final exam new material

Microbes that infect the cells can cause either the death of the cell or they can induce a change in the morphology of the infected cells. This is called the

"cytopathic effect"

Treatments for myasthenia gravis include plasmapheresis, IVIG and monoclonal antibody therapy: Plasmapheresis uses a filtering process similar to dialysis, the blood is routed through a machine that removes the antibodies from it. IVIG provides the body with normal antibodies. Monoclonal antibody Rituximab (Rituxan) given intravenously depletes B cells. Taking into account this information: How long will the benefits of plasmapheresis last?

A month

These antibodies can either activate complement, resulting in an inflammatory response and lysis of the targeted cells, or they can be involved in antibody-dependent cell-mediated cytotoxicity (____) with cytotoxic T cells

ADCC

A patient suffers muscle loss due to an infection with a virus. The virus infects the muscle cells but remains mostly dormant, only producing some small amount of a capsid protein that remains in the cytoplasm of the cell. Immune cells are activated, among them specific cytotoxic T cells. This could be an example of pathogen-induced damage mediated by :

CD8 T cells

Which of the following is a best match for a strategy that is NOT used by some microbes to escape the adaptive immunity?

Carrying efficient iron transporter complexes

Which of the following is NOT a strategy that microbes use to avoid inflammation?

Carrying genetic information to induce NFKbeta activation

Which of the following immunosuppressive drugs have the broadest effect?

Corticosteroids

Which of the following explains why Streptococcus pneumoniae can infect an individual recurrently?

Immune responses against S. pneumoniae are serotype-specific and protect only against strains that possess the same capsular polysaccharide antigens.

Which of the following strategies is/are used by bacteria to avoid being killed by phagocytes?

Impaired fusion of lysosomes with phagosomes

is hostile to intracellular bacteria, often relying on the production of nitric oxide to kill the bacteria inside the macrophage

Macrophage oxidative metabolism

Which of the following best matches hyperacute rejection?

Preformed antibodies attack the vessels of the graft

Which of the following statements is correct?

Signals 1, 2 and 3 are all possible targets for anti-rejection drugs

Which of the following statements is correct?

Treg are created both in primary lymphoid organs and in the periphery

this defect is inherited on the ___ chromosome and is characterized by the absence of immunoglobulin in the serum; it is called Bruton X-linked agammaglobulinemia (XLA). The defective gene, BTK, in XLA is now known to encode a tyrosine kinase called Bruton tyrosine kinase (Btk)

X

​Deficiencies in B cells due to defective differentiation lead to a lack of specific antibody production known as

X-linked agammaglobulinemia

If autoreactive T cells are in the periphery, microbes can generate autoimmunity

by inducing signal 2 in APCs carrying self-antigens

The adaptive immune response is based on the mechanism of ______ _________

clonal selection

The action of the immune system against intracellular pathogens can also cause be ________, in particular when the infected cells can not be replaced. For example, if infected neurons are killed by cytotoxic T cells, this immune response can create irreparable damage to the host

deleterious

_______ damage is the damage to our tissues caused by the action of the pathogens on our cells. This damage can be mediated by toxins or caused by the infection of the cells by the pathogens

direct

Pathogens can induce damage to our bodies in two main different ways?

direct damage or indirect damage

One strategy favored by some pathogens, in particular RNA viruses, is to have higher mutation rates. That determines that within the viral progeny there will be variants that will express new antigens and therefore, the immune response against the parental strain will not be effective against them. An example of this is influenza viruses. These viruses accumulate mutations constantly from one season to another. This process of generation limited mutations is named antigenic _______. This typically involves point mutations affecting the proteins of the viral capsid (i.e., hemagglutinin). In this case, the host retains some degree of protection from a previous infection or a vaccine

drift

infections that are not resolved (_____) can lead to chronic inflammation. Constant activation of macrophages and PMN with their production of reactive oxygen species can harm the tissues.

eliminated

are intrinsic components of the microbes. They get released when the microbe is damaged or killed

endotoxins

Late-phase reactions in type I hypersensitivities may develop 4-12 hours after the early phase and are mediated by

eosinophils, neutrophils, and lymphocytes that have been recruited by chemotactic factors released from mast cells.

Toxins are products of microbes that are either exported outside the microbe as soluble molecules (______) or are part of the microbial structure (endotoxin). To act, the toxins need to interact with a cell receptor. Toxins can induce the death of the cell that harbors the receptor (cytotoxic effect) or they can activate an inflammatory response

exotoxins

Patients who lack antibody production suffer from recurrent infections almost exclusively due to ______ pathogens that cause pyogenic infections

extracellular

When immunocompetent T cells are transplanted into a tissue incompatible immunodeficient recipient:

graft vs host disease happens

Preformed components that are released from granules include

histamine, serotonin, and bradykinin

The _____ theory is the idea that the immune system is geared to respond to antigens, and if pathogens are not present, it will respond instead to inappropriate antigens such as allergens and self-antigens. This is one explanation for the rising incidence of allergies in developed countries, where the response to non-pathogens like pollen, shrimp, and cat dander causes allergic responses while not serving any protective function.

hygiene

Type I ________ reactions involve immunoglobulin E (IgE) antibody against a soluble antigen, triggering mast cell degranulation

hypersensitivity

Type II ______ reactions involve IgG and IgM antibodies directed against cellular antigens, leading to cell damage mediated by other immune system effectors

hypersensitivity

Type III ______ reactions involve the interactions of IgG, IgM, and, occasionally, IgA antibodies with antigen to form immune complexes. Accumulation of immune complexes in tissue leads to tissue damage mediated by other immune system effectors

hypersensitivity

Type IV _______ reactions are T-cell-mediated reactions that can involve tissue damage mediated by activated macrophages and cytotoxic T cells

hypersensitivity

IgM antibodies in plasma that cross-react with blood group antigens not present on an individual's RBCs are called

isohemagglutinins

In these types of deficiency, ______ have genetic defects in the expression of adhesion molecules which prevent them from interacting with endothelial cells and therefore extravasating towards sites of infection, among other issues

leukocytes

The activated mast cells also release newly formed lipid mediators

leukotrienes and prostaglandins from membrane arachidonic acid metabolism

is adaptive immunity that develops after natural exposure to a pathogen (Figure 15.1). Examples would include the lifelong immunity that develops after recovery from a chickenpox or measles infection (although an acute infection is not always necessary to activate adaptive immunity). The length of time that an individual is protected can vary substantially depending upon the pathogen and antigens involved. For example, activation of adaptive immunity by protein spike structures during an intracellular viral infection can activate lifelong immunity, whereas activation by carbohydrate capsule antigens during an extracellular bacterial infection may activate shorter-term immunity.

natural active immunity

Antibodies generated by the individual against influenza virus __.

protect by targeting the viral hemagglutinin.

occurs as a result of an acquired impairment of the function of B cells, T cells, or both. Secondary immunodeficiencies can be caused by

secondary immunodeficiency

When following antibody responses in patients with a particular disease such as a virus, the clearance of the microbe is referred to as ________ (sero = "serum"). Thus, seroconversion is the reciprocal relationship between virus levels in the blood and antibody levels. As the antibody levels rise, the virus levels decline, and this is a sign that the immune response is being at least partially effective (partially, because, in many diseases, seroconversion does not necessarily mean a patient is getting well)

seroconversion

Some bacteria carry iron-binding molecules that compete with ______ for iron. This ion is an important factor for bacterial growth. Transferrin present in the lysosomes can capture it, thus preventing bacterial growth. Carrying robust systems to trap iron prevents the action of transferrin

transferrin

Treatments of type III hypersensitivities include preventing further exposure to the antigen and the use of anti-inflammatory drugs. In the case of autoantigens (e.g. DNA) avoidance is not possible. Some conditions can be resolved when exposure to the antigen is prevented. Anti-inflammatory corticosteroid inhalers can also be used to diminish inflammation to allow lung lesions to heal. Systemic corticosteroid treatment, oral or intravenous, is also common for type III hypersensitivities affecting body systems. Treatment of hypersensitivity pneumonitis includes avoiding the allergen, along with the possible addition of prescription steroids such as prednisone to reduce inflammation. Cyclophosphamide reduces B-cell proliferation and hence autoantibody levels and is often used in severe SLE

treatment

Allergy tends to run in families

true

The difference between type II and type III hypersensitivity is that the in type-II the antigen is associated with a large structure but in type III the antigen is soluble.

