Which cells secrete interleukin-1?
Macrophages
What are the effects of interleukin-1 secretion?
Acute inflammation; interleukin-1 induces recruitment of leukocytes, activates the endothelium to express adhesion molecules, and serves as an endogenous pyrogen
What are the effects of interleukin-2?
Interleukin-2 stimulates growth of helper and cytotoxic T cells
What are the functions of interleukin-3?
Growth and differentiation of stem cells in the bone marrow
Which cell type secretes interleukin-3?
Activated T cells
What are the functions of interleukin-4?
Promotion of B-cell growth and induction of class switching to immunoglobulin E and immunoglobulin G
What is the function of interleukin-5? By what type of cells is it secreted?
Interleukin-5 is involved in promotion of differentiation of B cells and induction of class switching to immunoglobulin A; it also stimulates production and activation of eosinophils; it is ecreted by Th2 cells
What is the function of interleukin-6? By what cells is it produced?
Interleukin-6 stimulates production of acute-phase reactants and immunoglobulins; it is produced by helper T cells and macrophages
Which cytokine is a major chemotactic factor for neutrophils?
Interleukin-8
Which cell type secretes interleukin-8?
Macrophages
Which cytokine, released by regulatory T cells, inhibits actions of activated T cells?
Interleukin-10
What is the function of interleukin-12? Which cells secrete interleukin-12?
Interleukin-12 activates natural killer and Th1 cells; it is secreted by B cells and macrophages
What cytokine that is secreted by Th1 cells stimulates macrophages?
γ-Interferon
Which cytokine, secreted by macrophages, is an important mediator of septic shock?
Tumor necrosis factor
What are the effects of tumor necrosis factor secretion? By which cells is tumor necrosis factor secreted?
Tumor necrosis factor mediates leukocyte recruitment and vascular leak; it is secreted by macrophages
Which cytokine stimulates bone marrow?
Interleukin-3
Which cell surface proteins are found on helper T cells?
CD4, TCR, CD3, CD23, CD40L
Which cell surface proteins are found on cytotoxic T cells?
CD8, TCR, CD3
Which cell surface proteins are found on B cells?
IgM, CD19, CD20, CD21, CD40, MHCII, B7
Which cell surface proteins are found on macrophages?
MHCII, B7, CD40, CD14, receptors for Fc and C3b
Which cell surface proteins are found on natural killer cells?
Receptors for MHC I, CD16, CD56
True or False? All human cells have major histocompatibility complex I.
False; mature red blood cells do not have major histocompatibility complex I
Which two types of immunoglobulins activate complement via the classic pathway?
Immunoglobulin G and Immunoglobulin M
What triggers the activation of complement via the alternative pathway?
Microbial surfaces (especially endotoxin)
What triggers the activation of complement via the classic pathway?
Antigen-antibody complexes
What triggers the activation of complement via the lectin pathway?
Microbial surfaces
In the complement system, the plasma proteins C1, C2, C3, and C4 are important for the neutralization of what types of infectious agents?
Viruses
The membrane attack complex of complement is especially important in the defense against what type of bacteria?
Gram-negative bacteria
In the complement system, what is the function of the plasma protein C3b?
Opsonization
In the complement system, the activation of what two plasma proteins can cause anaphylaxis?
C3a and C5a
Which complement protein is responsible for neutrophil chemotaxis?
C5a
In the complement system, the membrane attack complex performs what function?
Cytolysis of target antigen
The membrane attack complex is composed of which complement proteins?
C5b, C6, C7, C8, and C9
The deficiency of what plasma protein leads to overactive complement and hereditary angioedema?
C1 esterase inhibitor
What are the clinical sequelae of hereditary complement C3 deficiency?
Recurrent pyogenic sinus and respiratory tract infections
In the complement system, the deficiency of which plasma proteins can predispose someone to Neisseria bacteremia?
C5-C8
In the complement system, the deficiency of which plasma protein leads to paroxysmal nocturnal hemoglobinuria?
