IMUNOLOGY Flashcards
What is the primary function of lymph in the immune system?
Lymph is interstitial fluid that drains from tissues and enters the lymphatic system.
Its primary function is to circulate through lymph nodes and activate the immune system in response to pathogens present in tissues.
Lymph eventually drains into the subclavian veins and returns to the venous system.
What are the primary and secondary lymphoid organs, and their roles?
-
Primary lymphoid organs: Where lymphocytes form and mature.
* Bone marrow: Produces B and T cells, maturates B cells.
* Thymus: Maturation site for T cells. -
Secondary lymphoid organs: Sites where B and T cells activates and proliferate in response to infections.
Includes: lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT) (e.g., tonsils, Peyer’s patches in the intestines)
What are T-cells and where do they mature?
T-cells are part of the adaptive immune system.
They mature in the thymus.
What types of antigens can T-cells recognize?
T-cells recognize only peptide antigens.
Polysaccharides (like in bacterial capsules) cannot be recognized by T-cells.
What are MHC Class I and II, and what do they present?
Major Histocompatibility Complex
MHC Class I molecules are found on the surface of all nucleated cells. They present endogenous (intracellular) antigens, such as viral peptides, to CD8+ cytotoxic T cells.
MHC Class II molecules are expressed mainly on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells. They present exogenous (extracellular) antigens, derived from pathogens or foreign particles taken up by the cell, to CD4+ helper T cells.
What is MHC restriction?
T-cells only react to antigens presented on self-MHC molecules.
What is the role of CD3 in T-cell activation?
CD3 complex transmits the signal from the bound T-cell receptor (TCR) into the T-cell, initiating the immune response.
What are the two main subsets of T-cells and their functions?
- CD4+ T-cells (helper T-cells) coordinate immune responses:
1. Stimulate B-cells to produce antibodies and class switch.
2. Activate CD8 T-cells (cytotoxic T-cells)
3. Activate macrophages. - CD8+ T-cells (cytotoxic T-cells) kill virus-infected and tumor cells by recognizing antigens presented by MHC Class I molecules
What are Th1 and Th2 cells and their functions?
Th1 and Th2 cells are mature CD4 T-cells
- Th1: Promote cell-mediated immunity (activate CD8+ cells, macrophages). Important for intracellular infections.
- Th2 cells: Promote humoral immunity (activate B-cells). Important for extracellular infections and allergic responses.
What cytokines are associated with Th1 and Th2 cells and their roles?
Th1:
Cytokines Th1 differentiation promoters:
* IL12 secreated from APCs
* INF-γ secreated by NK and Th1
Cytokines Th1 response mediators:
* IL-2 –> stimulate T-cells growth, activate B-cells and NK
* INF-γ –> activates macrophages and Th1 response, promotes MHC expression, suppresses TH2 response.
Th2:
Cytokine Th2 differentiation
promoter:
* IL-4 secreated by Th2 and mast cells
Cytokines Th2 response mediators:
* IL-4 –> promotes IgE production, suppresses TH1and activate Th2 response
* IL-5 –> activates eosinpphils and promote IgA production
* IL-10 –> anti-inflammatory, suppresses TH1 response
What is co-stimulation in T-cell activation?
CD28 on T-cells must bind to B7 on APCs along with MHC-TCR binding to fully activate T-cells.
What are the differences between Th1 and Th2 responses in diseases?
Back:
Th1 response: Key for intracellular infections like TB, granulomatous diseases, listeria.
Th2 response: Key for extracellular infections, allergic responses, and humoral immunity (IgE and IgA).
How do CD8+ T-cells kill infected cells?
CD8+ T-cells use perforins, granzymes, and granulysin to induce apoptosis in infected cells.
They also use the Fas-FasL pathway (extrinsic apoptosis pathway).
What is the role of regulatory T-cells (Tregs)?
Tregs suppress the immune response to prevent autoimmunity.
They express CD25 and produce anti-inflammatory cytokines like IL-10 and TGF-beta.
What are Th17 cells, and why are they important?
Th17 cells produce IL-17 and are essential for mucosal immunity, particularly in the GI tract.
They recruit neutrophils and macrophages and are involved in protection against bacterial infections.
What is the function of the thymus in T-cell development?
Back:
The thymus is where T-cells mature, undergoing positive and negative selection to ensure they can bind MHC but do not bind strongly to self-antigens.
What is positive and negative selection in the thymus?
Positive selection: T-cells that can bind self-MHC survive.
Negative selection: T-cells that bind too strongly to self-antigens undergo apoptosis.
What are AIRE genes, and what happens if they are defective?