true

and cytokines such as

tumor necrosis factor

The tissue damage in autoimmunity can be mediated by:

type II or III hypersensitivities type IV

The chemical mediators released by mast cells collectively cause the inflammation and signs and symptoms associated with type I hypersensitivity reactions. Histamine stimulates mucus secretion in nasal passages and tear formation from lacrimal glands, promoting the runny nose and watery eyes of allergies. Interaction of histamine with nerve endings causes itching and sneezing. The ______ caused by several of the mediators can result in hives, headaches, angioedema (swelling that often affects the lips, throat, and tongue), and hypotension (low blood pressure)

vasodilation

Active infections treated by artificial passive immunity include cytomegalovirus infections in immunocompromised patients and Ebola virus infections. In 1995, eight patients in the Democratic Republic of the Congo with active Ebola infections were treated with blood transfusions from patients who were recovering from Ebola. Only one of the eight patients died (a 12.5% mortality rate), which was much lower than the expected 80% mortality rate for Ebola in untreated patients1. Artificial passive immunity is also used for the treatment of diseases caused by bacterial toxins, including tetanus, botulism, and diphtheria.

yes

Acute GVHD typically develops within weeks after a bone marrow transplant, causing tissue damage affecting the skin, gastrointestinal tract, liver, and eyes. Besides, acute GVHD may also lead to a cytokine storm, an unregulated secretion of cytokines that may be fatal. In addition to acute GVHD, there is also the risk for chronic GVHD developing months after the bone marrow transplant. The mechanisms responsible for chronic GVHD are not well understood.

yes

Another group of immunosuppressive drugs, such as cyclosporine and tacrolimus, do not kill lymphocytes but inhibit their activation.

yes

Autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis can also involve damaging type III hypersensitivity reactions when auto-antibodies form immune complexes with self-antigens.

yes

Corticosteroids are broad-spectrum anti-inflammatory agents used as immunosuppressive agents. Their many actions involve decreasing the production of inflammatory cytokines such as IL-1, and TNF by macrophages, decreasing the expression of adhesion molecules, with the consequent decrease in extravasation, and inducing the apoptosis of lymphocytes.

yes

Other immunosuppressant agents are classified as cytotoxic drugs. Examples of these compounds are azathioprine (AZA), cyclophosphamide, and mycophenolate. Collectively, these compounds interfere with DNA synthesis and their major pharmacological action is on actively dividing cells, such as lymphocytes, but will also affect other cells, particularly bone marrow cells, therefore inducing myelosuppression.

yes

The different types of grafts described above have varying risks for rejection (Table 20.1). Rejection occurs when the recipient's immune system recognizes the donor tissue as foreign (non-self), triggering an immune response. The major histocompatibility complex markers MHC I and MHC II, more specifically identified as human leukocyte antigens (HLAs), play a role in transplant rejection. The HLAs expressed in tissue transplanted from a genetically different individual or species may be recognized as non-self molecules by the host's dendritic cells. If this occurs, the dendritic cells will process and present the foreign HLAs to the host's helper T cells and cytotoxic T cells, thereby activating them. Cytotoxic T cells then target and kill the grafted cells through the same mechanism they use to kill virus-infected cells; helper T cells may also release cytokines that activate macrophages to kill graft cells.

yes

The most common cause of hypothyroidism in the United States is Hashimoto thyroiditis, also called chronic lymphocytic thyroiditis. Patients with Hashimoto thyroiditis often develop a spectrum of different diseases because they are more likely to develop additional autoimmune diseases such as Addison disease (discussed later in this section), type 1 diabetes, rheumatoid arthritis, and celiac disease. Hashimoto thyroiditis is a TH1 cell-mediated disease that occurs when the thyroid gland is attacked by cytotoxic lymphocytes, macrophages, and autoantibodies. This autoimmune response leads to numerous symptoms that include goiter (Figure 18.1), cold intolerance, muscle weakness, painful and stiff joints, depression, and memory loss.

yes

Whereas live attenuated and inactive vaccines expose an individual to a weakened or dead pathogen, subunit vaccines only expose the patient to the key antigens of a pathogen—not whole cells or viruses. Subunit vaccines can be produced either by chemically degrading a pathogen and isolating its key antigens or by producing the antigens through genetic engineering. Because these vaccines contain only the essential antigens of a pathogen, the risk of side effects is relatively low. Table 15.1. lists examples of subunit vaccines.

yes

Without treatment, this intense inflammatory reaction promotes the development of a pathologic tissue called pannus. Pannus is the abnormal growth of tissue engulfing the joint space and causing destruction itself. Cartilage becomes damaged in this process and periarticular bone suffers resorption, seen as erosions on radiographs. All these changes are responsible for the deformity and disability observed in RA patients.

yes

mRNA vaccine is a technology with a combination of molecular biology and immunology. The foreign mRNAs encoding antigens are introduced into the cells of the vaccinee where it is translated into proteins (antigens). These antigens can induce the immune response. As early as the year 1990, scientists used mRNA expression vectors to inject mRNAs into mouse cells in vivo to express luciferase, beta-galactosidase and chloramphenicol acetyltransferase.

yes

​A form of rejection called graft-versus-host disease (GVHD) primarily occurs in recipients of bone marrow transplants and peripheral blood stem cells. GVHD presents a unique situation because the transplanted tissue is capable of producing immune cells; APCs in the donated bone marrow may recognize the host cells as non-self, leading to activation of the donor cytotoxic T cells. Once activated, the donor's T cells attack the recipient cells, causing acute GVHD.

yes

​DNA vaccines represent a relatively new and promising approach to vaccination. A DNA vaccine is produced by incorporating genes for antigens into a recombinant plasmid vaccine. Introduction of the DNA vaccine into a patient leads to the uptake of the recombinant plasmid by some of the patient's cells, followed by transcription and translation of antigens and presentation of these antigens with MHC I to activate adaptive immunity. This results in the stimulation of both humoral and cellular immunity without the risk of active disease associated with live attenuated vaccines.

yes

______ cells, however, can recognize virally infected class I-negative cells and destroy them. Thus, NK and cytotoxic T cells have complementary activities against virally infected cells.

NK

involves the natural passage of antibodies from a mother to her child before and after birth. IgG is the only antibody class that can cross the placenta from mother's blood to the fetal blood supply. Placental transfer of IgG is an important passive immune defense for the infant, lasting up to six months after birth. Secretory IgA can also be transferred from mother to infant through breast milk.

Natural passive immunity

A principal mechanism of central tolerance is:

Negative selection of B cells in the bone marrow

The mode of evolution responsible for the production of recombinant influenza viruses that are highly pathogenic is named ___.

None of the above is correct had gene conversion, latency, immune evasion, antigenic drift, )

Which of the following is a characteristic of an effective vaccine?

Not needing to be kept at very low temperatures to avoid lose of efficacy

Crohn's disease is characterized in some patients by mutations in particular

PRR genes

The biphasic response observed in the context of type-I hypersensitivities is due to:

Rapid effect of preformed compounds followed by synthesis of new inflammatory compounds

Which of the following is NOT a CURRENT option for IgE allergy treatment, but rather a PROPOSED treatment?

Regulatory T cell depletion

The second most frequently described RBC antigens are

Rh factors

If an Rh− woman carries an Rh+ baby to term, the mother's immune system can be exposed to

Rh+ fetal red blood cells.

Which of the following is NOT an ORGAN-SPECIFIC autoimmune disease?

Rheumatoid Arthritis

Which of the following is an autoimmune disease characterized by being associated with both type III and type IV hypersensitivities?

Rheumatoid arthritis

To prevent Rh factor-mediated HDN, human Rho(D) immune globulin (e.g., ____) is injected intravenously or intramuscularly into the mother during the 28th week of pregnancy and within 72 hours after delivery

RhoGAM

The most common form is X-linked SCID, which accounts for nearly 50% of all cases and occurs primarily in males. Patients with _____ are typically diagnosed within the first few months of life after developing severe, often life-threatening, opportunistic infection

SCID

​Patients who suffer from severe combined immunodeficiency (____) have B-cell and T-cell defects that impair T-cell dependent antibody responses as well as cell-mediated immune responses

SCID

The first time that an individual is exposed to an allergen

Sensitization happens

Which of the following is NOT a IgE mediated allergic reaction?

