Week 5 Immunology Flashcards
1
Q
What cell types are part of adaptive immunity ?
A
B cells
T cells
2
Q
what cell types are part of innate immunity?
A
Natural killer cells
Dendritic cells
Monocytes
Granulocytes
3
Q
What cells come from common lymphoid progenitors ?
A
B cells
T cells
Natural killer cells
4
Q
What cells come from a common myeloid progenitor ?
A
Monocytes
Granulocytes
5
Q
What cells produce antibodies
A
B cells and plasma cells
6
Q
What role do complement proteins play in the immune system ?
A
Plasma proteins that cleave and active each other to kill extra cellular pathogens
Bind directly to pathogens or to antibodies coating pathogens
7
Q
What role do cytokines play in immune response
A
They act on nearby or distant cells to influence innate and adaptive immunity
8
Q
What are chemokines and what role do they play in immune response ?
A
Cytokines that attract other cells to the site of infections
9
Q
What are primary lymphoid organs ?
A
Organs where lymphocytes develop from progenitor cells
Bone marrow: B cells and T cell progenitors
Thymus: T cells
10
Q
What are secondary lymphoid organs ?
A
Where lymphocytes interact with each other and nonlymphoid cells
Initiate adaptive immune responses
Lymph nodes and spleen
11
Q
What are the roles of neutrophils ?
A
Phagocytosis
Kill pathogens
Major white blood cell
Identify pathogens using receptors that recognize common patterns found in microbes
12
Q
What are the roles of macrophages ?
A
Phagocytosis
Kill pathogens
Antigen presenting cells
Identify pathogens using receptors that recognize common patterns found in microbes
13
Q
What are the roles of dendritic cells ?
A
Phagocytosis
Best antigen presenting cell
Identify pathogens using receptors that recognize common patterns found in microbes
14
Q
How do innate cells recognize microbes ?
A
PAMPs derived from microbes bind to PRRs on innate immune cells
15
Q
What roles do eosinophils and mast cells have ?
A
Protect against helminth infections
Implicated in allergic responses
16
Q
What role do basophils have in innate immune reponse ?
A
Implicated in allergic responses
17
Q
What function do natural killer cells have in innate immunity ?
A
Destroy infected or cancerous cells
18
Q
What are the 3 classical antigen presenting cells ?
A
B cells
Macrophages
Dendritic cells
19
Q
How many different B cell receptors are there ?
A
Each B cell generates a unique cell-surface bound antibody (B celll receptor) that recognizes a specific antigen
20
Q
What do T cell receptors recognize ?
A
Peptide antigens that are presented on the surface of cells in an MHC molecule
21
Q
What is the role of CD4+ T helper cells ?
A
Help activate other immune cells
22
Q
What type of pathogens do TH1 cells protect against
A
Intracellular (cell-mediated immunity)
23
Q
What type of pathogens do TH2 cells protect against
A
Extra cellular (humoral immunity)
24
Q
What is the role of CD8+ cytotoxic T cells ?
A
Defend against cytosolic pathogens
Kill cells infected with intracellular pathogens
Protection against neoplasms
25
MHC class I molecules location and importance
On all nucleated cells
Bind to CD8+
Allow cytotoxic T cells to recognize virally infected or cancerous cells
26
MHC class II molecules location and importance
On the 3 classic antigen presenting cells
Binds to CD4+
Initiates adaptive immune response
27
What is the primary cell type that is recruited to sites of infection ?
Neutrophils
28
What do dendritic cells do once they take up antigens?
Bring to nearest lymph node —> present to T cell —> initiate adaptive immune response
29
Once in lymph nodes during immune reponses what do dendritic cells do ?
Present antigen to CD4+ T cell on MHC II molecule —> produce costimulatory molecules and cytokines —> antigen recognized —> activated T cell differentiates into TH2 cell
30
How do activated TH2 cells provide help to B cells during active immune response ?
Helps form cytokines and co-stimulation
—> activated B cells proliferate —> antibody-secreting plasma cells
—> some B and T cells —> long lived memory cells
31
Length of AA sequence on MHC I and MHC II molecules respectively
8-11
| 10-30
32
What is often needed for cell activation ?