AIRE genes help thymus cells express self-antigens for T-cell selection.
Mutations in AIRE genes lead to autoimmune diseases like chronic mucocutaneous candidiasis and endocrine disorders.
What are superantigens, and how do they affect T-cells?
Superantigens activate a massive number of T-cells by linking MHC and TCR directly.
This leads to a huge release of cytokines (like IFN-γ and IL-2), causing toxic shock syndrome.
Question 1:
A 25-year-old woman receives a tuberculin skin test (PPD) for tuberculosis screening. Forty-eight hours after injection, she develops an indurated and erythematous area at the site of injection. This reaction is primarily due to the activity of which of the following?
A. B-cells producing antibodies against Mycobacterium tuberculosis antigens
B. Neutrophils directly lysing Mycobacterium tuberculosis-infected cells
C. CD8+ T-cells recognizing Mycobacterium tuberculosis antigens on MHC Class I
D. Th1 CD4+ T-cells releasing interferon-gamma and activating macrophages
E. Th2 CD4+ T-cells releasing IL-4 to promote antibody production
Answer: D
Rationale: The PPD test is an example of a delayed-type hypersensitivity reaction (Type IV), which is mediated by Th1 CD4+ T-cells. These T-cells release interferon-gamma to activate macrophages, resulting in local swelling and erythema.
A 5-year-old boy presents with recurrent bacterial and viral infections. Genetic testing reveals a defect in the IL-12 receptor on his T-cells. What immune function would be most impaired in this patient?
A. Antibody production by B-cells
B. Activation of CD8+ cytotoxic T-cells by IL-2
C. Activation of Th2 cells and humoral immunity
D. Activation of Th1 cells and macrophage-mediated immunity
E. Differentiation of regulatory T-cells
Answer: D
Rationale: IL-12 is critical for the differentiation of naive CD4+ T-cells into Th1 cells. Th1 cells produce interferon-gamma, which activates macrophages to combat intracellular pathogens. A defect in the IL-12 receptor results in impaired Th1 response and susceptibility to intracellular pathogens like mycobacteria and salmonella.
Question 3:
A 30-year-old man is diagnosed with lepromatous leprosy, characterized by diffuse skin lesions and poor immune control of the disease. Biopsy of the skin lesions reveals numerous intracellular Mycobacterium leprae organisms. Which of the following best describes the predominant immune response in this patient?
A. Strong Th1 response with interferon-gamma production
B. Strong Th2 response with IL-4 and IL-10 production
C. Excessive neutrophil recruitment by Th17 cells
D. Excessive Treg cell activity suppressing CD8+ cytotoxicity
E. Deficient Th1 response with lack of IL-2 production
Answer: B
Rationale: Lepromatous leprosy is associated with a predominant Th2 response, which is inadequate for controlling intracellular infections like Mycobacterium leprae. Th2 cells secrete IL-4 and IL-10, promoting humoral immunity but failing to activate macrophages effectively.
Answer: B
Rationale: Lepromatous leprosy is associated with a predominant Th2 response, which is inadequate for controlling intracellular infections like Mycobacterium leprae. Th2 cells secrete IL-4 and IL-10, promoting humoral immunity but failing to activate macrophages effectively.
Question 4:
A researcher is studying the role of regulatory T-cells (Tregs) in preventing autoimmunity. Tregs are known to suppress immune responses through the production of which of the following cytokines?
A. IL-2 and interferon-gamma
B. IL-4 and IL-5
C. IL-10 and TGF-beta
D. TNF-alpha and IL-12
E. IL-17 and IL-23
Answer: C
Rationale: Regulatory T-cells (Tregs) suppress the immune response primarily through the production of anti-inflammatory cytokines such as IL-10 and TGF-beta. These cytokines prevent excessive immune activation and help maintain self-tolerance, reducing the risk of autoimmune disease.
Question 5:
A 40-year-old man presents with fever and shock after a recent surgery. Blood cultures grow Staphylococcus aureus, and toxic shock syndrome is suspected. The bacterial toxin causing this syndrome acts by stimulating a large number of T-cells. Which of the following mechanisms best explains this phenomenon?
A. The toxin binds to the T-cell receptor and MHC Class I, inducing CD8+ T-cell proliferation
B. The toxin binds directly to the MHC Class II-TCR complex, bypassing antigen processing
C. The toxin induces B-cell class switching to produce IgE
D. The toxin stimulates neutrophil recruitment to the infection site
E. The toxin inhibits regulatory T-cell function, leading to autoimmunity
Answer: B
Rationale: Superantigens like the toxic shock syndrome toxin (TSST-1) produced by Staphylococcus aureus bind directly to the MHC Class II molecule and the T-cell receptor (TCR) outside of the normal antigen-binding groove. This bypasses normal antigen processing and leads to massive, non-specific T-cell activation and cytokine release, resulting in toxic shock.
