Immunology Test 4

Omalizumab

- Anti-IgE antibody - Binds to soluble IgE to prevent binding to Fc-epsilon-RI on masts, basophils, and eosinophils - Cannot bind to IgE already bound to Fc-epsilon-RI so it will not act as a surrogate antigen - Cannot bind to Fc-epsilon-RII to suppress IgE activity

Compare and contrast central memory T and effector memory T cells

-Both of them are memory cells -TCM has both L-selectin and CCR7 in order to bind to and enter secondary lymphoid tissues like effector T cells. While they have little effector function before activation, they have a low threshold for activation such that lots of IL-2, cell proliferation, and differentiation into effector cells occurs quickly -TEM does not have either L-selectin or CCR7, but instead has CCR3, CCR4, CCR5, and CCR6. Those are helpful in its entry into non-lymphoid tissues to quickly respond to an infection.

How can one distinguish memory B cells from effector and naive B cells?

-Contain surface bound immunoglobulins and do not secrete antibody (unlike plasma cells) -Have CD27 to distinguish from both effector and naive cells

Describe the two types of polio vaccines that have been created

1. Salk vaccine: First one created by Jonas Salk in 1955. It contained killed virus of three different strains and was injected into the skin 2. Sabin vaccine: introduced in 1963, it was orally administered to children. It is also a trivalent oral polio vaccine (TVOP)

Describe the features that made smallpox an ideal candidate for worldwide eradication via a vaccine

1. Smallpox and its epitopes evolve really slowly so immunity an infant receives is good for life 2. It is a live vaccine that establishes an infection at the injection site in the skin 3. It only infects humans so there are no reservoirs in other animals

Describe how eosinophils are increased in number and trafficked into the correct tissue during an infection (name cytokines, chemokines, etc.)

1. Th2 release IL-5 and other cytokines in bone marrow to increase eosinophil production + release into blood 2. CCL5, CCL7, CCL11, and CCL13 bind to the CCR3 receptor on eosinophils to get into tissues

Describe two ways by which memory T cells are distinguished from naive T cells

1. They recirculate in peripheral tissues over secondary tissues so memory cytotoxic and effect T cells can be directly activated at site of infection by DC and macrophages 2. Do not require co-stimulation through CD28 receptor so less demanding to activate them

Reverse vaccinology

A technology that screens human pathogens for many unknown genes that may not have been uncovered in previous studies of physiology and virulence. It is used to discover new possible vaccines

For the genes relating to asthma, describe their purpose below. ADAM33 Beta2-adrenergnic receptor 5-lipoxygenase

ADAM33: helps to repair damaged bronchial tissue Beta2-adrenergnic receptor: influences bronchial activity and is receptor for epinephrine/norepinephrine 5-lipoxygenase: involved in synthesis of leukotrienes

What is another term for a memory response?

Anamnestic response

Memory cells

B and T cells that remain after a primary immune response is made against a pathogen. They are long-lived and serve to quickly clear an infection for a secondary immune response

Polyreactive

Broadly neutralizing antibodies that can react with a variety of structurally unrelated antigenic molecules. This increases the probability the antibody will bind both of their antigen binding sites: one to gp120 and another to a separate component of the virus or infected human cell

HIV exploits the ______ receptor found on ___________, ___________, and _________.

CD4 macrophages; dendritic cells; CD4 (helper) T cells

Hereditary angioedema (HAE)

Caused by a deficiency in the compliment regulator C1 inhibitor (C1INH). This disease is characterized by swelling of the face, larynx, and abdomen. Too many vasoactive C2a fragments are floating around, as well as bradykinin in HAE, that causes fluid to leak into tissues

Give an example of protective immunity

During the course of seasonal allergies, the body will make antibodies against a cold that will stick around. Then, if it tries to invade again, the pathogen will be coated with IgG and/or IgA to prevent reinfection

Adults that get _________ tend to develop infectious mononucleosis or granular fever. For children, the infection is usually just a mild cold.

Epstein-Barr virus

True or False: Distinguishing naive CD8 T cells from memory CD8T cells is just about as easy as trying to distinguish memory CD4 T cells from memory CD4T cells. Both of the T cells have a large variety of differences between them. Defend your answer.

False It is harder to distinguish CD4 T cells between naive and memory. There are more genes that can distinguish CD8 T memory cells from their naive counterparts

True or False: The violent reactions of sneezing, vomiting, and diarrhea prove to be successful in completely expelling a worm

False Usually only succeeds in reducing the population and severity of helminths, not completing eliminating

True or False: A majority of eosinophils can be found in the blood.

False Usually residents in tissue such as respiratory, urogenital, and gastrointestinal tissues

What cytokine can NK cells secrete to kill virally-infected or cancerous cells?

IFN-gamma

Severe Combined Immunodeficiency (SCID)

Patients unable to make T-cell dependent antibody responses or cell mediated immune responses (both arms of the AIR are compromised)

Anaphylactoid reactions

Resembles anaphylaxis but there is an absence of interaction between an allergen and IgE

What tissues are most at risk for exposure to allergens?

Respiratory & GI tracts, blood, and connective tissue

Urticaria (hives)

Same as the immediate wheal and flare reaction. Mast cells in the skin are activated by allergens to release histamine for itchy swellings

Allergic asthma

Triggered by allergens that activate the submucosal mast cells in the lower airways of the respiratory tract. The airways are constantly infiltrated with TH2 cells, eosinophils, and neutrophils. Air is trapped in the lungs, making it difficult to breathe

Describe a type I hypersensitivity

Triggered by interaction of allergen with IgE bound to Fc-epsilon-I receptor of mast, basophils, and eosinophils. Pollen is an example that will cause immediate hypersensitivity

True or False: While EBV causes an unusually large amount of WBCs to proliferate and produce virus, CD8 T cells will be able to control the infection by killing infected B-cells

True

What coat proteins of rotavirus are targeted by vaccines?