Serum sickness

Splenectomy increases:

Susceptibility to encapsulated bacteria

Secondary immunodeficiencies can be caused by

Systemic disorders such as diabetes mellitus, malnutrition, hepatitis, or HIV infection Immunosuppressive treatments such as cytotoxic chemotherapy, bone marrow ablation before transplantation, or radiation therapy Prolonged critical illness due to infection, surgery, or trauma in the very young, elderly, or hospitalized patients Extensive burns, that will determine a loss of the skin barrier Splenectomy, removal of the spleen due to injury

​Austrian pediatrician Clemans von Pirquet (1874-1929) first described allergy mechanisms, including type III serum sickness.4 His interest led to the development of a test for tuberculosis (TB), using the tuberculin antigen, based on earlier work identifying the TB pathogen performed by Robert Koch. Pirquet's method involved scarification, which results in simultaneous multiple punctures, using a device with an array of needles to break the skin numerous times in a small area. The device Pirquet used was similar to the tine test device with four needles seen

TB test

Which type of T helper response is associated with type-1 hypersensitivities

Th2

Which of the following statements BEST MATCHES the events associated with mast cell degranulation in Type I hypersensitivity reactions?

The antigen binds to more than one IgE already present on the surface of the mast cells

Greave's disease is different in immunological terms from hemolytic disease of the newborn becaue:

The hemolytic disease causes damage to the cells while Grave's doesnt

Which of the following BEST MATCHES the definition of hypersensitivity reactions?

They are conditions in which the immune response damages our body

In the context of a patient that needs a bone marrow transplantation due to leukemia, if the patient can't find a matching donor:

They can be transplanted with their own stem cells

Which of the following is an important disadvantage of using immunosuppressive agents?

They can increase susceptibility to infections

Endotoxins are:

Toxic compounds that are constituents of the microbial structure

Type I diabetes is an example of an autoimmune disease in which tissue damage is mediated by

Type IV hypersensitivity

___ is a strategy used by Leishmania sp. to promote its survival upon infection of macrophages.

Upsetting the Th1/Th2 balance

Which of the following statements is accurate?

We inherit 3 MHC-I genes from one parent and 3 MHC-I genes from the other parent

______ immunodeficiencies are more likely to develop later in life, and the pathogenic mechanisms of many remain obscure

acquired

​All forms of adaptive immunity can be described as either

active or passive

(1) Genetic mutations associated with autoimmunity:

affect genes that induce inflammation affect genes that decrease inflammation

For instance, if a person with type B blood receives a transfusion of type A blood, their anti-A antibodies will bind to and _____ the transfused RBCs

agglutinate

An allergic reaction is an immune response to a type of antigen called an

allergen

​When a presensitized individual is exposed to an ______, it can lead to a rapid immune response that occurs almost immediately. Such a response is called an allergy and is classified as a type I hypersensitivity

allergen

Systemic type I hypersensitivity reactions are referred to as

anaphylaxis or anaphylactic shock

A patient may require a blood transfusion because they lack sufficient RBCs (____) or because they have experienced a significant loss of blood volume through trauma or disease

anemia

______ are effective against viruses mostly during protection, where an immune individual can neutralize them based on a previous exposure. Antibodies do not affect viruses or other intracellular pathogens once they enter the cell, since antibodies are not able to penetrate the plasma membrane of the cell. Many cells respond to viral infections by downregulating their expression of MHC class I molecules. This is to the advantage of the virus, because without class I expression, cytotoxic T cells have no activity

antibodies

A unique characteristic of type III hypersensitivity is

antibody excess (primarily IgG), coupled with a relatively low concentration of antigen, resulting in the formation of small immune complexes that deposit on the surface of the epithelial cells lining the inner lumen of small blood vessels or on the surfaces of tissues

Although the immune system protects the body by attacking invading "enemies" (pathogens), in some cases, the immune system can mistakenly identify the body's cells as the enemy, resulting in

autoimmune disease

In some cases, the antigen may be a self-antigen, in which case the reaction would also be described as an

autoimmune disease

When excess allergen-specific IgG antibodies are produced and bind to the allergen, they can act as ______ antibodies to neutralize the allergen before it can bind IgE on mast cells.

blocking

Like ABO incompatibilities, ____ transfusions from a donor with the wrong Rh factor antigens can cause a type II hypersensitivity HTR. However, in contrast to the IgM isohemagglutinins produced early in life through exposure to environmental antigens, the production of anti-Rh factor antibodies requires the exposure of an individual with Rh− blood to Rh+ positive RBCs and activation of a primary antibody response

blood

For students first learning about immunohematology, understanding the immunological mechanisms involved is made even more challenging by the complex nomenclature system used to identify different blood-group antigens, often called

blood types

Without treatment, babies with SCID do not typically survive infancy. In some cases, a _____ marrow transplant may successfully correct the defects in lymphocyte development that lead to the SCID phenotype, by replacing the defective component. However, this treatment approach is not without risks

bone

The fungal _____ ______ contains polysaccharide and lipid moieties that activate immune responses via PRR activation. These interactions facilitate signaling responses by innate immune cells such as macrophages and dendritic cells and the induction of antifungal effector mechanisms.

cell wall

____ are classified as Rh positive (Rh+) if the Rho/D antigen is present or as Rh negative (Rh−) if the Rho/D antigen is absent

cells

Rituximab is a monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells. It is used for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein-Barr virus-positive mucocutaneous ulcers. This antibody is:

chimeric

Examples of exotoxins are

cholera toxin or the botulinum toxin -Some of these toxins are resistant to heat so they will remain active even after heating

Are defects in the NADPH oxidase system of phagocytic cells, including neutrophils and macrophages, that prevent the production of superoxide radicals in phagolysosomes

chronic granulomatous disease (CGD)

Some bacteria and viruses can interfere with the ________ system. For example, the insertion of C5,6,7 complex is prevented by polysaccharide capsules. Some microbes produce enzymes that degrade complement factors

complement

Examples of primary immunodeficiencies include

complement deficiencies, leukocyte adhesion deficiencies, chronic granulomatous disease, X-linked agammaglobulinemia, hyper IgM syndrome, selective IgA deficiency, and severe combined immunodeficiency disease

Some viruses use the strategy of ______ antigens. In this scenario, virus-infected cells do not present viral antigen on the surface of the infected cell, therefore remaining virtually invisible to cytotoxic T cells or antibodies. This is typical of some viruses from the herpesvirus family which can establish latent infections in B cells (Epstein Barr virus) or neurons (Herpesvirus type I or II). In this context, several viruses can block the expression of MHC-I molecules in infected cells, therefore becoming impervious to the action of cytotoxic CD8 T cells

concealing

Bronchiole _____ caused by some of the chemical mediators leads to wheezing, dyspnea (difficulty breathing), coughing, and, in more severe cases, cyanosis (bluish color to the skin or mucous membranes). Vomiting can result from the stimulation of the vomiting center in the cerebellum by histamine and serotonin. Histamine can also cause relaxation of intestinal smooth muscles and diarrhea

constriction

an immune response against a microbial antigen will target also these self-antigens. This is a process named

cross-reaction -mediated either by antibodies or T cells can cause tissue damage

​Immune reactions categorized as type II hypersensitivities, or ____ hypersensitivities, are mediated by IgG and IgM antibodies binding to cell-surface antigens or matrix-associated antigens on basement membranes

cytotoxic

On subsequent exposure, allergens bind to multiple IgE molecules on mast cells, cross-linking the IgE molecules. Within minutes, this cross-linking of IgE activates the mast cells and triggers _______, a reaction in which the contents of the granules in the mast cell are released into the extracellular environment

degranulation

Allergic reactions can be treated in various ways. Prevention of allergic reactions can be achieved by

desensitization (hyposensitization) therapy -which can be used to reduce the hypersensitivity reaction through repeated injections of allergens

​Type III hypersensitivities can often be misdiagnosed because of their nonspecific inflammatory nature. The symptoms are easily visible, but they may be associated with several other diseases. Strong, comprehensive patient history is crucial to a proper and accurate diagnosis. Tests used to establish the diagnosis of hypersensitivity pneumonitis (resulting from type III hypersensitivity) include bronchoalveolar lavage (BAL), pulmonary function tests, and high-resolution computed tomography (HRCT)

diagnosis

The accumulation of ______ in nematode-infected sites has been reported and it is mediated by IL-5. In this context, IgE and eosinophil cytotoxicity (antibody-dependent cellular cytotoxicity) has been widely reported as a mechanism for helminth exclusion

eosinophils

Antibody-mediated immunity to fungal pathogens has been extensively reported. The development of Th2 and Th17 responses will induce B cell isotype class-switch recombination towards IgG antibodies that will help fight the ______ infection

fungal

IgA deficiency predisposes these individuals to lung and ________ infections for which secretory IgA is normally an important defense mechanism. Infections in the lungs and gastrointestinal tract can involve a variety of pathogens

gastrointestinal

______ deficiencies in complement factors are associated with diverse conditions

genetic

the combining of gene segments from two different pathogens—is an efficient form of immune evasion. For example, the influenza virus contains gene segments that can recombine when two different viruses infect the same cell. Recombination between human and pig influenza viruses led to the 2010 H1N1 swine flu outbreak.

