Midterm Flashcards

1
Q

Immunization Types

A

Active-Natural: Infection
Active-Induced: Vaccination
Passive-Natural: mother’s breast milk & mother to fetus
Passive-Induced: antiserum

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2
Q

Primary (central) Lymphoid Organs

A

Bone Marrow

Thymus (above heart)

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3
Q

Secondary (peripheral) Lymphoid Organs

A

Lymph nodes
Spleen
Malt/Payer’s Patch (in gut)

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4
Q

Leukocyte

A

immune system cell (white blood cell)

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5
Q

Lymphoid lineage cells

A
B cells
T cells
NK cells
innate lymphoid cells
some dendritic cells
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6
Q

Myeloid lineage cells

A

macrophages
neutrophils (and other granulocytes)
monocytes
some dendritic cells

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7
Q

Leukocyte lineages

A

Lymphoid, Myeloid

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8
Q

Lymphocytes & properties

A

B cells and T cells (adaptive immunity)

Arise from bone marrow

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9
Q

Lymphocyte receptors

A
BCR:
 - secreted or membrane bound
 - bounds antigen in natural form
TCR 
 - membrane bound
 - binds MHC with small piece of antigen on it
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10
Q

MHC

A

Major Histocompatibility Complex

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11
Q

Clonal Deletion

A

lymphocytes binding self-antigens are eliminated

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12
Q

Naive lymphocyte

A

mature lymphocyte not yet activated by an antigen

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13
Q

Innate immunity barriers/obstacles

A

Barriers: skin, epithelium (gut, respiratory tract)
Obstacles: saliva, hair, mucus, tears

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14
Q

Lyzozyme

A

digests peptidoglycan

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15
Q

Defensins

A

disrupts cell membrane by forming pores

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16
Q

Phagocytosing cells

A

macrophages
neutraphils & other granulocytes
immature dendritic cells

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17
Q

Phagocytosis steps

A
  • receptors bind pathogen
  • phagosome formed by invagination
  • phagolysosome formed by fusion with lysosome
  • digestion
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18
Q

Phagocytosis digestion methods

A

acidification
ROSs
enzymes
antimicrobial peptides

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19
Q

microglia

A
  • phagocyte working in the central nervous system

- cleans up myelin debris from neurons

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20
Q

multiple sclerosis

A

demyelination of neurons

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21
Q

Leukocyte migration process

A

cytokines/chemokines released at site of infection

  • > blood vessels dilate and adhesion molecules expressed
  • > leukocytes extravasate
  • > bloot clotting, pain, redness, edema
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22
Q

Extravasation process

A

chemokines bind to endothelial cell

  • > leukocytes roll into and bind tightly to endothelium
  • > cells change shape
  • > induced diapedesis
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23
Q

