Immuno Flashcards
1
Q
Lymph drainage: What does the right lymphatic duct drain?
A
Right arm and right half of head
2
Q
Lymph drainage: What does the thoracic duct drain?
A
Everything except for the right arm and the right half of head
3
Q
Splenic sinusoids: What are they?
A
Long, vascular channels in red pulp with fenestrated “barrel hoop” basement membrane and macrophages nearby. Adjacent to splenic cords and contain blood.
4
Q
How can the spleen be distinguished from a lymph node on histologic section?
A
Spleens have no subscapsular sinus and no cortex or medulla. They have white pulp and red pulp.
5
Q
What does the white pulp of the spleen contain?
A
Contains:
- Lymphoid follicles with germinal centers (mostly B cells). Can see aggregation of dark basophilic lymphocytic nuclei.
- Characteristic central arterioles. Surrounded by a Periarterial lymphatic sheath (PALS) which is a collection of T-lymphocytes.
6
Q
Where is the red pulp of the spleen located?
A
Around and between the lymphatic nodules of the white pulp
7
Q
Splenic cords: What are they?
A
Structures containing macrophages, plasma cells, lymphocytes, and few RBCs. Separated from each other by splenic sinusoids.
8
Q
Thymus: Function
A
Site of T-cell differentiation and maturation (T cells differentiate in the Thymus. B cells differentiate in the Bone marrow)
9
Q
Thymus: Embryological origin
A
Epithelium of 3rd branchial pouches
10
Q
Lymphocytes: Embryological origin
A
Mesenchyme
11
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:
- Densely packed (dark) immature T cells.
- Large epithelial reticular cells which appear as holes within the cortical cells.
12
Q
Thymus: What does the medulla contain and what does it look like?
A
Pale
Contains:
Thymic (Hassall’s) corpuscles which have a lamellated or whorled appearance due to degenerating epithelial reticular cells.
13
Q
What is positive selection of T cells?
A
Retention of T cells that have functioning T cell receptors
14
Q
Where do positive and negative selection of T-cells occur in the thymus?
A
At the corticomedullary junction
15
Q
What is negative selection of T cells?
A
Destruction of T-cells that react to self-antigen
16
Q
Innate immunity vs adaptive immunity: How are receptors that recognize pathogens encoded?
A
Innate: Germline encoded
Adaptive: Undergo VDJ recombination during development
17
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.
18
Q
Innate immunity or adaptive immunity: Neutrophils
A
Innate immunity
19
Q
Innate immunity or adaptive immunity: Macrophages
A
Innate immunity
20
Q
Innate immunity or adaptive immunity: Dendritic cells
A
Innate immunity
21
Q
Innate immunity or adaptive immunity: Complement
A
Innate immunity
22
Q
Innate immunity or adaptive immunity: T cells
A
Adaptive immunity
23
Q
Innate immunity or adaptive immunity: B cells
A
Adaptive immunity
24
Q
Innate immunity or adaptive immunity: Circulating antibody
A
Adaptive immunity
25
T-cell differentiation: Where do T-cell precursors come from and where do they go?
From the bone marrow to the thymus
26
T-cell differentiation: What CD?
CD3
27
T-cell differentiation: What happens to T-cell precursors when they enter the thymus, and what are they called?
Once T-cell precursors acquire and display CD4 and CD8, they are cortical thymocytes.
28
T-cell differentiation: Where is the T-cell in its development when it undergoes positive selection?
Both CD4 positive and CD8 positive
29
T-cell differentiation: Where in the thymus are cells which are positive for both CD4 and CD8 located?
Thymic cortex
30
T-cell differentiation: Where is the T-cell in its development when it undergoes negative selection?
Either CD4 positive or CD8 positive, not both
31
T-cell differentiation: Where in the thymus are cells which are positive for either CD4 or CD8 located?
Thymic medulla
32
T-cell differentiation: What are the two types of helper T cells and where do they differentiate?
In the lymph node, helper T cells differentiate into Th1 cells, and Th2 cells.
33
Differences between Th1 and Th2 cells: Stimulant for differentiation from archetypical helper T cell.
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
34
Differences between Th1 and Th2 cells: Cytokines produced by both types
Both: IL-2
Th1: IFN-gamma, TNF-alpha
Th2: IL-4, IL-5, IL-6, IL-10, IL-13
35
Cytokine effects: Interleukin 2
Stimulates T-cell growth and proliferation
Mnemonic for first 5 interleukins: Hot T-bone stEAk
36
Cytokine effects: Interferon gamma
1. Inhibits Th2 cytokines
2. Induces class I and II MHC
3. Stimulates differentiation of monocytes into macrophages.
4. Activates macrophages.
37
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 lysis
5. Increased proliferation of B-cells
6. Increased synthesis of IL-2 receptors by Th cells.
7. Stimulates dendritic cell migration to lymph nodes.
38
Cytokine effects: Interleukin 4
1. Growth of B-cells
2. Growth and proliferation of T-cells
3. Synthesis of IgE
4. Class switching of IgG to IgE
5. Inhibits IL-8, IL-1, and TNF-alpha
Mnemonic for first 5 interleukins: Hot T-bone stEAk. E as in stimulates IgE production.