genetic recombination

The inability to produce superoxide radicals impairs the antibacterial activity of phagocytes. As a result, infections in patients with CGD persist longer, leading to a chronic local inflammation called a

granuloma

It is important to highlight that not all the same MHC molecules (HLA molecules) are carried by an individual in a population. Every human being expresses six class I MHC alleles (one allele of HLA-A, -B, and -C from each parent) and at least six class II MHC alleles (one allele of HLA-DQ and -DP and one or two of -DR from each parent, and some combinations of these). These alleles can be inherited and expressed in many different combinations in a population. Therefore every individual is likely to express some MHC/HLA proteins that appear foreign to another individual's immune system, except in identical twins. The particular set of HLA molecules that an individual carries is often referred to as a

haplotype.

The mechanism by which chemical compounds penetrate the skin and bind to self protein is named:

haptenization

Localized type I hypersensitivity reactions include

hay fever (allergic rhinitis), hives, and asthma

There is evidence that the IgE produced during type I hypersensitivity reactions is meant to counter

helminth infections

The immune response against _______ is associated with the development of systemic and mucosal CD4+ T helper cell type 2 (Th2) responses. These are typically characterized by increased expression of cytokines such as interleukin-4 (IL-4), IL-5, and IL-13, eosinophilia, production of immunoglobulin E (IgE), and stimulation of alternatively activated (M2) macrophages and type 2 innate lymphoid cells (ILC2). The alternatively activated macrophages are considered to play an important role in repairing the tissue damage caused by the helminth infection.1 These Th2 cytokines also promote an increase in the number of eosinophils and basophils in blood and tissues

helminths

Besides, activation of the classical complement cascade will lead to a strong inflammatory response, and the complement membrane attack complex (MAC) will mediate a massive ______ of the transfused RBCs

hemolysis

Rh factor incompatibility between mother and fetus can also cause a type II hypersensitivity hemolytic reaction, referred to as

hemolytic disease of the newborn (HDN)

Two examples of type II hypersensitivity reactions involving RBCs are

hemolytic transfusion reaction (HTR) and hemolytic disease of the newborn (HDN)

Type III - This localized reaction to non-self serum proteins was called an Arthus reaction. An Arthus reaction occurs when soluble antigens bind with IgG in a ratio that results in the accumulation of antigen-antibody aggregates called

immune complexes

_______ are inherited (primary) or acquired (secondary) disorders in which elements of host immune defenses are either absent or functionally defective

immunodeficiencies

is the study of blood and blood-forming tissue in relation to the immune response

immunohematology

Pathogens can produce _______ molecules that impair immune function, and there are several different types. Viruses are especially good at evading the immune response in this way, and many types of viruses have been shown to suppress the host immune response in ways much more subtle than the wholesale destruction caused by HIV

immunosuppressive

An _______ can also cause damage to our tissues due to the action of the immune system. For example, antibodies interacting with microbial antigens can generate immune complexes that accumulate in the tissues or organs such as joints or kidneys, generating local inflammation that leads to tissue injury

infection

Many viruses produce proteins that inhibit the activation of the ______ signaling pathway. For example, some viruses can inhibit dsRNA binding proteins, others can inactivate nucleic acid degradation molecules, others block the capacity of IFN to stop protein synthesis

interferon

______ have activity in slowing viral replication and are used in the treatment of certain viral diseases, such as hepatitis B and C, but their ability to eliminate the virus is limited. The cytotoxic T cell response, though, is key, as it eventually overwhelms the virus and kills infected cells before the virus can complete its replicative cycle. Clonal expansion and the ability of cytotoxic T cells to kill more than one target cell make these cells especially effective against viruses. In fact, without cytotoxic T cells, it is likely that humans would all die at some point from a viral infection (if no vaccine were available)

interferons

Celiac disease is largely a disease of the small intestine, although other organs may be affected. People in their 30s and 40s, and children are most commonly affected, but celiac disease can begin at any age. It results from a reaction to proteins, commonly called gluten, found mainly in wheat, barley, rye, and some other grains. The disease has several genetic causes (predispositions) and poorly understood environmental influences. On exposure to gluten, the body produces various autoantibodies leading to an inflammatory response. The inflammatory response in the small intestine leads to a reduction in the depth of the microvilli of the mucosa, which hinders absorption and can lead to weight loss and anemia. The disease is also characterized by diarrhea and abdominal pain, symptoms that are often misdiagnosed as

irritable bowel syndrome.

A primary immunodeficiency

is congenital

is the most common cause of immunodeficiency and would be categorized as an acquired immunodeficiency

malnutrition

The fragment crystallizable (Fc) regions of the IgE antibodies bind to specific receptors on the surface of _____ _____ throughout the body. It is estimated that each mast cell can bind up to 500,000 IgE molecules, with each IgE molecule having two allergen-specific fragment antigen-binding (Fab) sites available for binding allergen on subsequent exposures. By the time this occurs, the allergen is often no longer present and there is no allergic reaction, but the mast cells are primed for a subsequent exposure and the individual is sensitized to the allergen.

mast cells

Activated macrophages secrete chemokines capable of recruiting other immune cells to the synovium; among them neutrophils. In recent years, several studies have postulated the role of neutrophils as co-conspirators of the disease. At the level of the synovium, neutrophils can be activated by the immune complexes present in the environment and produce reactive oxygen species that toxic for the tissue.

mhm

Activation of synovial fibroblasts by macrophages and TG cells also contribute to the pathogenesis of the disease. These fibroblasts produce inflammatory cytokines and proteases that contribute to cartilage destruction. The inflammatory environment also increases chondrocyte catabolism and synovial osteoclastogenesis which contribute to articular destruction.

mhm

Besides, structural similarities between pathogen antigens and our own self-antigens can lead to cross-reactivity and autoimmunity, a process named

molecular mimicry

Microbial antigens cross-reacting with self-antigens is an example of

molecular mimicry

Treatments for myasthenia gravis include plasmapheresis, IVIG and monoclonal antibody therapy: Plasmapheresis uses a filtering process similar to dialysis, the blood is routed through a machine that removes the antibodies from it. IVIG provides the body with normal antibodies. Monoclonal antibody Rituximab (Rituxan) given intravenously depletes B cells. Taking into account this information: Which of the following strategies will take longer to show an effect in the patient?

monoclonal antibody

in _______ tissues, such as the gastrointestinal tract, Th2 cytokines induce goblet cell hyperplasia and mucin production, as well as the accumulation of mast cells.2. Additionally, IL-13 released by Th2 cells acts on smooth muscle cells to increase peristalsis. These cooperative effects remove nematodes from the intestinal mucosa

mucosal

Another method of immune evasion is _____. Because viruses' surface molecules mutate continuously, viruses like influenza change enough each year that the flu vaccine for one year may not protect against the flu common to the next. New vaccine formulations must be derived for each flu season

mutation

______ are relevant in the immune response against unicellular fungi, or small multicellular fungi, rapidly internalizing conidia (spores) and/or yeast cells. Also, the production of ROS induces the death of the phagocytosed microbe. Fungal hyphae and pseudohyphae induce the generation of neutrophil extracellular traps which help capture and eliminate the pathogen. Similarly, in macrophages, NADPH oxidase activation upon phagocytosis also helps kills the ingested microbe.

neutrophils

Patients with secondary immunodeficiencies develop an increased susceptibility to an otherwise benign infection by ________ pathogens

opportunistic

his leads to the coating of the RBCs by antibodies, activation of the complement cascade, and complement-mediated lysis of RBCs, as well as ______ of RBCs for phagocytosis

opsonization

there are some general trends within ______ infections: Th1-type immune responses typically develop in response to protozoan infections, whereas Th2-type immune responses develop in response to helminthic infections

parasitic

Thus it may be that allergies are an unfortunate consequence of strong selection in the mammalian lineage or earlier for defense against

parasitic worms.

