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John Step 1 > Immunology > Flashcards

Immunology Flashcards

1
Q

Lymph drainage: What does the right lymphatic duct drain?

A

Right arm and right half of head

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2
Q

Lymph drainage: What does the thoracic duct drain?

A

Everything except for the right arm and the right half of head

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3
Q

What does the white pulp of the spleen contain?

A

Contains: 1. Lymphoid follicles with germinal centers (mostly B cells). Can see aggregation of dark basophilic lymphocytic nuclei. 2. Characteristic central arterioles. Surrounded by a Periarterial lymphatic sheath (PALS) which is a collection of T-lymphocytes.

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4
Q

Where is the red pulp of the spleen located?

A

Around and between the lymphatic nodules of the white pulp

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5
Q

Splenic cords: What are they?

A

Structures containing macrophages, plasma cells, lymphocytes, and few RBCs. Separated from each other by splenic sinusoids.

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6
Q

Thymus: Function

A

Site of T-cell differentiation and maturation (T cells differentiate in the Thymus. B cells differentiate in the Bone marrow)

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7
Q

Thymus: Embryological origin

A

Epithelium of 3rd branchial pouches

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8
Q

Lymphocytes: Embryological origin

A

Mesenchyme

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9
Q

Thymus: What does the cortex contain and what does it look like?

A

The lobules resemble lymphatic nodules except they are angular, not round.Contains:1. Densely packed (dark) immature T cells.2. Large epithelial reticular cells which appear as holes within the cortical cells.

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10
Q

What is positive selection of T cells?

A

Retention of T cells that have functioning T cell receptors

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11
Q

Where do positive and negative selection of T-cells occur in the thymus?

A

At the corticomedullary junction

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12
Q

What is negative selection of T cells?

A

Destruction of T-cells that react to self-antigen

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13
Q

Innate immunity vs adaptive immunity: How are receptors that recognize pathogens encoded?

A

Innate: Germline encoded
Adaptive: Undergo VDJ recombination during development

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14
Q

Innate immunity vs adaptive immunity: How fast is response to pathogens?

A

Innate: Always fast, no memory response.
Adaptive: Slow on 1st exposure but memory response is faster and more robust.

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15
Q

T-cell differentiation: What CD?

A

CD3

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16
Q

T-cell differentiation: What happens to T-cell precursors when they enter the thymus, and what are they called?

A

Once T-cell precursors acquire and display CD4 and CD8, they are cortical thymocytes.

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17
Q

T-cell differentiation: Where is the T-cell in its development when it undergoes positive selection?

A

Both CD4 positive and CD8 positive

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18
Q

T-cell differentiation: Where in the thymus are cells which are positive for both CD4 and CD8 located?

A

Thymic cortex

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19
Q

T-cell differentiation: Where is the T-cell in its development when it undergoes negative selection?

A

Either CD4 positive or CD8 positive, not both

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20
Q

T-cell differentiation: Where in the thymus are cells which are positive for either CD4 or CD8 located?

A

Thymic medulla

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21
Q

T-cell differentiation: What are the two types of helper T cells and where do they differentiate?

A

In the lymph node, helper T cells differentiate into Th1 cells, and Th2 cells.

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22
Q

Differences between Th1 and Th2 cells: Stimulant for differentiation from archetypical helper T cell.

A

Th1: IL-12 from both other Th1 cells and antigen-presenting dendritic cells
Th2: IL-4 from other Th2 cells and presumably an unknown factor from dendritic cells

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23
Q

Differences between Th1 and Th2 cells: Cytokines produced by both types

A

Both: IL-2
Th1: IFN-gamma, TNF-alpha
Th2: IL-4, IL-5, IL-6, IL-10, IL-13

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24
Q

Cytokine effects: Interleukin 2

A

Stimulates T-cell growth and proliferationMnemonic for first 5 interleukins: Hot T-bone stEAk

