MLS immuno exam practice questions

What are the signals that induce B cell responses to protein antigens and polysaccharide antigens?

Binding of protein to membrane Ig on the B cell, and subsequent signals delivered by Tfh cells, including secreted cytokines that bind to cytokine receptors on the B cell, and CD40 ligand on activated Th cells, which bind to CD40 on the B cell.

What are the major differences between primary and secondary antibody responses to a protein antigens?

Secondary antibody responses develop more quickly and are of greater magnitude than primary immune responses. Secondary responses to protein antigens also differ from primary responses in that the antibodies produced are higher-affinity IgG, IgA or IgE antibodies, whereas low-affinity IgM antibodies are mainly produced in the primary responses.

How do helper T cells specific for an antigen interact with B lymphocytes specific for the same antigen?

B cells express membrane Ig molecules that bind intact proteins and facilitate their endocytosis. The internalized proteins are processed into peptides, and the peptides are bound to class II MHC molecules and displayed on the B cell surface. Th cells specific for peptide-MHC complexes presented by a B cell lead to activation of the T cell. The B cell recognition occurs first and is independent of a T cell, and T cell recognition is second and requires B cell presentation.

where in a lymph node do helper T cells interact with B lymphocytes specific for the same antigen occur?

The initial B-T interactions occur at the interface of the B and T cell zones of lymph nodes or spleen, just outside the follicles. These interactions drive differentiation of helper T cells into Tfh cells, and then both cells migrate into the follicle, where a germinal center reaction ensues, and proliferation occurs.

What are the signals that induce heavy-chain class switching?

Signals (CD40L, cytokines) delivered by Th cells induce heavy-chain isotype switching in B cells. The cytokine signal determine which heavy-chain gene locus will become accessible for switch combination, and the CD40 signal induces expression of the AID enzyme.

what is the importance of heavy-chain class switching for the host defense against different microbes?

It allows for the antibody responses develop to be specialized to particular locations and type of microbes.

What is affinity maturation?

The increase in the average affinity of antibodies for a protein antigens also that occurs as an immune response develops over time.

How is affinity maturation induced and how are high-affinity B cells selected to survive?

The process occurs in the germinal center and requires signals from Th cells, which induces expression of the AID enzyme in the B cell, causing DNA breaks and error-prone repair. Rapidly dividing B cells undergo point mutations in the variable-region genes of the heavy-chain and light-chain loci. B cells with mutation have an increased affinity of the Ab they produce have a selective advantage

What are the characteristics of antibody responses to polysaccharides and lipids?

Antibodies produced in response to T-independent polysaccharide and lipid antigens are predominantly IgM antibodies of relatively low affinity. These antigens are inefficient at generating long-lived plasma cells and memory B cells because of the absence of Th cell signals, so the IgM response to TI antigens wanes relatively quickly.

What region of antibody molecules are involved in the functions of antibodies?

The N-terminal variable regions of antibodies are involved in antigen binding and neutralization of microbes and toxins. The Fc portion of the HC constant region is involved in binding and activating complement and binding to Fc receptors in various cells.

How do heavy-chain class (isotype) switching and affinity maturation improve the ability of antibodies to combat infectious pathogens?

Class switching allows antibodies to perform different effector functions that are particularly suited to certain infections, and it allows delivery of the antibody to certain sites of infection.

In what situations does the ability of antibodies to neutralize microbes protect the host from infections?

Neutralization prevents microbes located in mucosal secretions, blood, or extracellular tissue fluid from binding to cellular receptors. Neutralization also inhibits the spread of microbes from an infected cell to another cell.

How do antibodies assist in the elimination of microbes by phagocytes?

The various domains of IgG antibodies specifically bind to antigens on microbial surfaces (opsonization) then constant domains in the Fc region of the IgG antibodies bind to Fc receptors on macrophages or neutrophils. Binding of the Ab to the Fc receptors stimulates internalization of the microbe by phagocytosis and activates the phagocyte, the microbe is killed.

How is the complement system activated?

The classical pathway is activation when C1 binds to the Fc region of IgM or IgG. In the alternative pathway, C3 is spontaneously hydrolyzes to form C3b. In the lectin pathway, MBL binds to mannose residues on microbial surfaces.