2 signals, cross linking
33
What do proteases do ?
Chop antigens into small AA fragments
34
Activating signal for neutrophils/macrophages/dendritic cells
DAMPs and PAMPs cross link TLRs
35
Activating signal for B cells
3D antigen binding to and crosslinking surface mounted Ig molecules (BCR)
36
Activating signal for CD4+ T helper cells
Linear AA sequence mounted on specific MHCII molecule which cross links TCR
37
Activating signal for CD8+ cytotoxic T cell
Linear AA sequence mounted on specific MHCI molecule which cross links TCR
38
Response to antigen intake in dendritic cell
Naive T cell activation:
| Clonal expansion and differentiation into effector T cells
39
Response to antigen uptake bu macrophage
Effector T cell response:
| Macrophage activation
40
Response to antigen intake by B cell
Effector T cell response:
| B cell activation and antibody production
41
Where are T precursor cells produced ?
Bone marrow
42
Where do T cells mature ?
Thymus
43
Where are T cells activated ?
Secondary lymphoid organs
44
What is the variable region of a T cell composed of ?
V,D and J segments
45
How is the variable region of a T cell synthesized ?
1. Synapsis
2. Cleavage
3. Hairpin opening and end-processing
4. Joining
46
How can the number of T cells someone has generated be measured ?
Measure # of T cell receptor excision circles (TRECs)
47
What is positive selection
T cells must interact with MHC (-90%)
48
What is negative selection ?
T cells must not activate too strongly to self peptide (-5%)
49
What is required for 2 factor authentication of T cells ?
Co-stimulation
50
When does T cell anergy occur and what is it’s effect?
When there is antigen specific signal alone without stimulation from APC.
Cell can no longer respond to antigen —> incapable of being activated
51
What treatment are molecules that block co-stimulation or enhance inhibition being used in ?
Treatment of autoimmune and allergic diseases
52
What are molecules that enhance co-stimulation or block inhibition recently being used to treat ?
Cancer
53
3 key events during B cell maturation
1. Rearrangement and expression of immunoglobulin genes in a precise order
2. Selection and proliferation of developing B cells at the pre-antigen checkpoint
3. Selection of the mature B cell repertoire
54
What process is the RAG gene involved in ?
VDJ recombination in both B and T cells
55
What is VDJ recombination ?
Random combo of germline gene segments being brought together and by the random addition or deletion sequences at the junctions between segments before they are united.
56
What results when there are defects in RAG, Artemis or DNA ligand IV ?
Severe combined immunodeficiency (SCID)
57
What is another word for negative selection
Central tolerance
58
What happens to mature B cells that migrate back to the bone marrow following antigen exposure ?
Called plasma cells and they secrete antibodies
59
B cell response to T-dependent antigens
Initiated by binding of the protein antigen to specific Ig receptors of naive B cells —> recruit T and B cells into germinal centres of spleen/nodes
60
B cell response to T-independent antigen
Initiated by recognition of non-protein antigens by specific Ig receptors of naive B cells —>
Induction of B cell clonal expansion and IgM secretion
61
What type of B cell activation can occur in the mucosal tissues and peritoneal cavity ?
T- independent, Short lived plasma cells
62
What is the co-stimulation interaction that is needed for B cell proliferation and differentiation?
CD40-CD40L interaction
63
What are the two types of antibodies produced by B cells ?
Membrane bound
| Secreted
64
Function of membrane bound anti-bodies vs secreted anti-bodies
Antigen receptors
| Neutralize toxins
65
What is the core structure of an antibody ?
2 identical lambda or kappa light chains
2 identical heavy chains
Each chain has amino-terminal variable region (V)
And a carboxyl terminal constant region (C)
66
What are the 5 different classes of antibodies ?