Decay-accelerating factor
True or False? Decay accelerating factor and C1 esterase inhibitor help prevent complement activation on host cells.
TRUE
In the complement system, the cleavage of which plasma protein is the first shared step for both the alternative and classic pathways?
C5
What is the name for the complex of MC5b, 6, 7, 8, and 9 in the final step of the complement system, which lyses target cells?
Membrane attack complex
What are the two primary opsonins used to defend against bacteria?
C3b and immunoglobulin G
Name the class of plasma proteins secreted to place uninfected cells in an antiviral state and that inhibit viral protein synthesis.
Interferons
Name three mechanisms by which interferons interfere with viral protein synthesis.
Interferons induce viral mRNA-destroying proteins, increase major histocompatibility complex I and II expression, and activate natural killer cells to kill virus-infected cells
Which interferons increase major histocompatibility complex I and II expression and antigen presentation in all cells?
γ-Interferon
Which interferons inhibit viral protein synthesis?
-Interferon and -interferon induce production of ribonucleases that inhibit viral protein synthesis
Which cytokines activate natural killer cells to kill virus-infected cells?
Interferons
Interferons activate _____ (natural killer cells/macrophages) to kill virus-infected cells.
Natural killer cells
How does active immunity differ from passive immunity?
In active immunity, the host forms antibodies; in passive immunity, the host receives preformed antibodies
Give four examples of diseases for which preformed antibodies are given after exposure.
Tetanus, botulism, hepatitis B, and rabies (remember: To Be Healed Rapidly)
What is the approximate half-life of antibodies transferred from one host to another in passive immunity?
3 weeks
Which antigen in breast milk confers passive immunity to newborns?
Immunoglobulin A
Antigenic _____ (drift/shift) is the natural mutation over time of known strains of influenza to evade the immune system.
Drift; this is the source of the annual influenza epidemics
Antigenic _____ (drift/shift) is the process by which two strains of influenza combine to form a new subtype that has a mixture of the surface antigens of the two original strains.
Shift; this is the source of worldwide influenza pandemics such as the 2009 H1N1 flu
In what way does Salmonella bacteria exhibit antigenic variation?
Via flagellar variants
In what way does Neisseria gonorrhea exhibit antigenic variation?
Pilus protein variation
In what way does influenza demonstrate antigenic variation?
RNA shifts and drifts
In what way do trypanosomes demonstrate antigenic variation?
Programmed rearrangement
Describe the process of T-cell anergy.
Self-reactive T cells become nonreactive when they do not receive a costimulatory molecule
True or False? Both B cells and T cells can develop anergy to self-antigens, but B cells display more complete tolerance.
False; tolerance to self-antigens is greater in T cells than in B cells
List four bacterial infections that can cause granulomatous disease
Tuberculosis, syphilis, leprosy, and cat scratch fever
What are three noninfectious conditions associated with granulomatous disease?
Sarcoidosis, Crohn’s disease, berylliosis
Name the four cell types found in granulomas.
Epithelioid cells and giant cells are specialized macrophages; fibroblasts and lymphocytes are also found in granulomas
Which type of hypersensitivity reaction involves antigen cross-linking immunoglobulin E on mast cells and basophils, triggering the release of histamine?
Type I
Which type of hypersensitivity reaction develops rapidly after antigen exposure as a result of preformed antibody?
Type I
Which type of hypersensitivity reaction involves immunoglobulin M and immunoglobulin G binding to the body’s own cells, thereby leading to lysis by complement or phagocytosis?
Type II hypersensitivity reaction
Which type of hypersensitivity reaction causes fever, urticaria, arthralgias, proteinuria, and lymphadenopathy 5 to 10 days after antigen exposure?
Serum sickness (a type III hypersensitivity reaction)
Which type of hypersensitivity reaction is caused by immune complexes that activate complement and attract neutrophils that release lysosomal enzymes?
