Exam 2 FCs Flashcards
(96 cards)
1
Q
Name the 3 pathways of complement activation.
A
- Classical (antigen:antibody complexes)
- Lectin (Lectin binding to pathogen surfaces)
- Alternative (pathogen surfaces)
2
Q
Activation of classical complement pathway
A
(1) C1q portion of C1qrs binds to side by side antibodies+antigen complexes on pathogen surface
(2) C1r is activated
(3) C1r cleaves C1s and it becomes activated
3
Q
Activation of lectin complement pathway
A
Analogous Functions: MBL = C1q; MASP-1 = C1r; MASP-2 = C1s
(1) MBL binds to mannose
(2) activation of MASP 1/2
4
Q
What do the spare cleavage components (C3a, C4a, C5a) on the path to create C3b get used for?
A
Inflammation
5
Q
C3b general function
A
Powerful opsonin and the foundation of complement function
6
Q
C4b2a serves as a…
A
C3 convertase (cleaving it to C3a and b)
7
Q
C4b2a3b serves as a…
A
C5 convertase (cleaving it to 5a and b)
8
Q
MAC
A
Membrane Attack Complex
Generated from 5b which goes on to recruit C6,7,8 and 9 (several of them) to form this pore in the pathogen.
9
Q
First step of Alternative Complement activation
A
C3 hydrolysis into C3(H2O). After this comes factor B binding.
10
Q
Function of C3bBbC3b
A
C5 convertase
11
Q
Inhibitors of C1
A
C1INH– inhibits C1 by dissociating C1r and C1s from the C1 complex
12
Q
Inhibitors of C3 convertase
A
- Decay-accelerating factor (DAF)
- C4-binding protein (C4BP)
- Complement receptor 1 (CR1)
- Membrane cofactor Protein (MCP)
- Factor I (I)
13
Q
Inhibitors of C5 convertase
A
- Factor I (I)
- Factor H (H)
- Complement receptor 1 (CR1)
14
Q
Inhibitors of Membrane Attack Complex
A
CD59
15
Q
Deficiencies with classical pathway components
A
C1, 2, and 4
Leads to immune-complex disease
16
Q
Deficiencies in Lectin Pathway components
A
MBL, MASP1/2, C2 and 4
Bacterial Infections (childhood)
17
Q
Deficiencies in Alternative Pathway
A
Factor D, P
Infection of pyogenic bacteria + Neisseria but NO immune complex disease
18
Q
Deficiencies of C3b deposition
A
Infection of pyogenic bacteria + Neisseria with SOME immune complex disease
19
Q
Deficiencies of Membrane-attack components
A
C5, 6, 7, 8, 9
Infection with Neisseria ONLY
20
Q
Hereditary Angioneurotic Edema
A
C1 INH deficiency
Failure to regulate C1 results in fluid accumulation and epiglottal swelling
21
Q
Paroxysmal Nocturnal Hemoglobinurea
A
CD59 function failure
Loss of MAC assembly regulation. Results in RBC lysis
22
Q
Describe the immune reaction induction process for MALT
A
(GALT is the example here)
(1) Antigen entering the digestive tract is either goes through the M cell to the DC, or is directly grabbed by the DC through tight junction walls
(2) Antigens are then presented to lymphocytes located in the peyer’s patch (in the case of GALT)
(3) Activated T cells travel through lymph to the lymph nodes and then via the thoracic duct to the circulation, and then “home” to mucosal positions throughout the body for function.
B lymphocytes within peripheral tissues proliferate and secrete IgA.
23
Q
Signals that activated T cells express to home to the gut
A
a4:B and CCR9
They bind MAdCAM-1 of the gut
24
Q
IEL
A
Intraepithelial lymphocytes
- mostly CD8+
- found in gut epithelium
- readily kill infected epithelial cells (other than this, their function is unclear)
25
Innate mucosal response to infection.
Innate immune mechanisms eliminate most intestinal infections rapidly via local inflammatory cells which are activated by PRR's (TLR, NOD, etc.)
26
Reasons to suspect IgA deficiency
(1) Family History
(2) Freq. oral Infections
(3) Freq. respiratory infections
(4) Chronic diarrhea
27
Diseases often associated with IgA deficiency.
Autoimmune:
SLE (lupus), juvenile rheumatoid arthritis, and thyroiditis
28
sIGA
IgA in mucous secretions
29
Functions of IgA at mucosal surfaces.
(1) Barrier functions
(2) Intraepithelial viral neutralization
(3) Excretory Immunity
(4) Passive Immunity
30
Sites of peripheral lymphoid organs
aka secondary lymphoid organs
Lymph nodes, Spleen, MALT
31
Stromal cells
Direct the developmental program of the progenitor cells and eventually B cells within the bone marrow.
