Exam 1 Flashcards
(404 cards)
1
Q
Parasites
A
Most diverse of all living microorganisms
Some are multicellular with their own organ systems
- Complex life cycles needing multiple vertebrate and invertebrate hosts
- Some depend on combinations of animals, Arthropoda, or crustacean hosts for survival
2
Q
Fungi
A
Distinct from animals and plats- - considered Eukaryotic
Exists as yeast or molds. Most are free living-ubiquitous in nature
3
Q
Bacteria
A
Smallest independently living cell-Cytoplasmic membrane surrounded by a cell wall.
No organelles.
Divides by binary fission.
4
Q
Viruses
A
Smallest and simplistic infectious agent:
Protein coat surrounding nucleic acid
5
Q
Obligate intracellular paraste
A
Require a host
6
Q
Tissue Tropism
A
Only infect certain cells
7
Q
Symbiotic
A
Benefit host
Ex. Gut bacteria
8
Q
Commensalism
A
Neutral relationship to the host
Oral streptococci
9
Q
Parasitic Relationship
A
Harm to host
Ex. tape worms
10
Q
Residents
A
Established niche at a particular body site
11
Q
Transients
A
Acquired from the environment and establish themselves briefly
(Inhibited by resident bacteria or by host immune system)
12
Q
Carrier State
A
Potentially pathogenic organisms becomes resident
Ex. Streptococcus mutans
13
Q
Babies are Sterile at birth
A
First microbe are from the mothers vagina
14
Q
Bacteria colonize the locations______
A
Best suited to their physiology
15
Q
Factors bacteria consider when determining to colonize
A
- Nutrients
- pH
- Oxidation reduction potential
- Resistant to locals antibacterial substances
- Adhesion mediated affinity to receptor on host cells
- Microbial interactions (who else is already there—competition and inhibition)
16
Q
Skin Bacteria
A
Skin is dry slightly acidic aerobic environment
Flora is resitent to bactericidal effects of skin lipids and fatty acids
17
Q
Bacterial skin flora is highest where
A
Armpits perineum and between toes
Moist skin
18
Q
Proprionibacteria
A
Microaerophilic or anaerobic gram positive rods can grow on sebum and break down skin lipids to fatty acids
19
Q
Mouth and Pharynx
A
Many bacteria
Species differ at different sites
Lots of streptococci- also high number of neisseria and Moraxella
20
Q
Orthopharynx
A
Back of throat
Mostly Neisseria and Streptococci
21
Q
Stomach and small bowel
A
PH 1-4
Few organisms more toward lower ileum
22
Q
Colon
A
Most abundant and diverse microbiota
Feces 25%
-90% are anaerobes
Bactericides
Fusobacterium
Eubacteria
Clostridium
Remainder are facultative organisms like E. coli, enterococci, yeasts, and others
23
Q
Anterior Nares
A
Similar to skin flora
Primary sites of carriage for pathogens- staph aureus
24
Q
Nasopharynx
A
Similar flora as mouth
Site for carriage of pneumococci meningococci and haeophilus species
25
Larynx and lower respiratory tract
Protected in health by epithelial cilia and by movement of mucocilary blanket (only transient inhaled organisms in trachea and larger bronchi)
26
Accessory sinuses
Normally sterile protected by epithelium and estancias tubes
27
Urinary Tract
Bladder and upper urinary tract are sterile in health (except for about 1 cm of distal urethra)
28
Valiant tract
Flora is influenced by hormonal fluctuations and is different at different ages
29
Pre puberty vag
| After menopause vag
Mixed nonspecific and relatively scanty-mostly organisms derived from skins flora and colon
30
Childbearing years vag
Mostly lactobacillus and some anaerobic gram neg rods, gram pos cocci and yeats
31
Due to estrogen _____is deposited in vaginal epithelia tissue which ______ feed on
Glycogen
| Lactobacilli
32
Opportunistic infections
Can occur when microbes invade normally sterile locations or reduced host defenses or immunologic response results in invasion by flora
33
Exclusionary effect
Competition between normal flora and potential invades
Ex antibiotics wipe out normal flora, may give pathogens a competing advantage
34
Priming the immune system
Presence of microbiota is important for the development of our immune system
35
What separates a pathogen from commensal
Ability to attach to host tissues
| Ability to adapt to new environemnt
36
Persistent and invasion do not necessarily lead to disease
Must cause damage to host
37
Host response to organism
Can cause damage or symptoms
38
Organisms must cause damage to host
Immune response
Bacteria Toxins
Enzymes
39
Bacteria can produce toxins that act on host cells
Diphtheria makes a toxin that inhibits host protein synthesis
40
bacteria can secrete enzymes that degrade host tissues
Cuases inflammations and facilitate spread
Collagenases
Pro teases
Hydrologic enzymes
41
Pathogens have ways to evade the immune response
Pathogens can
Attack immune effector cells
Secrete enzymes that degrade host effector molecules
Changes surface structure to evade the immune response
hide inside host cells
42
Competition between normal flora and potential invaders is an example of
Exclusionary effect
43
Which locations in the body is normally sterile
Accessory sinuses
| Upper urinary tract
44
Specimen collection is critical
Otherwise can be challenging to distinguish normal flora or environmental contaminates from causative agent of disease
45
Direct specimen
Localized in an otherwise sterile location
-deep abscess or CSF
Highest risk and quality
46
Indirect sample
Must pass through a site containing normal flora
Expectorated sputum and voided urine
47
Sample from site with normal flora
Pathogen and nonpathogenic flora are mixed (throat and stool)
48
Issues with sample collections
Time between sample collection and isolation is critical (3 to 4 hours)
49
Viability
Some organisms don’t survive long outside the body
-Gonorrhoea requires transport media
50
Bacterial growth
After collection can be particularly problematic for enteric gram negative rods and if found in low numbers
51
Transport Media
Buffered fluid or semisolid media
Designed to maintain a neutral pH and prevent sample from drying out
Contains minimal nutrients to minimize growth of bacterial contaminants
52
Primary Stains
Crystal Violet
| Carbon fuschsin
53
Crystal violet
Gram stain
Stains ribonuclear proteins inside cell
54
Carbon fuchsia
Acid fast stain
Stains myucolic acid of acid fast bacteria
55
Counter Stains
Safranin
| Methylene blue
56
Safranin
Gram stain
57
Methylene blue
Acid fast stain
58
Gram Stain
Gram positive = purple
Gram negative=pink
59
Acid fast Stain
Acid fast bacteria=red
Non acid fast bacteria= blue
60
Differential Media
Distinguish between closely related species of bacteria based on characteristics on media.
