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ENT Rhinology, Allergy, and Immunology > Rhinology Immunology > Flashcards

Rhinology Immunology Flashcards

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1
Q

What are the two major types of immunity?

A

● Innate (nonspecific): First line of defense; antigen
independent, immediate maximal response, no immu-
nologic memory

● Adaptive (specific immunity): Antigen dependent, delayed
maximal response, immunologic memory, lymphocytes
and lymphocyte-derived immunity

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2
Q

What are the three major components of innate

(nonspecific) immunity?

A

● Anatomical boundaries: Epithelium; mechanical move-
ment and trapping from cilia, tears, saliva, and mucus;

competition from normal flora
● Humoral barrier: Cytokine system, complement system,
coagulation; fatty acids, lysozyme, lactoferrin, transferrin,

phospholipase, defensins, surfactants, IL-1, TNF-α, inter-
ferons (IFNs)

● Cellular barrier: Polymorphonuclear cells, macrophages,
NK cells, and eosinophils

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3
Q

In what type of immunity do toll-like receptors
coordinate the responses of cytokine-complement-
phagocytic responses?

A

Innate (nonspecific) immunity

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4
Q

How do NK cells differ from NK T cells?

A

They are part of the innate immune system but can
participate in the adaptive immune response. They arise
from the lymphoid progenitor cell, which gives rise to T and
B cells, do not have common T cell–specific markers (CD3,
TCR, MHC, etc), they express CD-16, CD-56, and often CD8.
They can be activated by IFN to target virally infected or
tumor formation within 3 days based on the absence of
“self” markers.

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5
Q

The anti-tumor effect of NK cells is thought to be

due to their unique ability to recognize what?

A

The absence of self. Although T cells and many other immune
effector cells are programmed to recognize nonself proteins
produced by viruses or bacteria, NK cells have the ability to
recognize when self peptides and proteins have been
downregulated as a result of tumor transformation or what
might be seen with viral infections. The most commonly
encountered down regulated self molecule that might be
“recognized” by NK cells are MHC molecules.

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6
Q

The adaptive immune system reacts specifically to
individual antigens (proteins, polysaccharides, or
macromolecules). What is the region of the
antigen that is recognized by antigen-specifc
receptors (T and B cells) and immunoglobulins
within the adaptive immune system called?

A

Epitope (determinant)

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7
Q

What is the term that defines the ability of a host to ignore self and demonstrate immunologic unre-
sponsiveness to self for both innate and adaptive immune responses?

A

Tolerance

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8
Q

Name the two subtypes of adaptive immunity.

A

● Humoral immunity → B cells, antibodies

● Cell-mediated → T cells, cytokines

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9
Q

Describe the three basic steps of adaptive

immunity.

A

● Recognition of antigen
● Lymphocyte activation → production of cytokines,
cytokine receptors, and other proteins; clonal expansion
of lymphocytes; cellular differentiation (i.e., B cell into
plasma cell)
● Removal of the offending antigen (clearance)

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10
Q

What are the primary lymphoid organs?

A

● Thymus

● Bone marrow

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11
Q

What are the secondary lymphoid organs, and

what is their purpose?

A

● Systemic (spleen and lymph nodes)

● Mucosal immune system (tonsils, Peyer patches, intra-
epithelial lymphocytes, lamina propria of mucosal tissues)

● Cutaneous immune system

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12
Q

Where do myeloid (erythrocytes, neutrophils,
platelets, basophils, eosinophils, monocytes/macro-
phages, and dendritic cells) and lymphoid cells (T cells, B cells, NK cells, plasma cells) arise from?

A

Bone marrow

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13
Q

Name the immature dendritic cell found in the
skin and mucosa that contains Birbeck granules, is
most prominent in the stratum spinosum of the
skin, and is involved in antigen processing.

A

Langerhans cells

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14
Q

Name the specialized mucosal immune cell that is
responsible for transocytosis (pinocytosis) of
antigens across the follicular epithelium to
germinal centers within Peyer patches within
tonsillar tissue.

A

M (microfold) cells

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15
Q

Immune responses to hematogenous antigens
and encapsulated organisms occur predominantly
in the spleen, where lymphoid follicles surround
small arterioles forming what structure?

A

Periarteriolar lymphoid sheaths

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16
Q

Lymphocytes can be identified by what specialized
molecules on their surface that can help other
cells (and researchers/clinicians) recognize their
level of maturity, lineage, and extent of immune
activation?