How do lymph nodes contribute to the immune system?
Lymph nodes filter lymphatic fluid and provide a site for immune cells to interact with antigens. They contain B and T cells, and they are sites where immune responses are initiated against pathogens that have entered the lymphatic system.
What are the major structural components of a lymph node?
The major structural components of a lymph node include the cortex, paracortex, medulla, afferent lymphatic vessels, efferent lymphatic vessels, and sinuses. The cortex contains follicles with B cells, the paracortex houses T cells, and the medulla contains plasma cells and macrophages.
What is the function of the thymus?
Back: The thymus is the site of T-cell maturation and differentiation. It is particularly active during early life, and it shrinks (undergoes involution) as a person ages. T cells learn to distinguish self from non-self in the thymus.
What is the role of the bone marrow in the immune system?
Back: The bone marrow is the primary site of hematopoiesis, where all blood cells, including immune cells (B-cells, T-cell precursors, macrophages, etc.), are produced. It is also the site of B-cell maturation
What are the main functions of the spleen in immunity?
Back: The spleen filters blood, removes old red blood cells, and is a major site of immune surveillance and response. It houses both red pulp (which filters blood) and white pulp (which contains immune cells like lymphocytes).
What is the primary role of the paracortex in lymph nodes?
Back: The paracortex contains mainly T cells and dendritic cells. It is where T cells become activated after encountering antigen-presenting cells (APCs), like dendritic cells. It expands during cell-mediated immune responses (e.g., viral infections).
What is found in the medulla of a lymph node, and what is its function?
Back: The medulla contains medullary cords (full of plasma cells secreting antibodies) and medullary sinuses (which contain macrophages). It plays a crucial role in filtering lymph and initiating immune responses through antigen-antibody interactions.
What is the function of germinal centers in lymph nodes?
Back: Germinal centers are sites within secondary follicles where B cells proliferate, differentiate, and undergo somatic hypermutation to produce high-affinity antibodies during an immune response. They play a critical role in adaptive immunity.
What is the role of the sinuses in lymph nodes?
Sinuses (subcapsular, trabecular, and medullary) are spaces that allow lymph to flow through the node. They are lined with macrophages, which trap and process pathogens and debris for presentation to lymphocytes.
Postsplenectomy findings:
- Howell-Jolly bodies (nuclear remnants)
- Target cells
- Thrombocytosis (loss of sequestration and
removal) - Lymphocytosis (loss of sequestration)
What are the two main regions of the spleen, and what are their functions?
The spleen consists of two main regions:
Red pulp: Responsible for filtering and removing old or damaged red blood cells (RBCs).
White pulp: Involved in immune surveillance, containing lymphocytes that respond to blood-borne pathogens.
What is the role of the red pulp in the spleen?
The red pulp filters the blood, removes old or damaged red blood cells and platelets, and stores iron from hemoglobin breakdown. It also contains macrophages that help clear pathogens and debris.
What immune cells are found in the white pulp, and what is their function?
The white pulp contains B and T lymphocytes. B cells are found in follicles and produce antibodies, while T cells are located in the periarteriolar lymphoid sheath (PALS), where they respond to blood-borne antigens
What is the PALS, and what is its function in the spleen?
The periarteriolar lymphoid sheath (PALS) is a region of the white pulp surrounding central arterioles. It contains mainly T cells and is where T-cell activation occurs when they encounter antigens carried in the blood.
What is the marginal zone of the spleen, and why is it important?
The marginal zone lies between the red and white pulp and contains specialized macrophages and B cells. It is important for trapping antigens from the bloodstream and initiating an immune response, particularly against encapsulated bacteria.
What is the role of splenic macrophages in immunity?
Splenic macrophages, located in the red pulp and marginal zone, are responsible for phagocytosing old red blood cells and pathogens. They also present antigens to lymphocytes to initiate an immune response.
Does the spleen store blood? If so, what is stored and why?
Yes, the spleen stores platelets and red blood cells in its red pulp. It acts as a blood reservoir, releasing these cells during times of hemorrhage or increased demand for oxygen, such as during physical activity or trauma.
What is the primary function of the thymus?
The thymus is the site of T-cell maturation and differentiation. Immature T cells (thymocytes) migrate from the bone marrow to the thymus, where they undergo positive and negative selection to ensure self-tolerance and proper immune function.
What are the two main regions of the thymus, and what are their roles?
