Rhinology Immunology Flashcards Preview

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Flashcards in Rhinology Immunology Deck (86)
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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

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

3
Q

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

A

Innate (nonspecific) immunity

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.

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.

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)

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

8
Q

Name the two subtypes of adaptive immunity.

A

● Humoral immunity → B cells, antibodies

● Cell-mediated → T cells, cytokines

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)

10
Q

What are the primary lymphoid organs?

A

● Thymus

● Bone marrow

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

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

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

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

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

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

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
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
19
Q

What percentage of CD4 + and CD8 + T cells

survive selection in the thymus?

A

Less than 5%; most say 2% or less

20
Q

Where does negative selection of developing

T cells occur?

A

Thymic medulla

21
Q

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

A

Negative selection

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

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

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

25
Q

How does the immunologic T-cell response to oral antigens differ compared with more systemic re-
sponses?

A

Oral antigens are more likely to induce T-cell anergy or T-

cell tolerance than T-cell activation.

26
Q

What are the two types of MHC molecules?

A

● 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
Q

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?

A

MHC class I

28
Q

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?

A

MHC class II

29
Q
What type of T cell recognizes antigen presented
by MHC class II molecules?
A

TH cells (CD4 +)

30
Q
What type of T cell recognizes antigen presented
by MHC class I molecules and kills cells presenting
that antigen?
A

Cytotoxic T cells (CD8 +)

31
Q

What are the components of MHC molecules?

A

● Extracellular peptide binding region
● Pair of Ig-like domains (bind CD4 and CD8)
● Transmembrane region
● Cytoplasmic tail

32
Q
To activate TH cells, antigen-presenting cells must
present antigen via an MHC class II molecule, as
well as secrete which important cell signal?
A

IL-1

33
Q

Which cells secrete antibodies, and how are they

activated?

A

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
Q

What cell type can be identified by the CD

markers 19 and 21?

A

B cells

35
Q

How is antibody isotype switching induced

in B cells?

A

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
Q

What glycoprotein molecules are produced by
plasma cells in response to humoral immune
stimulation?

A

Immunoglobulins

37
Q

What are the basic functions of immunoglobulins?

A

● 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
Q

What is the basic structure of an immunoglobulin?

A
Four chains (two heavy, two light), variable regions (bind
antigen), constant regions, and hinge regions
39
Q

What component of an immunoglobulin molecule
is responsible for most of the effector functions of
an antibody?

A

Fc domain of the antibody

40
Q

What component of an immunoglobulin molecule

is responsible for the specificity of antibodies?

A

Variable region of the antibody

41
Q

Cleavage at the hinge region of an immunoglobulin

results in production of what three fragments?

A

● 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
Q

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?

A
● IgA (serum, monomer; secretions, dimer)
● IgD (monomer)
● IgE (monomer)
● IgG (monomer)
● IgM (pentamer)
43
Q

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?

A

IgA

44
Q

How do IgA molecules primarily mediate mucosal

immunity?

A

They are weak activators of complement and mediate their
affects primarily via neutralization of antigen and preven-
tion of systemic access.

45
Q

What are the two subclasses of IgA?

A

● 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
Q

What are the two forms of IgA found in the

body?

A

● 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
Q

How does IgA gain access to extravascular

secretions and tissues?

A

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
Q

Which immunoglobulin deficiency is largely
asymptomatic, correlating with the poorly under-
stood function of its associated monomeric
glycoprotein?

A

IgD

49
Q

What is the structure of IgM?

A

IgM is a pentamer made up of five immunoglobulin

subunits linked by a J chain.

50
Q

What immunoglobulin is produced first in a
humoral immune response and is excellent at
binding complement?

A

IgM

51
Q

What monomeric immunoglobulin is implicated

in allergic responses to environmental allergens?

A

IgE

52
Q

What conditions can lead to high levels of IgE

antibodies?

A

Allergic diseases, lymphoma, IgE myeloma, systemic para-
sitosis, tuberculosis, HIV infection, Churg-Strauss, among
others

53
Q

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?

A

IgG

54
Q

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.

A

● 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
Q

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?

A

Complement system

56
Q

What are the four pathways involved in

complement activation?

A

● 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
Q

How is the mannose-binding lectin pathway of

complement activated?

A

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
Q

How is the alternative pathway of the complement

system activated?

A

Microbial structures neutralize inhibitors of spontaneous
complement activation leading to unimpeded complement
activation.

59
Q

What are considered the anaphylatoxins produced

by the complement cascade?

A

C3a, C4a, and C5a

60
Q

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?

A

Cytokines

61
Q

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

A
● INF
● Lymphokine
● Interleukin
● TNF
● Colony stimulating factor
62
Q

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

A
● IL-2
● IL-3
● IL-4
● IL-5
● Transforming growth factor (TGF)-β
63
Q

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?

A

IL-10

64
Q

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

A

● TNF-α
● IL-1
● Type I interferons (INF-α and INF-β)
● INF-γ

65
Q

What is the clinical impact of IgG1 deficiency?

A

Generalized hypogammaglobulinemia. Often associated with IgG3 deficiency.

66
Q

When patients have significant IgG1 deficiency in
combination with IgA and/or IgM deficiency.
What is the diagnosis?

A

Common variable immunodeficiency

67
Q

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?

A

Upper (i.e., sinuses) and lower respiratory tracts.

68
Q

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?

A

IgG2 deficiency.
Streptococcus pneumoniae, Haemophilus influenza type b,
Neisseria meningitidis

69
Q

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?

A

IgG1

70
Q
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?
A

IgG4 (IgG4-related systemic disease). May also result in

autoimmune pancreatitis

71
Q

What is the clinical impact of IgA deficiency?

A

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
Q

A patient has eczema, thrombocytopenia, and
recurrent otitis media, pneumonia, and sinusitis.
What immunodeficiency syndrome do you suspect,
and how is it inherited?

A

Wiskott-Aldrich syndrome (X-linked)

73
Q

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?

A

Bruton agammaglobulinemia: X-linked, defect in tyrosine
kinase (Bruton tyrosine kinase), resulting in inability of pro-
B cells to mature

74
Q

Patients with Bruton agammaglobulinemia develop

masses in what organ?

A

Thymus (thymoma)

75
Q

Patients with X-linked agammaglobulinemia have
recurrent infections secondary to a low level of
which antibody isotype(s)?

A

All antibody isotypes

76
Q

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?

A

DeGeorge syndrome (22q11.2 deletion)

77
Q

What form of immune responses are impaired in

DeGeorge syndrome?

A

T-cell–mediated immune responses are impaired or absent

secondary to thymic agenesis.

78
Q

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?

A

Bone marrow transplantation

79
Q

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?

A

HIV
Decreased T-cells, macrophages, and dendritic cells as a
result of direct cytotoxic effects, which causes progressive
immunodeficiency in the host

80
Q

How are HIV infections diagnosed?

A
● ELISA anti-HIV antibody (screening test)
● Western blot (confirmation test)
● PCR for viral DNA
● CD4 + count
● Viral load
● Viral susceptibility testing
81
Q

What are the diagnostic criteria for AIDS?

A

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
Q

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?

A

Chronic granulomatous disease (most commonly X-linked)

83
Q

At what age do patients with clinically significant
deficiencies in antibodies typically begin to have
recurrent infections and why?

A

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
Q

What is the most common cell lineage to be

defective in immunodeficiency?

A

B cells

85
Q

What are the recommended screening tests for
T-cell immunodeficiency if one is suspected based
on clinical history?

A

● 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
Q

What are the recommended screening tests for
B-cell immunodeficiency if one is suspected based
on clinical history?

A

● 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