123 Flashcards
(158 cards)
1
Q
Phagocytosis
A
the process by which a cell uses its plasma membrane to engulf a large particle, creating a phagosome
2
Q
How large is the particle that’s being engulfed
A
Larger than 0.5 micrometer
3
Q
Phagocytosis is a type of
A
Endocytosis
4
Q
Phagocytosis greek terminology
A
Phagein: eat
Cyte: cell
Osis: process
Cell eating process
5
Q
Phagocytosis cells
A
Neutrophils Macrophages Monocytes Dendritic cells Osteoclasts Eosinophils
6
Q
Which of the phagocytes are professional phagocytes
A
Neutrophils, macrophages, monocytes
7
Q
Steps of phagocytosis are
A
- Recognition and adherence
- Engulfment
- Intracellular Killing
8
Q
PRR
A
Pattern recognition receptors which is a receptor that directly recognize the specific molecular structures on the surface of pathogens eg: toll like receptors found in plasma
9
Q
When lysosomes bond with phagosome it’s called
A
Phagolysosome
10
Q
What happens to the indigestible material in phagocytosis
A
It’s removed through exocytosis
11
Q
Killing the microbe in the phagocyte is accomplished by:
A
Hydrogen peroxide
Nitric oxide
12
Q
Neutrophils
A
a type of phagocyte, are normally found in the bloodstream
13
Q
Neutrophils other names
A
Heterophils
Neutrocytes
14
Q
The most abundant type of granulocytes are?
A
Neutrophils
40-70% of WBC
15
Q
Granulocytes are
A
A type of WBC
16
Q
Neutrophils phagocytose via what receptors
A
Fcγ receptors and complement receptors 1 and 3.
17
Q
3 methods of neutrophils for attacking micro organisms
A
Phagocytosis (ingestion)
Degranulation
Generation of NETs
18
Q
NETs
A
neutrophil extracellular traps
19
Q
Degranulation is
A
release of soluble anti-microbials
20
Q
What are the secretory vesicles in neutrophils
A
Plasma proteins and membrane receptors
21
Q
Degranulation
A
Release of proteins in a type of granule
22
Q
Types of granules for neutrophils
A
Azurophilic (primary) granules
Specific (secondary) granules
Gelatinase (tertiary) granules
23
Q
Azurophilic (primary) granules carry what proteins
A
Myeloperoxidase BPI Defensins Serine proteases neutrophil elactase Cathepsin G Proteinase 3 Auzorcidin
24
Q
BPI
A
Bactericidal/ permeability-increasing protein
25
Specific (secondary) granules carry what proteins
```
Alkaline phosphatase
Lysozyme
NADPH oxidase
Collagenase
Lactoferrin
Histamine
Cathelicidin
Gelatinase
Lipocalin
```
26
Gelatinase (tertiary) granules carry what proteins
Cathepsin
Gelatinase
Collagenase
Acyl transferase
27
What is the Neutrophil extracellular traps
web of fibers composed of chromatin and serine proteases that trap and kill extracellular microbes.
28
NETs may serve as
physical barrier that prevents further spread of pathogens
29
How does a NET function
provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes independent of phagocytic uptake.
30
Macrophages were first discovered
Metchnikoff, a Russian zoologist
31
macrophages digest
```
cellular debris,
foreign substances,
microbes,
cancer cells,
and anything else that does not have the type of proteins specific to healthy body cells on its surface
```
32
Location of:
Adipose tissue macrophages
Monocytes
Kupffer cells
Adipose tissue (fat)
Bone marrow/ blood
Liver
33
Sinus histiocytes
Alveolar macrophages (dust cells)
Tissue macrophages leading to giant cells
Lymph nodes and spleen
Pulmonary alveoli
Connective tissues
34
What is a histiocyte
Tissue macrophage (a less phagocytic form of a macrophage)
35
Location of
Microglia
Hofbauer cells
Intraglomerular mesangial cells
Central nervous system
Placenta
Kidney
36
Location of
Osteoclasts
Epithelioid cells
Red pulp macrophages
Bone
Granulomas
Red pulp of spleen
37
Location of
peritoneal macrophages
LysoMac
Peritoneal cavity
| Peyer’s patch
38
Macrophage subtypes
M1, M2
39
M1 macrophages are ....
Killer macrophages
40
M2 macrophages are .....
Repair macrophages
41
M1 macrophages are activated by
LPS
| IFN- Gamma
42
M1 macrophages secrete high levels of.... but low levels of ......
IL 12
| IL 10
43
Functions of M1 macrophages
Pro inflammatory, bactericidal, phagocytic functions
44
M2 macrophages function
constructive processes like wound healing and tissue repair
| turning off damaging immune system activation
45
How does:2 macrophages turn off damaging immune system activation
by producing anti-inflammatory cytokines like IL-10.
46
Opsonization
The process of covering bacteria with capsules (such as polysaccharide capsules) with opsonins (antibodies) before phagocytes ingest them.
47
What are the opsonin receptors and the binding opsonin to each one
Collagen domain receptor: MBL, C1q
Complement receptor: complement components.
