13 Immunology (161) Flashcards
Case
A 43-year-old woman presents with a history of itchy eyes, dry mouth, and changes in her facial appearance for the past few months. During the physical exam, the patient shows dry eyes, white patches on the tongue, and enlargement of the parotid glands. There is no clinical evidence of active arthritis.
What antibody is most likely be positive in this patient?
1 Cytoplasmic antineutrophil cytoplasmic autoantibodies (C-ANCA)
2 Anti-DNA topoisomerase I antibodies (Scl-70)
3 Antinuclear antibodies AntiSm
4 Antinuclear antibodies ds-DNA
5 Anti-ribonucleoprotein antibodies SS-A (Ro)
Anti-ribonucleoprotein antibodies SS-A (Ro)
Sjögren syndrome is an autoimmune disease, most common in women, manifested usually by dry eyes and dry mouth as result of destruction of the lacrimal and parotid glands, which are enlarged (Mikulicz syndrome). These patients can also have mild arthritis, but sometimes Sjögren syndrome may also be associated with other autoimmune diseases, such as SLE, where the compromise of the joints can be more severe. Anti-ribonucleoprotein antibodies SS-A (Ro) and SS-B (La) are positive. Recent studies show that there are specific kinds of anticentromere antibodies that can be also positive.
Cytoplasmatic antineutrophil cytoplasmatic autoantibodies (C-ANCA) are positive in granulomatosis with polyangiitis.
Anti-DNA topoisomerase I antibodies (Scl-70) are positive in patients with diffuse scleroderma.
Antinuclear antibodies AntiSm and antinuclear antibodies ds-DNA are positive in systemic lupus erythematosus (SLE).
A 9-year-old boy presents with a rash on his buttocks. The patient states that the rash has been present for the past few days and is accompanied with joint pain in his knees and wrists. Blood work is drawn and is notable for a serum creatinine clearance of 1.3mg/dL. Vital signs are normal. Physical exam demonstrates palpable purpura on the buttocks. There is mild tenderness in the knee and wrist joints. The patient was diagnosed with Henoch-Schonlein purpura. Which of the following is the most likely mechanism of this disease?
1 Type I hypersensitivity
2 Type II hypersensitivity
3 Type III hypersensitivity
4 Type IV hypersensitivity
5 Type V hypersensitivity
Type III hypersensitivity
Henoch-Schonlein purpura occurs due to type III hypersensitivity reaction or immune-complex mediated reaction. Henoch-Schonlein purpura is a disease characterized by palpaple purpura, joint pain, gastrointestinal symptoms, and glomerulonephritis. The disease is usually seen in children, and is more common in boys than in girls. The mechanism of Henoch-Schonlein is a type III hypersensitivity also known as immune complex hypersensitivity. Other examples include serum sickness, SLE, arthus reactions, and rheumatoid arthritis.
Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.
Type II hypersensitivity is also known as cytotoxic hypersensitivity. The antigens are normally endogenous, although chemicals (i.e. drugs) can also lead to type II hypersensitivity. A classic example is myasthenia gravis.
Type IV is also known as delayed type hypersensitivity and is seen in tuberculosis, and poison ivy (contact dermatitis).
A reaction in which a directly stimulatory autoantibody acts through a target receptor is called Type V hypersensitivity reaction. An example is Graves’ disease in which the antibody against the TSH receptor stimulates the thyroid gland to cause hyperthyroidism.
You perform a kidney transplant on a 62 year-old male. Unfortunately, the lab mis-typed the organ and your patient begins to reject the graft within a week of receiving it. As your patient’s macrophages and cytotoxic T cells begin to reject the grafted organ, what cells specifically are they rejecting?
Answer Choices
1 Cells of the loop of Henle
2 Capillary endothelial cells
3 Granular juxtaglomerular cells
4 Glomerular capsular cells
5 Cells of the collecting tubules
Capillary endothelial cells
The first cells that the host’s immune system encounter are those of the capillaries in which they travel. All of the immune response is directed against these cells. Microthrombi form in the capillary beds of the transplanted organ and it dies from hypoxia.
A proud mother brings her healthy, six week old daughter in to your office for her first “shots.” As your nurse administers the vaccine, you reflect upon what you know about vaccines and humoral immunity. You realize that this infant is naive to the antigen that is being introduced to her system, so her initial antibody response will be weak. You take comfort in that subsequent introductions of the antigen will produce a more protective immune response. What class of antibodies will be produced by your young patient against the vaccine?