Some self-reactive T cells may escape negative selection, complete their maturation, and enter peripheral tissues. There are mechanisms in the periphery (outside the thymus) that can still control the activation of those autoreactive cells that escaped the negative selection process. These mechanisms of control are named

peripheral tolerance

one way in which microbes can escape the action of the immune system is by evading

phagocytosis -strategy typically used by bacteria that infect phagocytes

If a subsequent ______ with an Rh+ fetus occurs, however, the mother's second exposure to the Rh factor antigens causes a strong secondary antibody response that produces larger quantities of anti-Rh factor IgG. These antibodies can cross the placenta from mother to fetus and cause HDN, a potentially lethal condition for the baby

pregnancy

Diagnosis of type I hypersensitivities is a complex process requiring several diagnostic tests in addition to well-documented patient history. Serum IgE levels can be measured, but elevated IgE alone does not confirm the allergic disease. As part of the process to identify the antigens responsible for a type I reaction allergy, testing through a

prick-puncture skin test (PPST) or an intradermal test can be performed

_______ immunodeficiencies, which number more than 250, are caused by inherited defects of either nonspecific innate or specific adaptive immune defenses. In general, patients born with primary immunodeficiency (PI) commonly have an increased susceptibility to infection. This susceptibility can become apparent shortly after birth or in early childhood for some individuals, whereas other patients develop symptoms later in life

primary

In other cases, antibodies may bind to naturally occurring, but exogenous, cell-surface molecules such as antigens associated with blood typing found on

red blood cells (RBCs)

Other pathogens can infect immune-privileged sites or regions where the immune system has _____ access. One case would be that of fungi that colonize the outer skin layers (e.g. those responsible for athlete's foot infections). Immune privileged sites are regions of the body where there is restricted access to lymphocytes or antibodies or where there is an immunosuppressive environment. Examples of the former are the central nervous systems, the testes, or the eyes. An example of the latter is the placenta which is an organ with highly immunosuppressive characteristics

restricted

​The most common inherited form of immunoglobulin deficiency is

selective IgA deficiency, affecting about one in 800 people. -Individuals with selective IgA deficiency produce normal levels of IgG and IgM but are not able to produce secretory IgA.

Systemic type III hypersensitivity (_____ _____) occurs when immune complexes deposit in various body sites, resulting in a more generalized systemic inflammatory response

serum sickness

More drastic mutation in influenza happens due to the recombination of large portions of its genomic material. This usually happens when two different types of influenza A strain (for example, one with the capacity to infect humans and another to infect birds), infect a third host, for example, pigs. The RNAs of the human and bird variants of influenza recombine and a new viral strain appears for which humans have no defenses. This process is named antigenic _____ and is responsible for influenza pandemics

shift

What is clonal selection?

specific clones against microbial antigens are originated before the body has contact with that antigen as described regarding the acquisition of in TCR and BCR variability

______ patients, are also more prone to infection. Removal of the spleen, oftentimes due to the rupture of this fragile organ in the context of physical injury, increases susceptibility to bacteremias with encapsulated bacteria such as Streptococcus pneumoniae since specialized B cells (T-independent) in this organ are critical for mounting antibody responses to polysaccharide antigens carried in the capsule of some bacteria. Besides, macrophages present in the spleen also collaborate in eliminating microbial antigens from circulation via phagocytosis.

splenectomized

In the _______ (meaning in the absence of infection), if an autoreactive T cell encounters its specific antigen on an antigen-presenting cell this will leads to anergy o deletion of the T cell. Our own antigens can be presented through MHC-I (old proteins that are degraded and access the ER) or MHC-II (due to phagocytosis of apoptotic cells). These are natural, non-inflammatory processes. In the absence of infection, the antigen-presenting cells will not express high levels of costimulatory molecules. Thus, if it encounters the specific T cell it will deliver Signal 1 (TCR-MHC) in the absence of Signal 2 (B7 molecules-CD28). This leads to anergy or apoptosis of said T cell

steady-state

Bacteria sometimes evade immune responses because they exist in multiple ______, such as different groups of Staphylococcus aureus

strains

Animals that are identical to one another (and grafts exchanged among these animals) are said to be:

syngeneic

​Type I hypersensitivity reactions can be either localized or _____

systemic

IL-3 and IL-9, products of _____ cells, synergistically induce the accumulation of mucosal mast cells in the mucosa of the small intestine. 2. These mast cells release chondroitin sulfate, preventing nematode adhesion to, and penetration of, the mucous membrane

th2

MHC genes are highly polymorphic. This means:

that each MHC/HLA gene locus has many alleles in a population

Activation of coagulation pathways also occurs, resulting in ____ (blood clots) that occlude blood vessels and cause ischemia that can lead to vascular necrosis and localized hemorrhage

thrombi

Which of the following is NOT an example of a condition responsible for secondary immunodeficiency

thymic aplasia

Autoimmune diseases are those in which the body is attacked by its own specific adaptive immune response. In normal, healthy states, the immune system induces tolerance, which is a lack of an anti-self immune response. However, with autoimmunity, there is a loss of immune tolerance, and the mechanisms responsible for autoimmune diseases include type II, III, and IV hypersensitivity reactions.

tolerance

Most transplant recipients, even those with tissues well matched to their MHC genes, require treatment with immunosuppressant drugs for the rest of their lives. This can make them more vulnerable than the general population to complications from infectious diseases. It can also result in transplant-related malignancies because the body's normal defenses against cancer cells are being suppressed. The goal of immunosuppressive treatments is to block unwanted immune responses against the graft while avoiding tissue damage, and loss of tissue function. Immunosuppressive treatments involve the use of different compounds, alone or in combination.

transplant rejection treatment

Treatment for type II hypersensitivity aims to reduce effector antibody levels or prevent effector cells from causing damage (particularly for autoimmune diseases). Plasmapheresis reduces autoantibody levels and is reserved for cases in which the antibody needs to be rapidly removed Immunosuppressive drugs can reduce B-cell autoantibody secretion, although the benefits only take place gradually, over several weeks

treatment

Treatment of type IV hypersensitivities includes antihistamines, anti-inflammatory drugs, analgesics, and, if possible, eliminating further exposure to the antigen. Reducing inflammation can be achieved by using corticosteroids and antagonists against cytokines such as TNF alpha; and inhibiting T cell responses with immunosuppressive drugs such as cyclosporine. For example, antagonists of TNF alpha have proved to be beneficial in patients with rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

treatment

In type II and type III hypersensitivities, complement and neutrophils can play an important role.

true

​Juvenile diabetes, or type 1 diabetes mellitus, is usually diagnosed in children and young adults. It is a T-cell-dependent autoimmune disease characterized by the selective destruction of the β cells of the islets of Langerhans in the pancreas by CD4 TH1-mediated CD8 T cells, anti-β-cell antibodies, and macrophage activity. There is also evidence that viral infections can have either a potentiating or inhibitory role in the development of type 1 diabetes (T1D) mellitus. The destruction of the β cells causes a lack of insulin production by the pancreas. In T1D, β-cell destruction may take place over several years, but symptoms of hyperglycemia, extreme increase in thirst and urination, weight loss, and extreme fatigue usually have a sudden onset, and diagnosis usually does not occur until most β cells have already been destroyed

type 1 diabetes

is a form of artificial immunity

vaccination

By artificially stimulating the adaptive immune defenses, a ____ triggers memory cell production similar to that which would occur during a primary response

vaccine

Patients with SCID also cannot develop immunological memory, so _______ provide them no protection, and live attenuated vaccines (e.g., for varicella-zoster, measles virus, rotavirus, poliovirus) can cause the infection they are intended to prevent

vaccines

The primary mechanisms against ______ are NK cells, interferons, and cytotoxic T cells

viruses

Both the PPST and the intradermal tests are observed for 15-20 minutes for a

wheal-flare reaction to the allergens

Regarding transplant rejection, direct alloantigen recognition occurs:

when T cells bind directly to intact allogeneic MHC molecules on professional APCs that come in a graft

