Exam 1 Flashcards
(385 cards)
1
Q
According to Sir William Osler, what is humanity’s greatest enemy?
A
Fever
2
Q
Who are considered the grandfathers of microbiology?
A
Pasteur and Koch
3
Q
The period that spanned from 1875-1910 was known as what? Why?
A
First golden age of Microbiology bc many bacteria/pathogens were defined
4
Q
Who discovered Penicillin? When?
A
Alexander Fleming, 1929
5
Q
When was Penicillin-resistant Staph discovered?
A
1940
6
Q
Who purified penicillin for mass production? When?
A
Howard Florey and Ernst Boris Chain in 1944
7
Q
What resistant strain resulted from Tetracycline
A
Shigella
8
Q
What resistant strain resulted from Erythromycin
A
Streptococcus
9
Q
What resistant strain resulted from Methicillin
A
Staphylococcus
10
Q
What resistant strain resulted from Gentamicin
A
Enterococcus
11
Q
What resistant strain resulted from Vancomycin
A
Enterococcus
12
Q
Name a nitrogen-fixing bacteria and its symbiotic plant
A
Rhizobia, legumes
13
Q
Ruminants are bacteria that break down what?
A
Cellulose
14
Q
What must be used to visualize bacteria?
A
Light microscope
15
Q
What must be used to visualize viruses?
A
EM
16
Q
What are the largest classes of microbes?
A
Protozoa and fungi
17
Q
Most complex and diverse microorganism?
A
Parasite
18
Q
C. albicans is a causative agent for what types of infection?
A
Thrush, vaginal yeast infection
19
Q
Smallest independently living cell
A
bacteria
20
Q
bacterial cell division
A
binary fission
21
Q
Viruses ability to only infect certain types of cells is known as:
A
tissue tropism
22
Q
Define symbiotic bacteria and give example
A
Benefit host. Gut bacteria that participate in digestion.
23
Q
Define comensals and give example
A
Neutral relationship with host. Oral streptococci
24
Q
Define parasitic relationship and give example
A
Harm to host. Tape worms
25
Define residents
Established niche at particular body site
26
Define transients
Acquired from environment and establish themselves briefly before being inhibited by residents or immune system.
27
Define carrier state and give example
Potentially pathogenic organism becomes a resident. S. mutans
28
Example given as a possible microorganism treatment for autoimmune disease
Tape worm - decreases inflammation
29
First microbes are acquired when
Mother's vaginal canal
30
Principal bacteria genus in vagina
Lactobacilus
31
Principal bacterial genuses in male urethra
Similar to colon - Enterococcus, Mycobacterium, E. coli
32
Principal skin bacterium
S. epidermidis
33
Where might Staph aureus be found?
Nose, skin
34
At what body sites should potential pathogens not be found?
Blood, tissues, stomach, small intestine
35
Where on skin is bacterial flora concentration highest?
Moist areas - armpits, perineum, between toes
36
What type of bacteria can grow on sebum? Why are they not subject to bactericidal effects of skin lipids?
Gram-positive rods break down skin lipids to fatty acids. Proprionibacteria are also resistant.
37
Three principal bacteria types of mouth and pharynx
Streptococci first. Also Neisseria and Moraxella
38
Principal organism of stomach and small bowel
H. pylori
39
Where in body is the most abundant and diverse microbiota?
Colon
40
Primary site of carriage for pathogens
anterior nares
41
Three principal bacterial species in nasopharynx
Pneumoccoci, menigococi, Haemophilus
42
What protects accessory sinuses from colonization?
Epithelium and Eustachian tubes
43
Describe the microbiota of the urinary tract
Bladder and upper urinary tract are sterile. 1 cm of distal urethra has similar flora to perineum.
44
What influences concentration of vaginal flora
Hormonal fluctuations
45
At what points in life does the vaginal tract display mixed, nonspecific and relatively scanty microbiota
Pre-puberty and after menopause.
46
Why are lactobacilli able to thrive in the vagina during childbearing years?
High estrogen concentration causes deposition of glycogen (food source) in vaginal epithelium.
47
Explain exclusionary effect
Competition between normal flora and invaders. Pathogens may gain advantage from antibiotics killing normal flora.
48
What separates a pathogen from a commensal
Pathogen must cause damage to host
49
How might an S. pneumoniae infection in lungs cause damage?
Lungs fill with neutrophils - can't exchange O2.
50
How does Diptheria affect cellular machinery
Toxin released inhibits host protein synthesis
51
Bacterial enzymes that degrade host tissues (3)
Collagenases, proteases, hydrolytic enzymes
52
Four ways pathogens can evade immune response
1) Attack immune effector cells
2) Secrete enzymes that degrade antibodies
3) Camouflage by changing surface structure
4) Hide inside host cells
53
Three methods of specimen collection? Which method presents highest quality, but also highest risk?
1) Direct - localized in sterile locations (CSF)
2) Indirect - Passes through site containing normal flora (Sputum, urine)
3) Site with normal flora - pathogen and nonpathogen are mixed (throat and stool)
1 is highest quality and risk*
54
How soon must isolation occur after sample collection?