Type III
Which type of hypersensitivity reaction is the Arthus reaction?
Type III
What is the Arthus reaction?
A reaction caused when intradermal injection of an antigen leads to tissue edema and necrosis due to immune complex formation and complement activation (type III hypersensitivity reaction)
What is serum sickness?
An immune complex disease (type III hypersensitivity) in which antibodies to foreign proteins are produced and deposited in tissues where they fix complement and lead to tissue damage
What are the signs and symptoms of serum sickness?
Fever, urticaria, arthralgias, proteinuria and lymphadenopathy
How long does it take after exposure to antigen for the fever, urticaria, and arthralgias characteristic of serum sickness to develop?
5-10 days
What is the cause of most cases of serum sickness?
Drugs
What two components make up the immune complexes that cause type III hypersensitivity reactions?
Antigens and antibodies; antigen-antibody complexes activate complement to cause tissue damage
What type III sensitivity reaction is characterized by local edema, necrosis, and the activation of complement?
Arthus reaction
Which type of hypersensitivity reaction is mediated by T cells?
Type IV hypersensitivity reaction
What cellular processes underlie a type IV hypersensitivity reaction?
Sensitized T cells encounter antigen and then release lymphokines that lead to macrophage activation
How does the mnemonic ACID help one remember important features of the four different types of hypersensitivity reactions?
Type I: Anaphylactic and Atopic; type II: Cytotoxic (antibody mediated); type III: Immune complex; and type IV: Delayed (cell mediated)
What three mechanisms are involved in the tissue damage of antibody-mediated (type II) hypersensitivity reactions?
- Opsonization/activation of complement;
- antibody recruitment of neutrophils and macrophages leading to tissue damage;
- antibody binding to normal cells and interfering with function
Which two tests can evaluate whether a type II hypersensitivity reaction is causing hemolysis?
Direct and indirect Coombs tests
Which type of hypersensitivity reaction is provoked by a PPD injection?
Type IV
What are the 4 Ts associated with type IV hypersensitivity reactions?
T lymphocyte-mediated, Transplant rejection, TB skin tests, and Touching (contact dermatitis)
Which type of hypersensitivity reaction includes contact dermatitis?
Type IV
Which type of hypersensitivity reaction is anaphylaxis?
Type I
Which type of hypersensitivity reaction is allergic rhinitis?
Type I
Hemolytic anemia is a type _____ hypersensitivity reaction.
Type II
Which type of hypersensitivity reaction is pernicious anemia?
Type II
Idiopathic thrombocytopenic purpura is a type ____ hypersensitivity reaction.
Type II
Which type of hypersensitivity reaction is erythroblastosis fetalis?
Type II
Which type of hypersensitivity reaction describes rheumatic fever?
Type II
Goodpasture’s syndrome is caused by which type of hypersensitivity reaction?
Type II hypersensitivity reaction
Which type of hypersensitivity reaction causes the skin conditions bullous pemphigoid and pemphigus vulgaris?
Type II
Which type of hypersensitivity reaction is Graves’ disease?
Type II; Graves’ disease is a special case because the antibodies involved cause cell activation (thyroid hormone secretion) rather than tissue damage
Myasthenia gravis is a type _____ hypersensitivity reaction.
Type II
Which type of hypersensitivity reaction causes systemic lupus erythematosus?
Type III
Rheumatoid arthritis is a type _____ hypersensitivity reaction.
Type III; in the case of rheumatoid arthritis, the body’s own antibodies are the antigens to which the immune system reacts and forms immune complexes
Polyarteritis nodosa is a type _____ hypersensitivity reaction.
Type III
What type of hypersensitivity reaction causes poststreptococcal glomerulonephritis?
Type III hypersensitivity reaction
Swelling and inflammation following a tetanus vaccine represents the _____ _____, a type _____ hypersensitivity reaction.
Arthus reaction; type III
Hypersensitivity pneumonitis is a type _____ hypersensitivity reaction.
