Adaptive Flashcards
(85 cards)
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
2
Q
What is the role of IL-17?
A
Stimulation of acute inflammation
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
4
Q
Where do most plasma cells reside?
A
Bone Marrow
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)
6
Q
Which etiological agent is most commonly associated with infectious mononucleosis (mono)?
A
Epstein Barr Virus (EBV)
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)
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
9
Q
What is Wiskott-Aldrich Syndrome?
A
- X-linked recessive disease, defective antigen presentation
- Abnormal platelets, eczema, recurrent infection
10
Q
What are the 3 main types of mature B cells?
A
- Follicular B cells- most mature B cells, lypmh node and spleen follicles
- Marginal-zone B cells- found in margins of slpenic follicles
- B1 lymphocytes- lymphoid organs and peritoneal cavity
11
Q
Where in the body does antigen presentation occur?
A
The lymph nodes and the spleen
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+)
13
Q
What are the 4 main antibodies and their key function(s)?
A
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:
- Promotes B cells to proliferate (plasma cell formation)
- Increases costimulation by increasing CD28 expression
- Increases macrophage activity and TNF release
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)
16
Q
What are the three main types of antigen presentation?
A
- Extracellular/surface
- Multi-molecular
- Multi-cellular
17
Q
Where is IgD mostly found?
A
- Found on surface of newly matured B cells
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
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
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
21
Q
When do dendritic cells mature?
A
After antigen capture and activation, when they are in migration to the lymph node.
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
23
Q
How many antibodies can a B cell express?
A
One, in order to make each B cell specific
24
Q
What are the 2 main ways T helper cells assist cytotoxic T cells?
A
- Attach to APC and directly produce cytokines that stimulate CTL differentiation
- Attach to APCs and enhance APC ability to stimulate CTL differentiation
25
What are the two important processes of "thymic education"?
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*)
26
What is role of TLRs in B cells?
Provide cell-intrinsic mechanism for innate signals regulating adaptive immune responses
27
What is DiGeorge Syndrome?
* 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
28
What are the three main types of antigen processing?
* Intracellular
* MHC 1 (intrinsic)
* MHC 2 (extrinsic)
29
What are the 4 main adaptive immune system lymphocytes?
## Footnote
(Hint: 1B and 3T)
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
30
What is a double negative (DN) thymocyte?
An early/immature thymocyte that lacks TCR and CD4/CD8 expression. It will up-regulate expression after TCR gene arrangement
31
What is the only cell in the human body that makes antibody?
Plasma Cell (mature B cell)
32
How are Th1 and Th2 differentiation inhibited?
* Th1 differentiation is inhibited by IL-4 and IL-10 (from Th2)
* Th2 differentiation is inhibited by IFNgamma (from Th1)
33
What is the differentiation and role of Th17 cells?
* 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
34
What is a naive T cell?
A single-positive (CD4 or CD8) thymocyte that has left the thymus, but is "resting" (unactivated)
35
What is Chronic Mucocutaneuos Candidiasis?
* Non-invasive skin infections with candida (yeast)
* Leads to T cell immune deficiency
36
What is the difference between partial and complete DiGeorge Syndrome?
* Partial- variable and non-life threatening immune defect, may improve with age
* Complete- usually fatal in first year, form of SCID
37
How does complement help B cell activation?
* 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
What is the role of IL-5?
Activation of eosinophils (severe allergies)
39
Naive T cells enter the peripheral lymph nodes through which specialized vessel?
(post-capillary) High endothelial venules (within in the paracortex)
40
What are the 3 main functions of the adaptive immune system?
1. Recognition of specific "non-self" antigens
2. Eliminate specific pathogens or pathogen-infected cells
3. Immunologic memory
41
What percentage of peripheral blood T cells are CD4+ and CD8+?
65% are CD4+ and 35% are CD8+
42
Which cytokine is critical for all T cell subtypes to proliferate and grow?
IL-2
43
How long can naive T cells live in the blood stream without becoming activated by pathogens?
5-7 weeks (If activated, they can live several years!)
44
What are the effector products of B cells and humoral immunity?
Antibodies (secreted by antibody-secreting plasma cells, which are mature B cells)
45
What are some restrictions of MHC molecules?
* Can only present peptides
* Can only present one peptide at a time
* Only expressed on surface when peptide is present
46
Where is IgM mostly found?
* First antibody made in response to infection
* Found in blood and lymph
47
What is a memory T cell?
Subset of antigen-specific T cells, quickly expand upon re-exposure to antigen (can be CD4+ or CD8+)
48
Where is IgA mostly located in the body?
* Protects body surfaces exposed to foreign surfaces
* Nose, breathing passages, digestive tract, ears, eyes, vagina
49
What is the role of IL-4?