39
Cytokine effects: Interleukin 5
1. Differentiation of B cells 2. Class switching of IgA
3. Production and activation of eosinophils
Mnemonic for first 5 interleukins: Hot T-bone stEAk. A as in stimulates IgA production.
40
What cytokines stimulate the acute phase response?
1. IL-1
2. IL-6
3. TNF-alpha
41
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)
42
Cytokine effects: Interleukin 10
Big picture: Stimulates Th2 while inhibiting Th1
Specifically inhibits:
1. IL-8
2. IL-1
3. TNF-alpha
4. IFN-gamma
43
What releases: Interleukin 10
1. Th2 cells
| 2. Macrophages
44
Differences between Th1 and Th2 cells: Major effects
Both: Downregulate each other
Th1: 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
45
What releases: Interleukin 2
Th cells
46
What releases: Tumor Necrosis Factor alpha
Macrophages (emphasized) and Th1 cells
47
What releases: Interferon gamma
Th1 cells (emphasized) and NK cells
48
What releases: Interleukin 5
T cells (especially Th2) and mast cells
49
What releases: Interleukin 6
T cells (especially Th), macrophages, and endothelial cells
50
What is MHC and what codes for it?
Major Histocompatability Complex encoded by Human Leukocyte Antigen (HLA)
51
What genes code for MHC I?
1. HLA-A
2. HLA-B
3. HLA-C
52
What genes code for MHC II?
1. HLA-DP
2. HLA-DQ
3. HLA-DR
53
MHC I and II: What cells are they expressed on?
I: All nucleated cells except sperm.
II: Antigen Presenting Cells
54
MHC I and II: Where in the cell is antigen loaded onto the MHC?
I: RER (mostly intracellular peptides)
II: Acidified endosome
55
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
56
B cells and T cells: Method of killing
B cells: IgG opsonizes bacteria and viruses
T cells: (CD8) Directly kills virus-infected cells
57
B cells and T cells: Allergy mechanism
B: Type I hypersensitivity, through IgE
T: Type IV hypersensitivity
58
B cells and T cells: Organ rejection speed
B: Fast, through antibodies
T: Slow
59
CD/MHC: What binds MHC II?
CD4 T-cell receptors
60
What does MHC I pair with (allosteric interaction)
beta2-microglobulin
61
CD/MHC: What binds MHC I?
CD8 T-cell receptors
62
CD/MHC: What binds CD4 T-cell receptors?
MHC II on antigen presenting cells
63
CD/MHC: What binds CD8 T-cell receptors?
MHC I on virus-infected cells
64
Cytokine effects: Interleukin 1
Big picture: Stimulates growth differentiation or product synthesis by T cells, B cells, neutrophils, fibroblasts, and epithelial cells
1. Endogenous pyrogen
2. Activates T cells
3. Upregulates adhesion molecules
4. Induces acute phase reactants
5. Synergizes with TNF-alpha
Mnemonic for first 5 interleukins: Hot T-bone stEAk. Hot as in fever.
65
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)
66
How does Interleukin 1 cause fever?
Steps
1. Migrates to the circumventricular organs
2. Binds with endothelial receptors.
3. Receptors activate Phospholipase A2-COX2-PGE2 pathway
4. Prostaglandin E2's presence in the hypothalamus elevates the thermoregulatory set point and activates neuroendocrine determinants of fever.
67
What are the professional antigen presenting cells?
1. Macrophages
2. B cells
3. Dendritic cells
68
What is the CD3 complex?
Cluster of polypeptides associated with a T-cell receptor. It is important in signal transduction.
69
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
70
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.
71
Antibody structure/function: What are the components of the heavy chain?
Variable: VH
Constant: CH1, CH2, CH3
72
Antibody structure/function: What are the components of the light chain?
Variable: VL
Constant: CL
73
What part of an antibody recognizes antigen?
Variable portion of Fab fragment
74
What part of an antibody fixes complement?
Constant part of H chain of IgM and IgG
75
Antibody structure/function, True or False: Light chain contributes to Fab
TRUE
76
Antibody structure/function, True or False: Heavy chain contributes to Fab
TRUE
77
Antibody structure/function, True or False: Light chain contributes to Fc
FALSE
78
Antibody structure/function, True or False: Heavy chain contributes to Fc
TRUE
79
What is the middle of the variable component of an antibody component chain called?
Hypervariable region
80
Antibody structure/function: Where on an antibody is the hypervariable region?
The majority of the variable segments excluding the edges
81
How are the four chains of an antibody connected?
Interchain disulfide bonds at:
1. between the two heavy chains on the Fc side of the hinge region
2. between corresponding light and heavy chains on the Fab side of the hinge region
82
What disulfide bonds does an antibody have?
Interchain: Bonds between both heavy chains and between corresponding light and heavy chains
Intrachain: On each segment
83
Where on an antibody is the Amino terminal?
At the variable edges of the chains
84
Where on an antibody is the carboxyl terminal?