Type III
What type of hypersensitivity reaction causes Hashimoto’s thyroiditis?
T-cell-mediated type IV reaction
Which type of hypersensitivity reaction is type 1 diabetes mellitus?
Type IV
Multiple sclerosis is mediated by _____ (B/T) cells.
T cells; multiple sclerosis involves a type IV hypersensitivity reaction
Placement of a PPD test elicits which hypersensitivity reaction?
Type IV
True or False? Graft-versus-host disease and hyperacute transplant rejection are both antibody-mediated.
False: Graft-versus-host disease is a T-cell mediated hypersensitivity reaction (type IV); hyperacute transplant rejection is antibody-mediated, but is not a hypersensitivity reaction
Guillain-Barr syndrome is a type _____ hypersensitivity reaction.
Type IV
What disorder is most commonly associated with antinuclear antibodies?
Systemic lupus erythematosus (although antinuclear antibodies are nonspecific)
What disorder is most commonly associated with anti-double stranded DNA and anti-Smith autoantibodies?
Systemic lupus erythematosus (more specific than antinuclear antibodies)
What disorder is most commonly associated with antihistone autoantibodies?
Drug-induced lupus
What disorder is most commonly associated with anti-immunoglobulin G autoantibodies?
Rheumatoid arthritis (anti-immunoglobulin G antibodies are also known as rheumatoid factor)
What family of disorders is most commonly associated with anti-neutrophil (C-ANCA, P-ANCA) autoantibodies?
Vasculitides
What disorder is most commonly associated with anticentromere autoantibodies?
Scleroderma (CREST syndrome)
What disorder is most commonly associated with anti-Scl-70 (anti-DNA topoisomerase I) autoantibodies?
Scleroderma (diffuse)
What disorder is most commonly associated with antimitochondrial autoantibodies?
Primary biliary cirrhosis
What disorder is most commonly associated with antigliadin and antiendomysial autoantibodies?
Celiac disease
What disorder is most commonly associated with anti-basement membrane autoantibodies?
Goodpasture’s syndrome
What disorder is most commonly associated with antidesmoglein cell autoantibodies?
Pemphigus vulgaris
What disorder is most commonly associated with antimicrosomal autoantibodies?
Hashimoto’s thyroiditis
What autoantibodies are associated with Hashimoto’s thyroiditis?
Antimicrosomal and anti-thyroglobulin autoantibodies
What disorder is most commonly associated with anti-Jo-1 autoantibodies?
Polymyositis or dermatomyositis
Which two autoantibodies should be tested for if Sjögren’s syndrome is suspected?
Anti-SS-A (anti-Ro) and anti-SS-B (anti-La)
Mixed connective tissue disease can be associated with which autoantibodies?
Anti-U1 ribonucleoprotein
If autoimmune hepatitis is suspected, which autoantibodies should be tested?
Anti-smooth muscle antibodies
Anti-glutamate decarboxylase antibodies are most commonly associated with which autoimmune disease?
Type 1 diabetes mellitus
Wegener’s granulomatosis is a vasculitis associated with what autoantibody?
c-ANCA
What X-linked recessive genetic defect is associated with low levels of all classes of immunoglobulins and is caused by a defective tyrosine kinase gene?
Bruton’s agammaglobulinemia
Which X-linked recessive genetic defect is associated with recurrent bacterial infections after 6 months of age, when levels of maternal immunoglobulin G antibody decline?
Bruton’s agammaglobulinemia
Name the immune deficiency in which the thymus and parathyroids fail to develop.
DiGeorge’s syndrome (thymic aplasia)
Which immune deficiency is caused by failure of the third and fourth pharyngeal pouches to develop?
DiGeorge’s syndrome (thymic aplasia)
What are the clinical manifestations of DiGeorge’s syndrome?
Tetany as a result of hypocalcemia and recurrent viral and fungal infections caused by a T-cell deficiency
What is the inheritence pattern of Bruton’s agammaglobulinemia?