Color change or colony morphology
61
Selective Media
Used to select (isolate) specific groups of bacteria
-Media might contain chemical substances that inhibit the growth of one type of bacteria while permitting growth of another
62
Blood agar is an example of a _______type of media that is used to differentiate between closely related organisms based on growth characteristics
Differential media
63
Culture characteristics
Nutritional requirements pigment production etc
64
Biochemical tests
Ability to attack various substrates or produce metabolic by products
65
Toxin Prodcution and pathogenicity
Only conducted in specialized labs
66
Antigenic Structure
Serology-ability to interact with antibodies
67
Genomic Structure
DNA sequences relatedness as determined by homology or direct sequence comparison
68
Precipitation reactions
When antibody and antigen interact they form a precipitate
69
Hemagglutination
Cross linking of red blood cells
70
Hemagglutination
Some viruses bind to red blood cells causing cross linking
| -can be neutralized by antibodies from patients blood against suspected virus
71
Mononucleosis test
Uses horse or sheep red blood cells which cross react to antibodies against EBV resulting in agglutination of red blood cells
72
DNA Hybridization and probes
Target DNA is bound to a membrane and complementary DNA probe attached to a color producing enzyme is reacted with membrane. Signal is produced only if DNA finds its target
73
Polymerase Chain Reaction
DNA specific primers are used to amplify a target DNA molecule. A product signifies target is present in sample
74
Cocci
Spheres
75
Bacilli
Rods
| Straight or bent
76
Spirilla
Spirals
77
All bacteria have
DNA
Cytoskeleton
Plasma membrane
Cell wall
Bacteria DO NOT have organelles
78
Nucleiod
Region in cytoplasm where the genomic DNA is located.
Most bacteria have a single circular supercooled double stranded DNA chromosomes
Attached to cell membrane and central structures of the cell
79
Cytoplasm
Densely packed with ribosomes (70S)
Cytoskeleton-provides shape to cell
Inclusion bodies-granules that contain reserve materials
80
Cell Wall and its function
Rigid structure that surround the plasma membrane
Provides physical protection, lysis, barrier against toxic agents, determines cell shape
81
Gram Positive Bacteria
Many Layers of peptidoglycan
Teichoic Acid
Specific cell wall components
82
Teichoic Acid
is a polymer of glycerol phosphate or ribitol phosphate and various sugars, amino acids-function unknown
83
Lipoteichoic acid
Variation of teichoic acid that anchors cell wall to membrane through glycolipids
84
Peptidoglycan (murein) Structure
Peptidoglycan consists of a linear glycan chain (backbone) of two alternating sugars, N-acetyleneglucosamine and N-actelymuramic acid. A peptide side chain and a pentylglycine interbred gets form crosslinking between the glycan chains
85
Gram - bacteria peptidogluycan structure
Has a diaminopimelic acid instead of lysine
86
Lysozyme
Present in tears, saliva, and mucus (innate immune system)
| -Cleaves beta 1-4 glycosidic bonds between NAG and NAM polysaccharides of peptidoglcuan
87
Penicillin
Antibiotic affective against Gram positive bacteria
Blocks cell wall synthesis by inihibiting cross links
88
Gram Negative Cell Wall
Two membranes and thing single layer of peptidoglycan in between
Impermeable outer membrane
Periplasmic space
89
Impermeable outer membrane (gram - cell wall)
Porins that allow diffusion of hydrophilic solute molecules and excludes harmful molecules from the environment
90
Periplasmic space (gram - cell wall)
Contains a gel like matrix proteins important for transport chemotactic and hydrolyctic roles
91
Lipopolysaccharide
Endotoxin protection against phagocytosis
92
Mycoplasma
NO cell-exception
Smallest known bacterial species
Membrane contain a sterile like molecule
Usually inhabit osmotically protected environments
Parasitism hsot cells-walking pneumonia
93
This portion of LPS makes up the toxin
Lipid A
94
TA is unique to which structures
Gram positive cells
95
Peptidogluycan contains
A glycan backbone
Glycine interbrdige
A tetrapeptide side chain
96
LPS Components
O antigen polysaccharide side chain
Core polysaccharide
Lipid A-toxin
97
Capsule
A thick hydrophilic gel that surrounds the bacterial cell. Usually polysaccharides. Some are polypeptides if discrete layer=capsule
If amorphous=slime layer
98
Purpose of capsule
Protects bacteria from immune system
Nutrient source-can be digested by enzymes
Presence or absence is dependent on growth conditions
99
Flagella
Found in gram + and -
Large and rotating helical protein
100
Fimbriae
Small hair like projection function in attachment
| + and -
101
Pili
Longer and thicker than fimbriae function in attachment and or DNA transfer.