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25
Cytokine effects: Interferon gamma
1. Inhibits Th2 cytokines2. Induces class I and II MHC3. Stimulates differentiation of monocytes into macrophages.4. Activates macrophages.
26
Cytokine effects: Tumor Necrosis Factor alpha
1. Activates macrophages, neutrophils (also attracts them), and CD8 cells.2. Induces neutrophil-endothelial cell adhesion.3. Constitutional: sepsis, cachexia ("wasting away"), fever, acute phase proteins. 4. Tumor cell lysis5. Increased proliferation of B-cells6. Increased synthesis of IL-2 receptors by Th cells.7. Stimulates dendritic cell migration to lymph nodes.
27
Cytokine effects: Interleukin 4
1. Growth of B-cells2. Growth and proliferation of T-cells3. Synthesis of IgE4. Class switching of IgG to IgE5. Inhibits IL-8, IL-1, and TNF-alphaMnemonic for first 5 interleukins: Hot T-bone stEAk. E as in stimulates IgE production.
28
Cytokine effects: Interleukin 5
1. Differentiation of B cells 2. Class switching of IgA3. Production and activation of eosinophilsMnemonic for first 5 interleukins: Hot T-bone stEAk. A as in stimulates IgA production.
29
What cytokines stimulate the acute phase response?
1. IL-12. IL-63. TNF-alpha
30
What are acute phase response proteins used for?
1. Augment immune response (complement, Ig)2. Regulate the extent of response (protease inhibitors like alpha-1-antitrypsin)3. Stimulate additional responses (alpha-2-macroglobulin)
31
Cytokine effects: Interleukin 10
Big picture: Stimulates Th2 while inhibiting Th1Specifically inhibits:1. IL-82. IL-13. TNF-alpha4. IFN-gamma
32
What releases: Interleukin 10
1. Th2 cells2. Macrophages
33
Differences between Th1 and Th2 cells: Major effects
Both: Downregulate each otherTh1: Activates all lymphocytes and APCs, especially CD8 cells and macrophages.Th2 cells: 1. B cells: Increased differentiation, proliferation, antibody, and class switching.2: Activation of eosinophils
34
What releases: Interleukin 2
Th cells
35
What releases: Tumor Necrosis Factor alpha
Macrophages (emphasized) and Th1 cells
36
What releases: Interferon gamma
Th1 cells (emphasized) and NK cells
37
What releases: Interleukin 5
T cells (especially Th2) and mast cells
38
What releases: Interleukin 6
T cells (especially Th), macrophages, and endothelial cells
39
What is MHC and what codes for it?
Major Histocompatability Complex encoded by Human Leukocyte Antigen (HLA)
40
MHC I and II: What cells are they expressed on?
I: All nucleated cells except sperm. II: Antigen Presenting Cells
41
B cells and T cells: Effect on Ig
B cells: Make it | T cells: (CD4) Help B cells make it and release IFN-gamma to activate macrophages
42
B cells and T cells: Method of killing
B cells: IgG opsonizes bacteria and virusesT cells: (CD8) Directly kills virus-infected cells
43
B cells and T cells: Allergy mechanism
B: Type I hypersensitivity, through IgET: Type IV hypersensitivity
44
B cells and T cells: Organ rejection speed
B: Fast, through antibodiesT: Slow
45
CD/MHC: What binds MHC II?
CD4 T-cell receptors
46
What does MHC I pair with (allosteric interaction)
beta2-microglobulin
47
CD/MHC: What binds MHC I?
CD8 T-cell receptors
48
CD/MHC: What binds CD4 T-cell receptors?
MHC II on antigen presenting cells
49
CD/MHC: What binds CD8 T-cell receptors?
MHC I on virus-infected cells
50
Cytokine effects: Interleukin 1
Big picture: Stimulates growth differentiation or product synthesis by T cells, B cells, neutrophils, fibroblasts, and epithelial cells1. Endogenous pyrogen2. Activates T cells3. Upregulates adhesion molecules4. Induces acute phase reactants5. Synergizes with TNF-alphaMnemonic for first 5 interleukins: Hot T-bone stEAk. Hot as in fever.
51
What releases: Interleukin 1
1. Professional antigen-presenting cells (macrophages, monocytes, dendritic cells, and B cells)2. Some non-professional antigen presenting cells (fibroblasts, endothelial cells, others)
52
How does Interleukin 1 cause fever?
Steps1. Migrates to the circumventricular organs2. Binds with endothelial receptors.3. Receptors activate Phospholipase A2-COX2-PGE2 pathway4. Prostaglandin E2's presence in the hypothalamus elevates the thermoregulatory set point and activates neuroendocrine determinants of fever.