diapedesis

A

Passage of cells through wall of capillaries, inducing inflammation

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24
Q

Monocyte

A

circulating leukocyte

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25
Neutrophil
- innate immune system phagocyte - circulating - must be recruited - pus is product of dead/dying neutrophils - produces NETs (neutrophil extracellular traps) matrix that traps microorganisms
26
Complement molecule properties
- mostly proteases - usually named C_ (number), and C_a, C_b... when cleaved - mostly produced by liver - part of chain reactions that amplify inflammation and clearing of pathogens
27
Complement mechanisms of action
Increase vascular permeability and chemotaxis Destroy pathogen membranes Opsonization
28
Opsonization
- Coating a pathogen to make it more easily ingested by phagocytes (by antibodies and similar molecules) C3b coats bacteria - > binds C3b receptors on phagocyte - > cascade leading to phagocytosis
29
Complement Activation (general)
Complement components begin as inactive pro-proteases Cascade of events leads to proteolotic cleavages - small piece that has a function - large piece that acts as protease to another substrate All pathways converge to C3 convertase cleaving C3 to C3a and C3b Main pathways: - lectin pathway - classical pathway - alternative pathway
30
Lectin Pathway
Specific PRRs bind directly to pathogen cell membrane - > signaling cascade on surface - > C3 convertase generated - > C3a and C3b produced PPRs: - mannose-binding lectin, ficolins - circulating in blood - upregulated during infection
31
Classical Pathway
C1q in blood binds either to pathogen cell membrane (direct) or to antibody bound to pathogen membrane (indirect) - > signaling cascade on surface - > C3 convertase generated - > C3a and C3b produced
32
Alternative Pathway
Triggered by existing C3b present due to spontaneous hydrolysis, or production from other pathways C3b binds other factors - > produce a particular unstable C3 convertase - > stabilized by Properdin - > more C3b produced
33
Properdin
aka Factor P Produced by neutrophils Stabilizes the alternative pathway C3 convertase
34
Complement induced inflammation
C3a & C5a increase vascular permeability and chemotaxis (too much -> anaphylactic shock) C3a & C5a bind receptors on granulocytes and macrophages -> stimulate release of proinflammatory cytokines & degranulation
35
Complement induced pathogen lysis
Cascade of events creating MAC (membrane attack complex) - > pore on pathogen surface - > cell lysis
36
Innate Lymphoid Cell
- three types (ILC1, ILC2, ILC3) - mainly tissue resident (recent studies show otherwise) - important in gut mucosa - activated by cytokines (IL-25 is well known to) - release other cytokines that contribute to pathogen death - recent finding shows migration of ILC2 between guts and lungs through lymph vessels
37
Natural Killer Cells
- kills own infected cells - found in tissues and in circulation - receptors are germ-line encoded - recognize MHC1 & similar proteins Non-Disease State: inhibitory signals on cell prevent NK activation Disease State: inhibitory signal not present -> NK releases toxic granules -> apoptosis OR -> receptor-mediated apoptosis
38
Common Proinflammatory Cytokines
TNF-alpha, IL-1beta, IL-6
39
Proinflammatory Cytokine effects
- vascular permeability and chemotaxis - have different effects on different tissues/organs ex: hypothalamus -> fever, liver -> acute inflammatory response
40
Local infection process
local TNF-alpha release - > vasodilation & leukocyte migration - > clearing of infection - > draining of extracellular fluids to lymph nodes
41
Sepsis process
systemic TNF-alpha release - > system vasodilation - > lowering of blood pressure - > collapse of blood vessels - > intravascular coagulation - > organ failure and death
42
TNF-alpha
released by macrophages | target of some autoimmune drugs
43
Acute Inflammatory Response
Increased production from liver: - mannose-binding lectin - complement components - C-reactive proteins Positive feedback loop until clearing of infection
44
PRRs
- Recognize PAMPs - Activate signaling pathways, typically involving phosphorylation and ubiquination cascades - expressed by many cells
45
PRR groups
``` Toll-like receptors NOD-like receptors RIG-like receptors C-type lectin receptors ficolins ```
46
Toll-like Receptors
Location: - cellular membrane (for bacteria, parasites) - endosome membrane (for viruses, bacteria) Usually have adapter proteins ``` Activates TFs -> proinflammatory cytokine genes Common Pathways: - NF-kB - IRF - MAP kinase ```
47
RIG-like Receptors
Location: cytosol Recognize viral dsDNA Triggers TFs Common Pathways: - NF-kB - IRF
48
NOD-like Receptors
Location: cytosol Recognize peptidoglycans Can trigger NF-kB TFs Can activate caspase-1 (protease) - cleaves IL-1/IL-18 to activate them, then release