Sex pili-transfer DNA between gram - bacteria
Composed of Pailin protein
102
Spores
Resistant to heat can germinate after centuries
103
Difference between prokaryotes (bacteria) and eukaryotes
Speed- much faster metabolism
Versatility-bacteria use a greater variety of compounds
Simplicity-no organelles
Uniqueness-some biosuntheitc process are unique to bacteria
104
Catabolism
Breakdown of carbon source into atp
105
Anabolism
Uses energy to synthesize and assemble subunits of macromolecules
106
Embedded Meyerhof glycolysis pathway
ATP, metabolic intermediate and pyruvate—> fermented or TCA cycle
107
Penrose phosphate Pathway
Generates NADPH and Penrose’s and ribose 5 phosphate
108
Kern’s Cycle
Generates ATP from oxidative phosphorylation
109
Facilitated diffusion
Based on concentration gradient using carrier protein
110
Active Transport
Soluble binding proteins binds the substrate
| Transporte complex cleaves ATP providing energy for transport
111
Fermentation
Transfer of electrons and protons via NAD+ directly to an organic acceptor to make characteristic end products
Substrate-level phosphorylation
112
Respiration
Substrate oxidation coupled to transport of electrons through a chain of carriers in the membrane to an acceptor molecule. More efficient than fermentation
Oxidative phosphorylation
113
H2o2
Hydrogen peroxide
When electrons and protons are transferred to O2 as final acceptor
Catalase or peroxidase
114
o2
Superoxide anion
Produced as intermediate when O2 is reduced
Superoxide dismutase
115
Organisms that lack catalase and superoxide disumates are_____
Strict anaerobes
116
Obligate Aerobes
Require O2 to grow
Respiration only
117
Obligate anaerobes
Can not grown when O2 is present
Fermentation only
118
Faculative Aerobes
Contains genes for fermentation and or respiration can grow with or without O2
119
Aerotoleratn anaerobes
Anaerobic metabolism-fermentation but can tolerate oxygen
120
Acidophiles
Optimal growth at low pH
121
Alkaliphiles
Optimal growth above pH 7
122
Neutrophils
Optimal growth at neutral pH
123
Halophile
Require high concentration of salt for growth
124
Osmophile
Capable of growth in high sugar concentrations
125
thermophile
Organism that can grown between 45 and 122 c
126
Doubling time
Time it takes a single bacteria to divide in tow
127
Phase of Growth
Lag phase
Exponential phase
Stationary phase
128
Chromosomal Replication
Initiation
Elongation
Termination
Bidirectional
Semi conservative
129
Rate of DNA replication is determined by
Rate of initiation
130
Base Subsitution
When a nucleotide is changed
131
Insertion
When a nucleotide is inserted
Frame shift
132
Deletion
When nucleotide is deleted
Frame shift
133
Nonsense
When a nucleotide change results in a stop codon
Truncated protein
134
Missense
When a nucleotide change results in a amino acid change
135
Duplication
When DNA sequence is abnormally copied
136
Double stranded break model of homo recombination
Donor DNA must have large region of identical nucleotide sequence to host chromosome
Recipient cell must have recA gene which controls the entire process
137
Natural transformation
Ability to take DNA from the environment
138
Conjugation
Transfer of plasmid DNA through sex pili
139
Transduction
Bacteria phage accidentally inject bacterial DNA into host bacterial cell
140
Transposable elements
DNA that can insert or excise itse self from the chromosomes or plasmid
141
Bacterial Transformation
Once in the cell DNA either:
gets degraded by nuclease used for raw material
Integrated into he chromosome via recombination pathway
142
Natural transformation mediated by______
Quorum sensing-peptide pheromones produced by other bacteria are sensed by bacteria and tun on genes for competence
Ability to take DNA from the environment
143
Conjugation
Transfer of DNA usually by sex pili
plasmid DNA gets degraded and recombined with chromosome
144
Transposable ELemnts
DNA that insert or excise itself
If is elemnts insertt into the coding sequence of a gene they cause a mutattion
Larger transposing carry genes for antibiotic resistance or virulence genes
145
Bacterial genetic regulation
Making mRNA and protein is energetically expensive
-bacteria must tightly control expression of genes so that only the proteins needed for a particular condition are expressed
146
Bacteria can sense their environment through quorum sensing
Control when certain proteins are made
147
Promoter Elements
RNA polymerase binds to promoter located upstream of gene start codon
148
Virulence Factors
Genes directly related to ability of bacteria to cause disease-knockout of these genes reduces or eliminates virulence
149
Some genes are
Essential others are dispensable
150
Mammalian Immune response
Innate or adaptive
151
Innate
No specific
Rapid inflammatory response
Very broad
152
Adaptive Immune Response
Targeted to a specific antigen
Delayed response
Memory
153
After birth, hematopoietic occurs in the bone marrow
```
Platelets
RBC
WBC
-myeloid
-lymphoid
```
154
Myeloid Lineage: Granulocytes
Neutrophils
Basophils
Eosinophils
155
Neutrophils
Most abundant leukocyte in circulation
Also called polymorphonuclear leukocyte
156
Basophils
Involved inflammatory and allergic responses
157
Eosinophils
Involved in combating parasitic infections and allergic response
158
Myeloid Lineage: Phagocytes
Monocytes
Macrophages
Conventional Dendritic Cells
159
Monocytes
Phagocytosis
| Circulate in the blood then enter tissue to differentiate into macrophage or dendritic cell
160
Macrophages
Phagocytosis cells reside in all tissues
Antigen presenting cell
161
Conventional Dendritic Cells
Similar function to a macrophage
Can activate naive T cells
162
Mast Cells
Contain preformed granules but not a granulocyte
Involved in defense against parasitic worms and ALLERGIC response
163
Lymphoid Lineage
T Lymphocytes
B lymphocytes
NK cells
164
T Lymphoytes
Cytotoxic (CD8)
Helper (CD4)
Suppressor regulatory
165
B Lymphocytes
Differentiate into plasma cells Antibody production
166
Natural Killer Cells
Involved in innate Immune Response (NOT antigen specific)
167
Antigen
Ag molecule capable of inducing an immune response
168
Antibody
An protective protein made by B cells that RECOGNIZES 1 SPECIFIC Ag
169
Cell Communication
Secretion of Signaling molecules
- Cytokines
- Chemokines
Activation of receptors
- Internal
- External
170
Cytokines
Group of secreted proteins that are involved in regulating the innate and adaptive immune responses
Activation/proliferation
Inflammation
Cell migration and movement
Immunosuppression
171
Lymphoid Tissue: Follicle
Organized clusters
172
Lymphoid Tissue: Patch
Many follicles grouped together
Peters patches
173
Lymphoid Tissue: organ
Groups of follicles that are encapsulated
174
Primary Lymphoid Tissue
```
Bone marrow (hematop.)