B cell switching to IgE (allergies)
50
What is the role of Ifn-gamma?
* Activation of macrophages
* Inihbits Th2 differentiation
* Activates NK cells to kill virus-infected cells
* Increases MHC expression and antigen presentation by cells
51
What is the difference between MHC 1 and MHC 2?
* **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
What is the difference between B and T cell recognition?
* 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
What are heterophile antibodies?
Antibodies produced during mono that react with the antigens of unrelated species (e.g. horse RBC)
54
Both MHC 1 and 2 are made in the ER, but where are they loaded with peptide?
* MHC 1- loaded in the ER (involves TAP)
* MHC 2- loaded by specialized vesicles (involves invariant chain-CLIP and DM)
55
What happens to a T cell attached to antigen if co-stimulation does not occur?
The T cell becomes anergized and will no longer be responsive to antigen stimulation (self-tolerance induction)
56
What is the differency between primary and secondary antibody responses?
* 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
What is the difference between Type 1 and Type 2 Hyper IgM syndrome??
* Type 1- caused by CD40L mutation (X-linked)
* Type 2- caused by AICDA mutation (autosomal recessive)
58
Do CD8+ cytoxic T cells always receive signals from intracellular peptides?
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
True or False: Both B & T cells originate in the bone marrow
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
What is the similarities and difference between phagocytes and APCs?
* 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
What are the binding cleft and CD4 binding domains in MHC class 2 molecules?
* Binding cleft- alpha 1 and beta 1
* CD4 binding domain- beta 2
62
Why is important for humans that MHC genes are highly polymorphic (with over 5,000 alleles)?
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
What are the main proteins secreted by the adaptive immune system?
Immunoglobulins
64
At what point in T cell development does VDJ recombination occur?
In the Pre-T cell, located in the thymus (no CD4 or CD8 expression)
65
What are some benefits of MHC molecules?
* 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
Which T cell type directly kills T cells?
CD8+ cytotoxic T cells (CD4+ helper T cells recruit or help phagocytes mount a reponse to microbes)
67
What are the 4 general steps of T cell activation?
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
What are the binding cleft and CD8 binding domains in MHC class 1 molecules?
* Binding Cleft- alpha 1 and alpha 2
* CD8 binding- alpha 3
69
What is a gamma-delta T cell?
A T cell that is both CD4 and CD8 negative
70
What is the significance of IgG in the body?
* Found in all body fluids
* Only antibody that can cross the placenta and protect fetus
* Also the most concentrated antibody in humans
71
What is the role of TGF-Beta?
Inhibition of T cell activation; Differentiation of regulatory T cells
72
What is the differentiation and role of Th1 cells?
* 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
What is the differentiation and role of Th2 cells?
* 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
Which cells express toll-like receptors?
All leukocytes, including:
* Dendritic Cells
* Macrophages
* NK Cells
* B and T cells
* Epithelial, Endothelial, and fibroblasts too
75
What are the gene products for MHCs?
Human Leukocyte Antigens (HLAs), all are located on chromosome 6
76
Do naive B cells in the lymph node present antigens to naive helper T cells or differentiated helper T cells?
Differentiated helper T cells in order to form germinal centers that can increase antibody production
77
Which cells have Fc receptors that can bind to the Fc portion of Ig?
* Macrophages/monocytes
* Neutrophils
* NK cells
* Mast Cells
* Basophils
* Eosinophils
78
What is a chemistry panel?
Checks for organ system function and urinalysis (useful for intial screening)
79
What test(s) should be done to evaluate for antiobody deficiency or defects?
* Measure total serum IgG, IgA, IgM
* Measure IgG and/or IgE subclasses (if needed)
* Check IgD only for periodic fever (not ID)
80
How can you test antibody function if numbers of antibodies are normal?
Titer to vaccine (known exposure)
81
What test(s) should you consider if cellular immunity defects are suspected?
* CBC with differential (primary vs. secondary)
* Use flow cytometry to quantitate lymphocytes
82
What are the main lymphocyte markers?
* T cell- CD3
* Helper T cell- CD4
* Cytotoxic T cell- CD8
* B Cells- CD19
* NK cell- CD16/CD56
83
What is an assay that can evaluate T cell function?
Commonly use mitogen test (in vitro), can be used to measure reponse to specific antigens or peripheral T cell proliferation
84
What is cutaneous Delayed-Type Hypersensitivity (DTH)?
* In vivo test of cellular immunity (PPD)
* Positive test requires an immune response (exposure)
85
What test can be used for neutrophil defects?
CBC with differential (if normal numbers the function should be tested, like NBT test)