1 IgG1
2 IgG2
3 IgG3
4 IgM
5 IgE
IgM
Under normal circumstances, IgM is produced during the initial response to an antigen. Subsequent exposure to the same antigen results in class-switching by the B cells to produce IgG1.
What characteristics of IgM make it a good antibody for initial exposure to an antigen?
1 It does not fix complement very well, so it would be less likely for host cells to be damaged by complement
2 Its pentameric structure make it ideal for being secreted and binding to mucosal surfaces to protect the body from invading
organisms
3 Its low affinity and high avidity make it less specific but highly effective at binding to invading antigens
4 In its monomeric form, it binds readily to the surface of mast cells, which, in turn, can release inflammatory mediators that will help eliminate the antigen
Its low affinity and high avidity make it less specific but highly effective at binding to invading antigens
IgM is an excellent fixer of complement. Its pentameric form precludes IgM from leaving systemic circulation. Initial production of IgM has lower affinity but higher avidity due to multiple binding sites. This provides less opportunities for the antigen to escape. Monomeric IgM binds to B cells, not mast cells.
Which of the following interleukins that are produced by macrophages stimulate T helper 1 cell activity?
1 IL-1
2 IL-6
3 IL-12
4 TNF-α
5 IL-4
IL-12
IL-1 stimulates T helper 2 cell activity. IL-6 stimulate antibody production by B cells. IL-12 stimulates Th1 cells to produce IL-2 and IFN-α. TNF-α is not an interleukin. IL-4 is produced by Th2 cells.
In which of the following scenarios will tolerance to a foreign antigen be induced in T cells?
1 Binding of antigen by the TCR, but lack of secondary signal mediated through CD 28
2 During development, binding of MHC expressed on thymocytes by TCR on developing T cells
3 Specific antigens such as pneumococcal polysaccharide block the TCR, preventing further activation
4 Repeated exposure to high concentrations of antigen will result in clonal exhaustion
5 Addition of an antigen with an adjuvant will induce tolerance
Binding of antigen by the TCR, but lack of secondary signal mediated through CD 28
Binding of TCR and CD 28 is required for activation of a T cell. If TCR only is bound, the T cell will not respond to the antigen. While recognition of MHC on thymocytes is essential for T cells to become tolerant, this tolerance is to self-antigens. Certain antigens such as pneumococcal antigen or repeated exposure to high concentrations of antigen will induce tolerance in B cells, and have not been demonstrated to induce tolerance in T cells. Addition of an adjuvant to an antigen is a way to break tolerance.
Which of the following is an example of Type II hypersensitivity?
1 Acute serum sickness
2 Chronic serum sickness
3 Hemolytic disease of the newborn
4 Hypersensitivity pneumonitis
5 Metal allergies
Hemolytic disease of the newborn
Type II hypersensitivity is usually mediated through antibodies and complement and is directed against erythrocytes. Acute & chronic serum sickness as well as hypersensitivity pneumonitis are initiated by immune complex deposition within the walls of a capillary bed, and are examples of type III hypersensitivity. Metal allergies are classified as type IV hypersensitivity.
A delayed hypersensitivity reaction is characterized by
1 An infiltrate composed of eosinophils
2 An infiltrate composed of lymphocytes and macrophages
3 An infiltrate composed of neutrophils
4 Edema without cellular infiltrate
An infiltrate composed of lymphocytes and macrophages
Delayed hypersensitivity is a function of helper (CD4) T lymphocytes. The response starts hours after contact with antigen. It consists of mainly mononuclear cell infiltration (macrophages and helper [CD4] T cells) and tissue induration, an example of which is the tuberculin test.
Acute poststreptococcal glomerulonephritis is characterized by:
1 Low complement levels and lumpy deposits of immunoglobulin and C3 seen along the glomerular basement membranes
2 High levels of complement
3 Intravascular clumping of platelets
4 Tissue induration
Low complement levels and lumpy deposits of immunoglobulin and C3 seen along the glomerular basement membranes
Acute poststreptococcal glomerulonephritis is a well-accepted immune-complex disease. Its onset follows several weeks after a group A beta-hemolytic streptococcal infection esp with nephritogenic serotypes of Streptococcus pyogenes . The complement levels are low and lumpy deposits of immunoglobulin and C3 are seen along glomerular basement membranes by immunofluorescence suggesting the presence of antigen-antibody complexes. It is postulated that streptococcal antigen-antibody complexes, after being deposited on glomeruli, fix complement and attract neutrophils, which start the inflammatory process.