Thymus (T cell differentiation and proliferation)
```
175
Secondary Lymphoid Tissues
Lymphoid Nodes
Spleen
MALT (NALT, BALT, GALT)
Skin associated Lymphoid Tissue (SALT)
176
Immune Cell movement
Follow chemokines
Tethering then start rolling until activation. This slows them downs hits the brakes. Then they transmigrate through the cells.
177
Can Lymphocytes recirculate
Yup
178
Importance of Innate Immune Response
Helps maintain physical and chemical barriers against microbial entry
Initial response to pathogen
Removal of damaged cells
Initiates tissue repair and wound healing
Stimulates adaptive immune response
179
Innate Immunity
NONSPECIFIC
Response can be triggered by infectious or non infection material
Innate response helps coordinate the adaptive immune response and in turn the adaptive immune response helps to boost the innate response
180
Innate Mechanisms
Inducible
Noninducible
181
Non-Inducible Innate Mechanisms
Physical
- skin
- mucus
- commensalism bacteria
```
Chemical
-lysozyme
-antimicrobial peptides
—defensins
—cathelicidin
```
182
Inducible Innate Mechanisms
```
Innate Immune Cells
Neutrophils
Macrophages
Dendritic cells
NK cells
Mast cells
```
Neutralizing antibodies
Secretory IgA
183
How do we activate our innate immune cells
NOT specific
They can recognize non-self cells and danger signals through the recognition of certain patterns
184
PAMPs: Bacterial
Pathogen associated molecular patterns
Bacterial-Lipopolysaccharide, peptidoglycan CpG flagellum
185
PAMPs: Viral
Double stranded RNA, Single stranded RNA
186
PAMPs: Fungal
Chitin Zymosan
187
Pattern Recognition Molecules
PAMPs
DAMPS (damage )
Pattern recognition Receptors (PRRs)
188
DAMPs
Complement productions-C3b C4b
Reactive oxygen intermediates- H2O2, OH, O2
Stress induced molecules-heat shock proteins, chaperone proteins, lactose rein, hyaluronic acid fragments
Metabolic products-potassium, ATP, uric acid, cholesterol saturated fatty acids
Nucleus acids-mRNA, ssRNA, chromatin components
Exogenous substances-Alum, Silica, asbestos
189
PRRs
Can be cell associated or unassociated
```
Toll like
NOD
RIG
C type
Scavenger
Collections
```
190
Toll Like Receptors
Membrane Bound Receptors
TLR1:TLR2
TLR2: TLR6
191
TLR2
Bacterial Peptidoglucan
192
TLR4
LPS
193
TLR5
Bacterial Flagellin
194
TLR1
Bacterial lipopeptides
195
TLR6
Bacterial lipopeptides
196
TLR9
CpG DNA
197
TLR3
dsRNA
198
TLR7
SsRNA
199
TLR8
ssRNA
200
Toll like receptors are highly expressed in
Dendritic cells
Monocytes/macrophages
Neutrophils
201
Toll Like Receptors
Activation leads to:
```
DC maturation
Stimulation of antigen presentation
Phagocytosis
Cellular activation
Productions of proinflammatory cytokines/chemokines
```
202
NOD-like Receptors
Free cytoplasmic receptors
Can recognize PAMPs and DAMPs
Some NLRs can form large complexes called inflammasomes
- leads to cascade 1 activation
- needed to fully activate IL-1 and IL-18
NLR activation can also lead to apoptosis
203
Toll-like receptors and NOD Like Receptors often
Work together
204
Retinoids Acid inducible Gene 1: RIG receptors
Cytoplasmic receptors
Recognize Viral RNA
Activation leads to the production of antiviral proteins
-interferon alpha and beta
205
C-Type Lectin Receptors
Lectin:proteins that bind to carbs
CLRs recognize carbs based DAMPs and PAMPs
Group 1-Mannose
Group 2- Asialgycoprotein
206
Scavenger Receptros
Bind to lipids
| -Can be from host or foreign
207
Collectins
Collagen domain fused to a Lectin domain
Found in blood
Upon binding their ligand (carbs) they can:
Activate complement
Phagocytosis
Agglutination
208
Complement Activation
Serum based mechanism to destroy pathogens
NO cells involved (30proteins)
```
Outcomes:
Pathogen destruction
Pathogen ospsonization
Clearance of immune complexes
Creation of peptides to help the inflammatory response
```
209
3 ways to activate complement
Classical pathway
Lectin Pathway
Alternate pathway (C3 hydrolysis)
All activate C3b
Results in lysis of pathogen
210
Which of the 3 pathways is very delayed
Classical pathway
211
Steps of complement activation
```
C3a: inflammation
—->
C3b: opsoniaztion and phagocytosis
—->
C5a: INflammation
```
—> lysis of microbe
212
Other Roles of C3b
Solubilization of Immune complexes
Virus neutralization
213
Late Stage Complement Activation: MAC complex formation
C5b binds to C6 and C7
| —> binds to membrane—>C8 binds to complex—>c9 bind and polymerizes—> form a pore
214
Macropinocytosis
Engulfment of fluid and macromolecules
215
Clathrin mediated endocytosis
Similarly to macropinocytosis but is Receptor mediated
216
Phagocytosis
Ingestion of large Extracellular particles, receptor mediated