IgE, IgG, IgA, IgD, IgM
67
Effector functions of IgG antibodies
Opsonization of antigens for phagocytosis
Activation of the classical pathway of complement
Antibody dependent cell-mediated cytotoxicity
Neonatal immunity
Feedback inhibition of B cell activation
68
Effector functions of IgM antibodies
Activation of classical pathway of complement
| Antigen receptor of naive B lymphocytes
69
Effector functions of IgA antibodies
Mucosal immunity
70
Effector functions of IgE antibodies
Mast cell degranulation: immediate hypersensitivity reactions
71
Effector functions of IgD antibodies
Antigen receptor of naive B lymphocytes
72
What antibody isotype makes up almost 80% of circulating antibodies
IgG
73
What is somatic hypermutation ?
Process that introduces random mutation in the variable region of the BCR Ig heavy and light chains at a high rate during B cell proliferation.
74
What is the effect of hypermutation ?
Increased affinity of antibodies for antigen impart selective survival advantage to B cells producing those antibodies and lead to affinity maturation of the humoral response
75
Somatic hypermutation is only seen in T-___________ protein antigens ?
Dependent
76
What is affinity maturation ?
Process that leads to increased affinity of antibodies for a particular antigen, is result of hypermutation followed by selective survival of B cells
77
What cells make antibodies
B cells only !
78
What structures does the innate immune system look for ?
Structures that are unique to pathogens and injured self:
| PAMPs and DAMPs
79
Would do TLRs recognize and where are they located ?
Bacteria, viruses, fungi
| Plasma and endosomal membranes
80
What do NOD-like receptors recognize and where are they located ?
Bacteria, cell membrane damage
| Cytosol
81
What do RIG-like receptors recognize and where are they located ?
Viruses
| Cytosol
82
What do natural antibodies recognize and where are they located ?
Bacteria, fungi, injured self
| Plasma
83
What does complement recognize and where is it located ?
Bacteria
| Plasma
84
What 2 major groups opsonize ?
1. Antibodies
| 2. Complement system
85
What does the cell signaling from PRR activation result in ?
1. Increased vascular permeability
2. Influx of important proteins (complement, antibodies, clotting factors)
3. Influx of cells (innate and adaptive)
86
Result of PRR activation
1. Cytokines
2. Chemokines
3. Cell adhesion molecules
4. Microbe specific responses
87
What cell type bridges the innate and adaptive immune systems ?
Dendritic cells
88
Complement floats around inactive in the blood until it has contact with either a ___ or an ______
Pathogen, antibody
89
What is C3 convertase composed of and what is it’s role ?
C4b+C2a or alternatively C3b + Bb
| Cleaves C3
90
What is C5 convertase composed of and what is its role ?
C4b + C2a + C3b or (C3b + Bb +C3b)
| Cleaves C3 and C5
91
Actions of complement
Opsonization
Call for help
Augment immune response
Punching holes in cells
92
Membrane Attack Complex (MAC) formation steps (5)
1. C5b binds C6 and C7
2. C5b67 complexes bind to membrane via C7
3. C8 binds to the complex and inserts into the membrane
4. C9 molecules bind to the complex and polymerize
5. 10-16 molecules of C9 bind to form a pore in the membrane
93
Complement activation: lectin pathway
```
Ficolin/MBL + MASPs bind carbohydrates —> activate C4 and C2
C4–> C4a+C4b
C2 —> C2a + C2b
C4b+C2a= C3 convertase
C3 convertase + C3b = C5 convertase
```
94
Complement activation: classical pathway
```
C1q, C1r and C1s bind antibodies —> activate C4 and C2
C4–> C4a+C4b
C2–> C2a+C2b
C4b+C2a = C3 convertase
C3 convertase + C3b = C5 convertase
```
95
Complement activation alternative pathway
```
C3 activation —> C3a + C3b
Factor B is cleaved by factor D —> Bb
C3b binds to Bb —> C3bBb = C3 convertase
C3bBb is stabilized by Factor P
C3bBb + C3b = C5 convertase
```
96
Why is fast clearance of self-antigens important ?
Prevents autoimmunity
97
What happens in terminal complement deficiency ?
No MAC can be formed
98
What pathogenesis accompanies C1q deficiency ?