VP4 and VP7 as they undergo frequent mutation and, therefore, define different viral serotypes

Killed or inactivated virus vaccines

Viral particles that cannot replicate because they have been treated chemically with formalin or physically with heat/irradiation. This is only effective if the virus can be reliably inactivated and large batches of virus have to be made for this kind of vaccine

Mucosal mast cells produce _______a______ while connective mast cells produce _____b_____.

a. protease tryptase b. chymotryptase

Which of the following pathogens will coat themselves in human proteins to trick the immune system? Select all that apply. a. Listeria monocytogenes b. Treponema pallidum c. Salmonella typhimirium d. Schistosoma mansoni

b & d

While _________ leads to limited and rapidly passing epidemics, ___________ can lead to more serious pandemics that can inflict severe disease and greater mortality than epidemics. a. antigenic shift; antigenic drift b. influenza; SARS c. antigenic drift; antigenic shift d. gene recombination; gene assortment

c. antigenic drift; antigenic shift

When testing someone for allergies, the appearance of a wheal and flare on the skin is an example of a(n) a. type II hypersensitivity b. late-phase reaction c. type IV hypersensitivty d. immediate reaction

d. immediate reaction

The book mentions that it is believed that eczema stems from a weakness in the protective barrier of the skin. This allows for allergens to enter and cause a TH2 mediated response. By this regard, about 20% of all people with eczema have a mutant.... a. profilagrase b. eczematase gene c. stratum corneum d. profilaggrin gene

d. profilaggrin gene

What is the purpose of the Wiskott-Aldrich syndrome protein (WASP)?

Needed to help reorganize the cytoskeleton of T cells and deliver cytokines/signals to B cells, macrophages, and other targets it forms cognate pairs with.

Broadly neutralizing antibodies

Neutralizing antibodies that are able to target multiple strains of HIV-1. It recognizes the gp120 component of HIV

What happens during a late phase reaction to an allergen?

Occurs 6-8 hours after an immediate reaction that sees a more widespread/diffuse area of swelling. More leukotrienes, chemokines, and cytokines are synthesized by mast cells

What is variolation?

One of the first procedures developed to try to stop the progression of smallpox. This involved taking dried pustules from patients experiencing a mild form of the disease. Then, the material was given to healthy people either intranasally or intradermally through a scratch in the arm

Approximately how many effector CD8 T cells are left as memory CD8 T cells after a virus is successfully cleared?

Only 5% 95% die and only 5% are left that express the IL-7 receptor...must be able to respond 100-1000 fold stronger than naive counterparts did for first infection

Where do opportunistic pathogens first infect in AIDS patients? Who are the culprits?

Oral and respiratory tracts Canidia and mycobacterium tuberculosis

What features of a secondary immune response make it better at responding to an infection?

Pathogen-specific memory cells outnumber their naive counterparts, memory cells are readily activated, and already undergone isotype switching, somatic hypermutation, and affinity maturation

What is the link between XLA and bronchiectasis?

Patients diagnosed with XLA are usually healthy minus pyogenic bacterial infections. While they can clear those infections, they may develop bronchiectasis due to successive rounds of infection and antibiotic treatment as it can lead to tissue damage from excessive protease release from bacteria and phagocytes

Chronic granulmatous disease

Phagocytes cannot produce the superoxide radical (O2 -) and undergo a respiratory burst. Patients have chronic bacterial infections that lead to granuloma formations

Chediak-Higashi syndrome

Phagocytosed material cannot be delivered to lysosomes, leads to persistent bacterial infections

What are the three different approaches one can take when trying to reduce the effects of allergic diseaes?

Prevention, pharmacological, and immunological

How does Mycobacterium tuberculosis evade the immune system?

Prevents the lysosome and phagosome from fusing into an acidic phagolysosome. From here, it can survive in the cell's vesicular system

Describe how an IFN-gamma receptor deficiency differs in a recessive vs. dominant mutant

Recessive: No IFN-gamma-R1 (one of the dimers) is expressed to interact with IFN-gamma-R2. Since only IFN-gamma-R2 is on the surface, it cannot successfully bind to IFN-gamma Dominant: IFN-gamma-R1 is made but it is defective due to missing its cytoplasmic tail. It still, however, goes to the cell surface to bind to IFN-gamma-R2. This is an issue because the IFN-gamma receptors with a defective IFN-gamma-R1 subunit will compete with healthy IFN-gamma receptors

Genome sequencing seems to be an effective method to quickly synthesize a vaccine that could, potentially, prevent another outbreak of something like H1N1 (swine flu in 2009). Why, then, are vaccine manufactures still intent on utilizing chicken embryos for vaccine creation?

Regulatory agencies have their own procedures of regulation and quality control that were put in place back in the 1950s. It is difficult to try to convince them to change their ways

endogenous retroviruses

Retrovirus-like sequences that have been permanently integrated into the host cell genome and have lost their ability to function

Rotatrix and RotaTeq...describe the differences between these two vaccines for rotavirus

Rotatrix is the attenuated human virus having the common VP4 and VP7 variants. On the other hand, RotaTeq is a mixture of 5 cattle rotaviruses that have been engineered to express different human VP4 or VP7 glycoprotein

What is the purpose of the staphylococcal superantigen-like protein SSLP7 found on Staphylococcus aureus?

SSLP7 binds to IgA to prevent the latter from binding to Fc-alpha-RI, found on neutrophils, and to something on C5 to prevent complement activation.

List the common ways that HIV is spread from one individual to another

Sexual contact, sharing of needles through drug use, breastfeeding, or blood transfusions/blood components from HIV positive individuals

The disease caused by reactivated herpesvirus varicella-zooster, normally latent in ganglia, is referred to as _________ and occurs only once in an individual's lifetime.

Shingles

What drives the survival and proliferation of memory B and T cells?

Signals from IL-7 and IL-15 receptors. This is thought o to occur in the bone marrow and driven by interactions with stromal cells and cytokines

NK cells are known for their cytotoxic activity, similar to CD8 T cells, that kill abnormal cells. That being said, NK cells are not sentient beings that are able to inquire individual cells on their health status. Thus, it could be theorized NK cells would kill indiscriminately. How, then, do healthy cells prevent NK cells from killing them?