217
Which 2 cells can phagocytosis a pathogen
Neutrophils and macrophages
218
Commensalism
Coexist neutral relationship
219
Opportunistic pathogens
Take advantage of breaks in host defense
220
Primary pathogens
Cause disease on their own
221
Pathogen
A bacterial species able to cause disease when present with favorable circumstances
222
Pathogenicity
Ability of any bacterial species to cause disease in a susceptible human host
223
Virulence
Presumes pathogenicity but allows expression of degrees from to extremely high
224
Primary pathogens must
Breach human cellular and an atomic barriers
Avoid host defenses
Transmission (ability to replicate )
225
Modes of pathogen transmission
```
Airborne
Food
Vector
Water
Blood
```
226
Inducible innate immunity
```
PAMPs
DAMPs
AMPs
IgA
Complement
Phagocytes
```
227
Non-inducible innate immunity
```
Lysozyme
Cilia
Stomach acid
Mucus
Intact skin
Commensalism bacteria
Flushing of urinary tract
Sequestrion of iron
```
228
Three stages to establish an infection
Adherence
Colonization
Damage
229
Entry: pathogen breach host innate defense
Many pathogens have unique mechanisms that allow them to get past innate defenses
- attachment to unique host molecules
- IgA protease
- Inherent restraint to lysozyme
- Siderophores
230
Entry adherence
Some bacteria can attach to host cells through specific pili or receptors
Many have multiple attachment mechanisms
231
Beating Host Innate Defenses
Some pathogens have enzymes that degrade immunoglobulin
sIgA protease
232
SIgA
Secreted into mucus prevents pathogens from adhering to mucosal surfaces
233
Beating Host Defense:Lysozyme
Outer membrane of gram - bacteria prevents penetration of lysozyme
234
Beating Host Defense: Siderophores
Bacteria need iron to grown ECF contains very low levels.
Pathogens produce siderophores which compete with human proteins for available iron
235
Phagocytosis avoidance
Invade and survive inside host cells
Avoid contact with phagocytes
Inhibit phagocytic engulfment
236
Pathogens come in 3 varieties
Extracellular,
facultative intracellular bacteria,
obligate intracellular bacteria
237
Extracellular pathogen
Not able to invade host cells
238
Facultative intracellular bacteria
Can invade host cells but can also serve in Extracellular environment
239
Obligate intracellular bacteria
Require host cells for survival
240
Invasins
Any protein produced by bacteria that allows the bacteria to invade no phagoycitc host cells or host tissues
- effector proteins
- secreted enzymes
- proteins that bind integrins
241
Effector proteins
Injected by a type III secretion systems allow invasion
Promote invasion of host cell or suppress host cell defenses
242
Secreted enzymes
Disrupt tight junction between cells allow invasion
243
Proteins that bind integrins
On host cell and facilite uptake and invasion
244
Invasions: Endocytosis
Endosome usually fuse with lysosomes creating an endolysome
Invasive pathogens must disrupt normal cell vehicle trafficking
Or
Be able toe scape the endosome into the cytoplasm
- Modify endosome
- Escape endosome
- Block endosome fusion
245
Avoid contact with phagocytes
Invade locations not surveillance by phs
Avoid inflammatory response
Inhibit phs chemotaxis
Something pathogens bind host molecules to hide antigenic surface no-opsonization by antibodies minimizes phs
246
Inhibit Phagocytosis
Some bacteria can avoid engulfment by phs through specialized surface adaptations
247
Antigenic variation
Varying surface antigens prevents PAMPs from being recognized
248
Induction of apoptosis of host cells
Some pathogens can activate apoptosic pathways in phs killing them
Prevents alarm bells and decreases defenders
249
Exotoxins
Bacterial secreted proteins-local and systemic if in blood
Have host cell specifity
Can be inhibitory stimulators or fatal
B subunit binds host cell surface receptor
A subunit gets transported by direct fusion or endocytosis into host cell
250
Endotoxin
Lipid A portion of LPS of gram - bacteria stimulates cytokines release
251
Hydrolytic enzymes
Facilitate tissue invasion
252
Superantigen
Exotoxins stimulate massive cytokines secretion
253
Inflammation
Prolonged immune response to bacteria can damage host tissues
254
Membrane active Exotoxins
Creates pores in host cell membrane
Causes loss of cell integrity and leakage through pore (DAMPs)
255
Biofilm
Multicellular community of bacteria attached to a surface encased in a self produced Extracellular polymer substance
256
Quorum Sensing
Form of bacterial communication-allows bacteria to coordinate and regulate gene expression in response to size of population or environmental cues.
