General Immunology Flashcards
Deficiency of this enzyme results in hereditary angioedema, in which swelling occurs because of uncontrolled activation of the classic pathway and a resulting increase in C2 kinin. In addition, absence of this enzyme leads to overproduction of bradykinin by kallikrein.
C1 esterase inhibitor (C1INH)
What is the protein that disrupts formation of C3 convertase, thus halting the complement cascade. In Paraxomal Nocturnal Hemoglobinuria, the protein that associates ___ with the red blood cell membrane is abnormal, thus making the RBC more susceptible to complement induced lysis.
Decay-accelerating factor (DAF).
In the presence of what protease can antibodies be broken into fragments by enzymatic digestion? What two antigen-binding fragments are formed?
Protease- papain
Antigen-binding Fragments: Fab and Fc.
Binding of IgG or IgM to antigens activates what system? This system leads to phagocytosis, anaphylaxis, and cytolysis.
Complement activation
During Genetic Recombination, VJ or VDJ recombination, various DNA segments are cut out of the genome. Which enzyme adds nucleotides to the sticky ends of the DNA strands?
Terminal deoxynucleotidyl transferase (TdT).
Immunoglobulin types: Expressed by: Mature B cell (surface or secreted). Structure: Monomer or pentamer Compliment fixation: Yes Crosses placenta: No Function: Primary Response
IgM - associated with acute inflammation
Immunoglobulin types: Expressed by: Mature B cell (surface) Structure: Monomer Compliment fixation: No Crosses placenta: No Function: Functions as B-Cell receptor for early immune response. Also found in serum.
IgD
Immunoglobulin types:
Expressed by: Plasma cells (secreted; high concentration in serum).
Structure: Monomer
Compliment fixation: Yes
Crosses placenta: Yes
Function: Important in secondary responses; opsonization and neutralization.
IgG - associated with chronic inflammation because initially its IgM, the does class switching to IgG.
Immunoglobulin types: Expressed by: Plasma cells (secreted). Structure: Monomer or dimer Compliment fixation: No Crosses placenta: No Function: Prevents pathogen attachment to mucous membranes; found in secretions.
IgA
Immunoglobulin types:
Expressed by: Plasma cells (secreted; low concentration in serum).
Structure: Monomer
Compliment fixation: No
Crosses placenta: No
Function: Type I hypersensitivity (induces mast cell degranulation); worm immunity.
IgE
CD19 and CD20 are markers for these lymphocytes. Another surface protein CD21 is involved in the complement pathway and is the receptor for EBV. It may also express CD40, which binds to CD40L, and this costimulatory signal is crucial for differentiation and isotope switching.
B Cells
Following activation of B cells, the variable regions of the immunoglobulin genes are subject to a high rate of random point mutations. What is this process known as?
Somatic hypermutation
At some point the mutations in B Cells result in antibody that is more specific to the antigen than the original antibody molecule. These B cells are selected to differentiate into plasma cells in a process known as what?
Affinity maturation
Which proteins are secreted from virus-infected cells that promote the transition of local cells to an antiviral state. They bind to specific receptors on the target cell surface, signaling the uninflected cell to degrade viral mRNA and increase antigen presentation. These proteins also activate NK cells and stimulate to kill infected cells. There are 3 types:
Interferons: Alpha and Beta, signal a cell to produce protein that degrades viral (but not host) mRNA.
INF-gamma: signals for increased expression of MHC I and MHC II, thus increasing antigen presentation in all cells that receive the signal. It’s also secreted by helper-T cells to stimulate phagocytosis by macrophages.
Protein secreted by macrophages and T cells. A key mediator of the inflammatory response during infection and autoimmune disease.
TNF-alpha: tumor necrosis factor alpha
B cells that react with self antigen can either be deleted or undergo receptor editing of the light chain during their development in the bone marrow. This receptor editing event serves as the last chance for the autoreactive B cells to escape deletion. Failing this, the cell is deleted. What is the name of this process?
“Negative Selection” in clonal deletion
What is the term that is used to describe: Self-reactive T-cells become nonreactive without costimulatory molecule. B cells also become nonreactive but tolerance is less complete than in T-cells.
Anergy
What is occurring? T cells are primed as effector cells specific to intracellular antigens or aberrant cells (foreign or mutated), causing the production of memory cells. On repeated exposure, effector cells are called to the site, where they proliferate and activate a macrophage response to clear the infection. This process takes one to two days. Response is delayed and does not produce antibodies.
Type IV: Cell-mediated (Delayed type) hypersensitivity RXN.
These mature cells express CD3 and either CD4 or CD8. CD40 ligand, is important for antibody isotope switching, and CD28, which is important for this cell type activation. What cell is this?
T Cells
Also called immediate hypersensitivity, can be anaphylactic (systemic) or atopic (local). After being sensitized to an antigen, the patient will experience an immune response to low concentrations of that same antigen. Genetic susceptibility plays a role in this reaction.
Hypersensitivity Reaction: Type I - IgE Mediated
What diseases are associated with the disorder? Multiple sclerosis, Guillain-Barré syndrome, graft-vs-host disease, PPD skin test, contact dermatitis (for poison ivy and nickel allergy).
