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Adaptive Flashcards

1
Q

What are some imporatant clinical roles for T cells?

A
  • High level of T cell activation (autoimmune diseases)
  • Low level of CD4+ T cells (HIV and AIDS)
  • Supression of T cells (successful organ transplant)
  • T cell activation by bacterial toxin (toxic shock syndrome)
  • T cell activation in immunotherapy of cancer
  • Immunosupression in graft acceptance
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2
Q

What is the role of IL-17?

A

Stimulation of acute inflammation

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3
Q

Is CD28-B7 interaction only useful for CD4+ T cell differentation?

A

No, CD8+ T cell differentiation is also dependent on CD28-B7 interaction for clonal expansion

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4
Q

Where do most plasma cells reside?

A

Bone Marrow

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5
Q

Are positive and negative selection during T cell maturation all-or-nothing reactions?

A

No, positive and negative selection only keep molecules with “low to moderate affinity”. No or low affinity and very high affinity T cells are deleted (risk of auto-reactivity)

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6
Q

Which etiological agent is most commonly associated with infectious mononucleosis (mono)?

A

Epstein Barr Virus (EBV)

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7
Q

What is the initial screening lab you should consider when faced with possible immune deficiency?

A

Complete blood count (CBC) with differential (number and morphology of cells)

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8
Q

What is the role of CD3 proteins in T cell stimulation?

A

CD3 proteins are closely associated with TCR and cytoplasmic tails contain immunoreceptor tyrsoine-based activation motifs (ITAMs) that will activate signals within T cell

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9
Q

What is Wiskott-Aldrich Syndrome?

A
  • X-linked recessive disease, defective antigen presentation
  • Abnormal platelets, eczema, recurrent infection
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10
Q

What are the 3 main types of mature B cells?

A
  1. Follicular B cells- most mature B cells, lypmh node and spleen follicles
  2. Marginal-zone B cells- found in margins of slpenic follicles
  3. B1 lymphocytes- lymphoid organs and peritoneal cavity
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11
Q

Where in the body does antigen presentation occur?

A

The lymph nodes and the spleen

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12
Q

What is the difference btw Humoral and Cell-mediated Immunity?

A
  • Humoral: mediated by B cells, blocks infections and eliminates extracellular microbes
  • Cell-mediated: medaited by T cells, eliminates phagocyotsed microbes (CD4+) and kills infected cells and elimates reservoirs of infection (CD8+)
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13
Q

What are the 4 main antibodies and their key function(s)?

A
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14
Q

What is the role of CD40 ligand in T cell activation?

A

Activated T helper cell presents ligand to B cell and binds CD40, which:

  1. Promotes B cells to proliferate (plasma cell formation)
  2. Increases costimulation by increasing CD28 expression
  3. Increases macrophage activity and TNF release
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15
Q

What are the different functions of major APCs after antigen presentation?

A
  • DC- initiation of T cell responses to protein antigens
  • Macrophage- effector phase of cell-mediated immune response
  • B Lymphocytes- CD4+ T helper cells in humoral immune responses (Tcell-Bcell interactions)
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16
Q

What are the three main types of antigen presentation?

A
  • Extracellular/surface
  • Multi-molecular
  • Multi-cellular
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17
Q

Where is IgD mostly found?

A
  • Found on surface of newly matured B cells
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18
Q

Why is co-stimulation required to activate T cells?

A
  • TCR binds a peptide:MHC complex to recognize antigen
  • CD28 binds B7 in order to increase expression of costimulators and secretion of cytokines
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19
Q

What is the significance of the germinal center?

A
  • Activated B/T cells migrate back into follicle
  • B cells undergo somatic mutation and isotype switching
  • High-affinity B cells selected
  • Long-lived plasma cells and memore B cells
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20
Q

What are the three types of dendritic cells?

A
  • Conventional DCs- CD11b/c high; secretes TNFalpha, IL6, IL12
  • Plasmacytoid DCs- B220 high, secretes IFNs
  • Follicular DCs
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21
Q

When do dendritic cells mature?

A

After antigen capture and activation, when they are in migration to the lymph node.

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22
Q

Where is IgE mostly found?