This disease is characterized by defective CD40L expression which prevents immunoglobulin class switch, due to lack of Signal 2 between T cells and B cells. In this condition, B cells are present, and very high levels of IgM but no IgG or IgA are observed in circulation. Besides, lymphoid organs present poorly organized germinal centers, and no or few B memory cells are generated. This condition can be treated with intravenous immunoglobulin(IVIG) or through bone marrow transplantation

x linked hyper IgM syndrome

Active immunity refers to the activation of an individual's own adaptive immune defenses, whereas passive immunity refers to the transfer of adaptive immune defenses from another individual or animal. Active and passive immunity can be further subdivided based on whether the protection is acquired naturally or artificially

yep

CD4+ T cells that recognize self-antigens with medium affinity in the thymus may differentiate into regulatory T cells (Tregs) in a process spearheaded by the transcription factor FoxP3. Tregs inhibit the activation of naïve, autoreactive T cells, and their differentiation into effector T cells. Tregs do this by cell-to-cell contact mechanisms or by secreting cytokines that inhibit T cell responses. Regulatory T cells can also be produced in the periphery if naïve T cells are activated by immunosuppressive DCs or macrophages

yep

In the first type IV subcategory, CD4 TH1-mediated reactions are described as delayed-type hypersensitivities (DTH). The sensitization step involves the introduction of antigen into the skin and phagocytosis by local antigen-presenting cells (APCs). The APCs activate helper T cells, stimulating clonal proliferation and differentiation into memory TH1 cells. Upon subsequent exposure to the antigen, these sensitized memory TH1 cells release cytokines that activate macrophages, and activated macrophages are responsible for much of the tissue damage. Examples of this TH1-mediated hypersensitivity are observed in tuberculin the Mantoux skin test and contact dermatitis, such as occurs in latex allergy reactions.

yep

In the second type IV subcategory, CD4 TH2-mediated reactions result in chronic asthma or chronic allergic rhinitis. In these cases, the soluble antigen is first inhaled, resulting in eosinophil recruitment and activation with the release of cytokines and inflammatory mediators

yep

These immune complexes involve non-self proteins such as antibodies produced in animals for artificial passive immunity, certain drugs, or microbial antigens that are continuously released over time during chronic infections (e.g., subacute bacterial endocarditis, chronic viral hepatitis). The mechanisms of serum sickness are similar to those described in localized type III hypersensitivity but involve widespread activation of mast cells, complement, neutrophils, and macrophages, which causes tissue destruction in areas such as the kidneys, joints, and blood vessels. As a result of tissue destruction, symptoms of serum sickness include chills, fever, rash, vasculitis, and arthritis. The development of glomerulonephritis or hepatitis is also possible

yep

Tolerance can be divided between central and peripheraltolerance as discussed in Chapter 10. Central tolerance involves clonal deletion of autoreactive T cells in the thymus or autoreactive B cells in the bone marrow by a process named negative selection.

yep

A conjugate vaccine is a type of subunit vaccine that consists of a protein conjugated to a capsule polysaccharide. Conjugate vaccines have been developed to enhance the efficacy of subunit vaccines against pathogens that have protective polysaccharide capsules that help them evade phagocytosis, causing invasive infections that can lead to meningitis and other serious conditions. The subunit vaccines against these pathogens introduce T-independent capsular polysaccharide antigens that result in the production of antibodies that can opsonize the capsule and thus combat the infection; however, children under the age of two years do not respond effectively to these vaccines. Children do respond effectively when vaccinated with the conjugate vaccine, in which a protein with T-dependent antigens is conjugated to the capsule polysaccharide. The conjugated protein-polysaccharide antigen stimulates the production of antibodies against both the protein and the capsule polysaccharide. Table 15. 1 lists examples of conjugate vaccines.

yes

Activated auto-reactive CD4 T cells also stimulate the production of rheumatoid factor (RF).

yes

Antigens from the transplanted organ can activate the immune system of the recipient by different pathways. In the case of direct alloantigen recognition, (Fig. 20. 1) antigen-presenting cells from the transplanted organs, migrate toward the lymph nodes of the recipient and there they activate T cells. Therefore, recipient T cells bind directly to intact allogeneic MHC molecules on antigen-presenting cells of graft origin.

yes

Both indirect and direct alloantigen recognition happens at the same time in the context of transplantation, and both contribute to organ rejection.

yes

Diagnosis of celiac disease is accomplished from serological tests for the presence of primarily IgA antibodies to components of gluten, the transglutaminase enzyme, and autoantibodies to endomysium, a connective tissue surrounding muscle fibers. Serological tests are typically followed up with endoscopy and biopsy of the duodenal mucosa. Serological screening surveys have found that about 1% of individuals in the United Kingdom are positive even though they do not all display symptoms.1 This early recognition allows for more careful monitoring and prevention of severe disease.

yes

Effects on the brain and nervous system can lead to headaches, numbness, tingling, seizures, vision problems, and personality changes. There may also be abdominal pain, nausea, vomiting, arrhythmia, shortness of breath, and blood in the sputum. Effects on the skin can lead to additional areas of skin lesions, and vasoconstriction can cause color changes in the fingers when they are cold (Raynaud phenomenon). Effects on the kidneys can lead to edema in the legs and weight gain.

yes

Finally, the third type of immune rejection is named chronic rejection with graft arteriosclerosis. This can happen several years after an organ has been transplanted. In this type of rejection, T helper cells react against graft alloantigens and produce cytokines and growth factors that promote endothelial and intimal smooth muscle cell proliferation in the grafted organ. The proliferation of these cells will lead to a narrowing of the graft's vessels, and eventually to luminal occlusion hindering the grafted organ's blood supply. From the immunological point of view this is a chronic delayed-type hypersensitivity (DTH) reaction to the alloantigens harbored by the grafted organ.

yes

If preformed antibodies against transplanted antigens are present in the donor, perhaps in response to a previous blood transfusion from the same donor (or in case of a mismatch between donor and recipient blood types [blood antigens can be expressed by endothelial cells of the transplanted organ]), these antibodies can react with alloantigens on the vascular endothelium of the graft. This antigen-antibody interaction will activate complement, triggering rapid intramuscular thrombosis and necrosis of the vessel wall, rapidly harming the transplanted organ in a process named hyperacute rejection. In this case, transplanted organs do not survive further than hours.

yes

Immune privileged organs were originally defined as sites in the body where foreign tissue grafts could survive for extended or indefinite periods, whereas similar grafts placed at regular sites in the body were rejected (Medawar, 1948, Br.J. Exp.Pathol. 29, 58-69.). These sites include the eye, the brain, testis, and the pregnant uterus.

yes

In some cases, masters regulators of negative selection can be affected leading to the apparition of several immune deficiencies in the same individual. An example of this is the autoimmune regulator (AIRE) gene. This gene is expressed by thymic cells and orchestrates the expression of tissue-specific antigens by thymus epithelial cells. Therefore, these cells can present antigens expressed by all tissue bodies to T cells, driving the negative selection process. Genetic defects in AIRE determine impairment in the negative selection process, leading to the output of autoreactive T cells from the thymus. Individuals with this genetic defect tend to accumulate several immunodeficiencies throughout their life

yes

In the case of acute rejection, cytotoxic lymphocytes are activated by indirect or direct allorecognition, and attack the transplanted organ. Targets for this attack are alloantigens present on the graft's endothelial and parenchymal cells. The inflammation of the endothelium is called endothelialitis. Alloreactive antibodies also may contribute to organ injury. This rejection takes around two weeks to establish, the typical time to an immune response towards an antigen that the system sees from the first time.

yes

In the case of indirect alloantigen recognition, MHC molecules from graft cells are taken up and processed by the recipient antigen-presenting cells. Thus, processed fragments of the allogeneic MHC molecules are presented by recipient MHC molecules to T cells, which will mount a response against the transplanted organ.

yes

In the third type IV subcategory, CD8 cytotoxic T lymphocyte (CTL)-mediated reactions are associated with tissue transplant rejection and contact dermatitis (Figure 17.5). For this form of cell-mediated hypersensitivity, APCs process and present the antigen with MHC I to naïve CD8 T cells. When these naïve CD8 T cells are activated, they proliferate and differentiate into CTLs. Activated TH1 cells can also enhance the activation of the CTLs. The activated CTLs then target and induce granzyme-mediated apoptosis in cells presenting the same antigen with MHC I. These target cells could be "self" cells that have absorbed the foreign antigen (such as with contact dermatitis due to poison ivy), or they could be transplanted tissue cells displaying foreign antigen from the donor.

yes

Increased levels of acute-phase proteins, such as C-reactive protein (CRP), are also produced as part of the inflammatory process and participate in complement activation with the antibodies on the immune complexes.

yes

Like subunit vaccines, toxoid vaccines do not introduce a whole pathogen to the patient; they contain inactivated bacterial toxins, called toxoids. Toxoid vaccines are used to prevent diseases in which bacterial toxins play an important role in pathogenesis. These vaccines activate humoral immunity that neutralizes the toxins. Table 15.1. lists examples of toxoid vaccines.