257
Autoinducer Molecule
Secreted by all members of a species-binds to a transcriptional regulator and signals transcription of target genes when the autoinducer molecule reaches a threshold
258
Quorum sensing can regulate
```
Can regulate expression of
Toxins
DNA uptake
Adherence factors
Secretion systems
Biofilm formation
```
259
Oral cavity is dominated by
Streptococci
S. Minis is found in every location in mouth
Sanguis is and gordonni were found on tooth surface
260
Major species in plaque
S sanguinis
S gordonii
S Oralia
(Mitis major group)
(Mutans minor)
261
Non Specific Plaque Hypothesis
Dental caries results from a perturbation in bacterial populations due to a disruption in the environment rather than a specific bacteria or infectious agent
262
Treatment of Dental Caries
Probiotics-commensalism bacteria associate with health
263
S. Oligofermentans
Metabolizes lactic acid
264
S. Austrtalis
Arginoluytic strains
| Produce NH3 which raise plaque pH
265
S. Gordonii
Degrades CSP from s mutans
266
Periodontitis
A biofilm induced chronic inflammatory disease which affects the tooth supporting tissues or periodontist and also increases a patients risk of developing atherosclerosis diabetes and rheumatoid arthritis
267
Socransky’s Red Complex
Periodontal most common bacterial species
Porphyromanos gingivalis
Tannerella forsythia
Treponema denticola
268
P. gingivalis virulence factors
Capsule-antiphagocytic
Gingipains-degrades Extracellular matrix
Fimbriae-bind to host cell
LPS-Lipid A modification
269
S. Mutans
Can contribute to disease because it is acidogenic (lowers mouth pH) acid tolerant (growth at low pH) has glycosyltransferases and glycan binding proteins
270
Autophagy
is the process of cellular recycling. It is used for the clearance of intracellular pathogens such as viruses and some types of bacteria and parasites
271
Immunoglobulin Proteins
(Antibody)
Large glycoproteins that recogonize specific Ag
- Membrane bound
- Nonmembrane bound (Ab)
A B cell can only produce one kind of heavy chain and light chain
272
Papain
Can cleave heavy and light chains to view immunoglobulin
273
Variable region vs Nonvariable region
Both heavy chain and light chain have variable region where Antigen binds
274
Immunoglobulins are flexible
Can move side to side and twist better chance of making contact
275
Hypervariable region
Amino acid sequence demonstrate extreme variability between different Ig molecules
- occurs in 3 areas of variable region
- 5-7 amino acids long
- Enormous antigenic diversity
276
Constant Region
Very little variation
There can be minor differences that can affect the
-size
-charge
-solubility
-and structure of an Ig molecule giving rise to different isotopes
277
Light Chain Isotypes
Kappa
Lambda
Help contribute to diversity but not function
278
Heavy Chain Isotypes
```
IgM-Mu
IgD-Delta
IgG-Gamma
IgE-Epsilon
IgA- Alpha
```
There can also be subclasses
279
Isotype Switching (class switching)
When a naive B cell first encounters Ag it will produce IgM
Genetic rearrangements of the constant heavy region can lead to class switching
280
Which is an example of light chain isotype
Kappa
281
Structural Isoforms
Membrane bound
-Found on B cell plasma. Also called B cell receptor. Little piece at bottom transmembrane
Secreted
-found in blood
Secretory
-Secretory portion found in tears or mucous don’t have transmembrane and
282
Polymeric Immunoglobulins
IgM -5 bind together
IgA- 2 bound together
Both are secreted form
283
J Chain
Keeps polymeric immunoglobulins together
284
B Cell Receptors Complex
Always associates with IgAlpha and IgBeta to produce response by creating signaling pathway
285
Introns
No coding
286
Exons
Coding
287
Immunoglobulin Genes: Variable Regions
Variable Region
Diversity Region
Joining Region
*The Light Chain does not have D segment
288
V(D)J recombination
Somatic recombination characterized by random rearrangement of VD and J segments of the variable region
Occurs in EVERY naive B cell
Permanent, allows diversity, does not involve Ig isotype has to do with antigen binding
289
Antigenic Determinant
Epitope
Antigens do not necessarily bind to the entire Ag binding site.
Tends to make most contacts with CDR3 of Ig H chain
-possible to undergo conformational changes to better bond
290
During V(D)J recombination the constant region removes introns which contributes to antibody diversity: True or False
False
Not the constant region the variable region
291
Affinity
The strenght of the non-covalent association between one antigen binding site and one antigenic epitope
292
Avidity
The overall strenght of the bond between multitalented Ab and multitvalent Ag
-more chances of binding
293
Cross Reactivity
Occurs when one epitope is shared by 2 Ag or when two epitope on separate Ag are similar in Structure
294
Which of the following would have the greatest avidity
IgM
295
B Cell Development occurs in 2 stages
Maturation
| Differentiation
296
Where does B cell Development occur
Occurs in bone marrow only
Or
Begins in bone marrow then finishes in secondary lymphoid organ
297
B cell maturation
Begins in the bone marrow and ends in the periphery.
IN this stage B cells are naive
298
B cell differentiation
Begins once a B cell recognizes its specific Ag, ends with the generation of Ag specific plasma cells and memory cells
299
B cell maturation steps in bone marrow
Stem cell—early pro B—- late pro B——Pre B cell—-immature B cell
300
Pro-genitor B cells
First hematopoietic Cells that are recognizable as B cells
Immunoglobulin genes are still in their germ line configuration
301
Pre-cursor B cells
V(D)J recombination of both chains is complete
Late Pre B cells will produce membrane bound IgM plug IgAlpha/beta
302
Immature B cells
Development of Central Tolerance
Immature B cells get one last chance to rearrange the Ig loci in a process called receptor editing 2% survive selection
303
How could you distinguish between a pro B cell and pre B Cell
Pre B cells begin to express a membrane immunoglobulin
304
Transitional B Cells
Bone Marrow—>Blood—>Spleen
305
Transitional Type 1 B cells
Red purple then PALs
306
Transitional Type 2 B cells
Express both IgM and IgD
Follicular B Cells
Marginal Zone B cells
307
Mature B Cells
Express both IgM and IgD