3-4 hours
55
What bacterium requires special transport media to survive isolation?
Neisseria gonorrhoeae
56
Bacterial growth is a problem during isolation after collection. What normal flora is known to overgrow a sample?
Enteric gram-negative rods
57
2 functions of transport media
- maintain neutral pH to prevent sample from drying out
| - contain minimal nutrients to prevent overgrowth
58
A gram stain uses what material? What does it stain? what color
Crystal violet. Ribonuclear intracellular proteins. Purple
59
An acid-fast stain uses what material? What does it stain? Color?
Carol-fuchsin. Stains mycolic acid. Red
60
Two counter stains used in gram stain and acid-fast stain respectively?
Safranin, methylene blue
61
General composition of direct immunofluorescence
Fluorescein-labeled antibody binds to fixed antigen on slide
62
General composition of indirect immunofluorescence
Fluorescein-labeled immunoglobulin binds to fixed antibody which is bound to antigen on slide (antigen-antibody complex)
63
Potassium Tellurite is a selective media that inhibits growth of what
Gram-negative bac
64
Define differential media
Distinguishes between closely related
| species of bacteria based on characteristics on media
65
What provides evidence for viral infection
cytopathic effect
66
Which bac form endospores
Gram +
67
Which bac have periplasm
Gram -
68
DNA structure in bacteria
Circular supercoiled double-stranded
69
What structure is more prevalent in bacteria than eukaryotes
Ribosomes
70
Granules that contain reserve materials
inclusion bodies
71
Are there sterols in a bacterial cell membrane?
No, except mycoplasma
72
What cell wall components vary by species
Polysaccharides and proteins
73
Principal components of peptidoglycan
Teichoic acid (may help with attachment or secretion) and lipotechoic acid (Anchors cell wall to membrane through glycolipids)
74
Alternating sugars in Peptidoglycan glycan chains. What crosslinks them
NAG and NAM. Peptide side chain and pentaglycine interbridge
75
Instead of lycine, what might be observed in Gram - cell wall
DAP
76
Lysozyme is present in what? What does it do?
Tears, saliva and mucus. Cleaves beta 1-4 glycosidic bonds betwen NAG and NAM
77
What does Penicillin do? How?
affects Gram +. Blocks cell wall synthesis by inhibiting transpeptidase enzymes that form crosslinks between glycan chains
78
Which Gram (-) cell wall component in impermeable? How does it allow things in and what?
Outer membrane has porins. Allows diffusion of hydrophilic solutes.
79
Role of periplasmic space
Contains proteins important for transport and chemotaxis
80
Describe LPS structure
```
-O antigen polysaccharide side chain-linked
sugars- antigenic determinant
- Core Polysaccharide- similar between
species
-Lipid A (toxin)- phospholipid with
glucosamine instead of glycerol (located
in outer membrane)
```
81
What's the smallest known bacterial species? How is it different and what does it do?
Mycoplasma. Sterol-containing membrane, no cell wall. Parasitizes host cells - causes walking pneumonia
82
Thick hydrophilic gel that surrounds bac cell? What's it made of? Function?
Capsule (if discrete); slime layer (if amorphous). Made of polysaccharides, sometimes polypeptides. Protection from immune system
83
What environmental condition is required for S. mutans to form a capsule?
Sucrose
84
Function of fimbriae
Attachment
85
Pili functions
Attachment/DNA transfer
86
What species is known for sporulating?
Bacillus
87
Bacterial metabolism differences from eukaryotes
- Faster (10-100x)
- Can use many energy sources
- No organelles so macromolecule synthesis is streamlined
- Synthesis of Peptidoglycan/LPS
88
Three pathways for energy generation
1) E-M (glycolysis)
2) Pentose phosphate - generates NADPH* and ribose-5-phosphate for nucleotide synthesis
3) Krebs
89
"Strict anaerobe" is a designation based on the lack of what?
Catalase and superoxide dismutase
90
Obligate anaerobes and Aerotolerant anaerobescan only use___ for energy
Fermentation (substrate-level phosphorylation)
91
Enzyme that introduces supercoils in replication
DNA gyrase
92
Enzyme that relaxes upercoils in replication?
Topoisomerase
93
Prok. replication is what two things
Bidirectional, semi-conservative
94
What gene controls homologous recombination
recA
95
Define transduction
Bacterial DNA transfered via phage (lytic and lysogenic)
96
What binds to promoter
RNA polymerase
97
Two components in TCS
Protein kinase, response regulator
98
First immune response
Innate
99
Innate vs. Adaptive: response time and specificity?
Innate: fast, non-specific.
Adaptive: Delayed, antigen-specific
100
Two lines of white blood cell hematopoieses
Myeloid, lymphoid
101
With age, hematopoiesis occurs in what types of bones chronologically?