The thymus consists of:
Cortex: The outer region where immature T cells (thymocytes) undergo positive selection.
Medulla: The inner region where thymocytes undergo negative selection to eliminate self-reactive T cells.
What is positive selection in the thymus, and where does it occur?
Positive selection occurs in the thymic cortex, where T cells are tested for their ability to recognize self-MHC molecules. Only T cells that can bind to self-MHC molecules with moderate affinity survive, while others undergo apoptosis.
What is negative selection in the thymus, and where does it occur?
Back: Negative selection occurs in the thymic medulla. T cells that strongly bind to self-antigens presented by MHC molecules are eliminated through apoptosis to prevent autoimmunity. This process ensures self-tolerance.
What happens to thymocytes in the cortex of the thymus?
In the cortex, immature thymocytes undergo positive selection. They are tested for their ability to bind self-MHC molecules, and those that successfully bind with moderate affinity survive and move to the medulla for further development
What is the function of the thymic medulla in T-cell maturation?
The thymic medulla is responsible for negative selection, where thymocytes that strongly bind self-antigens are eliminated to prevent autoimmunity. Only T cells with weak or moderate affinity for self-antigens survive and mature.
What are Hassall’s corpuscles, and what is their function in the thymus?
Hassall’s corpuscles are structures found in the medulla of the thymus. They consist of epithelial cells and may play a role in the regulation of T-cell maturation and in promoting the development of regulatory T cells (Tregs).
What are the stages of T-cell development in the thymus?
T cells develop through several stages:
Double-negative (CD4−/CD8−): Immature T cells lack both CD4 and CD8 markers.
Double-positive (CD4+/CD8+): T cells express both CD4 and CD8 markers as they undergo positive selection.
Single-positive (CD4+ or CD8+): After positive and negative selection, T cells become either CD4+ helper T cells or CD8+ cytotoxic T cells.
What is the role of the AIRE gene in the thymus?
The AIRE gene (Autoimmune Regulator) is expressed in the thymic medulla and helps present self-antigens to developing T cells during negative selection. AIRE is crucial for eliminating self-reactive T cells, and mutations in AIRE can lead to autoimmune diseases like autoimmune polyendocrine syndrome type 1 (APS-1).
How does DiGeorge syndrome affect the thymus?
DiGeorge syndrome results from a deletion in chromosome 22, leading to thymic hypoplasia or aplasia. This results in T-cell deficiency, causing immunodeficiency and increased susceptibility to infections. It is associated with the absence or underdevelopment of the thymus.
Thymoma associations:
Myasthenia gravis
Superior vena cava syndrome
Pure red cell aplasia
Good syndrome
What is innate immunity?
Innate immunity is the first line of defense against pathogens. It is non-specific, present at birth, and responds rapidly to infections. It includes physical barriers (e.g., skin, mucosa), cellular defenses (e.g., macrophages, neutrophils), and chemical mediators (e.g., cytokines, complement system).
What is the role of macrophages in innate immunity?
Back: Macrophages are phagocytic cells that engulf and destroy pathogens, dead cells, and debris. They also produce cytokines that recruit other immune cells to the site of infection and present antigens to T cells, bridging innate and adaptive immunity.
How do neutrophils function in innate immunity?
Neutrophils are the most abundant white blood cells and the first to arrive at sites of infection. They kill pathogens through phagocytosis, release of reactive oxygen species, and secretion of antimicrobial enzymes. They also form neutrophil extracellular traps (NETs) to capture microbes.
What is the role of natural killer (NK) cells in innate immunity?
NK cells target and kill virus-infected cells and tumor cells. They do this by recognizing cells that have downregulated MHC I, a common feature of infected or transformed cells, and releasing cytotoxic granules to induce apoptosis.
What is the complement system, and how does it function in innate immunity?
The complement system is a series of proteins that enhance the ability of antibodies and phagocytic cells to clear pathogens. It promotes inflammation, opsonization (coating of pathogens for easier phagocytosis), and formation of the membrane attack complex (MAC), which directly lyses pathogens.
What are the three pathways of complement activation?
Alternative pathway: Spontaneous conversion of C3 to C3B.
Lectin pathway: Mannose-binding lectin binds mannose on pathogens, leading to C3B production, from C2b-C4b (C3 convertase).
Classical pathway: Activated by antigen-antibody complexes, leading to C3B formation, from C1- Antibody-antigen complex and C2b-C4b.
What is the function of C3B in the complement system?
C3B binds to bacterial surfaces, leading to bacterial cell death and the formation of the membrane attack complex (MAC). It can also act as an opsonin to promote phagocytosis by macrophages.
