thymus and contain surface protein antigens different from B cells

TH0 cell differentiation

to TH1, TH2, or TH17 cells is influence by different cytokine "cocktails" secreted by macrophages and natural killer cells during an infection

The primary antibody response

to an antigen begins when B cells differentiate into antibody-producing plasma cells and memory B cells, IgM antibodies are generally the first class of antibodies secreted during the primary response

T cells must be "educated"

to bind self MHC molecules weakly

Haptens are too small

to bind the MHC molecules

Major histocompatiblity complex (MHC)

transmembrane cell proteins important for recognizing self and for presenting foreign antigens to the adaptive immune system presentation of antigens on APCs requires that the antigen be placed on a membrane surface protein strucuture

Immunocompromised patients should not be given live attenuated vaccines. For this reason, it is very important that healthy people are vaccinated, as this reduces the spread of those preventable diseases.

true

The J chain joins

two IgAs by their Fc regions

One antibody molecule possesses

two identical antigen-binding sites, one of each "arm" of the Y-shaped molecule

An antibody of any heavy chain class may contain

two kappa chains or two lambda chains, but never one of each

No cross-protection occurs if these

two proteins differ significantly

Match prominent characteristics to the hypersensitivity type with which they are associated.

type I anaphylaxis IgE cross-linking type II allergen-displaying host cells killed by complement type III antigen-antibody complexes Type IV time of onset more than 24 hours postexposure allergen-displaying host cells killed by TC cells

T cells are divided into two broad groups distinguished by

whatever they carry cellular differentiation proteins CD4 or CD8 on their cell surface

Once decorated with antigen, the professional antigen-presenting cell travels the lymphatic system to secondary lymphoid organs (lymph nodes)

where B cells and T cells await

Each dimer then passes through a mucosal cell

where a sixth protein, the secretory piece is, wrapped around the IgA dimer during the final secretion process

Antibodies are also strategically situated on the surface of B cells

where they enable these lymphocytes to recognize specific antigens

TH0 precursor cells

which have surface CD4 molecules, can make TH1, TH2, and TH17 cells that support B-cell differentiation into antibody-producing plasma cells. TH1 cells also drive cell-mediated immunity mediated by CD8 T cells

The inability of haptens to bind to MHC proteins is

why these molecules must be attached to larger antigens in order to generate an immune response

A dose higher or lower than that threshold

will not generate as strong an immune response

Why is MHC II deficiency (bare lymphocyte syndrome) considered a T-cell disorder?

without antigen presentation, TH0 cells cannot be induced to form other types of T cells

Cross-protection, as in the case of vaccinia (cowpox) and variola (smallpox) viruses

works only if key virulence proteins from the two different organisms share epitopes