Since NK cells have MHC Class I sensors on their surface, healthy cells will take advantage of this feature. Essentially, a healthy cell will produce and express MHC I molecules that send an "I'm healthy!" signal to NK cells such that the NK cell will not accidentally kill them

What is the hygiene hypothesis?

States how improved hygiene, vaccination, and use of antibiotics has caused the current epidemic of allergies in developed countries. This causes the immune system to be poorly educated and unable to distinguish between harmful and harmless substances in the environment

Some factors that may trigger herpesvirus out of latency include...

Sunlight, bacterial infections, or hormonal changes (all types of stressors)

In addition to expressing Fc-epsilon-RII, what other receptors can mast cells express to contribute to the immune response?

TLRs and Fc receptors for IgA/IgG Produces cytokines to recruit neutrophils, eosinophils, and effector T to infected tissue + help with tissue repair

Mast cells can store ________ and release it on demand. This activates endothelial cells to increase adhesion molecules to increase WBCs and promote traffic from blood into inflamed tissue.

TNF-alpha

Explain how penicillin causes an allergic reaction.

The beta-lactam ring of penicillin can open up and produce covalent conjugates with proteins of the body to create "foreign" epitopes that will be dominated by a TH2 response

Antigenic Shift

The combination of two more different strains of virus, such as influenza, that are antigenically very different than strains people have protective immunity to. This can be very devastating to the immune system and these viruses have a competitive advantage to other strains

What is a common outcome for individuals that lack an IL-12 receptor?

The mutual macrophage and T-cell activation cannot occur so individuals suffer from persistent infections with strains of mycobacteria

Combination therapy

The practice of using many different drugs at once to destroy a population of viruses before any one of the them has accumulated enough mutations to resist all drugs

Herd immunity

The resistance of a population to the spread of an infectious disease like measles. While it could be achieved naturally, vaccines are useful tools for this such that enough children are vaccinated so that it protects the children who did not receive a vaccination, either due to medical reasons or their parents personal beliefs

How do the monomeric and trimeric forms of Fc-epsilon-RII differ in terms of B cells?

The trimeric soluble form of Fc-epsilon-RII will secrete synergistic signaling to promote differentiation of B cells into IgE producing plasma cells while the monomeric form will inhibit that

How are live attenuated vaccines made?

The virus is grown in non-human cells such that scientists can select for the viruses that grow very well in those kinds of cells. Also, there could be a strain that naturally passes through a human population to diversify and create a strain with reduced pathogenicity against human cells

How is HIV a retrovirus?

The virus uses an RNA genome to direct the synthesis of a DNA intermediate

Explain why viruses have the most complex mechanisms for subverting the human immune response as opposed to other pathogens such as bacteria, viruses, or parasites

Their replication and life cycle is completely dependent on metabolic and biosynthetic processes of the human cell, other pathogens are not as dependent

On the molecular level, what is happening in leukocyte adhesion deficiency?

There is a mutation in CD18 that makes it defective, CD18 is composed of CR3, CR4, and LFA-1 that help the leukocyte leave the blood and enter infected tissue (cannot do if its missing those things). Also, CR3 and CR4 function to as complement receptors so macrophages cannot engulf bacteria opsonized with complement

Describe protective immunity

These are plasma cells that persist after a primary infection has passed that secrete antibodies in marrow or under mucosal tissue to protect against any subsequent infection for several months after infection

What are toxoids?

They are bacterial toxins, such as diphtheria and tetanus, that have been purified and inactivated by formalin. While these toxoids are inactivated, they still retain sufficient antigenic activity to provide protection against disease

What feature of neurons makes them the ideal host for latent herpesvirus?

They express little to no MHC Class I so the virus can hide itself from CD8 T cells that would otherwise kill the infected cell

Describe how strains of streptococcus pneumoniae escape memory of the immune response

They have different serotypes that relate to their polysaccharides. So, a person will make antibodies that are successful at resolving an infection with one type of S. pneumoniae strain. But, those antibodies will be useless against a primary infection of another type of S. pneumoniae (genetic variation)

A majority of plasma cells will not live past the primary infection such that a pathogen specific antibody will gradually decrease over a year to reach a low amount. How, then, are some plasma cells kept alive?

They interact with marrow stromal cells and IL-6 that is secreted by them

Describe how trypanosomes are able to evade the immune response

They regularly change their surface antigens by a process of gene rearrangement. These are referred to as the viral surface glycoproteins (VSGs). Since trypanosomes can only have one VSG at a time, they undergo gene conversion to excise a gene and replace it with a different but homologous gene.

What is the depot that is kept by mast cells?

This is just referring to how long-lived mast cells will retain a variety of different antigen-specific IgE with Fc-epsilon-RI on their Fc region. This provides mast cells with a diversity of antigen receptors such that it can quickly respond and unload inflammatory mediators if one of its receptors encounters its antigen again

Describe clinical latency as it relates to HIV

This is the initial infection with HIV followed by an asymptomatic period that can last 2-15 years. During this time, without treatment, HIV persistently replicates in CD4 T cells to gradually decrease their numbers until it progresses to AIDS (too few CD4 T cells to fight off an infection)

True or False: An exploratory method immunologists and health professionals are using is introducing helminth worms into allergic individual's guts to dampen immune responses

True

True or False: In those diagnosed with AIDS, immunity mediated by CD4 Th1 cells is lost before the antibody or CD8 T response

True

True or False: It has been thought that most common allergens share structural features with helminth worms. An example of this would be papin looking like the cathepsin-beta-like cysteine protease of S. mansoni

True

True or False: NK are considered to be granular lymphocytes of the IIR with cytotoxins, like CD8 T cells, that is used to kill target cells

True

True or False: The reverse transcriptase of HIV means that mutations will arise such that an infection will produce many viral variants, known as quasi-species, that make HIV difficult to treat

True

True or False: While CMV is a common infection, it tends to maintain latency and is relatively harmless to healthy individuals. Defend your answer.

True CD8 T and NK cells will control CMV such that nothing is really happening. CMV gets to multiply and replicate comfortably within a host so long as it does not cause harm to its host

What type of sensitivity is a penicillin allergy?

Type II

What type of hypersensitivity falls under "delayed-type hypersensitivity"?