What is the membrane attack complex (MAC)?
The MAC is formed by complement proteins C5 to C9. It pokes holes in the bacterial cell membrane, leading to bacterial lysis and death.
C3b cleaves C5 and form C5b that binds to C6-9 = MAC
What are anaphylatoxins in the complement system?
C3A and C5A are anaphylatoxins.
- Stimulates histamine release and increases vascular permeability, possibly contributing to anaphylaxis.
C5A also recruits neutrophils to sites of complement activation (neutrophil chemotaxis).
What role does Factor H play in the complement system?
Factor H inhibits the alternative pathway of complement on host cells by accelerating the decay of C3 convertase and inactivating surface-bound C3B, protecting host cells from destruction.
What is the function of DAF (CD55) and CD59?
DAF (CD55) disrupts C3B attachment to prevent MAC formation.
CD59 directly inhibits the formation of the MAC.
Both protect host cells, particularly red blood cells, from complement-mediated lysis.
What are de the complement system regulation?
Factor H: inhibits the alternative pathway of complement on host cells by accelerating the decay of C3 convertase and inactivating surface-bound C3B.
DAF (CD55): disrupts C3B attachment to prevent MAC formation
CD59: directly inhibits the formation of the MAC.
What is the mechanism of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
PNH is caused by a deficiency in DAF (CD55) or CD59, leading to complement-mediated lysis of red blood cells. Symptoms include anemia, hemoglobinuria, abdominal pain, erectile dysfunction, and thrombosis.
What is hereditary angioedema?
A deficiency in C1 inhibitor (break down bradukinin) protein leads to unregulated bradykinin activity, causing recurrent episodes of swelling (angioedema), especially in the face, throat, and GI tract.
What medication should be avoid in patientes with Hereditary Angioedema and why?
ACE inhibitors should be avoided as they exacerbate symptoms by preventing bradykinin breakdown.
What are the clinical consequences of C3 deficiency?
Recurrent infections with encapsulated bacteria (e.g., pneumococci and Haemophilus influenzae).
Increased susceptibility to autoimmune diseases due to impaired clearance of immune complexes (C3b will not be formed and will not draw macrophage to clear antibody-antigen complexes):
- Glomerular nephritis from immune complex deposition in their kidneys
- Type III hypersensitivity syndromes
What is the significance of terminal complement pathway deficiencies (C5-C9)?
Deficiencies in C5 to C9 impair MAC formation, leading to recurrent Neisseria infections, especially Neisseria meningitidis.
What is the role of C1 in the classical complement pathway?
C1 binds to two Fc portions of antibodies close together (e.g., IgM), activating C1R and C1S to cleave C2 and C4, leading to the formation of C3 convertase and subsequent C3B production.
Why is IgM a better activator of the classical pathway than IgG?
IgM is a pentamer with multiple Fc regions close together, making it easier to activate C1 (needs two Fc portions bond) and the classical complement pathway, while IgG requires two molecules to be close together to achieve this.
What are the two main tests for complement system function?
CH50 test: Assesses the classical pathway by measuring the lysis of sheep red blood cells.
C3/C4 levels: Quantifies complement consumption and helps diagnose complement-mediated diseases like lupus nephritis.
What is the role of C3 nephritic factor in membranoproliferative glomerulonephritis type II?
C3 nephritic factor is an autoantibody that stabilizes C3 convertase, leading to excessive complement activation, hypocomplementemia, and kidney damage.
How does CRP (C-reactive protein) interact with the complement system?
CRP binds to bacterial polysaccharides, activating the early classical pathway and consuming C3 and C4, but it does not activate the terminal complement pathway
What is the role of C5B in MAC formation?
C5B binds to C6, C7, C8, and C9 to form the MAC, which pokes holes in bacterial cell membranes, leading to bacterial death.
A 3-year-old child presents with recurrent episodes of meningitis caused by Neisseria meningitidis. Laboratory analysis reveals normal levels of C3, but flow cytometry shows a deficiency of the complement proteins C6 through C9. Which of the following is the most likely underlying cause of the patient’s susceptibility to these infections?
A) Impaired formation of C3 convertase
B) Inability to form the membrane attack complex (MAC)
C) Impaired opsonization of bacteria
D) Defective Factor H production
E) Excessive activation of C1 complex
A 34-year-old man presents with sudden onset hemoglobinuria in the morning and fatigue. His medical history includes several episodes of thrombosis in unusual locations, such as the portal vein and cerebral veins. Flow cytometry reveals a deficiency of CD55 (DAF) and CD59 on his red blood cells. Which of the following best explains his symptoms?