A

Cluster of differentiation (CD) markers

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17
Q 
Name the cell associated with the following CD
markers:
● CD2
● CD3
● CD4
● CD8
● CD25
A 
● All T cells
● All T cells
● TH1 or TH2 cells
● T-suppressor cells (cytotoxic T cells)
● + CD4 = TH17 or T regulatory cells
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18
Q

What cell is required to undergo maturation in
the thymus, and what are the possible outcomes
of differentiation?

A 
T cells differentiate in the thymus via both positive and
negative differentiation:
● Apoptosis
● CD4 + helper T cell
● CD8 + precytotoxic T cell
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19
Q

What percentage of CD4 + and CD8 + T cells

survive selection in the thymus?

A

Less than 5%; most say 2% or less

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20
Q

Where does negative selection of developing

T cells occur?

A

Thymic medulla

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21
Q

The process by which developing T cells that react
too strongly with self peptides are deleted is called
what?

A

Negative selection

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22
Q

What is the process called by which developing
T cells that react appropriately with self peptides
are signaled to survive and continue to develop?

A

Positive selection

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23
Q

What cell type is stimulated to develop from naïve
CD4 cells (TH0) by intracellular pathogens and IL12
and subsequently inhibits B cells, produces INF-γ
and IL2, and stimulates cell-mediated immunity
(activates cytotoxic CD8 cells, etc)?

A

TH1 cells

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24
Q

What cell type is stimulated to develop from naïve CD4 cells (TH0) by allergens and IL-4 and subse-
quently recruits/activates eosinophils, activates B cells; produces IL-4, IL-5, IL-6, IL-10, and IL-13;
and is involved in both allergic disease and humoral
immunity?