Type IV

What type of hypersensitivity is chronic asthma?

Type IV

How are naive T cells different than naive B cells in terms of a secondary immune response?

Unlike naive B cells, naive T cells are able to be activated in a secondary response. It is a minor response, of course

How does a pharmacological approach to dealing with allergic disease work?

Use different drugs to reduce the impact of any contact with allergen. They could prevent binding of IgE with its Fc-epsilon-RI and Fc-epsilon-RII receptors, prevent histamine binding, block effector pathways of allergic responses, or help to dilate the bronchioles to be able to breathe

Subunit vaccine

Vaccine containing only specific antigenic proteins of the infectious agent. This was seen in the HBV vaccine in that the viral particles are not involved and there was no contact with them. The surface antigen for HBV was actually grown in baker's yeast via its genome

Basophil

WBC containing granules that stain blue; associated with release of histamine and heparin

Hemolytic anemia of the newborn/hemolytic disease of the newborn

When a baby's RBCs break down at an extremely fast rate

Seroconversion

When an infected person first exhibits detectable levels of anti-HIV antibodies in their blood serum

Angioedema

When mast cells in deeper subcutaneous tissue leads to a more diffuse swelling

What disease, more common in males, is defined by a defect in SH2D1A such that NK and EBV specific T cells are unable to control an EBV infection, sometimes progressing to lymphoma?

X-linked lymphoproliferative syndrome

On which cells is it possible to find Fc-epsilon-RII? Select all that apply. a. monocytes b. macrophages c. B cells d. T cells e. plasma cells f. follicular DC g. bone marrow stromal cells h. NK cells

a, c, d, f, and g

Which of the following best describes the outcome of patients that have been treated with anti IL-5 antibody for years in an attempt to relieve symptoms associated with allergy? a. No adverse side effects have been noted. This supports the theory that the TH2 response is aimed at helminths b. A few side effects, such as low-grade fevers and respiratory distress, were common. This has alerted scientists they may not fully understand the functions of IL-4, IL-5, and IL-13 c. Since it has been such a short period of time, only 6 years, scientists have not been able to come to a firm conclusion. More information may be necessary d. An increased amount of immune complexes and tissue damage have occurred. This may relate to the importance of IL-5 in helping erythrocytes bind and carry complexes to macrophages for phagocytosis

a. No adverse side effects have been noted. This supports the theory that the TH2 response is aimed at helminths

The vulnerability of AIDS patients to any and all opportunistic pathogens resembles.... a. children with inherited SCID b. athymic individuals c. X-linked agammaglobulinemia d. persistent pyogenic bacterial infections

a. children with inherited SCID

While basophils tend to resemble ____a_____, they are developmentally more similar to _____b____.

a. mast cells b. eosinophils

Immune system genes that can be lost with no drastic effect on immune function are members of _____________ _____________where something else can compensate for it. a. multigene families b. poly genes c. heterozygous genes d. gene clusters

a. multigene families

Which of the following accounts for up to 100 fatalities a year due to a systemic anaphylactic shock? a. penicillin b. tree nuts c. nickel d. cadmium

a. penicillin

Central memory T (TCM) cells are found ____________ while effector memory (TEM) cells are found _________. a. secondary lymphoid tissues; non-lymphoid tissues such as mucosal and inflamed tissues b. non-lymphoid tissues such as mucosal and inflamed tissues; secondary lymphoid tissues c. primary lymphoid tissues; secondary lymphoid tissues d. secondary lymphoid tissues; primary lymphoid tissues

a. secondary lymphoid tissues; non-lymphoid tissues such as mucosal and inflamed tissues

Primary immunodeficiency disease

any of a group of diseases detectable near birth and resulting from a genetic or developmental defect

With the collapse of CD8 T cells in AIDS patients, which of the following pathogens is likely to establish an infection? Select all that apply. a. Staphylococcus aureus b. Latent herpesviruses such as varicella zooster, Kaposi's sarcoma, and B-cell lymphoma via EBV c. Mycobacterium avium d. Treponema pallidum e. Pneumocystis jirovecii

b, c, and e

A good N. meningitis vaccine was made when... a. Scientists sequenced the bacteria's genome, leading to synthesis of a peptide B cells can recognize without growing large batches of the vaccine b. A conjugate vaccine was made that conjugated the bacterial polysaccharide with either a diphtheria or tetanus toxoid, allowing for a CD4 T response c. A live attenuated bacteria was made, similar to what happens with viruses. This ensured the bacteria was not successful in infecting human cells but good enough to stimulate an immune response d. Neutralizing antibodies were created for this bacteria. It was able to successful coat the sites on the bacteria that bind to a host cell and prevented it from binding

b. A conjugate vaccine was made that conjugated the bacterial polysaccharide with either a diphtheria or tetanus toxoid, allowing for a CD4 T response

The absence of ________ and ________ leads to an accumulation of nucleotide metabolites that are toxic to developing T and B cells a. AID; PNP b. ADA; PNP c. ATP; PIC d. SCID; AID

b. ADA; PNP

What genus does HIV belong to? a. Orthomyxoviruses b. Lentiviruses c. Picornaviruses d. Reoviruses

b. Lentiviruses

Which of the following would be another function of NK cells aside from killing virally infected cells? a. Functions as a bridge between the innate and adaptive immune response. It carries peptides to present to the T cells b. Uterine NK cells, found in the uterus, play an important role during pregnancy to remodel the maternal placenta to help the fetus c. In anemic individuals, they can also be given an infusion of NK cells. While not their normal function, NK cells can communicate with RBCs for their proliferation and survival d. Via a special receptor on their surface, individual NK cells are able to join with neighbors in the face of an infection to form a NK wall to block a large pathogen from escaping

b. Uterine NK cells, found in the uterus, play an important role during pregnancy to remodel the maternal placenta to help the fetus