A) Unregulated MAC formation on host cells
B) Increased clearance of immune complexes
C) Lack of C3 convertase formation
D) Increased C5A production causing neutrophil chemotaxis
E) Defective C1 inhibitor activity leading to excess bradykinin
Unregulated MAC formation on host cells
A) Correct: MAC forms without regulation, causing hemolysis in PNH
B) Increased immune complex clearance (not applicable to PNH)
C) C3 convertase formation unaffected in PNH
D) C5A production is unrelated to hemolysis in PNH
E) Bradykinin relates to hereditary angioedema, not PNH
A 25-year-old woman with a history of recurrent skin and throat infections presents to the clinic with facial swelling. Her father had similar symptoms. Laboratory testing shows a normal C3 and C4 level, but the C1 inhibitor protein level is undetectable. Which of the following best describes the patient’s condition?
A) Complement-mediated lysis of red blood cells
B) Overactivation of the lectin pathway
C) Increased bradykinin leading to recurrent angioedema
D) Increased susceptibility to Neisseria infections
E) Autoantibody-mediated C3 nephritis
Increased bradykinin leading to recurrent angioedema
A) RBC lysis (related to PNH, not applicable here)
B) Lectin pathway overactivation (not involved)
C) Bradykinin increase (correct) due to C1 inhibitor deficiency
D) Neisseria susceptibility (linked to C5-C9, not C1 inhibitor)
E) Autoimmune C3 nephritis (related to C3 nephritic factor, not this case)
A 4-year-old child presents with a history of recurrent respiratory infections. Blood work shows a low C3 level, and genetic testing reveals a mutation leading to complete deficiency of the C3 protein. Which of the following is most likely impaired in this patient?
A) Opsonization of bacteria
B) Formation of C5 convertase
C) Decay of C3 convertase on host cells
D) Activation of mannose-binding lectin
E) Activation of the C1 complex
Opsonization of bacteria
A) Opsonization of bacteria: Correct. C3b is a key opsonin that enhances phagocytosis of pathogens.
B) Formation of C5 convertase: Impaired as C3 is needed to generate C5 convertase.
C) Decay of C3 convertase on host cells: Factor H and DAF regulate this, not C3 deficiency.
D) Activation of mannose-binding lectin: Part of the lectin pathway, not directly dependent on C3.
E) Activation of the C1 complex: Involves the classical pathway, not C3-dependent.
A 5-year-old girl presents with recurrent respiratory tract infections and nephritic syndrome. Renal biopsy shows immune complex deposition in the glomeruli. Further testing shows low C3 levels but normal C4 levels. Which of the following is the most likely diagnosis?
A) Systemic lupus erythematosus
B) Hereditary angioedema
C) Membranoproliferative glomerulonephritis type II
D) Paroxysmal nocturnal hemoglobinuria
E) Classic pathway complement deficiency
Diagnosis: Membranoproliferative glomerulonephritis type II (MPGN II)
MPGN II: Low C3, normal C4, immune complex deposition in glomeruli.
Other options:
SLE: Both C3 and C4 are low.
Hereditary angioedema: Linked to C1 inhibitor deficiency (bradykinin-mediated swelling, not nephritis).
PNH: Complement-mediated hemolysis, not nephritis.
A patient with hereditary angioedema presents to the emergency department with severe swelling of the lips and throat. The patient is immediately treated with epinephrine, but her symptoms do not improve. Which of the following is the best explanation for why epinephrine was ineffective?
A) Bradykinin levels are elevated due to C1 inhibitor deficiency
B) Histamine is the primary mediator of the patient’s condition
C) Complement activation is responsible for the swelling
D) The alternative pathway of complement activation is hyperactive
E) Factor H deficiency leads to excessive complement activation
Reduced form for flashcard back:
Answer: A) Bradykinin levels are elevated due to C1 inhibitor deficiency
Hereditary angioedema: Caused by C1 inhibitor deficiency → elevated bradykinin.
Bradykinin causes swelling; epinephrine is ineffective.
Not histamine or complement activation directly.
Treatment: C1 inhibitor concentrate or bradykinin-targeted therapies.
A 30-year-old woman presents with fatigue and hematuria. Her symptoms have been recurring for several months. She has a family history of glomerulonephritis. Laboratory results show low serum C3 and C4 levels and the presence of an autoantibody stabilizing C3 convertase. Which of the following is the most likely diagnosis?
A) C3 nephritic factor-related glomerulonephritis
B) Systemic lupus erythematosus
C) Hereditary angioedema
D) Paroxysmal nocturnal hemoglobinuria
E) C5-C9 complement deficiency
Diagnosis: C3 nephritic factor-related glomerulonephritis
Key Point: Autoantibody stabilizes C3 convertase, causing low C3/C4.