32
Where do the final stages of development of immature B cells into mature B cells occur?
The peripheral lymphoid organs
33
Fates of immature B cells during central tolerance
(1) No self reaction = mature b cell
(2) Multivalent self reaction = apoptosis (or receptor editing)
(3) soluble self molecule reaction = anergic
(4) low-affinity non-cross-linking self molecule = clonally ignorant mature B cell
34
Thymic cortex
Outer region. Contains only immature thymocytes/macrophages. Most T cell development occurs here.
35
Corticomedullary junction
Where T cell progenitors enter
36
Thymic Medulla
Inner region. House more mature, single-positive thymocytes along with dendritic cells and macrophages.
37
Thymic cortical stroma
Where TEC resides for T cell development.
38
Positive selection
If double positive T cell can't recognize any self peptide it will die. Otherwise, it will become CD4+ or CD8+
39
Negative selection
If the single positive recognizes self too strongly, it will undergo apoptosis. Otherwise, it will be exported to the periphery.
40
How is the lymph node related to blood and lymph
They are the convergence points between blood and lymph.
41
HEV
High Endothelial Venules
How naïve lymphocytes get into the LN. Located in paracortical areas.
42
Where are B cells located in LNs?
The follicles
43
Paracortical area of LNs
Where T cells are diffusely scattered and where migrating DCs bring their antigens. Great meeting spot for presentation.
44
What attracts DCs to lymph node?
CCL21 secreted by stromal cells/ HEVs
45
What attracts T cells and B cells to lymph node?
CCL18/19 (and later CXCL13 just for B cells)
46
Spleen's role in immunology
(1) Maturation of T and B cells
(2) Filters blood for purpose of presentation.
Blood-borne microbes, soluble antigens and immune complexes are filtered from the blood by macrophages and immature dendritic cells within the marginal zones.. Then they migrate to T cell areas and activate the T cells.
47
Red Pulp
Majority of spleen; site of RBC disposal and stripping of antigens
48
White Pulp
Site where lymphocytes surround arterioles running through the spleen to be prepared to meet their antigen.
49
PALS
Periarteriolar lymphoid sheath
Sheath of lymphocytes (mainly T cells) around an arteriole.
50
Waldeyer's ring
Ring of lymphoid tissues (tonsils and adenoids) around the entrance of the gut and airway to protect mucosal entry.
51
factors causing T cell homing to Peyer's patches from blood vessels
CCR7 and L-selectin
52
Commensals and inflammation
Commensals balance pro- and anti-inflammatory immune mechanisms. Some bacteria induce an inflammatory response (Th1/Th17) while others induce anti-inflammatory response (Treg).
Changes in the commensals can tip this balance.
53
Hygiene Hypothesis
Early exposure to certain types of pathogens decreases the likelihood that people will develop allergies as they get older. Bacteria and viruses elicit Th1 response which downregulates Th2 response (IgE)
54
High fat diet and microbiata
High fat diet affects intestinal lymphoid cells to secrete IL-22 which induces expression of anti-microbial peptides which alter the microbiota.
55
Hypersensitivity disease type I
Allergies and asthma
56
Hypersensitivity disease type II
Diseases caused by antibodies
57
Hypersensitivity disease type III
Diseases caused by Immune Complexes
58
Hypersensitivity disease type IV
Diseases associated with TMMI
59
Immune complexes and inflammation
The inflammatory reaction is mediated via binding of antigen complexed withIgG to the Fc-gamma- R on monocytes and neutrophils. This leads to a wide spectrum of effects including inflammation.
60
Arthus Reaction
High levels of pre-existing antibodies causes an overwhelming formation of immune complexes when a vaccination is attempted. This leads to IL-8 secretion and pain, swelling and redness at the injection site.
61
Serum Sickness: What it is, assay(s) to test for it, and treatment
WHAT: When IC disposal mechanisms get overwhelmed due to large levels of foreign antigen.
ASSAY: Assay for C3 because complement levels will be expected to be grossly declined as they are being consumed like crazy (theoretical option)
TREATMENT: reduce antigen load (antibiotics, surgical draining, etc.) and suppress inflammation.
62
ITAM
Immunoreceptor Tyrosine-bases ACTIVATION Motif
When IgG-IC targets antigen to an FcyR receptor on a macrophage, monocyte, neutrophil or dendritic cell, the cell is prompted to phagocytose the complex due to this ITAM signal which is released. Affinity is extremely high and is activated by small levels of IC.