53
What are the professional antigen presenting cells?
1. Macrophages2. B cells3. Dendritic cells
54
What is the CD3 complex?
Cluster of polypeptides associated with a T-cell receptor. It is important in signal transduction.
55
How are Th cells activated?
1. APC phagocytoses foreign body. 2. APC presents antigen on MHC II. 3. Signal 1: Th cell's TCR recognizes antigen. 4. Signal 2 (costimulatory): APC's B7 molecule stimulates Th cell's CD28 molecule. 5. Autocrine IL-2 stimulates Th cell to produces cytokines
56
How are Tc cells activated?
1. Virus-infected cell presents endogenously synthesized proteins on MHC I. 2. Signal 1: Tc cell's TCR recognizes antigen. 3. Signal 2: IL-2 released from Th cell activates T c cell to kill virus infected cell.
57
What part of an antibody recognizes antigen?
Variable portion of Fab fragment
58
What part of an antibody fixes complement?
Constant part of H chain of IgM and IgG
59
Antibody structure/function, True or False: Light chain contributes to Fab
TRUE
60
Antibody structure/function, True or False: Heavy chain contributes to Fab
TRUE
61
Antibody structure/function, True or False: Light chain contributes to Fc
FALSE
62
Antibody structure/function, True or False: Heavy chain contributes to Fc
TRUE
63
What is the middle of the variable component of an antibody component chain called?
Hypervariable region
64
What disulfide bonds does an antibody have?
Interchain: Bonds between both heavy chains and between corresponding light and heavy chainsIntrachain: On each segment
65
Where on an antibody is the Amino terminal?
At the variable edges of the chains
66
Where on an antibody is the carboxyl terminal?
At the constant edges of the heavy chains
67
Antibody structure/function: What are the five Cs of Fc?
1. Constant 2. Carboxy terminal 3. Complement binding (IgG and IgM only) 4. Carbohydrate side chains 5. Complement binding fragment
68
3 main functions of the antibody
1. Opsonization 2. Neutralization (prevents bacterial adherence) 3. Complement activation
69
How is antibody diversity generated?
1. Random "recombination" of VJ (light chain) or VDJ (heavy chain) genes. 2. Random combination of heavy chains with light chains 3. Somatic hypermutation 4. Addition of nucleotides to DNA during "genetic recombination" by terminal deoxynucleotidyl transferase.
70
What does terminal deoxynucleotidyl transferase do?
Addition of nucleotides to DNA during "genetic recombination" in B cells
71
What does Tdt stand for?
Terminal deoxynucleotidyl transferase
72
Which immunoglobulins are expressed on the surface of mature B cells?
IgM and IgD
73
What is isotype switching?
Differentiation of B cells into plasma cells that secrete IgG, IgA, or IgE
74
What stimulates isotype switching?
Cytokines (IL-4 and IL-5) and CD40-Ligand on T-cells
75
Main antibody isotype in secondary immune response
IgG
76
Most abundant antibody isotype
IgG
77
Antibody isotypes which cross placenta
IgG
78
Antibody isotypes which fix complement
IgG and IgM in the classic complement pathwayMnemonic: GM makes classic cars
79
Antibody isotypes which opsonize bacteria
IgG (and IgA weakly)
80
Main antibody isotype in primary immune response
IgM
81
Antibody isotype with longest half life
IgG (26 days compared with 5 for IgM, the next longest)
82
Antibody isotype which prevents bacterial/viral attachment to mucous membranes
IgA
83
Antibody isotype found in secretions
IgA
84
Antibody isotype which mediates type I hypersensitivity
IgE
85
How does IgE cause an allergic response?
Type I hypersensitivity 1. IgE binds to basophils or mast cells 2. IgE binds antigen 3. These cells release histamine and leukotrienes.
86
Which cells have receptors for IgE?
1. mast cells 2. basophils 3. eosinophils 4. monocytes/macrophages 5. platelets
87
Antibody isotype which mediates immunity to worms
IgE
88
Least abundant antibody isotype
IgE
89
Define allotype
An individual's allele coding for the constant portions of the antibody's heavy chains.
90
Define isotype
Type of chain in an antibodyHeavy isotypes: alpha, gamma, delta, epsilon, muLight isotypes: kappa, lambda
91
Define idiotype
antibodies of one idiotype share structure of their variable region and thus, antigen binding specificity.