This type of molecule has similar activities to histamine but is about 100 times more potent. a. serglycan b. leukotrienes c. prostaglandin d. perforin

b. leukotrienes

C3 defects lead to ____________ while defects in C5-C9 relate to the _____________________, having fewer effects. a. deficiency in the membrane attack complex; complement problems b. susceptibility to pyogenic bacterial infections; membrane attack complex d. susceptibility to pyogenic bacterial infections; complement problems e. attack by obligate intracellular parasites; interferon receptor

b. susceptibility to pyogenic bacterial infections; membrane attack complex

_____________ are the least common WBC, only comprising about 1% of the total count in the body

basophils

The process herpesvirus utilizes to hide itself from the immune response is best described as a. Stealing MHC Class I and II molecules off of cells, disguising itself as a normal cell to confuse the immune system b. Hide in a cell and decrease the amount of MHC molecules mounted on the infected cell so lymphocytes cannot recognize the cell as infected c. Enter in epithelial cells and travel into neural cells into a state of latency until something triggers it to a productive infection d. Lodge itself beneath the mucosal tissue, out of the reach of any lymphocytes that could clear it.

c. Enter in epithelial cells and travel into neural cells into a state of latency until something triggers it to a productive infection

Which of the following answer choices describes why people will succumb to AIDS? a. HIV continues to rapidly replicate in CD4 T cells until no more are left in the body, killing the patient b. A mutated version of HIV arises that is able to attack neural cells, leading to massive neurological damage that kills the patient c. The depletion of CD4 T cells leaves an individual vulnerable to opportunistic pathogens, AIDS individuals tend to die from infections with bacteria most people can fight off d. HIV will acquire the ability to infect and replicate in neutrophils. It changes the behavior of neutrophils such that they cannot enter sites of infection. AIDS individuals die from persistent pyogenic bacteria infections

c. The depletion of CD4 T cells leaves an individual vulnerable to opportunistic pathogens, AIDS individuals tend to die from infections with bacteria most people can fight off

While both _______ and ________ cells will be made at the beginning of an infection, the body switches to _______ cells once the primary infection has cleared a. memory, helper; helper b. memory, effector; helper c. memory, effector; memory d. helper, plasma; memory

c. memory, effector; memory

Which of the following statements is most correct concerning the after effects of CD8 T cells clearing an EBV infection? a. CD8 T cells successfully eliminate the virus such that none remains in the body. The host does not have to worry about another infection b. CD8 T cells differentiate into memory T cells to survive as a depository in case EBV infects again c. EBV still remains, latently, within B cells by only allowing EBNA-1 to continue synthesis. This virus is subject to many different triggers for an active infection, affecting both healthy and immunocompromised individuals d. EBV still remains, latently, within B cells by only allowing EBNA-1 to continue synthesis. Healthy individuals tend to not get another EBV infection

d. EBV still remains, latently, within B cells by only allowing EBNA-1 to continue synthesis. Healthy individuals tend to not get another EBV infection

HIV variants that use the CCR5 co-receptor are called ___________ tropic while those that use the CXCR4 co-receptor are __________ tropic. The latter of which relates to activated CD4 T cells

macrophage; lymphocyte note: being "macrophage-tropic" does not mean it only binds to macrophages (also DC and and CD4 T cells)

While naive T cells express the CD45 isotype of _________, memory T cells tend to express the CD45 isotype of ______. Explain how these isotypes differ from each other

naive T are known for making the CD45RA while memory T make CD45RO isotype. They are different in that the RA isotype does not function so well with the T cell receptor, transducing a weak signal when the T-cell receptor recognizes a signal. On the other hand, the RO isotype has a smaller EC domain that interacts well with the T cell complex to transduce strong signals when the receptor recognizes an antigen

How is the cysteine protease of D. pteronymssimus responsible for about 20% of allergies in N. America? Explain how it moves and what it is thought to be related to.

-Heating and cooling systems in office and home spaces help it grow and spread its fecal matter. Additionally, the air currents from forced air, air conditioners, and vacuum cleaners help to move the particles in the air. -Similar to the cysteine protease papain from papaya fruit that is used as a meat tenderizer for cooking

How do memory B and T cells form the primary focus and germinal center during proliferation?

-Memory B cells have bound antigen on an MHC Class II molecule that was internalized by endocytosis. In the lymph node, they present this to the cognate pair of T_fh cells. Both will get signals to survive and proliferate. Competition and B cells with highest affinity will develop immediately into plasma body secreting cells -Other cells will move back to the primary follicle to form a germinal center. In the germinal center, the memory B cells will be induced to undergo further somatic hypermutation and isotype switching for affinity maturation

How do Tat and Rev contribute to the replication of HIV's genome?

-Tat binds to LTR of the viral mRNA, known as TAR, to prevent genome synthesis from being turned off and increasing transcript of viral RNA -Rev controls viral RNA supply to cytoplasm and extent that RNA is spliced.

IgG and IgE are noted to derive from a common ancestor. What are some features of IgE that distinguish it from IgG?

1. Concentrated in tissues to bind to Fc-epsilon-RI on mast cell (cross-linking) 2. Has a shrimp like structure that has a high affinity for its receptor in the absence of antigen and puts it in an advantageous position to capture antigens from mast cell surface

What three factors are thought to account for the death of a CD4 T cell that is infected with HIV within a few days?

1. Direct killing due to viral infection or virions binding to cell surface receptors 2. Increased susceptibility of cells to apoptosis 3. Mediated killing by CD8 T cells due to presentation of viral peptides on MHC Class I molecules

Describe the two ways that plasma cells will die

1. Does not contact stromal cells and get the survival signals from them 2. Complex of antigen-antibody will bind to FC(gamma)RIIB1 to induce apoptosis

The book mentions that vaccine development faces larger public scrutiny than drug development. Explain why this is so.