49
PRR Signaling Downstream Effects
- cytokine production (IL-1, IL-6, IFN) - B7.1 B7.2 - migration to secondary lymph organs (for APCs)
50
Type 1 IFN
IFN-alpha and IFN-beta | - triggers transcription of genes that inhibit viral replication
51
Cytokine
small glycoprotein
52
Cytokine communication mechanisms
Autocrine (self) Paracrine (nearby) Endocrine (far)
53
Cytokine categories
``` Interleukins Interferons (type 1, type 2) Tumor Necrosis Factor Hematopoetins or growth factors Chemokins ```
54
Lymph Node Migration
Activated DCs: enter by afferent lymph vessel T Cells: - enter by High Endothelial Venules (HEV) - leave by efferent lymph vessel
55
Plasmacytoid DC
- stays at infection site - produces large amount of type 1 IFN - produces many PRRs
56
Unactivated DC Characteristics
Highly phagocytic | Many dendrites
57
PAMP Induces what on DC
- receptors that target DC to LT - antigen processing genes (MHC) - costimulation proteins
58
Activated DC Characteristics
- can no longer phagocytose - less dendrites - homes into lymphoid tissues
59
Three Activation Signals
Activation Survival Differentiation
60
T-Cell Migration through Endothelium
rolling -> tight binding -> diapedesis -> chemokines | selectins and integrins guide T-Cell to different sites
61
T-Cell classes
CD8+ becomes Cytotoxic T Lymphocyte | CD4+ becomes helper T Cell of a particular subtype
62
CD4+ subtypes
TH1, TH2, TH17, Treg, Tfh - each subtype: - activated via different cytokine - has distinct cytokine profile - regulates distinct activities
63
Immunological synapse
tight binding between pMHC and TCR during activation
64
CD3
- flank TCR, helps with binding | - all T Cells express it
65
Zeta chains
transmembrane protein part of TCR
66
ITAM Motif
part of zeta chains on TCR | get phosphorylated as part of signalling cascade
67
TCR subunits
Heterodimer made of alpha and beta chains, or gamma-delta (90% alpha-beta) - conneced by disulfide bridge
68
Clonotypic
each cell expresses own type of something
69
MHC1
``` present endogeous peptides (usually) activates CD8+ T Cells alpha chain with 3 domains beta microglobulin domain (non-transmembrane) binds short 8-10 aa peptides expressed by all nucleated cells ```
70
MHC2
``` present exogenous peptides (usually) activates CD4+ T cells alpha chain with 2 domains beta chain with 2 domains only expressed by professional APCs binds peptides of any length ```
71
MHC Genetic Variation
Peptide binding cleft has lots of allelic variation | Rest of MHC is highly conserved
72
Co-Receptors Structures
CD4 - single chain, 4 Ig-like domains | CD8 - heterodimer linked by S bridge, alpha and beta Ig like domains
73
TAP
- transmembrane protein on ER - deliver peptides from cytosol to ER - site of peptide loading on MHC1
74
Calnexin
chaperone holding together partially folded MHC1 alpha chain
75
Tapasin
chaperone that links MHC1 and TAP
76
Invariant Chain
- binds and blocks peptide binding groove of MHC2 - directs MHC2 to vesicles (using tail) - degrades to CLIP
77
CLIP
- piece of invariant chain | - blocks peptide groove of MHC2
78
HLA-DM
- inside MHC2 vesicle | - binds MHC2 and releases CLIP
79
Cross-Presentation
CD4+ T cells license APCs to cross-present | - back and forth cytokine signal
80
Autophagy Ag presention
sends endogenous antigen to exogenous pathway
81
MHC Restriction
given T-cell can only recognize specific peptide bound to a specific self MHC
82
Allorecognition
1-10% of all T cells recognize and react to non-self MHC, regardless of presented peptide
83
MHC Gene
human leukocyte antigen (HLA) | codes for MHC
84
MHC1 Genes
HLA-A, HLA-B, HLA-C, code for the alpha chain
85
MHC2 Genes
HLA-DR, HLA-DQ, HLA-DP, etc. code for alpha and beta chains
86
MHC polymorphism
>100 different alleles | usually amino acid changes in peptide-groove
87
SH2 Domain
Adaptor/scaffold structure that bind protein to bring them in proximity/orientation
88
pMHC:TCR Signaling
pMHC:TCR - > co-receptor binding - > recruitment of Lck - > Lck phosphorylates ITAMs - > ZAP-70 is phosphorylated - > ZAP-70 activates four different signaling pathways - > transcription of genes necessary for T cell activation
89
Costimulation proteins
Ligands on APC: CD80 (B7.1) CD86 (B7.2) Receptors on T Cell: CD28
90
CD28
Transmembrane glycoprotein. Homodimer. Found in close proximity to TCR Expressed on all naive T cells at resting condition Binds CD80, CD86 -> triggers phosphorylation of CD28 Required for activation and proliferation
91
Clonal Anergy
Signal 1 in absence of Signal 2 results in transcription of anergy genes Anergetic T cell no longer responsive to stimulation
92
IL-2
Cytokine working in autocrine manner
93
IL-2 cascade
Signal 1 + Signal 2 | -> cascade leading to binding promoter region of IL-2 gene and IL-2Ralpha (or CD25) gene
94
IL-2R subunits
alpha, beta, gamma | beta and gamma are expressed at baseline level