Why is the complement system effective against microbes but does not react against host cells and tissues?

Host cells have regulatory proteins on their cell surfaces, including DAF, CR1, and C4bp that prevent the formation of the C3 convertase on healthy host cells. These are not expressed by microbes.

What are the functions of the complement system, and what components of complement mediate these functions?

The main functions of the complement system are to promote inflammation, opsonize microbes for phagocyte clearance, and directly lyse microbes. Inflammation is promoted by C5a and C3a. Opsonization is mediated mainly by C3b. Lysis is mediated by the MAC

How do antibodies prevent infections by ingested and inhaled microbes?

IgA and some IgM antibodies are transported by the poly-Ig receptor from the lamina propria, through mucosal epithelial cells, into the lumen of the gut or the airways, where they neutralize pathogens.

How are neonates protected from infection before their immune system has reached maturity?

Maternal IgG is transported by the neonatal Fc receptor into the fetal circulation through the placenta, so the baby is born with a full range of antibodies against microbes that the mother has been exposed to in the past. Maternal IgA and IgG in breast milk are ingested by the nursing baby and protect intestinal pathogens.

What is immunologic tolerance?

The adaptive immune system does not normally mount effective immune responses to self molecules, called immunologic tolerance

Why is immunologic tolerance important?

T and B cells expressing antigen receptors that may recognize self-antigens arise during lymphocyte development, and these lymphocytes must be controlled or eliminated to prevent autoimmune disease. These immune system also has to be tolerant of foreign antigens in the fetus and commensal microbes. These mechanisms may be therapeutically used to inhibit harmful immune responses to allergens, self antigens and transplants

How is central tolerance induced in T lymphocytes?

Induced in immature T cells in the thymus after they express TCRs. If a developing T cells recognizes peptides bound to self MHC presented by APCs, signals will be generated that lead to apoptosis of the T cell. Surviving CD4+ T cells may develop into protective Tregs. The T cells that recognize self proteins are deleted.

How is central tolerance induced in B cells?

After they express a functional membrane B cell receptor complex. Recognition of self antigens by immature B cells leads to apoptosis or to receptor editing, where a new round of V-J recombination in the light-chain genes generates new specificities that are not self-reactive

What is central tolerance?

The elimination or inactivation of self-reactive T and B cells during their development in the thymus or bone marrow

Where do regulatory T cells develop?

Tregs are CD4+ t cells that express the IL-2 receptor a chain CD25 and FOXP3. They develop into protective Tregs the thymus from immature thymocytes as a consequence of self antigen recognition. Also differentiate from mature naive T cells in peripheral lymph tissues.

how do Tregs protect against autoimmunity?

By suppressing activation of self-reactive T cells by antigen-presenting cells or by directly inhibiting the T cells. The principal mechanisms include blocking and removal of B7 costimulators on APCs by CTLA-4, secretion of immunosuppressive cytokines, and consumption of the growth factor IL-2.

How are T cells dysfunctional states of anergy and exhaustion induced in T cells and how may they contribute to to peripheral tolerance?

Anergy is induced in naive T cells when they recognize peptides bound- MHC antigen without costimulation when immature DCs have not been exposed to microbial stimuli. Or, when Tregs block costimulation via CTLA-4.exhaustion occurs when T cells are repeatedly stimulated and protect against self tissue damage by cross-reactive T cells

What are the mechanisms that prevent immune responses against commensal microbes and fetuses?

Abundant IL-10 producing Trgs, inhibitory signaling of TLRs in gut dendritic cells, and mucus and epithelial barriers keeping microbes away from the intestinal immune system. Tolerance to allogeneic fetus is maintained by Tregs

What are some of the genes that contribute to autoimmunity?

Particular MHC alleles are frequently in associated with autoimmunity. Several rare diseases are caused by single-gene mutations that interfere with tolerance including AIRE, CTLA-4, FOXP3, FAS and C2.

What are some possible mechanisms by which infections promote the development of autoimmunity?

By inducing costimulatory molecule expressions by APCs that present self antigens to lymphocytes, or by causing inflammation and tissue damage, which exposes normally sequestered self antigens to the immune system and molecular mimicry.

What are the main types of tumor antigens that the immune system reacts against?