Cannot undergo further V(D)J rearrangement
Considered naive
308
B Cell antigens
T dependent
-usually follicular B cells
T-Independent
-marginal zone B cells
309
B Cell activation
This process occurs in secondary lymphoid tissues
310
B Cell Activation Steps: Signal 1
Binding of multiple Ag to BCR. signal transmitted via IgAlpha/Beta
311
B Cell Activation Steps: Signal 2
Interaction with activated Ag specific T helper cell
312
B Cell Activation Steps: Signal 3
Cytokines stimulation by activated Ag specific T helper Cell
313
Plasma Cells: Long lived
Long Lived- Can live for months
Arise from germinal centers then migrate to the bone marrow, lymph node medulla or red pulp of spleen to secrete IgG, IgA or IgE
314
Plasma Cells: Short Lived
6-10 days
Secrete low affinity IgM
Can be made in response to Ti and Td antigen
315
What do Antibodies do
Aid with clearance and or destruction of antigen
1) Neutralizaiton
2) Classical Complement activation
3) Opsonization
4) Antibody dependent cell mediated cytotoxicity
316
Opsonization
Coating of an antigen with host protein to trigger phagocytosis
-IgG1, IgG3
317
MHC
Major histocompatability complex
The genes are polygenic extremely polymorphic and tend to be codominately expressed
Molecules are necessary to present Ag to T cells
318
MHC Class I
Present on all nucleated cells
Generally displayed endogenous peptides (self peptide)
Present peptides to CD8+ T cells-ALWAYS (killer T cells)
319
MHC Class II
Expressed on professional antigen presenting cells
Generally display exogenous peptides
Presents peptides to CD4+ T cells**
(2+2=4)
320
Antigen Presenting cells and what MHC class do they express
B cells
Dendritic cells
Macrophages
MHC class II
321
MHC II is associated with what
Peptides 13-18 amino acids in length
Exogenous peptides
322
Antigen Processing
The break down of macromolecules into smaller fragments in order to prepare them for presentation to a T cell
323
4 Major pathways of Ag processing
```
Exogenous-MHC class II
C4
```
```
Endogenous-cell recycling anything in cell MHC class I
C8
```
Cross Presentation-
Autophagic-internal pathogen detected cd4 activation
324
Dendritic Cells: Antigen presenting
High MHC 2
High capable of cross presentation
Activate Naive T cells
Activates effector memory T cells
325
Macrophages: APCs
High MHC 2
Somewhat cross presentation
No naive T
Yes memory T
326
B cells: APC
High MHC2
Yes/no cross presentation
No T naive
Yes memory T
327
Dendritic cell APC process
Activates Navie T cell: differentiation into effector T cells
328
Macrophage APC process
Effector t Cell activation
Cell mediated immunity
329
B Cell APC process
Effector T cell activation
B cell activation and antibody production
Humoral Immunity
330
Exogenous Pathway
1) uptake of extracellular proteins
2) Endosomal vesicles degrade antigen via lysozyme
3) MHC Class II molecules are assembled in the ER—Golgi—Endosome
Invariant chain is needed to keep alpha and beta chains stable
Lysine enzymes help break down invariant chain leaving CLIP molecule in peptide binding cleft. HLA-DM helps to remove CLIP so Ag can bind
MHC2 peptide travel via endosome to cell curface to present Ag to CD4 T cell
Macrophages B cells Dendrtiic cells use this
331
Endogenous Pathway
Internal proteins are degraded via proteasome then transported to ER via TAP
MHC I is synthesized and loaded in the ER
MHC I/Ag is transported to golgi then plasma membrane to present to CD 8 T cell
332
Cross presentation
APC ingests and processes virally infected cells. Viral proteins enter the cytoskeleton and is processed via endogenous pathway to activate a CD8 T cell via MHC 1
333
Class II must be degraded by
Lysozyme
334
Class I must be degraded by
Proteasome
335
Cross Reactivity
Reactions to something it was not suppose to react with
336
T Cell Receptor
Responsible for Ag recognition
337
AlphBeta T cells
Recognize MHC/Ag reside in secondary lymphoid Tissue
Must be able to recognize both
338
GammaDelta T cells
Recognize processed/unprocessed ligand
Intra epitheal tissues
Tons in gut
339
CD8
Cytotoxic cell
| MHC 1
340
CD4
Helper T cell
| MHC 2
341
What are the functions of CD4 and CD8
Signal transduction
342
T Cell Development
Begins in bone marrow
VDJ recombination of variable region of TCR leads to antigenic diversity
At one point cells express both CD4 and CD8
Undergo positive and negative selection
343
Thymocytes
After a leaving bone marrow they move to thymus to finish development
344
T Cell Steps
Pro T—> Pre T—->Double positive (starts expressing CD4/8)—> single positive —> Mature T cell (periphery)
345
Where does T cell positive and negative selection occur
Thymus
346
Who presents to T cells CD4
Dendrtiic cells
347
Naive T Cell Activation
Signal 1 Ag recognition
Signal 2 Costimulation
Signal 3 Cytokines
348
CD28
B7
349
Th1
Very good for intracellular pathogens
350
Th2
Extracellular pathogens and humeral immunity
351
Th17
Recruit neutrophils
Barrier function
Extracellular
352
The ____ portion of the TCR is made up of ______ and CD4/8 when the ________ recognizes self _____ bound to specific peptide then CD4/_____ will initiate the signaling cascade by ____the _____ ______ on the cd3 molecules
```
Signaling
CD3
TCR
MHC
CD8
Phosphorylation
ITAM
Segments
```
353
Systemic Immune Response
APC processes Ag
APC migrates to draining lymph node
APC activates Naive T cell
T cell activates and differentiates into effector
TCell moves to circulation to find its way back to infection site
APC at infection site activates effector T cell
354
Mucus contains
antimicrobial peptides enzymes
355
Type I mucosae main Ab
SLgA
356
Type II mucosae Ab is
IgG
357
Non-Inducible Defense of the GI tract
Acidity
Motility
Mucous layer and glycocalyx
Tight Junctions
358
NALT
Nasal submucoas glands
Tonsils
Epitheal cells (type II mucosa)
359
BALT
Bronchial Submucosal glands
Epithelial cells (Type I mucosa)
Follicles and diffuse lymphocytes
360
Macrophages in mucosa
Recognize microbes via pattern recognition receptors. This leads to activation of the macrophages and the ability to kill many microbes
—>also initiates inflammatory response
361
Adaptive Response in the Gut
Usually biased towards SIgA
| If the inflammatory response is needed a roubust Th1/17 Response will be activated
362
Mucosal SIgA
Constitutively in mucus