Young -> old:
- tibias
- femurs
- ribs
- sternum
- vertebrae
Long bones -> flat bones
102
Most abundant granulocyte
Neutrophil
103
Involved in inflammatory and allergy (granulocyte)
basophil
104
Granulocyte involved in parasite/allergy
eosinophil
105
Two general cell types from myeloid lineage?
Phagocytes, granulocytes
106
Phagocyte that can activate naive T cells
Conventional dendritic cells
107
Only granulocytic myeloid cell that isn't considered a granulocyte? What's its role?
Mast cell - parasite/allergy
108
What turns the immune response off?
Regulatory T cell
109
Are memory cells associated with T or B cells?
Both
110
First responder
Neutrophil
111
Three types of T cells
Cytotoxic (CD8)
Helper (CD4)
Suppressor/regulatory
112
B cells differentiate into what that produce what?
Plasma cells, antibodies
113
NK cells are involved with what immune system?
Innate
114
Molecule capable of
| inducing an immune response
Antigen
115
How many antigens does an antibody recognize?
Just 1, specific.
116
Activation of receptors occurs where most often?
Extracellularly
117
Signaling molecules (2)
Chemokines, cytokines
118
4 functions of cytokines
1) Activation/proliferation
2) Inflammation
3) Motility
4) Immunosuppresion
119
Organized clusters
Follicles
120
Follicles grouped together
Patches
121
Encapsulated follicles
Organs
122
Two structures of primary lymphoid tissue
Bone marrow, thymus
123
T cell arises in _____ and matures in ____
Bone marrow, thymus
124
4 types of MALT
Nasopharynx, bronchial, gut, skin
125
Outline infection response
1) Phagocytosis by DC
2) Presentation to T cells in lymph node
3) Clonal expansion of T cell
4) Migration of T cell to infection
126
Non-inducible immune components
Skin/mucus/commensal bacteria (physical)
Lysozyme, antimicrobial peptides (a and b-defensins, cathelicidin)
127
Inducible immune components
Innate immune cells, neutralizing antibodies (secetory IgA)
128
4 bacterial PAMPs
LPS, peptidoglycan, CpG DNA, flagellin
129
2 viral PAMPs
dsRNA, ssRNA
130
2 fungal PAMPs
Chitin, zymosan
131
6 classes of DAMPs
- Complement (C3b, C4b)
- ROS
- Stress-induced molecules
- Metabolites
- Nucleic acids
- Exogenous (alum, silica, asbesots)
132
What TLRs are bacteria-associated? Virus associated?
Bac: 1,2,4,5,6,9
Virus: 3, 7, 8
133
TLR2, 4, and 5 roles
2 - peptidoglycan
4 - LPS
5 - flagellin
134
TLRs are highly expressed in what 3 cells
DC, Monocytes/mac, neutrophils
135
Inflammasomes are formed from what? What does this lead to? This activation can also lead to what?
Nod-like receptor complexes. Caspase 1 activation to activate IL-1 and IL-18. NLR activation can also lead to apoptosis
136
What receptors recognize viral RNA? Activation leads to production of what?
RIG. IFN-a and IFN-b
137
Carbohydrate-based DAMPs and PAMPs are recognized by what?
CLRs
138
Scavenger receptors bind to what?
lipids
139
Collectins are comprised of what two components? Where are they found? What can they do once activated?
1) Collagen and lectin
2)blood
3:
a) activate complement
b) Phagocytosis
c) agglutination
140
4 outcomes of complement activation
1) Pathogen destruction
2) Pathogen opsonization
3) Clearance of immune complexes
4) Creation of peptides to help inflammatory response
141
What starts classical complement pathway
recognition of antigen-antibody complexes
142
What starts lectin complement pathway
mannose-binding ligand bound to pathogen
143
What activates alternative complement pathway
Binding of C3 to pathogen
144
The product of all 3 complement pathways that begins pathogen destruction/inflammtion
C3b
145
Which complement pathway is delayed? Why?
Classical, bc antibodies specific to antigen must be made.
146
Cleavage of C3 yields what 2 products? What are their roles?
C3a: inflammation
C3b: opsonization/phagocytosis
147
What leads to production of membrane attack complex (MAC)? What does mac do?
C5a. Lysis of microbe
148
What term describes engulfment of fluid and macromolecules? What process is similar, but receptor-mediated?
Macropinocytosis, Clathrin-Mediated Endocytosis
149
What method of pathogen capture requires a surface receptor
phagocytosis
150
Trace the process of phagocytosis
Binding of microbe to receptor, microge ingested into phagosome
- Phagosome fuses with lysosome
- bacteria killed by lysosomal enzymes and ROS.
- By-products can be uses as PAMPs or expelled
151
Cell recycling
Autophagy
152
A membrane-bound Ig is known as? Non-membrane-bound?
Bound: BCR
Non: antibody
153
How many different kinds of heavy and light chains can a B cell produce?
1
154
What attaches a heavy and light chain
disulfide bond
155
What connects two heavy chains?