Cannot clear apoptotic cells and 90% of patients will develop SLE
99
Why are C4 and C3 low in patients with SLE?
Presence of self antibody —> activation of classical pathway —> C4 and C3 undergo constant activation —> low levels
100
3 causes of hypersensitivity diseases
Reactions against:
Self
Microbes
Environmental agents
101
Definition of allergy or atopy
Combination of immediate hypersensitivity and late phase reaction
102
Allergen definition
Antigens that ellicit immediate hypersensitivity
103
Type I immediate hypersensitivity antigen isotype
IgE
104
Type II antibody-mediated hypersensitivity antibody isotype
IgM and IgG
105
Type III immune complex mediated hypersensitivity antibody isotype
IgM and IgG
106
Type IV T cell mediated hypersensitivity T cells involved ?
CD4+: inflammation —> delayed type hypersensitivity
| CD8+: directly kill target cell —> granulomatous inflammation seen in TB infection
107
IgE antibody production in Type I hypersensitivity is dependent on what ?
Activation of CD4+ effector T cells that produce IL-4
108
Broad outline of how type I hypersensitivities develop
1. First exposure to allergen
2. Activation of T cells and stimulation of IgE class switching
3. Production of IgE
4. Binding of IgE on mast cells
5. Repeated allergen exposure
6. Activation of mast cell —> release of mediators
7. Immediate and late phase reaction
109
What causes allergy symptoms ?
Mediators from mast cells
110
Common signs and symptoms of IgE mediated reactions
```
Urticaria
Laryngeal
Flush
Wheeze
Dizziness
Nausea/vomiting
Rhinitis
Headache
```
111
Two main functions of TD4+ effector T cells
Recruit and activate phagocytes
| Help B lymphocytes to produce antibodies
112
Characteristics of urticaria
```
Raised
Erythematous
Central cleaning
Irregular border
Often migratory
```
113
Characteristics of Angioedema
Localized to subcutaneous or sub mucosal tissues
Never involves gravity-dependent areas
Onset 2-3 hours as part of IgE mediated reaction
Usually asymmetric
114
How do IgG and IgM antibodies cause tissue injury ?
Activate complement system
Recruiting inflammatory cells
Interfering with normal cellular functions
115
Anaphylaxis is likely when
1. Acute onset of illness with skin/mucosal involvement AND at least one of:
- respiratory symptoms
| - reduced BP or signs of end-organ dysfunction
116
Anaphylaxis is likely when:
2. If there is a likely allergen for that patient, 2 of the following:
- skin-mucosal involvement
- respiratory compromise
- reduced BP
- persistent GI symptoms
117
Anaphylaxis is likely when:
| 3. Reduced BP after:
Exposure to known allergen for that patient
118
Alpha-1 adrenergic receptor effects of epinephrine
- vasoconstrictor effect in most body organ systems
| - ability to prevent and relieve airway obstruction caused by mucosal edema
119
Beta-1 adrenergic receptor effects from epinephrine
Increases cardiac contractility and HR
| Ability to prevent and relieve hypotension and shock
120
Beta-2 adrenergic receptor effects from epinephrine
- decreases mediator release from mast cells, basophils
Increases bronchodilation
Vasodilator effect on skeletal muscle
121
Second line treatments for anaphylaxis
H1 antihistamine
Glucocorticoids
Inhaled B-2 adrenergic agonists
122
Treatment options for primary immunodeficiences
Passive administration of antibodies by monthly IV infusion or weekly subcutaneous injection
Continuous prophylactic antibiotics
Hematopoietic stem cell transplantation
Gene therapy to replace the defective gene
123
Most common causes of immunodeficiency:
HIV
Malnutrition
Iatrogenic immunosuppression
124
Anti-IgE Antibody mechanism
Binds to free IgE —> reduce cell bound IgE — > reduce high affinity receptors —> reduces mediator release
125
Benefits of adjuvants in vaccines
Increase immunogenicity of vaccines
Reduce the dose of antigen required for effectiveness
Broaden repertoire of antibody responses
Modulate the phenotype of T cell responses