At the constant edges of the heavy chains
85
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
86
3 main functions of the antibody
1. Opsonization
2. Neutralization (prevents bacterial adherence)
3. Complement activation
87
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.
88
What does terminal deoxynucleotidyl transferase do?
Addition of nucleotides to DNA during "genetic recombination" in B cells
89
What does Tdt stand for?
Terminal deoxynucleotidyl transferase
90
Which immunoglobulins are expressed on the surface of mature B cells?
IgM and IgD
91
What is isotype switching?
Differentiation of B cells into plasma cells that secrete IgG, IgA, or IgE
92
What stimulates isotype switching?
Cytokines (IL-4 and IL-5) and CD40-Ligand on T-cells
93
Main antibody isotype in secondary immune response
IgG
94
Most abundant antibody isotype
IgG
95
Antibody isotypes which cross placenta
IgG
96
Antibody isotypes which fix complement
IgG and IgM in the classic complement pathway
Mnemonic: GM makes classic cars
97
Antibody isotypes which opsonize bacteria
IgG (and IgA weakly)
98
Main antibody isotype in primary immune response
IgM
99
Antibody isotypes associated with the J chain
IgM and IgA
100
Antibody isotypes associated with the SP
IgA
SP = Secretory Protein
101
Antibody isotype with longest half life
IgG (26 days compared with 5 for IgM, the next longest)
102
Antibody isotype which prevents bacterial/viral attachment to mucous membranes
IgA
103
Antibody isotype found in secretions
IgA
104
Antibody isotype which mediates type I hypersensitivity
IgE
105
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.
106
Which cells have receptors for IgE?
1. mast cells
2. basophils
3. eosinophils
4. monocytes/macrophages
5. platelets
107
Antibody isotype which mediates immunity to worms
IgE
108
Least abundant antibody isotype
IgE
109
Define allotype
An individual's allele coding for the constant portions of the antibody's heavy chains.
110
Define isotype
Type of chain in an antibody
Heavy isotypes: alpha, gamma, delta, epsilon, mu
Light isotypes: kappa, lambda
111
Define idiotype
antibodies of one idiotype share structure of their variable region and thus, antigen binding specificity.
112
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
113
What releases: Interleukin 3
T cells (emphasis on activated T cells) and thymic epithelial cells
114
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
115
What releases: Interleukin 4
Th2 cells
116
Cytokine effects: Interleukin 8
1. Major neutrophil chemotactic and adhesion factor
2. Angiogenesis
3. High levels associated with schizophrenia
117
What releases: Interleukin 8
1. Monocytes
2. Endothelial cells
3. Fibroblasts
118
Cytokine effects: Interleukin 12
1. Promotes differentiation of Th cells into Th1
| 2. Activates NK cells
119
What releases: Interleukin 12
Professional Antigen Presenting Cells:
1. Dendritic cells
2. Macrophages
3. B cells
120
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.)
121
Important cell surface proteins and their functions: Cytotoxic T cells
1. CD8
2. TCR
3. CD3 (Signal transduction)
122
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.)
2. CD19, CD21 (Subunits of co-receptor for BCR complex)
4. CD20 (Target in non-Hodgkin's lymphoma of monoclonal antibodies like rituximab)
123
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)
124
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)
125
Important cell surface proteins and their functions: Hematopoietic stem cells
CD34 (marker for this type of cell, and a receptor for CD62L, a selectin)
126
Complement: Viral neutralization
C1, C2, C3, C4
127
Complement: Opsonization
C3b
128
Complement: Anaphylatoxins
C3a, C5a
129
Complement: Neutrophil Chemotaxis
C5a
130
Complement: Membrane attack complex
C5b to C9
131
Deficiency of C1 esterase inhibitor leads to:
Hereditary angioedema (overactive complement)
132
Deficiency of C3 leads to:
Severe recurrent pyogenic sinus and respiratory tract infections
133
Deficiency of C6 through C8 leads to:
Neisseria bacteremia
134
What is Decay Accelerating Factor?
Prevents attachment of the alternative complement complex (C3 convertase) to the membrane
135
When is Decay Accelerating Factor missing?
In paroxysmal nocturnal hemoglobinuria
136
What kind of bacteria does complement defend against?
Gram negative bacteria
137
What activates the classic complement pathway?
IgG and IgM.
Mnemonic: GM makes classic cars.
138
What activates the alternative complement pathway?
Microbe surface molecules (especially endotoxin)
139
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.
140
PGH2
Synthesizes PGI2 with prostacyclin synthase in intact endothelial cells. Precursor of thromboxanes. Synthesized from PGG2.
141
PGE2
Vasodilation, pain and fever. Synthesized from PGH2
142
TxA2
Vasoconstriction, platelet aggregation and bronchoconstriction. Coverted from PGH2 by thromboxane synthase.
143
LTB4
chemotaxis and activation of neutrophil adhesion molecules
144
LTC4
Vasoconstriction, increased vessel permeability, bronchoconstriction
145
LTD4
Vasoconstriction, increased vessel permeability, bronchoconstriction
146
LTE4
Vasoconstriction, increased vessel permeability, bronchoconstriction