yes

On the other hand, trauma or infection in an immune-privileged site can alter the homeostatic balance of its environment, leading to an immune attack to the organ. This is exemplified by sympathetic ophthalmia. In this condition, physical trauma to one eye releases the sequestered eye antigens into surrounding tissues, making them accessible to peripheral T cells. The effector cells that are activated by these antigens attack the traumatized eye, but can also infiltrate and harm the healthy eye leading to blindness.

yes

Symptoms of AAD include weakness, nausea, decreased appetite, weight loss, hyperpigmentation (Figure 18.3), hyperkalemia (elevated blood potassium levels), hyponatremia (decreased blood sodium levels), hypoglycemia (decreased levels of blood sugar), hypotension (decreased blood pressure), anemia, lymphocytosis (decreased levels of white blood cells), and fatigue. Under extreme stress, such as surgery, accidental trauma, or infection, patients with AAD may experience an adrenal crisis that causes the patient to vomit, experience abdominal pain, back or leg cramps, and even severe hypotension leading to shock.

yes

The most common chronic inflammatory joint disease is rheumatoid arthritis (RA) (Figure 18.5) and it is still a major medical challenge because of unsolved questions related to the environmental and genetic causes of the disease. RA involves type III hypersensitivity reactions and the activation of CD4 T cells, resulting in the chronic release of the inflammatory cytokines IL-1, IL-6, and tumor necrosis factor-α (TNF-α). The activated CD4 T cells also stimulate the production of rheumatoid factor (RF) antibodies and anticyclic citrullinated peptide antibodies (anti-CCP) that form immune complexes. Increased levels of acute-phase proteins, such as C-reactive protein (CRP), are also produced as part of the inflammatory process and participate in complement fixation with the antibodies on the immune complexes. The formation of immune complexes and reaction to the immune factors cause an inflammatory process in joints, particularly in the hands, feet, and legs.

yes

To minimize the risk of GVHD, it is critically important to match the HLAs of the host and donor as closely as possible in bone marrow transplants. In addition, the donated bone marrow is processed before grafting to remove as many donor APCs and T cells as possible, leaving mostly hematopoietic stem cells.

yes

​A graft is the transplantation of an organ or tissue to a different location, to replace a missing or damaged organ or tissue. Grafts are typically moved without their attachments to the circulatory system and must reestablish these, in addition to the other connections and interactions with their new surrounding tissues. There are different types of grafts depending on the source of the new tissue or organ. Tissues that are transplanted from one genetically distinct individual to another within the same species are called allografts. An interesting variant of the allograft is an isograft, in which tissue from one twin is transplanted to another. As long as the twins are monozygotic (therefore, essentially genetically identical), the transplanted tissue is virtually never rejected. If tissues are transplanted from one area on an individual to another area on the same individual (e.g., a skin graft on a burn patient), it is known as an autograft. If tissues from an animal are transplanted into a human, this is called a xenograft.​

yes

​Autoantibodies directed against acetylcholine receptors (AChRs) in the synaptic cleft of neuromuscular junctions lead to myasthenia gravis (Figure 18.4). Anti-AChR antibodies are high-affinity IgGs and their synthesis requires activated CD4 T cells to interact with and stimulate B cells. Once produced, the anti-AChR antibodies affect neuromuscular transmission by at least three mechanisms: ​Complement binding and activation at the neuromuscular junction Accelerated AChR endocytosis of molecules cross-linked by antibodies Functional AChR blocking, which prevents normal acetylcholine attachment to, and activation of, AChR Regardless of the mechanism, the effect of anti-AChR is extreme muscle weakness and potentially death through respiratory arrest in severe cases.

yes

​Destruction of the adrenal glands (the glands lying above the kidneys that produce glucocorticoids, mineralocorticoids, and sex steroids) is the cause of Addison disease, also called primary adrenal insufficiency (PAI). Today, up to 80% of Addison disease cases are diagnosed as autoimmune Addison disease (AAD), which is caused by an autoimmune response to adrenal tissues disrupting adrenal function. Disruption of adrenal function causes impaired metabolic processes that require normal steroid hormone levels, causing signs and symptoms throughout the body. There is evidence that both humoral and CD4 TH1-driven CD8 T-cell-mediated immune mechanisms are directed at the adrenal cortex in AAD. There is also evidence that the autoimmune response is associated with autoimmune destruction of other endocrine glands as well, such as the pancreas and thyroid, conditions collectively referred to as autoimmune polyendocrine syndromes (APS). In up to 80% of patients with AAD, antibodies are produced to three enzymes involved in steroid synthesis: 21-hydroxylase (21-OH), 17α-hydroxylase, and cholesterol side-chain-cleaving enzyme.3 The most common autoantibody found in AAD is to 21-OH, and antibodies to any of the key enzymes for steroid production are diagnostic for AAD. The adrenal cortex cells are targeted, destroyed, and replaced with fibrous tissue by immune-mediated inflammation. In some patients, at least 90% of the adrenal cortex is destroyed before symptoms become diagnostic.

yes

​Graves disease is the most common cause of hyperthyroidism in the United States. Symptoms of Graves disease result from the production of thyroid-stimulating immunoglobulin (TSI) also called TSH-receptor antibody. TSI targets and binds to the receptor for thyroid-stimulating hormone (TSH), which is naturally produced by the pituitary gland. TSI may cause conflicting symptoms because it may stimulate the thyroid to make too much thyroid hormone or block thyroid hormone production entirely, making diagnosis more difficult. Signs and symptoms of Graves disease include heat intolerance, rapid and irregular heartbeat, weight loss, goiter (a swollen thyroid gland, protruding under the skin of the throat [Figure 18.1]) and exophthalmia (bulging eyes) often referred to as Graves ophthalmopathy

yes

​Inactivated vaccines contain whole pathogens that have been killed or inactivated with heat, chemicals, or radiation. For inactivated vaccines to be effective, the inactivation process must not affect the structure of key antigens on the pathogen. Because the pathogen is killed or inactive, inactivated vaccines do not produce an active infection, and the resulting immune response is weaker and less comprehensive than that provoked by a live attenuated vaccine. Typically the response involves only humoral immunity, and the pathogen cannot be transmitted to other individuals. In addition, inactivated vaccines usually require higher doses and multiple boosters, possibly causing inflammatory reactions at the site of injection.

yes

​Live attenuated vaccines expose an individual to a weakened strain of a pathogen with the goal of establishing a subclinical infection that will activate the adaptive immune defenses. Pathogens are attenuated to decrease their virulence using methods such as genetic manipulation (to eliminate key virulence factors) or long-term culturing in an unnatural host or environment (to promote mutations and decrease virulence).

yes

​Multiple sclerosis (MS) is an autoimmune central nervous system disease that affects the brain and spinal cord. Lesions in multiple locations within the central nervous system are a hallmark of multiple sclerosis and are caused by the infiltration of immune cells across the blood-brain barrier. The immune cells include T cells that promote inflammation, demyelination, and neuron degeneration, all of which disrupt neuronal signaling. Symptoms of MS include visual disturbances; muscle weakness; difficulty with coordination and balance; sensations such as numbness, prickling, or "pins and needles"; and cognitive and memory problems.​

yes

​Psoriasis is a skin disease that causes itchy or sore patches of thick, red skin with silvery scales on elbows, knees, scalp, back, face, palms, feet, and sometimes other areas. Some individuals with psoriasis also get a form of arthritis called psoriatic arthritis, in which the joints can become inflamed. Psoriasis results from the complex interplay between keratinocytes, dendritic cells, and T cells, and the cytokines produced by these various cells. In a process called cell turnover, skin cells that grow deep in the skin rise to the surface. Normally, this process takes a month. In psoriasis, as a result of cytokine activation, cell turnover happens in just a few days. The thick inflamed patches of skin that are characteristic of psoriasis develop because the skin cells rise too fast.​

yes

​Some autoimmune diseases are considered organ-specific, meaning that the immune system targets specific organs or tissues. Examples of organ-specific autoimmune diseases include celiac disease, Graves disease, Hashimoto thyroiditis, type I diabetes mellitus, and Addison disease

yes

​The damage and pathology of systemic lupus erythematosus (SLE) are caused by type III hypersensitivity reactions. Autoantibodies produced in SLE are directed against nuclear and cytoplasmic proteins. Anti-nuclear antibodies (ANAs) are present in more than 95% of patients with SLE,4 with additional autoantibodies including anti-double-stranded DNA (ds-DNA) and anti-Sm antibodies (antibodies to small nuclear ribonucleoprotein). Anti-ds-DNA and anti-Sm antibodies are unique to patients with SLE; thus, their presence is included in the classification criteria of SLE. Cellular interaction with autoantibodies leads to nuclear and cellular destruction, with components released after cell death leading to the formation of immune complexes.