2 disulfide bonds
156
Enzyme used to digest antibody
Papain
157
Enzyme digestion of Ig yields what two fragments? Which is involved in opsonization? Which is involved with Ag binding?
Fc - constant, opsonization
Fab - variable (distal half), Ag binding
158
The hinge region of an Ig is what
linking of heavy chains
159
Most variable hypervariable region? What's the purpose of hypervariable regions?
CDR3, antigenic diversity
160
The constant region can give rise to different what?
Isotypes
161
Two light-chain isotypes? which is more common in humans?
kappa and lambda. Kappa is
162
Heavy chain isogypes
IgM, IgD, IgG, IgE, IgA
163
What isotype is first produced upon encounter with Ag
IgM
164
Which structural isoform has a transmembrane domain?
Membrane-bound Ig
165
Where are Membrane-bound Ig(mig) found
B cell plasma membrane (BCR)
166
Where are secreted ig (sig) found
blood
167
Where are secretory ig (Sig) found
secretions (tears, mucus, saliva)
168
Most common polymeric immunoglobulins? (2) What keeps them together?
IgM pentadimer
IgA dimer
J chain
169
Receptor activation and subsquent intracellular phosphorylation results in what 3 things
1) gene transcription
2)actin rearrangement
or
3) mediator release
170
What transmembrane proteins are associated with BCR? What do they do
Ig-alpha, Ig-beta. Activate ITAMs
171
Variable regions are made up of what gene segments? Which chain is missing one and what is it?
Variable (V), Diversity (D) and Joining (J)
Light chain does not have D
172
What occurs in every naive B cell
VDJ recombination
173
Is vdj recombo permanent
yeah
174
Antigenic determinant is called:
epitope
175
What specificially do antigens tend to bind to
CDR3 of Ig heavy chain
176
The strength of the non-covalent
association between one
antigen-binding site and one
antigenic epitope
affinity
177
The overall strength of the bond
between a multivalent Ab and
multivalent Ag.
avidity
178
Define cross reactivity
when one epitope is shared by two Ag, or when two epitopes
| on separate Ag are similar in structure.
179
Outline 2 stages of B cell development
1) Maturation - begins in bone marrow and ends in periphery. *B cell is still naive here.
2) Differentiation – Begins once a B cell recognizes its specific Ag, ends
with the generation of Ag-specific plasma cells and memory B cells.
180
Outline stages of B cell maturation
* Hematopoietic stem cell
* Multipotent progenitor cell
* Common lymphoid progenitor
* Progenitor B cell (pro-B cell)
* Precursor B cell (pre-B cell)
* Immature naïve B cell
* Mature naïve B cell
181
What's the first hematopoietic cells that are recognizable as B cells? What's the status of Ig genes here?
Pro. Ig genes still in germline configuration.
182
Pre B cells are marked by what 2 things?
VDJ recombination is complete.
| -Late pre B cells will produce membrane-bound IgM and Ig-alpha/Igbeta
183
2 things happening in Immature B cell stage
- Development of central tolerance
| - Immature B cells get last chance to rearrange Ig loci via receptor editing.
184
What percentage of immature B cells survive positive/negative selection?
2-5%
185
Where does a transitional type 1 traditional B cell go?
red pulp then PALS
186
What's expressed by transitional type 2 B cells? What do they become?
Both IgM and IgD.
Become follicular B cells or marginal zone B cells
187
3 points for mature B cells
1) express both Igm and IgD
2) can't undergo further VDJ rearrangements
3) Considered naive
188
Distinguish between two types of B cell antigens
1) T-dependent - usually follicular B cells
| 2) T-independent - usually marginal zone B cells
189
End result of T-dependent B cell activation?
Isotype switched (to different Ig), high-affinity antibodies, memory B cells
190
End result of T-independent B cell activation?
Mainly IgM, low-affinity antibodies, short-lived plasma cells
191
T-dependent involves what kind of antigen
Protein
192
Where does B cell activation occur?
Lymphoid tissues
193
3 steps of B cell activation
- Antigen binding
- Costimulation - activated Th effectors
- Cytokine help (Released from T cell)
194
Outline the 3 signals in B cell activation
Signal 1 - Ag binds to BCR. Signal transmitted via Igalpha/Igbeta. Precedes T cell binding
Signal 2 - Interaction with Ag-specific Th cell; TCR (T) binds to MHC-II (B) and CD40L (T) binds to CD40 (B)
Signal 3 - Cytokine stimulation by Th cell. Involvement of IL-4, IL-2, IL-5 and IL-10. Macrophages and DC also contribute cytokines
195
During clonal expansion, a secondary follicle becomes what?
Germinal center
196
Three events within germinal centers
1) Somatic hypermutation
2) Affinity maturation
3) Isotype switching
197
Germinal centers give rise to what two types of cells?