Ag Specific but can bind adhesion molecules
Highly cross reactive
Does not activate complement well
Very resistant to host and microbial proteases
363
Negative side to inflammation
Inflam ctyokines (TNF-alpha) can disrupt tight junctions between epithelial cells
364
Cutaneous Immunity
Skin-Associated Lymphoid Tissue
Epidermis
Dermis
DC, mast cells, macrophages, T cells, but little to no B cells
Immune response: activation of nearby memory T cells or induction of systemic immunity
Often Th1/17 response
365
Both ___ and ____ are critical to defend against extracellular bacteria
Innate and adaptive immune response
366
Adaptive Immunity
```
B Cells and antibody
T Cells (indirect help by helper CD4+ T cells)
```
367
Innate Immunity
Macrophages
| Neutrophils
368
Examples of Extracellular Bacteria
Staph aureus
E. Coil
Strep. Pyogenes
Pseudo aeruginosa
369
Phagocytosis of Extracellular Bacteria
Neutrophils and macrophages will remove particulate antigen by phagocytosis
370
High Affinity Receptors
Mannose Receptor
Mac-1-Integrins
Scavenger Receptor
371
Mannose Receptor
Binds mannose on microbial cell wall mediating cell microbe binding and initiating phagocytosis
372
Mac-1-Integrins
Binds microbes opsonized with complement proteins
373
Scavenger Receptor
Binds microbes in a non-mannose specific manner
374
Opsonization
“Prepare for eating”
Antibodies
Complement protein
Lectin
Coated by an Opsonin to target it for phagocytosis
- more efficient than mannose receptor mediated phagocytosis
- Enhances inflammation and antimicrobicidal activity
375
ROS
Reactive Oxygen Species
- activated macrophages and neutrophils will convert molecule oxygen into ROS
- oxygen ions
- free radical
- peroxide’s
376
RNI
Reactive nitrogen intermediates
Nitric oxide
377
Macrophages secrete
Proinflammatory cytokines (IL TNF) and chemokines (CCL) that induce inflammation and immune chemotaxis
378
Neutrophils Role in Immunity against Extracellular microbes
Migrate toward the site of inflammation within an hour of tissue injury in response to chemotactic factors
Phacotyose microbes
Can also kill microbe by oxygen indecent mechanisms
379
B cell role in immunity against extracellular microbes
B Cells produce antibody
- neutralizaiotn
- opsonization
- memory
B cells express MHC II and can present antigen to T cells
bacterial products can directly activate B cells in a T cell independent manner
380
T cell role. In immunity against extracellular microbes
CD4+ cells can make inflammatory cytokines
- These activate macrophages and promote bacterial killing
- Called Th1 cells when they make inflammatory cytoskeleton
CD4+ produce cytokines (IL4/5)
- These cytokines are B cell growth factors which activate B cells
- Called Th2 cells when they make these B cell promoting cytokines
381
Mechanisms of immune Evasion by Extracellular Bacteria
Antigenic variation
Inhibition of complement activation
Resistance to phagocytosis
Scavenging of ROS
382
Which T cell mediated response is necessary for intracellular pathogens
Th1 and CTL
383
Dendritic Cell role in Immunity a gainst intracellular microbes
Professional APCs that present Ag to T cells
Carry Ag from site of infection to lymph node where they will present Ag to naive T cells
Produce cytokines such as IL-12 that regulate the differentiation of CD4+ T cells
384
NK Cell Role in Immunity against intracellular microbes
Main function is to kill virus infected cells
Secrete cytokines required for macrophage and Th1 development
Activation of NK is regulated between signals from activating and inhibitory receptors
385
CD4 +T cell Role in immunity against intracellular microbes
Recognize antigen in a MHC II restricted manner
Called Helper T cells as their main role is to help coordinate the response to other immune cells
Differentiate into Th1 or Th2 subsets producing distinct cytokines with distinct biological activity
386
Th1
Intracellular
Th2 not needed
387
CD*+T cell intracellular microbes
Recognize a tinge in MHC I Restricted manner
Called cytokines cells as they secrete performing and granzymes which will directly lose/kill infected cells
IFN and TNF alpha
388
Cells involved in acute inflammation
Neutrophils
Monocytes/macrophages
Mast cells
389
Cells involved in chronic inflammation
Monocytes/macro
T Cells
Neutrophils
390
Inflammatory mediators
TNF-alpha
IL (interlukin) beta
IL-6
391
Histamine
Released by mast cells involved in vasodilation
392
Prostaglandins
INvolved in inflamation and fever
393
Migration/recruitment
The general process of leukocyte movement from blood to tissue
394
Selectins
Low affinity adhesion molecules involved in the early stages of leukocyte capture
395
Integrins
Adhesion molecules involved in later stages of leukocyte migration, cab be low or high affinity
396
Chemokines
Chemotactic cytokines named based on the location of the n termina cysteine residues
397
Tethering
Slows the leukocyte down within the post capillary venue
Selectin mediated
398
Selectins
Plasma membrane adhesion molecules
Low affinity
P selectin are stored in cytoplasmic granules so they can be expressed almost immediately
E Selectin can take upwards of 2 hours to be expressed
L selectin only one not on blood vessel
399
Integrin Activation
Chemokines produced by tissue immune cells or nearby epithelial cells act on the rolling leukocyte
Chemokines interaction wit its chock in receptor changes integrin affinity from low to high
400
Chemokines
Chemotactic cytokines
Can be produced by leukocytes epitheal cells fibroblasts
Unregulated by the recognition of microbes and proinflammatory cytokines
Diffrerent combination of receptors are expressed on different types of leukocytes
401
Integrins
Cell adhesion molecules
High affinity integrins often cluster together to make more contacts with endothelial cell
402
Adherence
High affinity integrins bind to their ligand on the endothelial cell
The leukocyte eventually makes so many contacts it stops and flattens out along the endothelium
403
Diapedisis
The leukocyte can now move from the blood into the tissue after cytoskeleton is rearranged and loosen tight junction
The leukocyte follows Chemokines to the final site of infection
404
Steps to cell Trafficking
Tethering
Integrin Activation
Adherence
Migration (diapedisis )