92
Cytokine effects: Interleukin 3
Supports the growth and differentiation of bone marrow stem cells (similar to GM-CSF). Most important during early growth.Mnemonic for first 5 interleukins: Hot T-bone stEAk. bone, as in bone development
93
What releases: Interleukin 3
T cells (emphasis on activated T cells) and thymic epithelial cells
94
Cytokine effects: Interleukin 6
1. Differentiation and growth of B cells and T cells 2. Systemic effects (Acute Phase Response and Fever) 3. Stimulates Ig production
95
What releases: Interleukin 4
Th2 cells
96
Cytokine effects: Interleukin 8
1. Major neutrophil chemotactic and adhesion factor 2. Angiogenesis 3. High levels associated with schizophrenia
97
What releases: Interleukin 8
1. Monocytes 2. Endothelial cells 3. Fibroblasts
98
Cytokine effects: Interleukin 12
1. Promotes differentiation of Th cells into Th1 | 2. Activates NK cells
99
What releases: Interleukin 12
Professional Antigen Presenting Cells: 1. Dendritic cells 2. Macrophages 3. B cells
100
Important cell surface proteins and their functions: Helper T cells
1. CD4 2. TCR 3. CD3 (Signal transduction) 4. CD28 and CD40L (Receive costimulatory activation signal respectively from B7 and CD40 which are both on B cells and professional APCs. These two signaling pathways each upregulate the other.)
101
Important cell surface proteins and their functions: Cytotoxic T cells
1. CD8 2. TCR 3. CD3 (Signal transduction)
102
Important cell surface proteins and their functions: B cells
1. IgM 2. MHC II (Presents foreign antigens to Th cells) 2. B7 and CD40 (Costimulatory activation signal respectively to CD28 and CD40L which are both on T cells. These two signaling pathways each upregulate the other.) 3. CD19, CD21 (Subunits of co-receptor for BCR complex) 4. CD20 (Target in non-Hodgkin's lymphoma of monoclonal antibodies like rituximab)
103
Important cell surface proteins and their functions: Macrophages
1. MHC II (Presents foreign antigens to Th cells) 2. CD14 (Works with toll-like receptor 4 to bind lipopolysaccharide. Also a marker for monocytes) 3. Receptors for Fc and C3b (ie opsonins)
104
Important cell surface proteins and their functions: NK cells
1. Receptors for MHC I 2. CD16 (subunit of low-affinity Fc receptor [ie. opsonins]) 3. CD56 (adhesion molecule)
105
Important cell surface proteins and their functions: Hematopoietic stem cells
CD34 (marker for this type of cell, and a receptor for CD62L, a selectin)
106
Complement: Viral neutralization
C1, C2, C3, C4
107
Complement: Opsonization
C3b
108
Complement: Anaphylatoxins
C3a, C5a
109
Complement: Neutrophil Chemotaxis
C5a
110
Complement: Membrane attack complex
C5b to C9
111
Deficiency of C1 esterase inhibitor leads to:
Hereditary angioedema (overactive complement)
112
Deficiency of C3 leads to:
Severe recurrent pyogenic sinus and respiratory tract infections
113
Deficiency of C6 through C8 leads to:
Neisseria bacteremia
114
What is Decay Accelerating Factor?
Prevents attachment of the alternative complement complex (C3 convertase) to the membrane
115
When is Decay Accelerating Factor missing?
In paroxysmal nocturnal hemoglobinuria
116
What kind of bacteria does complement defend against?
Gram negative bacteria
117
What activates the classic complement pathway?
IgG and IgM.Mnemonic: GM makes classic cars.
118
What activates the alternative complement pathway?
Microbe surface molecules (especially endotoxin)
119
PGI2
Prostacyclin. Vasodilator and inhibits platelet aggregation. Aspirin does not inhibit its synthesis by endothelial cells. Synthesized from PGH2 by prostacyclin synthase in intact endothelial cells.
120
PGH2
Synthesizes PGI2 with prostacyclin synthase in intact endothelial cells. Precursor of thromboxanes. Synthesized from PGG2.
121
PGE2
Vasodilation, pain and fever. Synthesized from PGH2
122
TxA2
Vasoconstriction, platelet aggregation and bronchoconstriction. Coverted from PGH2 by thromboxane synthase.
123
LTB4
chemotaxis and activation of neutrophil adhesion molecules
124
LTC4, D4, E4
Vasoconstriction, increased vessel permeability, bronchoconstriction

John Step 1 (7 decks)

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