Long-lived memory B cell
or
Long-lived class switched plasma cell (IgA, IgG, or IgE)
198
4 functions of antibodies
- neutralization
- classical complement activation
- opsonization
- antibody-dependent cell-mediated cytotoxicity
199
Outline antibody neutralization
Pathogens that are usually endocytosed after binding to cell receptor are blocked from attachment via the action of binding antibodies that provide steric interference and induce capsid stabilization and structurral changes
200
4 antibodies that activate classical complement
IgM, IgG1, IgG2, IgG3
201
2 antibodies involved in opsonization
IgG1, IgG3
202
Outline antibody-dependent cell-mediated cytotoxicity and examples
Antibody binds large pathogen and presents to NK cells, which activates them to release granules to kill pathogen.
Pathogen/antigen undergoes this process bc it's too big for conventional phagocytosis.
E.g. Parasitic worms, virally infected cells, tumor cells
203
How was MHC discovered
Due to importance during tissue rejection
204
Where is MHC encoded
HLA complex, chromosome 6
205
3 qualities of MHC genes
-polygenic
0-polymorphic
-codominantly expressed
206
On what cells are MHC Class I found?
All nucleated cells
207
To what does MHC Class I present? What kind of peptides are presendted?
CD8+ T cells. Endogenous
208
On what cells are MHC class II found
APCs
209
What kind of peptides are displayed by MHC Class II? What do they present to?
Exogenous. CD4+ T cells
210
Difference in structure between MHC I and II
I: 3 alpha subunits and B2-microglobulin subunit
II: 2 alpha subunits, 2 beta subunits
211
MHC I or II, larger binding region?
II
212
Antigen processing involves:
• The breaking down of macromolecules into smaller fragments in
order to prepare them for presentation to a T cell
213
4 pathways of Ag processing
Exogenous, endogenous, cross-presentation, autophagic
214
Autophagy Ag processing switches from _ to _
Endogenous to exogenous pathway
215
Cross-presentation Ag processing switches from _ to _
Exogenous to endogenous pathway
216
Rank APCs from high to low levels of MHC II
DC, macrophage, B cell
217
Rank APCs from high to low level of constitutive costimulatory molecules
DC, Macrophage, B cell
218
Rank APCs from high to low capability of cross-presentation
DC, Macrophage, B cell
219
What APC activates naive T cell
DC
220
What APCs activate effector and memory T cells
all of them
221
Macrophage APC is involved with what type of immunity
cell-mediated
222
B cell APC is involved with what type of immunity
humoral
223
When is a dendritic cell most expressing Fc receptors
in tissue, resting, unactivated
224
Trace exogenous pathway
- Endocytosis
- antigen degradation.
- assembly of MHC II molecules (assembled in ER, travel to golgi then lysosome)
- Complex takes endosome to surface to present to CD4
225
What's the MHC II Ag binding issue? How's it solved?
Invariant chain blocks binding. Invariant chain is cleaved in vesicle, leaving CLIP FRAGMENT. CLIP blocks binding but it's released via action of HLA-DM. Then antigen can bind
226
Trace endogenous pathway
- Proteins degraded by proteasome and transported to ER via TAP.
- MHC I loaded in ER
- Complex transported to golgi then membrane to present to CD8
227
Outline cross-presentation
APC ingests and processes virally infected cell. Viral proteins
enter the cytosol and is process via endogenous pathway to
activate a CD8 T cell via MHC I.
228
Trace Autophagic pathway
- Collection of cellular degradable components
- Completion of autophagosome
- Fusion of autophagosome and lysosome
- Degradation
229
Two classes of TCR and their characteristics
1) alphabeta (90%) - recognize MHC/Ag and reside in secondary lymphoid tissue.
2) gammadelta (10%) - recognizes ligands. Intraepithelial tissues
230
TCR complex is what with respect to membrane
spanning
231
What happens in T cell after antigen presentation
TCR complex and coreceptors are clustered within membrane lipid rafts by antigen recognition.
Then Lck protein (intracellular) phosphorylates tyrosines in ITAMs
232
Do TCR do VDJ recombo
yes
233
4 ways that T cell development is similar to B cell development
* Begins in bone marrow
* V(D)J recombination of variable region of TCR leads to antigenic diversity
* At one point cells express both CD4 and CD8 (double positive)
* Undergo positive and negative selection
234
4 ways that T cell development is different from B cell development
• Begins with NK/T precursor cell
• After leaving the bone marrow thymocytes move to thymus to finish
development
• MHC molecules are involved in the establishment of central tolerance
• No possibilities for somatic hypermutation
235
What TCR is involved in cell adhesion? What TCR is an IL-2 receptor?
CD44, CD25
236
RAG expression is associated with what?
VDJ recombination
237
Stages of T cell differentiation
- Stem cell
- Pro-T
- Pre-T
- Double positive
- Single positive (immature)
- Mature T cell
238
At what T cell development stage is has cell moved to thymus?
Pro-T
239
At what T cell development stage is IL-2 receptor expressed?
Pro-T
240
At what T cell development stage does Beta chain rearrangement begin to occur?
Pro-T
241
What T cell development stage is a checkpoint? What does this mean?