1. Drugs are given to a wide variety of people that are suffering from a disease or illness. In contract, vaccines are usually given to young and relatively healthy individuals-adverse effects may concern their parents 2. Drugs are prescribed based on what kind of illness you have while vaccines are mandatory and applied indiscriminately to the population as a whole 3. People are able to see the effects a good drug has, such as relieving their symptoms or curing their illness. Vaccines, on the other hand, may or may be responsible for an individual not getting a disease. For polio, it is difficult to determine if you didn't get it bc of vaccine protection or because you just weren't exposed

Describe the journey of herpesvirus from its initial infection, latency, and the trigger out of latency (where does it go)

1. Herpesvirus infects epithelial cells to cause the characteristic cold sores 2. Spreads to sensory neurons serving the area of infection, goes into latency in the host cell 3. Virus is reactivated, travels down axons of neural cells and back into initial infection site in epithelial cells to cause another cold sore bout

How does IL-12 work in the innate immune response? Think in terms of neutrophils and macrophages

1. Macrophages will secrete IL-12 that binds to the IL-12 receptor on neutrophils. 2. In turn, neutrophils will then secrete IFN-gamma that binds to macrophages, activating phagocytosis and proinflammatory cytokine secretion.

What are some challenges the body faces when trying to get rid of a helminth infection?

1. They are more closely related to their human host in comparison to fungi, bacteria, and protozoa 2. Less antigenic and the antigens that do produce an immune response have counterparts in humans 3. Too large to be phagocytosed by phagocytic cells

Viremic controllers

2000 or less copies of viral RNA/mL of blood

What is the difference between a dominant effective allele and a recessive defective allele in regards to immunodeficiencies?

A dominant effective allele means the deficiency will be present in children with one healthy allele but a recessive defective allele means children need to have two defective alleles for the syndrome to appear

Live attenuated vaccine

A live type of virus that has been selected such that it grows rather poorly in human cells and is not pathogenic. They are able to replicate and infect cells to a certain extent, mimicking a real infection.

How does desensitization-a component of the immunological treatment of allergy-work?

A patient is given increasing amounts of the allergen, injections, over a course of time. This is supposed to shift the response from one mediated by IgE to one mediated by IgG4. Since IgG4 is monovalent, it forms immune complexes with the antigen but does not recruit the effector cells

What is a conjugate vaccine and why do we make them?

A vaccine by which different epitopes that are recognized by B and T cells are synthetically linked together. It is needed because, while B cells can recognize things such as polysaccharides, CD4 TFH cells cannot so an effective B cell response is not made. TFH cells are needed to stimulate B cells to make higher affinity IgG responses

Allergic Conjunctivitis

Affects conjunctiva of eye, same allergen as from rhinitis. Itchiness, tears, and inflammation are common

Chronic asthma

Airways are almost always filled with mucus plugs. Hyperreactivity in the airways develops as environmental factors such as smoke and sulfur dioxide can trigger asthma attacks.

Allergic rhinitis

Aka hay fever, it is caused by the diffusion of allergens across the mucosal membrane of the nasal passages to activate mast cells beneath nasal epithelium

Elite controllers

An HIV infected individual who is able to maintain a low/undetectable level of HIV in their blood without the help of drugs

Eosinophila

An abnormally high number of eosinophils. Patients can suffer damage of endocardium to the heart and nerves that leads to heart failure and neuropathy.

What occurs when histamine binds to the H1 receptor?

An acute allergic reaction that induces vessel permeability and entry of cells/molecules into allergen-containing tissue for inflammation. Airway constriction occurs as mucosal epithelia increase mucosal secretion

What is necessary to resolve an acute Hepatitis C Virus (HCV) infection?

An early acting and robust innate immune response (production of type I interferon, IFN-gamma) and followed by a forceful and adaptive immune response. The AIR involves strong CD4 and CD8 T-cell responses and neutralizing antibodies to prevent the virus from infecting hepatocytes

Adjuvant

Assists the toll-like receptors and other receptors of the innate immune response with recognizing macromolecules of microbial pathogens. Inflammation caused is necessary to react against antigens in vaccine

Generally speaking, how is susceptibility to asthma different than inherited immunodeficiency disorders?

Asthma is caused by a variety of different polymorphisms of different genes that contribute to the adaptive immune response

Superantigens

Bind directly to MHCII on professional APC and T-cell receptor simultaneously, activating large numbers of T-cells to stimulate release of IFN-gamma, IL-2, and TNF-alpha

What is the purpose of IFN-gamma (think in terms of macrophages)?

Binds to IFN-gamma receptors on macrophages to induce the cell to make changes in gene expression and become better at phagocytosing and destroying bacteria

The deletion of CCR5, one of the co-receptors for HIV, means that an individual cannot be infected with HIV. It appears to be found at the highest frequency within white populations. What is the proposed reasoning from this bias?

Both plague and smallpox that ravaged Europe in the past pushed the CCR5 co-receptor into deletion as a selective advantage

What happens in X-linked agammaglobulinemia?

Bruton's tyrosine kinase, which contributes to intracellular signaling and development of pre-B cells, is defective. Males do not produce functional B cells

Which chemokine is the eotaxin?

CCL11

What allows effector memory T cells to enter non-lymphoid tissue and swiftly respond to an infection at its site of origin?

CCR3, CCR4, CCR5, and CCR6

When trying to determine if we are looking at a memory T cell, what receptors will distinguish it from a naive T cells?

CD45RA, CD45RO, L-selectin, and CCR7

What kinds of T cells are represented by effector memory T cells (TEM)?

CD8, TH1, TH2, and TH17

Secondary immunodeficiency disease

Come from environmental factors such as immunosuppressant drugs that adversely impact the immune system

What receptor does EBV use on B cells to get in?

Complement Receptor 2 (CR2)

Explain how a fetus can be armed with the knowledge of defense against a helminth parasite in the womb

Complex of IgE + antigen is not able to cross the placenta but could be found in the amniotic fluid which the fetus uses for nutrients. Thus, the complex could pass to the child and bind to macrophage and Fc-epsilon-RII to give to CD4 T cells-->make IgE with same specificity

Which type of mast cell is present in T cell deficiencies? What does this indicate?