B) SLE: Causes low C3/C4 but no C3 convertase stabilization.
C) Hereditary angioedema: Linked to C1 inhibitor deficiency.
D) PNH: Causes hemolysis, not glomerulonephritis.
E) C5-C9 deficiency: Leads to Neisseria infections, not kidney disease.
A 45-year-old man with a history of cirrhosis presents with fever and chills. Blood cultures grow Streptococcus pneumoniae. Further testing reveals impaired opsonization but normal CH50 levels. Which of the following proteins is most likely deficient in this patient?
A) C1
B) C3B
C) C5
D) C9
E) Mannose-binding lectin
Answer: B) C3B
C3B is crucial for opsonization, marking pathogens for phagocytosis. Normal CH50 indicates a functioning classical pathway, but impaired opsonization suggests a C3B deficiency.
C1: Would lower CH50.
C5: Affects MAC, not opsonization.
C9: Lowers CH50, no effect on opsonization.
Mannose-binding lectin: Involves lectin pathway, unrelated to opsonization.
A 7-year-old boy presents with recurrent episodes of meningitis caused by Neisseria meningitidis. His C3 and C4 levels are normal. Which of the following complement deficiencies is most likely responsible for his infections?
A) C2
B) C5
C) C3
D) Factor H
E) DAF (CD55)
Answer:
B) C5 - Deficiency in C5-C9 leads to impaired MAC formation, increasing susceptibility to Neisseria infections.
A) C2 deficiency is linked to immune complex diseases, not Neisseria.
C) C3 deficiency causes severe bacterial infections, but C3 levels are normal.
D) Factor H affects regulation of complement but isn’t linked to Neisseria.
E) DAF deficiency leads to PNH, not recurrent infections.
A 28-year-old patient with a history of recurrent infections is found to have low C3 levels and is diagnosed with a deficiency in the alternative pathway of the complement system. Which of the following processes is most likely affected in this patient?
A) Spontaneous conversion of C3 to C3B
B) Activation of C1 by antigen-antibody complexes
C) Cleavage of C4 to C4B
D) Formation of the MAC
E) Activation of mannose-binding lectin
A) Spontaneous conversion of C3 to C3B - Correct. The alternative pathway relies on the spontaneous conversion of C3 to C3B, essential for pathogen opsonization and complement activation.
B) Activation of C1 by antigen-antibody complexes - Classical pathway, not the alternative.
C) Cleavage of C4 to C4B - Part of classical and lectin pathways, not the alternative pathway.
D) Formation of the MAC - Final step in all pathways, but not specific to the alternative pathway.
E) Activation of mannose-binding lectin - Involved in the lectin pathway, unrelated to the alternative pathway.
A patient with a history of lupus nephritis presents to the clinic with increasing fatigue. Laboratory studies show low C3 and C4 levels. Which of the following best explains the low complement levels in this patient?
A) Deficiency in Factor H
B) Increased consumption due to immune complex formation
C) Overactivation of the lectin pathway
D) Genetic deficiency in the MAC components
E) Deficiency of mannose-binding lectin
A) Factor H deficiency: Affects alternative pathway, lowering only C3, not C4.
B) Increased immune complex consumption: Correct. Immune complexes in lupus activate the classical pathway, consuming both C3 and C4.
C) Overactivation of lectin pathway: Affects innate immunity, not related to lupus nephritis.
D) MAC component deficiency: Causes susceptibility to infections, doesn’t reduce C3/C4.
E) Mannose-binding lectin deficiency: Impacts lectin pathway, doesn’t explain C3/C4
A patient presents with complaints of swelling in his extremities, especially after minor trauma. Genetic testing reveals a deficiency of C1 inhibitor. Which of the following would most likely be elevated in this patient?
A) C3 convertase
B) C5B
C) Bradykinin
D) Histamine
E) Factor H
Answer: C) Bradykinin
Hereditary angioedema is caused by C1 inhibitor deficiency.
This leads to elevated bradykinin, causing swelling due to increased vascular permeability.
Symptoms: recurrent, non-itchy, non-pitting swelling after trauma or stress.
Histamine is not involved, distinguishing this from allergic angioedema.
A patient with recurrent pneumococcal infections is found to have low CH50 levels and normal C3 and C4 levels. Which part of the complement pathway is most likely impaired in this patient?