63
ITIM
Immunoreceptor Tyrosine-bases INHIBITORY Motif
When IgG-IC targets an antigen to GcyR on its B cell, this is activated. It shuts down further B cell proliferation (tells it to chill out). Affinity is low for this receptor and therefore depends on much higher levels of IC
64
How do you handle the Rh problem?
Give mom a bunch of anti IgG during pregnancy (to stop further passing of IgG through the placenta) and within 72 hours after birth. This will shut down B cell response to it via ITIM signaling.
ONLY WORKS WITH IgG!!! IgM WILL CAUSE A MORE VIOLENT REACTION.
65
What types of immune related cells have receptors for catecholamines, ACh and neuropeptides?
T and B lymphocytes, neutrophils, mononuclear cells and NK cells.
66
Epi/ NE effect on immune cells
Increase leukocyte mobilization and increase NK cell activity.
67
Endorphin effect on immune cells. What neurotransmitter-like substance acts similarly?
Play an important role in analgesia (pain blocking) and feelings of euphoria.
Enkephalins.
68
Effects of acute stress on the immune system.
Increase the level of immune cells (via catecholamines) so that they are prepared to fight. Over time, cortisol is secreted and this turns the process off.
69
Key molecules in redistribution of immune cells to lymph nodes during stress response.
- CD11a
| - ICAM-1
70
Under stress, in addition to inflammatory cytokines, immune cells can secrete...
- ACTH
- Beta-endorphin
- Enkephalins
71
Sickness behavior
Behavior modification caused by the effect of IL-1, IL-6 and TNFa on the CNS. These molecules which were secreted by macrophages, are now used to cross BBB let the brain know their is infection or injury.
72
How CNS interacts with immune system to regulate excessive inflammation.
(1) APs from the splenic nerve cause NE release
(2) NE stimulates production of Ach by T lymphocytes
(3) Ach interacts with macrophages within the spleen to inhibit transcription of IL-1, 6, TNF-a
73
A normal IgE response occurs for...
Selective stimuli which are usually large and relatively biodegradable
74
What type of cells usually express Fc-epsilon receptors?
- Mast cells
- basophils
- some APCs
75
What are the 2 different human mast cell types?
(1) MCt: tryptase (mucosa)
| 2) MCtc: tryptase + chymase (connective tissues
76
A common component of many environmental antigens is that they contain...
chitin which is not found in mammals.
77
Arming of Fce receptors
Allergen specific IgE binds to the Fc-epsilon-R and waits there, with NO antigen bound. On second encounter, antigen binds causing quick activation.
78
Urticaria
hives
79
RAST
Radio Allergo Sorbent Test
(1) Patient serum added to a cellulose disc with covalently bound allergen.
(2) radio-labeled anti-IgE added after wash to see if patients IgE has bound.
80
Allergy treatment
- Allergen avoidance
- Anti-IgE therapy (monoclonal antibody which binds IgE)
- Allergen immunotherapy (stimulates Th1 or Th2 response with IgG)
81
2 main methods to assess histocompatibility
(1) Lymphocytotoxic antibodies
| (2) Mixed lymphocyte culture
82
Direct vs Indirect rejection
Direct: activation of immune system directly by foreign MHC marker
Indirect: (most common) Alloantigens phagocytized, processed and represented in the context of host class II MHCs
83
What is the mandatory rejection participant?
CD4
84
Gene that humans don't have that animals do.
a-1,3 GT gene
Will cause violent rejection
85
3 clinical rejection categories
(1) Hyperacute: first 48 hours due to preexisting antibodies
(2) Acute: 10-90 days. Appearance of effector cells in the graft. Vigor varies.
(3) Chronic: slow choking of vasculature
86
NK cells of pregnancy
No CD16
87
Leptin
- appetite suppressant
| - pro-inflammatory (IL-1, 6, TNF-a)
88
Adiponectin
- leptin antagonist
| - anti-inflammatory
89
MAC-1
Macrophage inhibitory cytokine
Member of TNF superfamily. Anorexigenic (negative correlation with body mass). Major stimulant of adiponectin production)
90
Visfatin
strongly expressed in WAT. Pro-inflammatory and pro-angiogenic
91
Osteopontin
Produced by activated macrophages. Pro-inflammatory and chemotactic for monocytes/macrophages.
92
Resistin
Direct antagonist of adiponectin. Promotes TNF-a and IL-6 production.
93
CCL2
Potent monocyte attractant secreted when WAT is overstuffed. Binds to CCR1 receptor.
94
What causes eosinophil release from bone marrow?
IL-5
95
Late allergic response
Eotaxin is released by eosinophils to call more eosinophils.
96
Specific site of T cell generation
Hassals Corpuscle of the thymus