A
  • Cause the body to react with foreign substances (allergies)
  • Located in the lungs, skin, and mucous membranes
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23
Q

How many antibodies can a B cell express?

A

One, in order to make each B cell specific

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24
Q

What are the 2 main ways T helper cells assist cytotoxic T cells?

A
  1. Attach to APC and directly produce cytokines that stimulate CTL differentiation
  2. Attach to APCs and enhance APC ability to stimulate CTL differentiation
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25
Q

What are the two important processes of “thymic education”?

A
  1. MHC Restriction- positive selection from cortical thymic epithelial cells (those that do not react are killed)
  2. Self Tolerance- negative selection from medulla thymic epithelial cells (those that do react are killed)
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26
Q

What is role of TLRs in B cells?

A

Provide cell-intrinsic mechanism for innate signals regulating adaptive immune responses

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27
Q

What is DiGeorge Syndrome?

A
  • Also known as thymic aplasia
  • May have heart defects, low calcium, T cell deficiency (classic triad)
  • Typically due to 22q11 deletion and failure to develop pharyngeal pouches
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28
Q

What are the three main types of antigen processing?

A
  • Intracellular
  • MHC 1 (intrinsic)
  • MHC 2 (extrinsic)
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29
Q

What are the 4 main adaptive immune system lymphocytes?

(Hint: 1B and 3T)

A
  1. B lymphocyte- Neutralization of microbe, phagocytosis, complement activation
  2. Helper T lymphocyte- Activation of macrophages, inflammation, and activation of B/T lymphocytes
  3. Cytotoxic T lymphocyte (CTL)-Killing of infected cell (apoptosis through cytolytics)
  4. Regulatory T lymphocyte- Suppression of immune response
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30
Q

What is a double negative (DN) thymocyte?

A

An early/immature thymocyte that lacks TCR and CD4/CD8 expression. It will up-regulate expression after TCR gene arrangement

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31
Q

What is the only cell in the human body that makes antibody?

A

Plasma Cell (mature B cell)

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32
Q

How are Th1 and Th2 differentiation inhibited?

A
  • Th1 differentiation is inhibited by IL-4 and IL-10 (from Th2)
  • Th2 differentiation is inhibited by IFNgamma (from Th1)
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33
Q

What is the differentiation and role of Th17 cells?

A
  • Differentiation requires IL-6 and TGFbeta
  • Release cytokines IL-17 and IL-22
  • Plays a role in protection against bacterial and fungal infections (epithelial barrier)
  • Neutrophilic and monocytic recruitment
  • Organ-specific autoimmunity
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34
Q

What is a naive T cell?

A

A single-positive (CD4 or CD8) thymocyte that has left the thymus, but is “resting” (unactivated)

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35
Q

What is Chronic Mucocutaneuos Candidiasis?

A
  • Non-invasive skin infections with candida (yeast)
  • Leads to T cell immune deficiency
36
Q

What is the difference between partial and complete DiGeorge Syndrome?

A
  • Partial- variable and non-life threatening immune defect, may improve with age
  • Complete- usually fatal in first year, form of SCID
37
Q

How does complement help B cell activation?

A
  • Opsonization by C3b (coats cell)
  • C3d binds B cells through complement receptor 2 and enhances antigen-dependent activation
  • Similar to costimulatory role of APCs for T cells
38
Q

What is the role of IL-5?

A

Activation of eosinophils (severe allergies)

39
Q

Naive T cells enter the peripheral lymph nodes through which specialized vessel?

A

(post-capillary) High endothelial venules (within in the paracortex)

40
Q

What are the 3 main functions of the adaptive immune system?

A
  1. Recognition of specific “non-self” antigens
  2. Eliminate specific pathogens or pathogen-infected cells
  3. Immunologic memory
41
Q

What percentage of peripheral blood T cells are CD4+ and CD8+?

A

65% are CD4+ and 35% are CD8+

42
Q

Which cytokine is critical for all T cell subtypes to proliferate and grow?

43
Q

How long can naive T cells live in the blood stream without becoming activated by pathogens?

A

5-7 weeks (If activated, they can live several years!)

44
Q

What are the effector products of B cells and humoral immunity?