yes

​Type IV hypersensitivities are not mediated by antibodies like the other three types of hypersensitivities. Rather, type IV hypersensitivities are regulated by T cells and involve the action of effector cells. These types of hypersensitivities can be organized into three subcategories based on T-cell subtype, type of antigen, and the resulting effector mechanism

yes

​Whereas organ-specific autoimmune diseases target specific organs or tissues, systemic autoimmune diseases are more generalized, targeting multiple organs or tissues throughout the body. Examples of systemic autoimmune diseases include multiple sclerosis, myasthenia gravis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.​

yes

This immune complex accumulation leads to a cascade of inflammatory events that include the following:

​IgG binding to antibody receptors on localized mast cells, resulting in mast-cell degranulation Complement activation with production of pro-inflammatory C3a and C5a Increased blood-vessel permeability with chemotactic recruitment of neutrophils and macrophages

example of endotoxin

-LPS (also named generically endotoxin). As we have discussed, LPS is a constituent of the outer membrane of Gram-negative bacteria. LPS is a PAMP recognized by TLR4. In response to this interaction, macrophages can activate the production of the endogenous pyrogens, leading to fever. Even when the bacteria die, fragments of the cell wall containing LPS can activate TLR4. That is why any device that is used for injections (syringes, needles) should not only be sterile (no live microbes) but also pyrogen (or endotoxin) free. Meaning, they should not harbor even bacterial fragments

During the first ____ to 5 days, the innate immune response will partially control, but not stop, pathogen growth. As the adaptive immune response gears up, however, it will begin to clear the pathogen from the body, while at the same time becoming stronger and stronger

4

Subsequent research by other scientists determined that the four blood types were based on the presence or absence of surface glycoproteins "A" and "B," and this provided the foundation for the

ABO blood group system

Treatments for myasthenia gravis include plasmapheresis, IVIG and monoclonal antibody therapy: Plasmapheresis uses a filtering process similar to dialysis, the blood is routed through a machine that removes the antibodies from it. IVIG provides the body with normal antibodies. Monoclonal antibody Rituximab (Rituxan) given intravenously depletes B cells. Taking into account this information: How do you think monoclonal antibodies can deplete B cells?

ADCC and complement activation

HIV infection and the associated acquired immunodeficiency syndrome (______) are the best-known secondary immunodeficiencies. AIDS is characterized by profound CD4 T-cell lymphopenia (decrease in lymphocytes). The decrease in CD4 T cells is the result of various mechanisms, including HIV-induced pyroptosis (a type of apoptosis that stimulates an inflammatory response), viral cytopathic effect, and cytotoxicity to HIV-infected cells.

AIDS

Which of the following immunizations route would mostly activate mucosal immunity?

Aerosolized

Which of the following is NOT true regarding desensitization?

Aims to promote Th2 responses against the allergen

Which of the following is TRUE regarding immune-privileged sites?

Are sites where lymphocyte circulation is less intense

is the foundation for vaccination. It involves the activation of adaptive immunity through the deliberate exposure of an individual to weakened or inactivated pathogens, or preparations consisting of key pathogen antigens.

Artificial active immunity

refers to the transfer of antibodies produced by a donor (human or animal) to another individual. This transfer of antibodies may be done as a prophylactic measure (i.e., to prevent disease after exposure to a pathogen) or as a strategy for treating an active infection. For example, artificial passive immunity is commonly used for post-exposure prophylaxis against rabies, hepatitis A, hepatitis B, and chickenpox (in high risk individuals)

Artificial passive immunity

In patients whose _ cells are unable to produce sufficient amounts of Btk, the B cell maturation and differentiation halt at the pre-B-cell stage of growth. B-cell maturation and differentiation beyond the pre-B-cell stage of growth are required for immunoglobulin production

B

A SCID condition affects

Both B cells and T cells

Deficiencies in __________ are associated with recurrent bacterial meningitis, mainly due to an increase in the susceptibility to Neisseria sp. infections caused by defective membrane attack complex assembly

C5, C6, C7, C8, or C9

If a GVH disease happens ten months after transplant it is called?

Chronic GVHD

Which of the following is an appropriate treatment for SCID?

Continuous administration of antibiotics

from the classical and lectin pathway, are associated with failure in clearing immune complexes from circulation, thereby promoting immune-complex diseases. Deficiencies in C3 are associated with generalized infections due to the incapability of the complement system to provide antimicrobial factors capable of performing opsonization, chemotaxis and direct lysis of the microbes via MAC assembly

Deficiencies in C4 and C2

Which of the following is evidence that the adaptive immunity is involved in transplant rejection?

Depletion of T lymphocytes by antibodies results in reduced graft rejection

____ is a strategy used by herpesviruses where replication and the generation of virus-derived peptides are avoided in order to hide from the immune response.

Establishing latency

Absence of expression of CD40 or CD40 L can induce

Excessive IgM production

Some bacteria carry proteins that can capture antibodies (IgG or IgA) for their ___ regions. Therefore, these captured antibodies are not able to activate complement, induce agglutination, or promote ADCC

Fc

Which of the following type II hypersensitivities is also an autoimmune disease?

Goodpasture's syndrome

An excellent example of this is seroconversion during ______

HIV disease

Which of the following statements regarding Herpes simplex virus (HSV) is FALSE?

HSV initial infection is in the neurons

Although this primary antibody response can cause an ____ in the transfusion patient, the hemolytic reaction would be delayed up to 2 weeks during the extended lag period of a primary antibody response

HTR

However, if the patient receives a subsequent transfusion with Rh+ RBCs, a more rapid ___ would occur with the anti-Rh factor antibody already present in the blood. Furthermore, the rapid secondary antibody response would provide even more anti-Rh factor antibodies for the HTR

HTR

transfusion with an incompatible ABO blood type may lead to a strong, potentially lethal type II hypersensitivity cytotoxic response called hemolytic transfusion reaction (___)

HTR

has nothing to do with an individual's ability to mount an effective immune response; rather, it occurs because there are too few susceptible individuals in a population for the disease to spread effectively.

Herd immunity

​The four kinds of immunity just described result from an individual's adaptive immune system. For any given disease, an individual may be considered immune or susceptible depending on his or her ability to mount an effective immune response upon exposure. Thus, any given population is likely to have some individuals who are immune and other individuals who are susceptible. If a population has very few susceptible individuals, even those susceptible individuals will be protected by a phenomenon called

Herd immunity

caused by a deficiency in C1 Inhibitor production. This is the most common inherited complement deficiency, and individuals with this disease, tend to have uncontrolled and spontaneous inflammatory reactions. The swelling typically affects the arms, legs, face, intestinal tract, and airway. The swelling of the airway can result in its obstruction, and it is a life-threatening complication of this condition

Hereditary angioedema

At mucosal surfaces, ______ is critical for antifungal immunity. Innate lymphoid, Th17, and γδ T cells produce IL-17 following fungal infections. IL-17 helps activate and recruit neutrophils to the site of infection

IL-17

​For susceptible individuals, the first exposure to an allergen activates a strong TH2 cell response (Figure 16.2). Cytokines interleukin (IL)-4 and IL-13 from the TH2 cells activate B cells specific to the same allergen, resulting in clonal proliferation, differentiation into plasma cells, and antibody-class switch from production of IgM to the production of ______

IgE

____ antibodies are the only class of antibody that can cross the placenta from mother to fetus; however, in most cases, the first Rh+ baby is unaffected by these antibodies because the first exposure typically occurs late enough in the pregnancy that the mother does not have time to mount a sufficient primary antibody response before the baby is born

IgG

Which of the following are associated with Type II hypersensitivities? Pick all that are correct

IgG and IgM

Which of the following are associated with Type III hypersensitivities? Pick all that are correct

IgG and IgM

Which of the following answers is correct?

Individuals inherit six MHC-1 alleles and six MHC-2 alleles from their parents

Which of the following is a PROPOSED (or under investigation) treatment for allergy therapies?

Inhibiting IL-4

Which of the following is NOT a mechanism of action of corticosteroids?

Interfering with DNA synthesis

Which of the following is a property of antigens capable of inducing type-I responses?

Low molecular weight