A

TH2 cells

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25
How does the immunologic T-cell response to oral antigens differ compared with more systemic re- sponses?
Oral antigens are more likely to induce T-cell anergy or T- | cell tolerance than T-cell activation.
26
What are the two types of MHC molecules?
● MHC Class I: Display self and nonself antigens (8–10 amino acids), membrane associated glycoprotein. ● MHC Class II: Display extracellular proteins (various length, generally longer, 18 to 20 amino acids) that are phag- ocytosed and processed intracellularly before presentation
27
What type of MHC molecules are expressed by almost all nucleated cells and when downregulated can result in targeted destruction by NK cells and present endogenous antigen?
MHC class I
28
What type of MHC molecules are expressed primarily on antigen-presenting cells and lympho- cytes (B cells, macrophages, endothelial cells, or dendritic cells primarily) and present processed exogenous antigen?
MHC class II
29
``` What type of T cell recognizes antigen presented by MHC class II molecules? ```
TH cells (CD4 +)
30
``` What type of T cell recognizes antigen presented by MHC class I molecules and kills cells presenting that antigen? ```
Cytotoxic T cells (CD8 +)
31
What are the components of MHC molecules?
● Extracellular peptide binding region ● Pair of Ig-like domains (bind CD4 and CD8) ● Transmembrane region ● Cytoplasmic tail
32
``` To activate TH cells, antigen-presenting cells must present antigen via an MHC class II molecule, as well as secrete which important cell signal? ```
IL-1
33
Which cells secrete antibodies, and how are they | activated?
B cells phagocytose antigen and present it to TH cells via MHC class II molecules. T-cell then stimulates the B cell via IL-2 and IL-4 to mature into an Ig-producing plasma cell. Alternatively, large antigens can crosslink enough B-cell receptors to lead to direct activation of the cells and antibody production.
34
What cell type can be identified by the CD | markers 19 and 21?
B cells
35
How is antibody isotype switching induced | in B cells?
B cells encounter antigen and migrate out of follicles to a B cell-T cell interface, where they encounter activated TH cells. The B cells present their processed antigen in the context of MHC class II recognized by the T-cell receptors. The costimulatory molecule CD40 L interacts with the CD40 receptor, providing survival signals and isotype switching. The type of cytokine environment encountered at the time this is happening helps determine which isotype is then secreted.
36
What glycoprotein molecules are produced by plasma cells in response to humoral immune stimulation?
Immunoglobulins
37
What are the basic functions of immunoglobulins?
● Antigen binding ● Effector functions: complement fixation, neutralization, or antibody-dependent cellular cytotoxicity via opsoniza- tion ("tagging" an antigen for ingestion and destruction by a phagocyte), stimulation of phagocytosis, etc.
38
What is the basic structure of an immunoglobulin?
``` Four chains (two heavy, two light), variable regions (bind antigen), constant regions, and hinge regions ```
39
What component of an immunoglobulin molecule is responsible for most of the effector functions of an antibody?
Fc domain of the antibody
40
What component of an immunoglobulin molecule | is responsible for the specificity of antibodies?
Variable region of the antibody
41
Cleavage at the hinge region of an immunoglobulin | results in production of what three fragments?
● 1–2. Fab fragments: Two identical fragments that contain the light chain and the variable and first constant domain of the heavy chains; binds antigen ● 3. Fc fragments: One fragment containing the remaining heavy chains and their constant regions; may stimulate complement
42
What are the five classes of immunoglobulins produced in the body, which vary based on the amino acid sequences in the constant region of the heavy chain?
``` ● IgA (serum, monomer; secretions, dimer) ● IgD (monomer) ● IgE (monomer) ● IgG (monomer) ● IgM (pentamer) ```
43
Which immunoglobulin makes up more than 70% of the total body immunoglobulin (only 15% of serum immunoglobulin), is found in mucosal secretions (nasal, pulmonary, lacrimal, salivary, colostrum, sweat, GI tract, and genitourinary), and is important in preventing microrganisms from invading the body?
IgA
44
How do IgA molecules primarily mediate mucosal | immunity?
They are weak activators of complement and mediate their affects primarily via neutralization of antigen and preven- tion of systemic access.
45
What are the two subclasses of IgA?
● IgA1 (~85% serum): Strong immune response to protein antigens. Some response to polysaccharide and lip- opolysaccharides ● IgA2 (~15% serum): Key player in defense against mucosal invasion via immune response to polysaccharide and lipopolysaccharide antigens
46
What are the two forms of IgA found in the | body?
● Monomeric serum IgA: Fc portion binds phagocytic cells, stimulating ingestion and destruction. ● Dimeric secretory IgA: Two IgA molecules + J (joining) chain and a secretory piece; secreted by plasma cells located below the basement membrane of the basement epithelial surfaces
47
How does IgA gain access to extravascular | secretions and tissues?
IgA is produced in a monomeric form and is joined with a J chain to form a dimer that is too large to diffuse across cellular membranes. The IgA dimer binds to polymeric IgA receptors on cells, which results in endocytosis and passes through the cell. The immunoglobulin is secreted on the luminal side of the cell still attached to the receptor. The receptor is then degraded, and the IgA molecule is free to diffuse throughout the lumen.