A

Antibodies (secreted by antibody-secreting plasma cells, which are mature B cells)

45
Q

What are some restrictions of MHC molecules?

A
  • Can only present peptides
  • Can only present one peptide at a time
  • Only expressed on surface when peptide is present
46
Q

Where is IgM mostly found?

A
  • First antibody made in response to infection
  • Found in blood and lymph
47
Q

What is a memory T cell?

A

Subset of antigen-specific T cells, quickly expand upon re-exposure to antigen (can be CD4+ or CD8+)

48
Q

Where is IgA mostly located in the body?

A
  • Protects body surfaces exposed to foreign surfaces
  • Nose, breathing passages, digestive tract, ears, eyes, vagina
49
Q

What is the role of IL-4?

A

B cell switching to IgE (allergies)

50
Q

What is the role of Ifn-gamma?

A
  • Activation of macrophages
  • Inihbits Th2 differentiation
  • Activates NK cells to kill virus-infected cells
  • Increases MHC expression and antigen presentation by cells
51
Q

What is the difference between MHC 1 and MHC 2?

A
  • MHC1- found on all healthy nucleated cells, display peptide antigens found within cytoplasm of cells (intracellular pathogens), recognized by CD8+
  • MHC2- found on specialized antigen presenting cells (dendritic cells, macrophages, B cells), display antigens from within cell’s vesicles (extracellular pathogens), recognized by CD4+
52
Q

What is the difference between B and T cell recognition?

A
  • B-cells recognize circulating antigens of many chemical structures (extracellular pathogens)
  • T-cells only recognize MHC molecules on surface of antigen presenting cells (intracellular pathogens)
53
Q

What are heterophile antibodies?

A

Antibodies produced during mono that react with the antigens of unrelated species (e.g. horse RBC)

54
Q

Both MHC 1 and 2 are made in the ER, but where are they loaded with peptide?

A
  • MHC 1- loaded in the ER (involves TAP)
  • MHC 2- loaded by specialized vesicles (involves invariant chain-CLIP and DM)
55
Q

What happens to a T cell attached to antigen if co-stimulation does not occur?

A

The T cell becomes anergized and will no longer be responsive to antigen stimulation (self-tolerance induction)

56
Q

What is the differency between primary and secondary antibody responses?

A
  • Primary- Takes longer, smaller peak, more IgM than other antibodies, low affinity
  • Secondary- Shorter (1-3 days), larger peak, relative increase in other Ig (IgG), and higher affinity
57
Q

What is the difference between Type 1 and Type 2 Hyper IgM syndrome??

A
  • Type 1- caused by CD40L mutation (X-linked)
  • Type 2- caused by AICDA mutation (autosomal recessive)
58
Q

Do CD8+ cytoxic T cells always receive signals from intracellular peptides?

A

Generally, yes. But the exception to the rule is when DC present CD8+ T cells with virus-infected cells and viral antigen is used to stimulate CD8+ T cell

59
Q

True or False: Both B & T cells originate in the bone marrow

A

True. Both originate from a common lymphoid precuror

B-cells continue to generate in the bone marrow before entering lymph.

T-cells move to the thymus where selection and maturation occurs.

60
Q

What is the similarities and difference between phagocytes and APCs?

A
  • Both cells will endocytose microbes, but APCs will not necessarily kill the cells (presents them to T cells)
  • Both can recruit helper T cells
  • Usually one in the same cell (Macrophage and Dendritic cells are both)
61
Q

What are the binding cleft and CD4 binding domains in MHC class 2 molecules?

A
  • Binding cleft- alpha 1 and beta 1
  • CD4 binding domain- beta 2
62
Q

Why is important for humans that MHC genes are highly polymorphic (with over 5,000 alleles)?

A

Because this means that within a given population, it is likely that at least some of the individuals will be able to mount an immune response to a pathogen (survive)

63
Q

What are the main proteins secreted by the adaptive immune system?

A

Immunoglobulins

64
Q

At what point in T cell development does VDJ recombination occur?

A

In the Pre-T cell, located in the thymus (no CD4 or CD8 expression)

65
Q

What are some benefits of MHC molecules?