X-linked recessive
What immune deficiency is associated with congenital defects of the heart and great vessels and with 22q11 deletion?
DiGeorge’s syndrome (thymic aplasia)
Which cell line is diminished in thymic aplasia?
T cells
Which cell line is diminished in Bruton’s agammaglobulinemia?
B cells
Is severe combined immunodeficiency characterized by the diminished production of B cells, T cells, or both B and T cells?
Both B and T cells
Which immune deficiency is caused by the decreased activation of T cells and results in patients presenting with disseminated mycobacterial infections?
Interleukin-12 receptor deficiency
Which immune deficiency is caused by a defect in the CD40 ligand on CD4 helper T cells that results in an inability to switch antibody classes?
Hyper-IgM syndrome; B-cells can produce immunoglobulin M without class switching
Which immune deficiency presents early in life with severe pyogenic infections and affects patients with high serum levels of immunoglobulin M and low levels of immunoglobulins G, A, and E?
Hyper-IgM syndrome
Which immune deficiency is caused by a failure of γ-interferon production by helper T cells that results in neutrophils failing to respond to chemotactic stimuli?
Job’s syndrome
List the symptoms of Job’s syndrome; use the mnemonic FATED
Coarse Facies; noninflamed staphylococcal Abscesses, retained primary Teeth, increased immunoglobulin E levels, and Dermatologic problems
Does interleukin-12 receptor deficiency result in the diminished activation of B cells, T cells, or macrophages?
T cells lacking the receptor are not activated by interleukin-12; as a result they do not produce interferon-γ to activate macrophages
Is hyper-IgM syndrome characterized by the diminished activation of B cells, T cells, or macrophages?
B cells are unable to switch antibody classes due to absent CD40 signaling
Is Job’s syndrome characterized by the diminished activation of B cells, T cells, or neutrophils?
Neutrophils fail to respond to chemotactic stimuli due to a failure of interferon-γ production
Which immune deficiency presents early in life with severe pyogenic and fungal infections and delayed separation of the umbilicus?
Leukocyte adhesion deficiency syndrome
Which immune deficiency involves patients presenting with recurrent skin and mucous membrane Candida infections?
Chronic mucocutaneous candidiasis
Which immune cells are dysfunctional in chronic mucocutaneous candidiasis?
T cells
Which immune deficiency involves patients presenting with recurrent sinus and lung infections, milk allergies, and diarrhea?
Selective immunoglobulin A deficiency
What is the most common selective immunoglobulin deficiency?
Selective immunoglobulin A deficiency
Which immune deficiency disease presents with normal numbers of circulating B cells but a decreased number of plasma cells?
Common variable immunodeficiency
Patients with common variable immunodeficiency have an increased risk of which two noninfectious conditions?
Autoimmune disease and lymphoma
Which disease, caused by defective DNA repair, presents with visible dilated capillaries in the skin, cerebellar dysfunction, and immunoglobulin A deficiency?
Ataxia-telangiectasia
What X-linked immune deficiency is associated with elevated immunoglobulin A levels, normal immunoglobulin E levels, and low immunoglobulin M levels?
Wiskott-Aldrich syndrome
Which immune deficiency presents with a triad of symptoms that includes recurrent pyogenic infections, thrombocytopenic purpura, and eczema?
Wiskott-Aldrich syndrome
Which autosomal-recessive immune deficiency presents with recurrent pyogenic staph and strep infections, partial albinism, and peripheral neuropathy?
Chdiak-Higashi disease
Which autosomal-recessive immune deficiency is caused by defective microtubular function causing impaired phagocytosis?
Chdiak-Higashi disease
Which immune deficiency is caused by a defect in microbicidal capability of neutrophils resulting from a lack of NADPH oxidase?
Chronic granulomatous disease
The presence of which immune deficiency is confirmed with a negative nitroblue tetrazolium dye reduction test?