The principal difference between cytotoxic (type II) and immune complex (type III) hypersensitivity is
1 The participation of T cells
2 The participation of complement
3 The distribution of antigen-antibody complexes
4 The class (isotype) of antibody
The distribution of antigen-antibody complexes
Cytotoxic hypersensitivity occurs when antibody directed at antigens of the cell membrane activates the complement. This generates a membrane attack complex, which damages the cell membrane. Immune-complex hypersensitivity occurs when antigen-antibody complexes induce an inflammatory response in tissues. The immune complexes occasionally persist and are deposited in tissues, resulting in several disorders.
AIDS is caused by a human retrovirus that kills
1 CD8-positive T lymphocytes
2 CD4-positive T lymphocytes
3 Lymphocyte stem cells
4 B lymphocytes
CD4-positive T lymphocytes
Patients with AIDS have greatly reduced helper T cell numbers caused by infection with the retrovirus that specifically infects cells with the CD4 receptor. The HIV virus has type-specific envelope glycoproteins called gp120 and gp41. gp120 protrudes from the surface and interacts with the CD4 receptor on the cell surface. gp41 is embedded in the envelope and mediates the fusion of the viral envelope with the cell membrane at the time of infection.
An 11-year-old boy goes on his first camping trip to a National forest with his scout troop. Upon arrival, he eagerly hikes through the forest to the campout area to pitch his tent. The next day he complains of intense itching and has blistering on his hands, arms and legs. What is the most likely diagnosis?
1 Serum sickness
2 Hay fever
3 Arthus reaction
4 Contact dermatitis
5 Farmer’s lung disease
Contact dermatitis
The boy likely has allergic contact dermatitis (contact hypersensitivity) where he may have encountered poison oak or poison ivy in the forest or in the camp area. Contact dermatitis is a cell-mediated, type IV hypersensitivity reaction. Poison ivy or oak produces urushiols (small molecular weight oils on the leaves that act as immunogens) that penetrate the skin and act as haptens after binding to large carrier proteins to become complete antigens. No one is born with sensitivity to poison ivy but if exposed enough most people become sensitized and remain allergic. The sensitized person develops erythema, itching fluid-filled vesicles, and sometimes necrosis generally seen within 12-48 hours after contact.
Hay fever, or allergic rhinitis, is usually caused by pollen spores, and can occur within minutes of exposure to an allergen.
Serum sickness is an example of type III hypersensitivity and is an immune complex disease in which antibodies to foreign proteins are produced. Serum sickness is now caused by drugs (not serum) and is manifested by fever, itching, arthralgias, proteinuria, and lymphadenopathy which occur 5-10 days after antigen exposure.
Arthus reaction is a local subacute antibody-mediated type III hypersensitivity reaction. Intradermal injection of the antigen induces antibodies which form antigen-antibody complexes in the skin causing edema, necrosis, and activation of complement. An example is hypersensitivity pneumonitis.
Farmer’s lung disease results from inhalation of spores from Actinomycetes species such as in moldy hay. Early lesions are thought to be an immune complex type III hypersensitivity followed by granulomatous interstitial inflammation of the lungs characteristic of type IV cell-mediated responses. Farmer’s lung disease is the most frequently reported type of hypersensitivity pneumonitis.
Which of the following statements about processing of exogenous and endogenous antigen is correct?
1 Exogenous antigen is processed by B cells, macrophages, and dendritic cells and presented to T cells on MHC class I molecules
2 Endogenous antigen is processed by B cells, macrophages, and dendritic cells and presented to T cells on MHC class I molecules
3 Endogenous antigen is processed by body cells and presented to B cells on MHC class II molecules
4 Endogenous antigen is processed by body cells and presented to T cells on MHC class I molecules
5 Exogenous antigen is processed by body cells and presented to T cells on MHC class II molecules
Endogenous antigen is processed by body cells and presented to T cells on MHC class I molecules
Exogenous antigen is antigen taken up by antigen-presenting cells (macrophages, B cells, and dendritic cells) and presented on MHC class II molecules to T cells. Endogenous antigen is processed by cells of the body and presented to CD 8 T cells on MHC class I molecules. Expression of MHC class II is limited to cells of the immune system.
Which of the following best describes thymic independent antigens?
1 Somatic antigens that are presented outside the thymus
2 Antigens that activate the immune response without relying upon T cells
3 Antigens that are presented to T cells in sites other than the thymus
4 Antigens that induce the immune response in cells that mature within the thymus
5 Antigens that are protein in nature
Antigens that activate the immune response without relying upon T cells
Thymic independent antigens are antigens that stimulate an immune response without the presence of T helper cells. These are often bacterial carbohydrates such as pneumococcal polysaccharides.