Pre-T. Determination of viability of T cell
242
At what T cell development stage does first semblance of a TCR appear
Pre-T
243
At what T cell development stage does alpha chain begin to undergo VDJ recombination?
End of Pre-T
244
At what T cell development stage does positive/negative selection occur?
Double positive
245
What T cells are negatively selected?
Self-reactive
246
Outline the mechanics of negative T cell selection
MHC presentation to a T cell. If affinity is too strong, it's negatively selected
247
At what T cell development stage doesw a T cell become Cd4 or Cd8
Single positive (immature)
248
What's the distribution of CD4 to CD8 in body
2x CD4
249
To where does a mature T cell travel?
Secondary lymphoid organ; usually lymph node
250
What cytokine does a naive T cell release to become effector?
IL-2
251
CD28 coreceptor binds to what on APC?
B7
252
Effector function of CD4
Activation of macrophages, B cells. Inflammation
253
Effector function of CD8
Killing of infected cells, macrophage activation
254
Four types of Th cells
Th1, Th2, Th17, iTreg
255
Name cytokine involved with differentiation to Th1
IFN-gamma
256
Name cytokine involved with differentiation to Th2
IL-4
257
Name cytokine involved with differentiation to Th17
TGF-beta
258
Name cytokine involved with differentiation to iTreg
TGF-beta
259
Function of Th1
T help for Tc responses against intracellular pathogens. Classical macrophage activation.
260
Function of Th2
T help for B cell responses against extracellular pathogens (humoral immunity).
261
Function of Th17
Combats infections of skin and mucosa. Autoinflammation, neutrophil recruitment, barrier function.
262
Function of iTreg
Peripheral tolerance
263
3 cytokines needed for CD8 T cells
IL-2, IL-12, Type 1 IFN
264
Type 1 mucosa and where it's found
Single layer of columnar epithelial cells in the gut and lungs
265
Type II mucosa and where it's found
Mnany layers, top layer is squamous epithelial cells - mouth and nose
266
Main Ab of type I mucosa
SIgA
267
MAin antibody of Type II mucosa
IgG
268
4 non-inducible defenses of GI tract
- Acidity
- Motility
- Mucus layer and underlying glycocalyx
- tight junctions
269
what secretes mucin
goblet cell
270
In what layer are immune cells of GALT
lamina propria
271
What DC is important in inducing Treg and sampling gut epithelial tissue.
CD103+
272
What type of mucosa is associated with NALT? BALT?
Type II, Type I
273
Adaptive response in the gut is usually biased toward what Ab
SIgA
274
If inflammatory respone is needed in gut, what Th are activated?
Th1/Th17
275
What kind of immunity is involved with intracellular vs extracellular pathogens?
Cell-mediated, humoral
276
Is SigA antigen-specific?
yes, but can bind to adhesion molecules found on many pathogens
277
What is SIgA's role in complement activation?
Does not activate complement well
278
What Ig is notably very resistant to host and microbial proteases?
SIgA
279
Drawback to initiating inflammatory response at mucosal surfaces?
Inflammatory cytokines (TNF-alpha) can disrupt epithelial cell tight junctions
280
What lymphoid tissue has little to no B cells?
SALT
281
2 parameters of pathogenicity
- Bacterial species is able to cause disease
| - Human host must be susceptible
282
Lowly virulent bacterium in oropharyngeal flora
S. salivarious
283
Moderately virulent bacterium in colon. Harmless there, but where can it cause acute infection?
E. coli. Bladder
284
Highly virulent bacterium that causes whooping cough
B. pertussis
285
5 modes of infection transmission
- airborne
- food borne
- vector borne
- water borne
- blood borne
286
Three stages to establish infection
- adherence
- colonization
- damage
287
Pili role in bacterial entry-adherance
Bind to cell-specific receptors (mannose, fibronectin) - attach cell and pull closer so second adhesin can bind host receptor
288
3 bacteria that use sIgA protease to cleave SIgA hinge region
N. gonorrhea
H. influenza
S. pneumonia
289
What keeps iron levels low in EC fluid? Why?
Lactoferrin, to prevent bacterial growth
290
How do pathogens sequester iron
Production of siderophores to compete with human proteins for Fe
291
3 methods of evasion from macrophages
- hide in host cells
- avoid contact
- inhibition
292
Three varieties of pathogens
Extracellular- not able to invade host cells
• Facultative intracellular bacteria- can invade host cells, but can also survive in extracellular
environment
• Obligate intracellular bacteria- require host cells for survival
293
Good example of obligate intracellular bacterium
Chlamydia
294
What class of pathogen can escape the phagosome
facultative intracellular bacteria
295
What class of bacteria utilizes a type III secretion system to inject effector proteins
Gram (-)
296
What do effector proteins do?
Promote invasion of host/suppress host cell defenses
297
After being phagocytosed, what does a bacterium do to survive? what's it known as?
Invasion - process by which bacteria modifies endosome, OR escapes it, replicates in cytoplasm, OR blocks endosome-lysosome fusion
298
What describes efficiency of a pathogen?