Connective mast cells Tells us that mucosal mast cell development depends on the presence of effector T cells in mucosal tissue

Immune-complex disease

Deficiencies in C1-C4 that impair formation of C3b and C4b. Complexes accumulate and damage tissues they settle in as well as cause lots of inflammation/more damage as phagocytes are activated by the complexes

Original antigenic sin

Describes how the immune response is now limited in response due to the first exposure with a virus. An example of this is influenza. Any exposure after the first one is limited because the immune system cannot activate any naive B cells that would be able to respond to different epitopes of the virus. Thus, this cycle can only be broken when an entirely new strain of influenza that lacks all previous B cell epitopes is encountered, thus freeing the naive B cells to make antibodies

Systemic anaphylaxis

Disseminated mast cell activation causes an increase in vascular permeability and widespread contraction of smooth muscle

Antigenic drift

Explains how influenza is an RNA virus that tends to make a lot of mistakes during RNA replication. This causes differences in the neuraminidase and hemagglutinin such that there are some epitopes that the immune response does not recognize. This is relatively mild and only leads to limited disease epidemics

True or False: It is possible for both Fc-epsilon-RI and Fc-epsilon-RII to bind to the same IgE Fc region.

False The conformation for each receptor does not permit binding for the other receptor

Sheddases

Family of proteins that enable cells to shed soluble forms of membrane proteins (ADAM10 is an example)

Is Fc-epsilon-RI or Fc-epsilon-RII (CD23) considered to be the low affinity receptor?

Fc-epsilon-RII (CD23)

Anaphylactic shock

Fluid leaves the blood, causing blood pressure to rapidly drop. Swelling of tissues will also occur such that organ damage as well as airway constriction occur

Provirus

For HIV, it is viral DNA that inserts into a host genome. It is flanked by long terminal repeats and utilizes host cell machinery to assemble its virions

How does human cytomegalovirus (CMV) prevent both a CD8 and NK response from being made against it?

For the CD8, it stops the presentation of its antigens on MHC Class I molecules by either degrading, interfering with proteasome, affecting TAP or tapasin, or retaining MHC Class I in ER. To stop the NK response, CMV uses saboteurs to interfere with inhibitory NK receptors that would sense missing MHC Class I molecules and activating NKG2D receptor

For pathogens like Trypansome brucei, the protozoan parasite the causes malaria, S. typhimrium, and N. gonorrhea, all use processes of gene conversion to successful evade the grasp of the human immune system. Why is this process so successful?

Gene conversion ensures that a different kind/form of something, whether it be surface antigens, pili, or flagella, can be expressed on the pathogen. Since the body can only make antibodies that respond to the dominant or most prominent one, this leads to a quasi-natural selection process. Even though the body will succeed in clearing the dominant variant, the recessive ones will survive to take its place. This leads to a seemingly never-ending cycle of pathogen vs. antibody as both try to outwit each other.

Name some foods that commonly cause food allergies

Grains, nuts, fruits, legumes, fish, shellfish, eggs, and milk

Although HAART can significantly reduce viral load, it will never be able to completely eliminate the virus from an HIV-positive individual. Explain why this is.

HAART gets active and naive CD4 T cells to stop producing virus, thus greatly decreasing the amount present in the blood. But, the virus will continue to persist on in macrophages, dendritic cells, and memory CD4 T cells

What allotypes have proven to slow down the progression of HIV to AIDS?

HLA-B*27 and HLA-B*57

Name the three types of herpesvirus that cause persistent infections that were listed in the book

Herpes simplex virus (I and II), Herpesvirus varicella-zooster, and Epstein Barr Virus (EBV)

Describe how Edward Jenner's vaccinia vaccine developed in the 19th century compared to variolation

His vaccine used the related cowpox virus to vaccinate individuals against smallpox. While it caused mild infections in people, the immunity provided protected against both smallpox and cowpox as their antigens are similar. It completely replaced variolation in the 20th century and was responsible for the eradication

What is contained in the granules of mast cells?

Histamine, heparin, TNF-alpha, chondroitin sulfate, neutral proteases, and other degradative enzymes/inflammatory mediators

Resident macrophages are responsible for secreting the cytokine _________ to recruit NK cells to an infection site

IL-12

What Th2 cytokines do basophils secrete at the beginning of an immune response?

IL-4 and IL-13

Describe a type II hypersensitivity

IgG responds to chemically reactive small molecules that are covalently bound to the outside cell surface. A chemical reaction will modify the structure of the human cell components such that it is now perceived as foreign. Penicillin is an example

What is the order of class switching from IgM to IgG isotypes?

IgG3>IgG1>IgG2>IgG4

IgM likes to class switch to IgG isotypes in a specific order. Which IgG isotype would you expect to see with the most mutations and, therefore, the most specificity to an antigen?

IgG4

In a secondary immune response, how are naive pathogen-specific B cells suppressed/stopped from activating?

Immune complexes composed of pathogen or its antigens bound to antibodies made by the B cells activated in the primary response. The complexes will bind to the B cell receptor of pathogen specific naive B cells and FC(gamma)RIIB1-only on naive B cells. Cross-linking of B cell receptor and Fc receptor give negative signals to inhibit naive B activation + induce apoptosis

Describe a type III hypersensitivity

Immune complexes of antigen and IgG deposit in the blood vessel walls or alveoli. Inflammation ensues to damage the tissue and impairs function. Bovine insulin and non-human antibodies are an example

Carrier

Individual who carries one normal allele and one defective allele.

Exogenous retroviruses

Infectious RNA or DNA viruses that are transmitted from one organism to another

Atopic dermatitis (Eczema)

Inflammatory response that causes chronic and itching skin rash with associated skin eruptions and fluid discharge. The response is similar to what occurs in the bronchial walls of asthmatics

Name some things that can cause anaphylaxis

Insect bites/stings, drug injections, and food like peanuts and brazil nuts

What is the job of ADAM10?

It can cleave the CD23/Fc-epsilon-RII receptor into a monomeric or trimeric form (both soluble)

Describe the mechanism by which a superantigen will be able to fully activate a CD4 response

It first binds to the MHC Class II molecule, next it binds to a variable domain on a CD4 T cell, and a third binding occurs on the T cell's CD28 co-stimulatory receptor. This means the superantigen substitutes for a specific antigenic peptide and fully activates the T cell

While the Sabin vaccine proved instrumental in eliminating polio in the US, it was found to induce polio and paralysis at a rate of about 3 people per million. Why did this occur and what was done about this?