48
Which immunoglobulin deficiency is largely asymptomatic, correlating with the poorly under- stood function of its associated monomeric glycoprotein?
IgD
49
What is the structure of IgM?
IgM is a pentamer made up of five immunoglobulin | subunits linked by a J chain.
50
What immunoglobulin is produced first in a humoral immune response and is excellent at binding complement?
IgM
51
What monomeric immunoglobulin is implicated | in allergic responses to environmental allergens?
IgE
52
What conditions can lead to high levels of IgE | antibodies?
Allergic diseases, lymphoma, IgE myeloma, systemic para- sitosis, tuberculosis, HIV infection, Churg-Strauss, among others
53
Which monomeric immunoglobulin class is the most prevalent both in the serum and in extravascular spaces, is the only immunoglobulin to cross the placenta; play an important role in immunologic memory; and function to fix complement and activate macrophages, monocytes, poly- morphonuclear cells, and some lymphocytes via opsonization?
IgG
54
Describe the function of the four IgG subclasses, which are divided based on structural variation of the Fc and hinge region, as well as the difference in number of disulfide bonds.
● IgG1 (60 to 70%): Opsonization, strong C1q binding, and classic complement cascade activation, response to protein and viral antigens ● IgG2 (20 to 30%): Opsonization, weak C1q binding and classic complement cascade activation, response to bacterial polysaccharide antigens (i.e., Pneumococcus) ● IgG3 (5 to 8%): Opsonization, strong C1q binding and classic complement cascade activation, response to protein and viral antigens ● IgG4 (1 to 4%): Minimal opsonization, no complement activation, may be involved in immune response to parasites (Schistosoma and Filaria spp.)
55
What component of the nonspecific immune system functions to opsonize bacteria, recruit and activate polymorphonuclear cells and macrophages, participate in antibody regulation, clear immune complexes, clear apoptotic cells, and can result in inflammation and anaphylaxis?
Complement system
56
What are the four pathways involved in | complement activation?
● Classic pathway (C1qrs, C2, C3, C4; C1-INH, C4-BP); antibody dependent ● Lectin pathway (mannan binding protein, mannan- associated serine protease); antibody independent ● Alternative pathway (C3, Factors B and D, properdin; decay accelerating factor, CR1, etc); antibody independ- ent ● Lytic (membrane attack) pathway (C5–9; protein S) Note: The classic, lectin, and alternative pathways can all result in the cleavage of C3 and activation of C5 convertase. C5 convertase is required for activation of C5 and the lytic (membrane attack) pathway.
57
How is the mannose-binding lectin pathway of | complement activated?
Microbes containing mannan are recognized by mannan binding lectins, which in turn activate serine proteases (MASPs) which mediate cleavage of C1, C4, and C2, leading to the C3 convertase
58
How is the alternative pathway of the complement | system activated?
Microbial structures neutralize inhibitors of spontaneous complement activation leading to unimpeded complement activation.
59
What are considered the anaphylatoxins produced | by the complement cascade?
C3a, C4a, and C5a
60
What nonantibody proteins act as mediators between cells, result in signaling cascades, and can be produced both by immune (innate and cell mediated) and nonimmune system cells?
Cytokines
61
Name the general cytokine subtype associated with the following: ● Results in an antiviral response ● Produced by lymphocyte ● Produced by leukocytes and effect the function of other leukocytes ● Result in an acute inflammatory response to Gram-negative bacteria ● Influence maturation and release of bone marrow cell populations
``` ● INF ● Lymphokine ● Interleukin ● TNF ● Colony stimulating factor ```
62
Name the cytokine associated with adaptive immunity system described by the following: ● Produced by TH cells, major growth factor for T cells, B cells, and NK cells ● Stimulated bone marrow immune cells to expand, especially mast cells and eosinophils ● Produced by macrophages, mast cells, and ``` T cells; stimulates development of TH cells, stim- ulates B-cell immunoglobulin class switch to IgE ``` ● Produces by TH cells, promotes maturation of B cells, and eosinophils ● Produced by T cells, among others, and inhibits proliferation of T cells and macrophages and inhibits the effect of proinflammatory cytokines on polymorphonuclear cells and endothelial cells
``` ● IL-2 ● IL-3 ● IL-4 ● IL-5 ● Transforming growth factor (TGF)-β ```
63
Which cytokine functions to regulate both the innate and adaptive immune system by inhibiting macrophages, cytokine synthesis, and antigen-pre- senting cells and is produced by macrophages and CD4 + T cells?
IL-10
64
Name the cytokine associated with the innate immunity described by the following: ● Produced by activated macrophages (response to lipopolysaccharide of Gram-negative bacteria), mediates acute inflammation, stimulates thalamus to produce a fever ● Produced by activated macrophages, mediates acute inflammation, stimulates T cells ● Produced by many different cells (i.e., lymphocytes, macrophages, endothelium, and keratinocytes) to inhibit viral replication, increase MHC class I expression in cells making them more susceptible to cytotoxic T cells, activate NK cells ● Produced by TH1 cells, produces a myriad of direct cytotoxic effects
● TNF-α ● IL-1 ● Type I interferons (INF-α and INF-β) ● INF-γ
65
What is the clinical impact of IgG1 deficiency?