Type IV hypersensitivity RXN- delayed type
Contact dermatitis usually involves CD4+ and CD8+ T cells, and can be as widespread as the area of contact. Exposure to a large volume of antigen increases the magnitude of the immune response, which consequently can cause severe local tissue damage.
These diseases are associated with what disorder?SLE, polyarteritis nodosa, poststreptococcal glomerulonephritis, serum sickness, Arthus reaction (e.g. Swelling and inflammation following tetanus vaccine, or desensitization allergy shots).
Type III hypersensitivity RXN
What is happening? Circulating antibodies are directed to cell surface antigens. Complement is activated. Cell falls victim to: opsonization, followed by phagocytosis; antibody-dependent cell-mediated cytotoxicity; cell death mediated by NK or T cells; immune response-mediated damage to healthy tissue.
Type II: Antibody-Mediated (Cytotoxic)
In autoimmune hemolytic anemia, the Px makes IgM to his/her own RBC antigens.
Presentation: recurrent and/or potentially severe bacterial infections. A naturally occurring deficiency of B cell-secreted immunoglobulins occurring in infants 3-6mo. of age. At this age, maternal IgG is disappearing but the infant’s B Cells are not yet producing sufficient quantities of antibodies to suppress infection. Dx is done by measuring circulating antibody levels and confirm that the level is lower than age-matched standards.
Transient Hypoagammaglobulinemia (of infancy).
Immune deficiencies:
Defect: defect in BTK, a tyrosine kinase gene–> no B-cell maturation. X-linked recessive (incr. in boys).
Presentation: Recurrent bacterial and enteroviral infections after 6 months (decreased maternal IgG)
Findings: Normal CD19+ B cell count, decreased pro-B, decreased Ig of all classes. Absent scanty lymph nodes and tonsils.
B-Cell disorders: X-linked (Bruton) agammaglobulinemia
Immune deficiencies
Defect: Unknown. Most common 1* immunodef.
Presentation: Majority asymptomatic. Can see airway and GI infections, autoimmune disease, atopy, anaphylaxis to IgA-containing products.
Findings: IgA<7mg/dL with normal IgG, IgM levels.
B-Cell disorders: Selective IgA deficiency
Immune deficiencies
Defect: Defect in B-cell differentiation. Many causes
Presentation: Can be acquired in 20s-30s; increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections.
Findings: decreased plasma cells, decreased immunoglobulins.
B-cell disorders: Common variable immunodeficiency
What is this describing? Soluble antigen-antibody complexes form when antigen is abundant. Complex deposition in tissues causes vasculitis and systemic manifestations. These complexes aggregate into clusters that activate the complement system. Smaller complexes escape detection and are deposited in the walls of blood vessels. They accumulate on the endothelium and synovial of joints.
Type III: Immune Complex-Mediated hypersensitivity
These diseases fall under what category of disorders? Erythroblastosis fetalis, Goodpasture’s syndrome, and incompatible blood transfusions.
Hypersensitivity RXN Type II
In incompatible blood transfusions, the recipient has preformed IgM antibodies to the donor’s major RBC antigens, resulting in rapid destruction of the infused RBCs.
What is occurring? Atopic reactions that include urticaria (or hives)- histamine release causes vasodilation and a visible wheal and flare. Allergic rhinitis, and asthma- results from inhalation of allergens. This causes inflammation of either the nasal mucosa leading to rhinitis or bronchial construction and air trapping (asthma) of the lower bronchi.
Type I hypersensitivity RXN.
Anaphylaxis would be the most severe where histamine and other mediators are released systemically. Widespread vasodilation and increased vessel permeability can result in hypotension and shock.
Immune deficiencies:
Defect: 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches–> absent thymus and parathyroids.
Presentation: Tetany (hypocalcemia), recurrent viral/fungal infections, conotruncal abnormalities (tetralogy of Fallot, truncus arteriosus).
Findings: Decr. T cells, decr. PTH, decr. Ca2+, absent thymic shadow on CXR. 22q11 deletion detected by FISH.
T-cell disorders: Thymic aplasia (DiGeorge syndrome)
Immune deficiencies:
Defect: Decr. Th1 response. Autosomal recessive.
Presentation: Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.
Findings: Decreased IFN-gamma
T-Cell disorders: IL-12 receptor deficiency
Immune deficiencies:
Defect: Deficiency of Th17 cells due to STAT3 mutation –> impaired recruitment of neutrophils to sites of infection.
Presentation: Coarse facies, cold (noninflamed) staphylococcal abscesses, retained primary teeth, increased IgE, dermatological problems (eczema).
Findings: Increased IgE, decreased IFN-gamma.
T-cell disorders: Autosomal Dominant hyper-IgE syndrome (Job Syndrome)
Immune deficiencies:
Defect: T-cell dysfunction
Presentation: Noninvasive Candida albicans infections of skin and mucous membranes.
Findings: Absent in vitro T-cell proliferation in response to Candida antigens. Absent cutaneous reaction to Candida antigens.
T-cell disorders: Chronic mucocutaneous candidiasis