It had to do with strain 3 in that a back mutation at one of the positions was sufficient enough for it to revert and become pathogenic again. To stop this from occurring, an inactivated polio vaccine (IPV) can be used first and followed by TVOP as a second immunization. This way, antibodies can be made against strain 3 to prevent any infection

Explain how DTP, a combination vaccine, works

It has the diphtheria toxoid, tetanus toxoid, and an inactivated B. pertussis bacteria. The adjuvant, the bacteria, helps to both trigger the innate immune response and also provide antigens that will stimulate an adaptive immune response against B. pertussis. Inflammation produces strong adaptive immune responses made against the toxoids

Summarize how an infant can be born with hemolytic anemia of the newborn or hemolytic disease.

It has to do with Rhesus D or RhD. If a mother is RhD-, it can become a problem if the father of her baby is RhD+ because the baby will be RhD+ as well. For the first pregnancy, it's okay because the low affinity IgM made against the fetus' RBCs cannot cross the placenta nor harm the fetus. For a second pregnancy, it is an issue because high affinity IgG that can cross the placenta will lyse the RBCs of the fetus. Unfortunately, this can lead to severe anemia when the fetus is born

How does highly active anti-retroviral therapy (HAART) work?

It is a combination therapy that prevents formation of provirus and establishing any infection. This treatment cannot stop virus production from cells that have already been infected.

How does Listeria monocytogenes evade the immune system?

It is able to escape the phagosome and go into the macrophage's cytosol. This, however, triggers CD8 T cells that will clear the infected cell

How does RhoGAM work?

It is an IgG antibody that will coats the RBCs when they cross the placenta. So, the RhD specific naive B cells from the mother are prevented from being activated. Essentially, it is treated as a secondary exposure over a first exposure

Why is a new influenza vaccine needed each year?

It is an RNA virus that frequently makes mistakes during replication, thus leading to mutations. This changes surface glycoproteins that would be neutralized by antibodies, such as neuraminidase and hemagglutinin. Thus, the virus has been allowed to evade the immunological memory of human immunity

What is the importance of the common gamma chain and what is the result of it is defective?

It is part of a signaling chain for the cell surface receptors for IL-2, IL-4, IL-5, IL-7, and IL-15. None of the five cytokines can induce intracellular signaling without the common gamma chain SCID is the ultimate result

What reasoning has been proposed on why bacterial superantigens found on S. aureus aim to activate a CD4 T cell response? Wouldn't this just get rid of the pathogen and benefit the host?

It is thought that this response may be confusing to the innate immune system. The massive amount of cytokines poured out by CD4 T cells means that neutrophils and macrophages have difficulty trying to phagocytose bacteria that have crossed the mucosa. Essentially, an AIR is made before an IIR

In the immune response, describe how IgG4 is different from other isotypes

It is unable to fix complement and tends to be bound by the inhibitory receptor of Fc-gamma-RIIB1. Thus, it more commonly produces immune complexes via cross-linking. If it is bound to the same immune complex as IgG1, it can actually decrease the immune response that IgG1 is triggering

Why is more difficult to make a good vaccine for chronic infections?

It is unclear what kind of immune response would be effective if activated by a vaccine (i.e. innate or adapative)

What is the vaccine given for smallpox? Is it the actual smallpox virus?

It's called the vaccinia virus and no, it is not the actual smallpox virus. The vaccinia virus is made from a close relative of smallpox

What components allow central memory T, like effector T, to enter secondary lymphoid tissue?

L-selectin and CCR7

What responses are made from leukotrienes and prostaglandin (PD2)?

Leukotrienes are for inflammation, smooth muscle contraction, air constriction, and mucus secretion. For prostaglandin, it functions to promote dilation, increase permeability of blood vessels, and act as a chemoattractant for neutrophils

What genes relating to asthma are involved with the function and production of antigen-specific IgE? (there are six)

MHC Class II, T-cell receptor alpha chain, IL-4, IL-4 receptor, TIM proteins, and Fc-epsilon-RI

Is an MHC Class II or MHC Class I more detrimental to individuals? Explain your answer

MHC class II is more detrimental This is because absence of MHC Class II means that CD4 T cells fail to develop properly and CD4 are integral to most aspects of the AIR. MHC Class I problem isn't as bad as it only hurts CD8T cells + cytotoxic responses

How do MIC glycoproteins work?

MIC-A and MIC-B are two types of activating signals found on distressed or damaged cells. NK cells have a receptor on their surface for MIC. When a MIC glycoprotein on a damaged cell engages with an NK receptor, this activates an NK cell to activate its cytotoxicity to get rid of the damaged cell

Describe how the lymphocyte tropic and macrophage tropic types of HIV relate to the disease as a whole.

Macrophage tropic variants are responsible for causing the disease, infecting macrophages and DCs at first, but the virus will switch to lymphocyte tropic to infect and greatly decrease CD4 T cells numbers. Also, it is the lymphocyte tropic variants that are responsible for both AIDS progression and its pandemic

Why does neutropenia, or the absence of neutrophils, occur in patients diagnosed with X-linked hyper IgM syndrome?

Macrophages cannot produce GM-CSF that helps to develop neutrophils in the marrow and release into the bloodstream. Therefore, individuals have lots of sores and blisters in mouth/throat areas as neutrophils are not patrolling mucosal tissue

What is another protozoan parasite that, similar to trypanosomes, will vary its surface antigens to escape the immune response (hint, it is a huge problem in Africa)?

Malaria (Plasmodium protozoan)

X-linked hyper IgM syndrome

Manifests due to the absence of a CD40 ligand on T cells that would induce B cells to undergo isotype switching. Patients are susceptible to pyogenic bacterial infections

Describe the process by which mast cells, eosinophils, and basophils work together in an immune response

Mast cells will initiate the immune response to recruit eosinophils and basophils. When eosinophils are degraunulated, they release the major basic protein to activate/degranulate mast cells and basophils. Then, cytokines like IL-3, IL-5, and GM-CSF influence baso + eosinophils growth and proliferation

Describe a type IV hypersensitivity

Mediated by antigen-specific effector T cells (CD4 TH1 T cells, specifically). Nickel allergy from belts/jewelry/coins and poison ivy response (CD8 T) are examples.