Number of organisms required to cause disease
299
What structure might a bacterium use to prevent phagocytosis? How does this work?
Capsule can interfere with complement deposition; capsule binds Factor H to degrade C3b
300
What's a notable area not patrolled by phagocytes
bladder
301
4 ways to avoid contact with phagocytes
- invade locations not surveilled by phagocytes
- Avoid inducing inflammatory response
- inhibit phagocyte chemotaxis (Streptococcus using Streptolysin).
- Bind host molecules to hide antigenic surface (T. pallidum (Syphilis))
302
3 ways manipulating pamps and amps helps bacteria's survival
1) Poorly recognized lipid A portion
2) Lipid A modification affects surface charge
3) Alter cell wall teichoic acids
303
How do bacteria avoid innate and adaptive immunity? give examples
Antigenic variation
- change pili structure (Neisseria)
- Vary M proteins (STrep)
- Change VSG coat (T. brucei)
- Change coat proteins (P. falciparum - Malaria)
- Mutated hemagglutinin and neuraminidase (Flu)
304
Induction of host apoptosis examples
- Strep and Staph make streptolysin and leukocidin respectively to target neutrophils.
- Psudomonas makes Exotoxin A to kill macrophages
305
5 ways bacteria cause host injury
• Exotoxins- bacterial secreted proteins- local and systemic if in blood
Endotoxin- lipid A portion of LPS of Gram-negative bacteria- stimulates cytokine release (inflammation)
• Hydrolytic enzymes- (i.e. collagenase or hyaluronidase)- facilitate tissue invasion
• Superantigen exotoxins- stimulate massive cytokine secretion (toxic shock)
• Inflammation- prolonged immune response to bacteria can damage host tissues (periodontal disease)
306
Do exotoxins bind to specific cell receptors
yes
307
Subunits of exotoxins and their roles
B and A
B binds surface receptor
A gets transported by endocytosis
308
What causes loss of cell integrity and leakage through pore? What would the immune system recognize this as?
Membrane active exotoxins that create pores in hose cell membranes (S. aureus, Group A Strep, E. coli)
DAMPs
309
Very prominent endotoxin that causes fever through release of what
Lipid A toxin of LPS - phospholipid with glucosamine instead of lycerol. Induces fever through release of IL-1 and TNF from macrophages
310
Action of superantigen. What do they cause?
Superantigens are polyclonal stimulators of T cells; they bind to MHC II to activate T cells. S. aureus and Group A strep do this to cause Toxic shock syndrome
311
Principal physiological function of immune system
defense against pathogens
312
Three high-affinity receptors on bacterial cell
1) Mannose
2) Mac-1 Integrin (Opsonized with complement proteins)
3) Scavenger receptor - non-mannose
313
Define respiratory burst
Conversion of O2 into ROS
314
Chemostatic neutrophil factors
IL-8, IFN-gamma, C5a
315
How can neutrophils kill microbes without ROS (4)
- degranulation
- defensins
- myeloperoxidase
- neutrophil extracellular traps (NETs)
316
Ab involved in B cell neutralization
IgG, IgM, IgA
317
Ab involved in opsonization and Fc receptor-mediated phagocytosis
IgG
318
Ab involved in phagocytosis of C3b-coated bacteria
IgM, IgG
319
CD4 make what inflammatory cytokines. When they make these, what are they called
IFN-gamma and TNF-alpha. Now called Th1 cells
320
CD4 make what B cell promoting cytokines? When they make these, what are they called?
IL-4, IL-5 IL-10
Th2
321
3 intracellular pathogens
-mycobacteria
L. monocytogenes
Salmonella
322
What cytokines are secreted by NK and why
IFN-gamma for macrophage and Th1 development
323
Outline T cell vs intracellular microbes
CD4 binds APC, releases IFN-gamma. Bacteria are liberated from phagolysosome into cytoplasm. CD8 binds APC and kills it
324
CD4 are _____ t cells
helper
325
TH1 CD4 produce what and promote what
IFN-gamma and TNF-alpha, cell-mediated immunity
326
TH2 CD4 produce what and promote what
IL-4, antibody-mediated (humoral)
327
CD8 are called ___ t cells and secrete what? Particularly important in what kind of immunity?
Effector. Anti-viral (IFN-gamma, TNF-alpha)
328
Define inflammation
A non-specific response to infection or injury that is characterized by
enhanced accumulation of immune cells and plasma proteins.
329
5 marks of inflammation
```
Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Loss of function (functio laesa)
```
330
Primary difference between acute and chronic inflammation? What type of immunity is involved in each?
Acute - innate
Chronic - adaptive
Chronic experiences ongoing stimulus
331
3 proinflammatory cytokines
- TNF-alpha
- IL-1Beta
- IL-6
332
3 inflammatory mediators involved in vasodilation
Histamine, bradykinin, leukotrines
333
What causes histamine release by mast cells?
Interaction with microbes, ligation of C5a, or interaction with IgE
334
What are prostaglandins derived from? What do they do?