Generalized hypogammaglobulinemia. Often associated with IgG3 deficiency.
66
When patients have significant IgG1 deficiency in combination with IgA and/or IgM deficiency. What is the diagnosis?
Common variable immunodeficiency
67
Although rare, selective IgG1 deficiencies (i.e., no other detectable immunoglobulin abnormality) can occur and can result in frequent and/or repeated infections of what two organs?
Upper (i.e., sinuses) and lower respiratory tracts.
68
You are evaluating a child with recurrent sinusitis, otitis media, and bronchitis. Immunologic workup suggests deficiency in the IgG subclass, which is important in the defense against polysaccharide capsular antigens. What is the likely diagnosis and to which bacteria is this child most susceptible?
IgG2 deficiency. Streptococcus pneumoniae, Haemophilus influenza type b, Neisseria meningitidis
69
IgG3 deficiency can result in increased susceptibility to viral infections, as well as Moraxella catarrhalis and Streptococcus pyogenes, resulting in recurrent sinopulmonary and GI infections, as well as recurrent lymphocytic meningitis. IWhat additional IgG subtype is often deficient in these patients?
IgG1
70
``` You are evaluating a patient with sialadenitis and salivary gland enlargement. Biopsy reveals lympho- plasmacytic infiltrate IgG + plasma cells and fibrosis. The condition seems to respond to glucocorticoids. Which IgG subclass is likely involved? ```
IgG4 (IgG4-related systemic disease). May also result in | autoimmune pancreatitis
71
What is the clinical impact of IgA deficiency?
Patients are often asymptomatic, although the deficiency may be one of the most common primary immunodefi- ciency syndromes. May have recurrent sinopulmonary or GI infections, skin infections, anaphylaxis with transfusions, or autoimmune disorders
72
A patient has eczema, thrombocytopenia, and recurrent otitis media, pneumonia, and sinusitis. What immunodeficiency syndrome do you suspect, and how is it inherited?
Wiskott-Aldrich syndrome (X-linked)
73
A 6-month-old patient has severe and recurrent otitis media, sinopulmonary infections, pneumonia, and associated autoimmune disorders and is found to have an underlying immunodeficiency affecting B cells, but not T cells. What are the most likely diagnosis, inheritance pattern, and genetic defect?
Bruton agammaglobulinemia: X-linked, defect in tyrosine kinase (Bruton tyrosine kinase), resulting in inability of pro- B cells to mature
74
Patients with Bruton agammaglobulinemia develop | masses in what organ?
Thymus (thymoma)
75
Patients with X-linked agammaglobulinemia have recurrent infections secondary to a low level of which antibody isotype(s)?
All antibody isotypes
76
Abnormality of the third and fourth branchial arches leading to thymic hypoplasia or agenesis, hypoplastic parathyroids with resultant hypocalcemia, and abnormalities of the face and aortic arch results in what syndrome?
DeGeorge syndrome (22q11.2 deletion)
77
What form of immune responses are impaired in | DeGeorge syndrome?
T-cell–mediated immune responses are impaired or absent | secondary to thymic agenesis.
78
Severe combined immunodeficiency (SCID) results from deficient or malfunctioning T and B cells. It presents early in life with severe infections (viral, bacterial, and fungal) involving the sinopulmonary system and other organ systems. Often these chil- dren present with severe oral candidiasis as well. If diagnosed early, this disease can be effectively managed with what treatment?
Bone marrow transplantation
79
What virus invades T cells via the CD4 + marker and synthesizes proviral DNA from reverse tran- scriptase, which is then integrated into the host DNA, and what is the result?
HIV Decreased T-cells, macrophages, and dendritic cells as a result of direct cytotoxic effects, which causes progressive immunodeficiency in the host
80
How are HIV infections diagnosed?
``` ● ELISA anti-HIV antibody (screening test) ● Western blot (confirmation test) ● PCR for viral DNA ● CD4 + count ● Viral load ● Viral susceptibility testing ```
81
What are the diagnostic criteria for AIDS?
An AIDS-defining illness (e.g., Kaposi sarcoma) or a CD4 + T cell count less than 200 cells/μL or a CD4% less than 14%
82
What disorder results in the inability of phagocytes to kill catalase-positive organisms as a result of dysfunction of intracellular hydrogen peroxide pro- duction via the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex?
Chronic granulomatous disease (most commonly X-linked)
83
At what age do patients with clinically significant deficiencies in antibodies typically begin to have recurrent infections and why?
7 to 9 months. As maternal antibodies begin to clear from the patient's system, his or her own immune system must take over.
84
What is the most common cell lineage to be | defective in immunodeficiency?
B cells
85
What are the recommended screening tests for T-cell immunodeficiency if one is suspected based on clinical history?
● Absolute lymphocyte count ● Chest X-ray looking for the presence of thymic shadow in children ● Delayed hypersensitivity skin testing to antigen ● Flow cytometry to quantitate T-cell subsets
86
What are the recommended screening tests for B-cell immunodeficiency if one is suspected based on clinical history?
● Quantification of serum immunoglobulins and subclasses ● Antibody (IgG) responses to a vaccine challenge after a minimum of 1 month. ● Protein antigen: Tetanus, diphtheria, Haemophilus influ- enzae type B ● Polysaccharide antigen: Pneumovax, meningococcal vaccine ● Flow cytometry to quantify B cells

ENT Rhinology, Allergy, and Immunology (12 decks)

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