Tumors often contain may mutated genes that produce neoantigens. They also may overexpress antigens that are normally expressed at low levels in normal tissues. Some tumors caused by oncogenic viruses may express viral antigens that induce immune responses

What is the evidence that tumor rejection is an immunologic phenomenon?

Some tumors occur more frequently in immunocompromised hosts. The presence of abundant CD8+ effector Th1, and memory T cells around tumors is predicative of a better prognosis. Drugs that block T cell inhibitory molecules enhance responses to tumors.

How do naive CD8+ T cells recognize tumor antigens?

By TCR binding to tumor-derived peptides displayed on class I MHC molecules on DCs.

How are naive CD8+ T cells activated to differentiate into effector CTLs?

The combination of antigen and costimulators activates clonal expansion and differentiation of the naive CD8+ T cells into effector cytotoxic T lymphocytes.

What are some of the mechanisms by which tumors may evade the immune response?

Includes downregulation of MHC molecular to avoid T cell recognition of tumor antigens; loss of expression of tumor antigens; secretion of immunosuppressive cytokines; engagement of inhibitory receptors on T cells. May also promote Tregs and myeloid-derived suppressor cells

What are some strategies for enhancing host immune responses to tumor antigens?

By treating the tumor-bearing patient with antibodies like anti-CTLA-4 and PD-1 that block T cell inhibitory receptors. Or, by adoptive transfer of a patient’s T cells genetically engineered ex vivo to express CARs specific for a tumor antigens bound. Passive immunity to tumors can be induced by antitumor antibodies or T cells expressing tumor-specific antigen receptors

Why do normal T cells, which recognize foreign peptide antigens bound to self MHC molecules, react strongly against the allogeneic MHC molecule of a graft?

Allogenic MHC molecules with any bound peptide are likely to resemble self MHC plus a foreign peptide, so T cells may cross-react with the allogenic molecules. Many allogenic MHC molecules on graft cells may be recognized by a graft recipient’s T cells

What are the principal mechanisms of rejection of allografts?

Allografts may be attacked by alloreactive T cells that are activated after transplant. CD8+ cytotoxic T lymphs recognize allogenic class I MHC molecules on graft cells and directly kill those cells. CD4+ T cells recognize allogenic class II MHC molecules and initiate inflammatory responses that damage the graft cells. Allografts may be rejected by antibodies against allogeneic MHC

How is the likelihood of graft rejection reduced in clinical transplantion?

Recipients may be types for the HLA alleles they have, and organs can be chosen with the best-matched alleles. HLA matching is essential for HSC transplant but not important for solid organs transplants. Rejection of solid organ grafts is prevented by immunosuppressive drugs

What are some of the problems associated with the transplantation of HSC?

T cells transplanted with the HSC can respond to minor histocompatibility molecules in the recipient causing GVHD. Recipients are also often immunodeficient as their immune systems are reconstituted.

What are the major types of hypersensitivity reactions?

Immediate hypersensitivity (type 1) is caused by the release of mediators from mast cells triggered by antigen cross-linking of IgE antibodies specific for cell or tissue antigens can cause damage by activating complement and engaging phagocytes (type 2), immune complexes deposit in blood vessels, causing inflammation and thrombosis leading to tissue injury (type 3). Reactions of T lymphocytes cause inflammation and tissue damage (type 4)

What types of antigens may induce immune responses that cause hypersensitivity reactions?

Damaging immune responses may be elicited by self antigens, environmental antigens and chemicals, and microbial infections

What is the sequence of events in a typical immediate hypersensitivity reaction?

Exposure to an environmental antigens induces differentiation of IL-4- producing T follicular helper T cells which induce IgE antibody responses to the antigen. The IgE binds to high-affinity IgE-specific Fce receptors on mast cells in tissues throughout the body, then cross-link with antigen.

What is the late phase reaction and how is it caused?

An inflammatory response that develops over hours in which blood leukocytes are recruited to the site of mast cells degranulation, caused by TNF and other cytokines secreted by the mast cells.

What are some examples of immediate hypersensitivity disorders?

Allergic rhinitis, sinusitis, food allergies, allergic bronchial asthma, atopic dermatitis (eczema), anaphylaxis

What are immediate hypersensitivity disorders pathogenesis?