CD 4+ lymphocytes play an active role in all but which of the following functions?
1 Activate cytotoxic T cells
2 Activate macrophages
3 Stimulate B cells to produce antibody
4 Present antigen
5 Secrete lymphokines
Present antigen
Antigen presentation is carried out by B cells, macrophages, and dendritic cells. CD 4 + T cells are “helper” cells that serve to activate both humoral and cell-mediated immunity.
CD 8+ lymphocytes play an active role in all but which of the following functions?
1 Lyse virally infected cells
2 Lyse tumor cells
3 Stimulate B cells to produce antibody
4 Suppress inappropriate immune
responses
5 Secrete lymphokines
Stimulate B cells to produce antibody
CD 8 + lymphocytes use MHC class I molecules to check for the presence of endogenous antigens. These antigens are produced in virally infected cells as well as is some tumor cells. Additionally, CD 8 + cells play a major role in avoidance of autoimmunity by either direct suppression or lysis of immune cells that respond to autoantigens. These cells secrete lymphokines as part of the immune response
B cells play an active role in all but which of the following functions?
1 Production of antibody
2 Secretion of lymphokines
3 Presentation of antigen
4 Induction of Type I hypersensitivity
5 Induction of Type IV hypersensitivity
Induction of Type IV hypersensitivity
B cells are primarily producers of antibodies. They do present antigen and secret low levels of lymphokines when doing so. IgE produced by B cells is instrumental in Type I hypersensitivity, or anaphylaxis. Type IV hypersensitivity is not mediated by antibodies
The immunoglobulin IgA is found primarily in what locations in the body?
1 On mucosal surfaces
2 In the serum
3 On the surface of mast cells
4 In the aqueous humor
5 In CNS
On mucosal surfaces
IgA is found primarily on mucosal surfaces. Although there is small amounts in circulation, it is found bound to bilirubin and other substances.
Which lymphokine initiates switching from IgM/IgD production to IgE production in B cells?
1 IL-2
2 IL-4
3 IL-5
4 IFN-γ
5 TNF-γ
IL-4
Interleukin 4 initiates switching from production of IgM/IgD to IgE in B cells. This is blocked by IFN-γ. Immunotherapy, or “allergy shots,” attempts to stimulate Th1 cells to produce IFN-γ.
Identify the immunological disease that results in high levels of IgE, but also the inability of neutrophils to respond to chemotactic stimuli.
1 Job’s syndrome
2 Chediak-Higashi syndrome
3 Wiskott-Aldrich syndrome
4 Fanguys syndrome
5 X-linked granulomatous disease
Job’s syndrome
Defects in antigen processing cells and innate immune response often lead to a wide variety of syndromes. Job’s syndrome is characterized by neutrophils that are unable to respond to chemotaxins.
Identify the immunological disease that results from a deficiency in C1 esterase inhibitor resulting in the indirect generation of vasoactive kinins
1 X-linked agammaglobulinemia
2 Hereditary angioedema
3 Common variable hypogammaglobulinemia
4 Adenosine deaminase and nucleotide phosphorylase deficiency
5 DiGeorge syndrome
Hereditary angioedema
When C1 esterase inhibitor is not produced, excessive production of vasoactive kinins results. This causes angioedema.
Identify the immunological disease that results in the inability to produce a specific immunoglobulin, attributable to recurrent bacterial infections during adolescence
1 X-linked agammaglobulinemia
2 Hereditary angioedema
3 Common variable hypogammaglobulinemia
4 Adenosine deaminase and nucleotide phosphorylase deficiency
5 DiGeorge syndrome
Common variable hypogammaglobulinemia
It is thought that recurrent bacterial infections during young adulthood, in concert with exhaustion of plasma cells leads to the loss of the ability to produce effective, long-term antibody protection.
Which of the following best describes DiGeorge syndrome?
1 Mild facial hypoplasia with below average levels of circulating immunoglobulins
2 Mild facial hypoplasia with inability of macrophages to process antigen
3 Mild facial hypoplasia with deficiencies in T cell number and function
4 Mild facial hypoplasia with high levels of serumal IgE
5 Mild facial hypoplasia with low affinity, low avidity binding capacity of IgG
Mild facial hypoplasia with deficiencies in T cell number and function
DiGeorge syndrome is a congenital hypoplasia of the IIIrd and IV th pharyngeal arches resulting in facial, thymic and parathyroid hypoplasia. T cell numbers and functions are drastically decreased. Transplants of thymic tissues are currently being evaluated as a treatment modality for DiGeorge syndrome.