A) C1 complex
B) Mannose-binding lectin
C) Factor H
D) C5-C9 (MAC)
E) Alternative pathway
Answer: D) C5-C9 (MAC)
C1 complex: Would show low C3/C4 levels, not normal.
MBL: Affects the lectin pathway, usually with low C3/C4, not isolated pneumococcal infections.
Factor H: Affects alternative pathway, causing low C3 levels, not seen here.
C5-C9 (MAC): Deficiency causes low CH50 with normal C3/C4, leading to recurrent infections, especially from encapsulated bacteria.
Alternative pathway: Would result in low C3 levels, not observed in this patient.
Key: Low CH50 + normal C3/C4 = C5-C9 (MAC) deficiency.
A patient with lupus is found to have nephritic syndrome and low serum complement levels. Which of the following tests would best assess the function of the classical complement pathway in this patient?
A) CH50
B) C3 level
C) Factor B assay
D) C9 level
E) Mannose-binding lectin assay
Answer: A) CH50
Explanation:
CH50: Best test for assessing classical complement pathway function (C1, C2, C3, C4), commonly low in lupus nephritis.
C3 level: Reflects complement activation but not specific to the classical pathway.
Factor B assay: Evaluates alternative pathway, not classical.
C9 level: Part of the terminal complement complex, not specific to classical pathway.
MBL assay: Tests the lectin pathway, irrelevant to classical pathway function.
What mediates Type I hypersensitivity reactions?
IgE antibodies bound to mast cells leading to immediate allergic reactions.
Which cytokine promotes IgE class switching in Type I hypersensitivity?
Interleukin-4 (IL-4).
Give examples of Type I hypersensitivity reactions.
Asthma, allergic rhinitis, anaphylaxis, food allergies (peanuts, shellfish).
Describe the early and late phases of Type I hypersensitivity reactions.
Early phase occurs within minutes (histamine release); late phase occurs hours later (cytokines and inflammatory cells).
What are the key mediators released in Type I hypersensitivity?
A: Histamine, leukotrienes, prostaglandins, cytokines.
Define atopy.
A genetic predisposition to develop Type I hypersensitivity reactions.
What is the treatment for anaphylaxis?
Immediate administration of epinephrine.
What mediates Type II hypersensitivity reactions?
A: IgG and IgM antibodies directed against self-antigens on cells or tissues.
List examples of Type II hypersensitivity disorders.
A: Rheumatic fever, autoimmune hemolytic anemia, Goodpasture’s syndrome, myasthenia gravis.
What mechanisms cause cell damage in Type II hypersensitivity?
Phagocytosis, complement-mediated lysis, antibody-dependent cellular cytotoxicity (ADCC).
How does Type III hypersensitivity differ from Type II?
A: Type III involves immune complex deposition in tissues; Type II involves direct antibody binding to cells/tissues.
Provide examples of Type III hypersensitivity reactions.
A: Serum sickness, Arthus reaction, lupus, post-streptococcal glomerulonephritis.
What is serum sickness?
A: A systemic Type III reaction due to circulating immune complexes causing fever, rash, arthralgia.
Define an Arthus reaction.
A: A localized Type III reaction where immune complexes form in tissues after antigen injection
What mediates Type IV hypersensitivity reactions?
A: Sensitized T cells (Th1 and CD8+ T cells); cell-mediated immunity.
Give examples of Type IV hypersensitivity reactions.
A: Contact dermatitis (poison ivy), PPD test for TB, multiple sclerosis.
What is the typical timeframe for Type IV hypersensitivity reactions?
A: Symptoms appear 24–72 hours after exposure.
Which cytokines are involved in Type IV hypersensitivity?
A: Interferon-gamma (activates macrophages), IL-12 (stimulates Th1 cells).
A 25-year-old woman presents with itchy, red, and watery eyes, nasal congestion, and sneezing during spring. She has similar symptoms every year. Skin prick testing shows a positive reaction to grass pollen. Which cytokine is most responsible for promoting the class switching that leads to her symptoms?
A) Interleukin-1 (IL-1)
B) Interleukin-2 (IL-2)
C) Interleukin-4 (IL-4)
D) Interleukin-5 (IL-5)
E) Interferon-gamma
Correct Answer: C) Interleukin-4 (IL-4)
Option A: IL-1 is involved in fever and inflammation but not in IgE class switching.
Option B: IL-2 stimulates T-cell proliferation but doesn’t promote IgE production.
**Option C: IL-4 induces B-cell class switching to IgE, central to Type I hypersensitivity reactions like seasonal allergies.
Option D: IL-5 activates eosinophils but doesn’t induce IgE class switching.
Option E: Interferon-gamma is associated with Th1 responses and inhibits IgE production.