Allergic rhinitis and sinusitis are reactions to inhaled allergens leading to upper airway mucosal mast secretion of histamine, IL-13 and chronic inflammation. Food allergies lead to intestinal mucosal mast cell histamine release causing increases peristalsis. Asthma causes bronchial constriction and airway obstruction. Eczema leads to local bacterial infections and the activation of keratinocytes. Anaphylaxis is shock and airway obstruction.

How are immediate hypersensitivity disorders treated?

By inhibiting mast cell degranulation, antagonizing the effects of mast cell mediators and reducing inflammation. Drugs include antihistamines, corticosteroids, epinephrine. Some patients benefit from repeated administration of small doses of allergens, called desensitization

How do antibodies cause tissue injury and disease?

By activating cytotoxic and inflammatory effector functions mainly complement activation and opsonization and phagocyosis via Fc receptors. Some antibodies may cause disease by binding to and interfering with the normal function of a particular protein

What are some examples of diseases caused by antibodies specific for cell surface or tissue matrix antigens?

Autoimmune thrombocytopenia or anemia, glomerulonephritis, rheumatic fever

How do immune complexes cause disase?

Immune complexes deposit in the walls of blood vessels and cause inflammation of the vessel leading to blood clotting in the vessel lumen and loss of blood supply to tissues supplies by vessels. The site is not related to the specificity of the antibodies.

How are the clinical manifestations of immune complexes different from most diseases caused by antibodies specific for cell surface or tissue matrix proteins?

Diseases caused by antibodies against cell surface or extracellular matrix proteins are usually characterized by injury and loss of function restricted to the particular organ or tissue that expresses the protein whereas immune complex deposition is not related to the specificity of the antibodies so immune complex disease may simultaneously affect different tissue sites

What are some examples of diseases caused by T cells and what is their pathogenesis?

Type 1 diabetes is caused by CD4+ and CD8+ T cells that are specific for pancreatic islet cell proteins and that destroy insulin-producing cells, leading to impaired glucose metabolism and cardiovascular disease. Multiple sclerosis is cause by CD4+ T cells specific for CNS myelin sheath proteins that cause inflammation, demyelination, and CNS motor and sensory symptoms. Contact hypersensitivity is caused by T cells specific for skin proteins leading to inflammation and blistering.

What are the most common clinicopathologic manifestations of immunodeficiency diseases?

Infections are the most common. B cell/antibody deficiencies result in increased infections with bacteria, fungi and viral infections. T cell deficiencies result in intracellular infection. Malignant tumors are also increased

What are some of the proteins affected by mutations that may block the maturation of T and B lymphocytes in human immunodeficiency diseases?

Mutations of the y chain of cytokine receptors, adenosine deaminase, RAG1/2, all block both T and B cell maturation leading to SCID/ mutations in the Bruton tyrosine kinase block B cell maturation causing x-linked agammaglobunemia. Mutations in transcription. Factors needed to induce MHC II cause the bare lymph syndrome, leading to impaired CD4+ T cells development. Digeorge syndrome is a deletion of chromosome 22 causing a defect in thymic development, leading to the failure of T cell maturation.

What are some of the mutations that may block activation or effector functions of both mature CD4+ T cells and B cells and what are the clinicopathologic consequences of these mutations?

MHC II deficiency results in poor cell-mediated immunity and T dependent B cells development responses. Mutations in CD40L result in X-linked hyper-IgM syndrome leading to the inability of helper T cells to activate both B cells and macrophages. Mendelian susceptibility is characterized by impaired Th1-mediated immunity against intracellular infections as a result of mutations of genes for IFN-y T cells.

How does HIV infect cells and replicate inside infected cells?

By binding to CD4 and the chemokine receptor CSCR4 or CCR5 leads to the fusion of the virus with the host cell membrane. Once inside, the virus is uncoated by viral protease, its RNA genome is copied into DNA via viral reverse transcriptase, and the DNA integrates into host cells DNA by viral integrase. The integrated viral DNA is transcribed into viral mRNA by host enzymes, viral proteins are translated, formed

What are the principal clinical manifestations of advanced HIV infection, and what is the pathogensis of these manifestations?