Derived from cell membrane phospholipids - involved in inflammatory response
335
Complement protein involved in monocyte/neutrophil recruitment
C5a
336
Complement proteins that can trigger mast cell degranulation
C3a, C5a
337
Two cytokines involved in turning off inflammation
IL-10, TGF-beta
338
Treatment for acute inflammation
Ice/elevation, NSAIDS
339
Treatment for chronic inflammation
Steroids, immunosuppressants, anti-leukotrienes
340
Outline first step of neutrophil migration to infection
Tethering/rolling - slows leukocyte down within post-capillary venule. Halted by selectins on endothelial surface that bind cell.
341
Affinity of selectins?
low
342
What do selectins recognize?
sialylated crabohydrates
343
Three types of selectins and where they're found
P and E on endothelial cells; L on leukocytes/lymphocytes
344
Activator for P selectin?
Histamine/thrombin
345
Activator for E selectin
Cytokines, microbial byproducts
346
Outline second step of migration to infection
Integrin activation:
| Chemokines from infected tissue signal to leukocyte. Integrin affinity becomes high to bind to endothelium
347
2 notable integrins and their selectin ligands
LFA-1 (I) : ICAM-1 (S)
| VLA-4 (I) : VCAM-1(S)
348
Outline third step of migration to infection
Adherence:
Integrin/selectin binding. Leukocyte stops rolling. cytoskeleton rearrangement
349
Outline fourth step of migration to infection
Migration:
| Leukocyte diffuses into tissue to follow chemokine scent after cytoskeleton rearrangement and tight junction loosening
350
8 prominent phyla of oral bacteria
- firmicutes
- fusobacteria
- bacterodetes
- actinobacteria
- proteobacteria
- spirochaetes
- synergistetes
- TM7
351
What bacterium is found in every location in the mouth? What two are on every tooth surface?
S. mitis
S. anguinis and S. gordonnii
352
Most common species in plaque
Mitis group Strep:
S. sanguinis, S. gordonii
S. oralis
353
Minor species in healthy plaque
Mutans group Strep:
S. mutans and S. sobrinus
354
3 early colonizers of plaque and a brief role
Strep (produce H2O2, co-aggregation)
- Veillonella - maintains neutral pH by metabolizing lactic acid
- Actinomyces - coaggreation
355
Late colonizers of plaque
- F. nucleatum (Removes oxygen)
- P. gingivalis - strict anaerobe
- T. denticola
- Prevotella
356
NOn-specific plaque hypothesis
Caries result from perturbation in bacterial populations due to disruption in enviornment. Not a specific bacteria
357
As dental caries progress, bacterial diverstiy _________
decreases
358
4 virulence factors of S. mutans
- acidogenic
- acid tolerant
- glycosyltransferases
- glucan binding proteins
359
What serotype of S. mutans is most common in oral cavity
C
360
Ubiquitous commensal that antagonizes bad oral species
S. sanguinis
361
Socransky's Red complex (3) - associated with periodontal disease
P. gingivalis
T. forsythia
T. denticola
362
What inhibits host immune response to oral flora? What's the morphology and oxygen demand of this org.
P. gingivalis. Gram - rod. Obligate anaerobe
363
Distingujish between disinfection and sterilization
D; kills everything except spores
| S: kills everything
364
Disinfectant that can be used on living tissue
Antiseptic
365
Prevention measures for contact with microorgs.
Asepsis
366
Hospital-acquired infections
Nosocomial
367
A higher MIC would mean what
Non-sensitivity and resistance to microbial growth
368
4 general targets of antibiotics
- cell wall synthesis
- protein synthesis (70s ribosome)
- Nucleic acid synthesis/folate synthesis
- cell membrane integrity
369
B- lactams inhibit what
Cell wall synthesis (penicillin)
370
How do b-lactams work?
Bind to transpeptidases and interfere cross-linking of amino acid side chains
371
How do non-B lactams work
inhibit assembly of peptidoglycan by binding to AA side chains to prevent cross linking (Vancomycin)
*Treatment for MRSA
372
What inhibits AA synthesis
Chloramohenicol
373
What inhibits 50s and 30sribosome
Aminoglycosides
374
What inhibits 30s ribosome
tetracylcine
375
What inhibits RNA polymerase
Rifampin
376
What breaks DNA
Metronidazole
377
What inhibits DNA topoisomerase and gyrase
Quinolones
378
What inhibits folate synthesis
Sulfonamides, Trimethoprin
379
What targets fungal cell membrane
amphotericin
380
what targets gram neg outer membrane
polymyxins
381
5 mechanisms of antibiotic resistance
-efflux pump
-blocked penetration
altered target
-enzymatic inactivation
genetic resistance
382
Why can't methicilin bind MRSA?
Altered PBPs
383
Treatment for MRSA?
Non-B-lactams (Vancomycin, Teicoplanin)
384
Why can't Vancomycin bind VRSA?
Altered peptide
385
Give example of enzymatic inactivation
B-lactamase is bacterial enzyme that breaks B-lactam ring