Chronic granulomatous disease
Which immune deficiency involves patients presenting with marked susceptibility to opportunistic infections with Staphylococcus aureus, Escherichia coli, and Aspergillus?
Chronic granulomatous disease; organisms that produce catalase resist neutrophil killing in this disease
What are three possible causes of severe combined immunodeficiency?
Failure to synthesize major histocompatibility complex II antigens, defective interleukin-2 receptors, or adenosine deaminase deficiency
Which immune deficiency results from a defect in LFA-1 (or CD18) on phagocytes?
Leukocyte adhesion deficiency syndrome
Which immune deficiency can result from a defect in stem cell differentiation and involves patients presenting with recurrent viral, bacterial, fungal, and protozoal infections?
Severe combined immunodeficiency; adenosine deaminase deficiency causes a failure of immune cell precursor maturation
Pro-T cells cannot mature when lacking which receptor?
Interleukin-2 receptor; a faulty receptor results in severe combined immunodeficiency
In DiGeorge syndrome _____ cannot fully mature.
Immature T cells
Severe combined immunodeficiency due to major histocompatibility complex II deficiency causes dysfunction of which immune cells?
CD4 T cells
Bruton’s agammaglobulinemia affects B-cell maturation at which point in development?
In Bruton’s, pre-B cells do not become immature B cells
Hyper-IgM syndrome results in a deficiency of which antibodies?
Immunoglobulin G, immunoglobulin A and immunoglobulin E; due to failure of class-switching
Which immune deficiency completely blocks further development of lymphoid stem cells?
Severe combined immunodeficiency due to adenosine deaminase deficiency
What disease results from an inability of B cells to become antibody-secreting plasma cells?
Common variable immunodeficiency
True or False? An autograft signifies that donor and recipient are the same person.
TRUE
A graft from an identical twin or clone is known as a ___ graft.
Syngeneic
An allograft is a graft taken from a non-identical individual from the _____ (same/different) species.
Same
A graft taken from a different species is known as a _______.
Xenograft
What is the cause of hyperacute rejection?
Preformed antidonor antibodies in the transplant recipient
True or False? In hyperacute rejection, the rejection of a donor organ occurs hours to days after transplantation.
False; rejection occurs within minutes as a result of the presence of preformed antidonor antibodies in the transplant recipient
What type of transplant rejection is cell mediated as a result of cytotoxic T cells reacting against foreign major histocompatibility complexes?
Acute rejection
How long after transplantation do patients develop symptoms of acute rejection? How can acute rejection be reversed?
Acute rejection occurs within weeks of transplantation; it can be reversed with immunosuppressants such as cyclosporine and muromonab-CD3 (OKT3)
True or False? Acute rejection can be reversed with immunosuppressants such as cyclosporine and muromonab-CD3 (OKT3).
TRUE
What process mediates chronic transplant rejection, and how can it be reversed?
Chronic rejection is caused by antibody- and T-cell-mediated vascular damage; it is irreversible
Which type of transplant rejection is caused by antibody- and T-cell-mediated vascular damage?
Chronic rejection
In chronic rejection of a transplant, vascular damage is mediated by _____ and _____.
Antibodies and T cells
What is the vascular damage in chronic rejection of a transplant called?
Obliterative vascular fibrosis
How long after transplantation do patients develop symptoms of chronic rejection?
Chronic rejection occurs over a period of months or years
What is the mechanism of graft-versus-host disease?
Grafted immunocompetent T cells proliferate in the immunocompromised host and reject cells with foreign proteins, resulting in host organ dysfunction
An organ transplant patient with a maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea may be suffering from what disease?
Graft-versus-host disease
True or False? Hyperacute, acute, and chronic transplant rejection are antibody-mediated processes.
False; only hyperacute and chronic transplant rejection are mediated by antibodies; acute rejection is cell mediated via cytotoxic T cells reacting against foreign major histocompatibility complexes