A
  • Present both self and non-self derived peptides
  • Number on the surface on the order of 105
  • Only 1% needed to activate T cell
  • Very slow turn-off rate
66
Q

Which T cell type directly kills T cells?

A

CD8+ cytotoxic T cells (CD4+ helper T cells recruit or help phagocytes mount a reponse to microbes)

67
Q

What are the 4 general steps of T cell activation?

A
  1. Specialized APC (dendritic) samples antigen, processes, and migrates to lymph node
  2. T cell activation (signal 1): antigen is presented on MHC 1 or MHC 2
  3. Proliferation and survival (signal 2): costimulatory signal via interaction of CD28 and B7 (APC)
  4. Th cell acitvates and produces cytokines or Tc activates and recognizes/kills virus-infected cell
68
Q

What are the binding cleft and CD8 binding domains in MHC class 1 molecules?

A
  • Binding Cleft- alpha 1 and alpha 2
  • CD8 binding- alpha 3
69
Q

What is a gamma-delta T cell?

A

A T cell that is both CD4 and CD8 negative

70
Q

What is the significance of IgG in the body?

A
  • Found in all body fluids
  • Only antibody that can cross the placenta and protect fetus
  • Also the most concentrated antibody in humans
71
Q

What is the role of TGF-Beta?

A

Inhibition of T cell activation; Differentiation of regulatory T cells

72
Q

What is the differentiation and role of Th1 cells?

A
  • Differentation requires IL-12 and IFNgamma
  • Releases pro-inflammatory TNFalpha and IFNgamma
  • Stimulates macrophages (IFNgamma)
  • Induces class switching by B cells (to IgG)
  • Plays a role in autoimmune diseases and tissue damage associated with chronic infections
73
Q

What is the differentiation and role of Th2 cells?

A
  • Differentiation requires IL-4 (basophils)
  • Releases IL-4 and IL-5
  • Plays a role in eliminating bacteria and viruses (B cell expansion) like helminth parasites
  • Mast cell, eosiniphil activation (allergic diseases) and anti-inflammation
74
Q

Which cells express toll-like receptors?

A

All leukocytes, including:

  • Dendritic Cells
  • Macrophages
  • NK Cells
  • B and T cells
  • Epithelial, Endothelial, and fibroblasts too
75
Q

What are the gene products for MHCs?

A

Human Leukocyte Antigens (HLAs), all are located on chromosome 6

76
Q

Do naive B cells in the lymph node present antigens to naive helper T cells or differentiated helper T cells?

A

Differentiated helper T cells in order to form germinal centers that can increase antibody production

77
Q

Which cells have Fc receptors that can bind to the Fc portion of Ig?

A
  • Macrophages/monocytes
  • Neutrophils
  • NK cells
  • Mast Cells
  • Basophils
  • Eosinophils
78
Q

What is a chemistry panel?

A

Checks for organ system function and urinalysis (useful for intial screening)

79
Q

What test(s) should be done to evaluate for antiobody deficiency or defects?

A
  • Measure total serum IgG, IgA, IgM
  • Measure IgG and/or IgE subclasses (if needed)
  • Check IgD only for periodic fever (not ID)
80
Q

How can you test antibody function if numbers of antibodies are normal?

A

Titer to vaccine (known exposure)

81
Q

What test(s) should you consider if cellular immunity defects are suspected?

A
  • CBC with differential (primary vs. secondary)
  • Use flow cytometry to quantitate lymphocytes
82
Q

What are the main lymphocyte markers?

A
  • T cell- CD3
  • Helper T cell- CD4
  • Cytotoxic T cell- CD8
  • B Cells- CD19
  • NK cell- CD16/CD56
83
Q

What is an assay that can evaluate T cell function?

A

Commonly use mitogen test (in vitro), can be used to measure reponse to specific antigens or peripheral T cell proliferation

84
Q

What is cutaneous Delayed-Type Hypersensitivity (DTH)?

A
  • In vivo test of cellular immunity (PPD)
  • Positive test requires an immune response (exposure)
85
Q

What test can be used for neutrophil defects?

A

CBC with differential (if normal numbers the function should be tested, like NBT test)

Immunology Block (6 decks)

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