Opportunistic infections, oncogenic virus tumors, neurocognitive defects, and wasting. Infection caused by a profound loss of T cell-mediated and T-dependent antibody-mediated immunity due to the death of infected CD4+ T cells.

What receptor is found on phagocytes that binds to C3b

CR1

What binds to C3d on pathogen surface

CR2

Location where antibody secreting plasma cells are initially produced

Primary focus/extrafollicular focus

Site of sustained B cell proliferation and differentiation

Germinal centers

Enzyme that alters nucleotides in switch regions

Activation-induced deaminase (AID)

B cells in dark zone undergoing rapid cell division

Centroblasts

FcR used by NK cells for ADCC

FcyRIIIA (CD16)

FcR expressed on macrophages and neutrophils; binds IgG1 and IgG3

FcgR1 (CD64)

Occurs when the viral strain that infects nonhumans recombines with strain that infected humans

Antigenic shift

Allows a virus to persist in the body undetected

Latency

When lymphocytes that become functionally inactivated

Anergy

Two inhibitory receptors expressed on T cells after activation

CTLA-4 and PD-1

Disease is the result of mutations in the FoxP3 gene

Ipex- immune dysregulation polyendocrinopathy enteropathy X-linked syndrome

Collection of diseases with defects in apoptosis caused by mutations in FAS gene

Autoimmune lymphoproliferative syndrome (ALPS)

Systemic autoimmune disease with immune complexes and antinuclear antibodies

Systemic lupus erythematosus (SLE)

Antigens that are newly expressed in tumors, but not normal cells

Neoantigens

T cell expresses extracellular Ig specific for tumor antigen and intracellular signal domains of TCR and costimulatory receptor

Chimeric antigen receptor (CAR T cells)

Transplant from one individual to an MHC-disparate individual of the same species

Allograft

Alloreactive T cells recognize unprocessed donor MHC on the surface of the graft

Direct recognition

Cause of GVHD

Mature alloreactive donor T cells carried in the graft

Type II autoimmunity of the skin; auto-abs against epidermal intracellular junctions

Pemphigus vulgaris

Type of hypersensitivity in which T cells play a central role

Type IV hypersensitivity

Three lipid mediators made by mast cells

Leukotrienes, prostaglandins, and PAF

Mediator immediately released by mast cells that causes vascular permeability

Histamine

Hypersensitivity mediated by auto-abs to acetylcholine receptor

Myasthenia gravis

Disease caused by mutations in NADPH oxidase gene

Chronic granulomatous disease

Phagocytic deficiency due to defects in lysosomal granules; characterized by recurrent bacterial infections

Chediak-higashi syndrome

Disease caused by a failure to express MHC class II

Bare lymphocyte syndrome

Defective in B cell heavy-chain isotype switching, so IgM is major serum Ig

Hyper IgM syndrome

Phase where there is a widespread dissemination of HIV which leads to seeding of the lymphoid organs

Acute phase of HIV infection

Disease caused by mutations in cytokine receptor y chain that causes marked decrease in lymphocytes

X-linked SCID

What is the major difference between a primary and secondary immune response to a protein antigen?

Low-affinity IgM are mainly produced during the primary immune response

What are the characteristics of antibody responses to polysaccharides and lipids?

Low-affinity IgM are mainly produced

What is the function of the Fc region of antibody?

Complement activation

Molecules involved in the classical pathway of complement include:

C1 binds to Fc regions of IgM or IgG

The main function of the complement system includes:

Opsonization mediated by C3b

The main isotype of antibody found at the mucosal surfaces in the gut include:

IgA and IgM

The major histocompatibility complex I genes encode for

Human leukocyte antigens A, B, C

What is the half-life of IgG? Why is the duration of the half-life significant

18-23 days; it binds with neonatal Fc receptor

A hapten can best be describes as

A nonimmunogenic material capable of stimulating an immune response only when bound to a carrier protein

The primary purpose of neutrophil granules is to

Provide microbicidal action

Class II major histocompatibility complex genes encode for:

Molecules that present antigen to CD4+ T cells

Which antibody class is best described with the characterisitic that it best activates complement?

IgM

A mechanism by which regulatory T cells protect against autoimmunity include:

Blocking and removal of B7 costimulation on APC by CTLA-4