Immunoglobulin Fc receptors (eg:FcyRs) : igG
48
What are the receptor types on phagocytes
PRR
C- type lectin receptor (CLRs)
Scavenger receptor
49
Macrophages role in adaptive immunity
Scavengers
Antigen presenting
Secretory cells (cytokine secretion)
50
Dendritic cells function
Antigen presenting
51
CLR examples and ligands that bind to each
Mannose receptor: mannans
Dectin: B glucans
DC-SIGN: mannans
52
Ligands that connects to PRR
Microbial ligands
53
Ligands that connects to scavenger receptors
```
SR-A: Lipopolysaccharide (LPS)
Lipoteichoic acid (LTA)
```
SR-B: LTA
diacylglycerides
B- glucans (fungi)
54
immune system functions
Protect us from infections (Viruses, Bacteria, Fungi, Parasitic protozoa, Worms)
Promote normal function of the body (tissue clean up, repair)
Removes abnormal cells including malignant one
55
How can immune system cause the disease
when it is not doing the right things (allergies, autoimmunity, transplant rejection, etc)
56
Components of innate immune system
Physical barriers
Defense mechanism
General immune response
57
Eg of physical barriers
Skin
Mucus membranes
Cilia
58
Eg of defense mechanisms of innate immune system
Secretion(saliva,tears,sweet)
Mucus
Bile
Gastric acid
59
Eg of general immune response
Inflammation
Complement
Non specific cellular responses
60
Define inflammation
The sum of the host’s defenses to infectious or noxious stimuli.
61
What is the purpose of inflammation?
to bring defense cells (immune cells) to the area of concern
| to inactivate or destroy any invaders pathogens to begin repair in that area.
62
Arthritis
inflammation of the joint
63
4 steps of local inflammatory response
1. Tissue damage causes release of vasoactive and chemotactic factors that trigger a local increase in blood flow and capillary permeability
2. permeable capillaries allow an influx of fluids
3. Phagocytes migrate to the site of inflammation
4. phagocytes and antibacterial exudate destroy bacteria
64
Chemotaxis
the movement of an organism or entity in response to a chemical stimulus.
65
Exudate
fluid that leaks out of blood vessels into nearby tissues.
66
What is the exudate in the local inflammatory system
Complement c reactive proteins
67
What does the innate immune system recognize
PAMPs
DAMPs
68
PAMPs are
(Pathogen-associated molecular pattern); molecular structures of microbial pathogen that required for survival.
69
DAMPs are
(Damage-associated molecular pattern); result of cell damage by infections.
70
Cellular receptors in the innate immune system that help recognize
PRR pattern recognition receptors
71
In the case of inflammation Mast cells produce.... which causes......
Histamine
| Vasodilation
72
Capillary widening causes..... which causes........
Increased blood flow
| Heat
73
Increase d capillary permeability causes....... which causes .........
Release of fluids
| Redness and tenderness
74
Attractions of WBC causes..... which causes......
Migration of wbc to the injury
| Tenderness and swelling
75
Systemic response causes....... which causes....
Fever and proliferation of WBC which causes pain
76
Diapedisis
movement or passage of blood cells, especially white blood cells, through intact capillary walls into surrounding body tissue.
77
..... causes capillaries to leak releasing............
Histamine
| Phagocytes and clotting factors
78
Why do platelets move out of the capillaries in inflammation
To seal the wounded area
79
Characteristics of acute inflammation in English, latin and their cause
```
Redness: rubor: hyperaemia
Warmth: calor: hyperaemea
Swelling: tumor: increased permeability
Pain: dolor: low ph
Loss of function: functio laesa: pain, swelling
```
80
First of all, the bacteria that enter into your body are going to be recognized by tissue- resident cells called
macrophages
81
These are the first defenders to “raise the alarm!”
Macrophages
82
release of cytokines will ...............blood vessels
Dialate
83
Histamine is released from
granules of cells
84
Histamine causes itching and pain by
stimulating nerve
| endings
85
..... are cells can be found as tissue residents, meaning they do not have to exit the blood in order to be a part of the immune response
Macrophages
86
Actions of cytokines in Local inflammation
(TNF, IL1): Activate leukocytes to release IL1, IL6, chemokines
(TNF, IL1):Attach to adhesion molecules in the endothelial cells to increase permeability and release chemokines and IL1, IL6
87
Systemic protective effects of cytokines
(TNF, IL1, IL6 )Stimulates the brain to create fever
(IL1, IL6 ) Stimulates the liver to go into acute phase proteins
(TNF, IL1, IL6 ) Stimulates the bone marrow to produce leukocytes
88
Systemic pathologic effects of cytokines
TNF:
Stimulates heart into low output
Causes increased permeability in blood vessels and thrombus
Builds insulin resistance in skeletal muscles
89
Thrombus
is a blood clot that forms in a vessel and remains there.
90
complement
a set of 50-plus serum proteins that cooperates with both the innate and the adaptive immune systems to eliminate pathogens, dying cells, and immune complexes from the body
91
Most complement components are synthesized
| in the...... by........
liver
| Hepatocytes
92
Some complement components are produced by:
blood monocytes,
tissue macrophages,
fibroblasts,
epithelial cells of the gastrointestinal and genitourinary tracts.
93
Complement components constitute approximately ......of the globulin protein fraction in plasma.
15%
94
Complement system is composed of
plasma proteins
95
Complement system operates in
plasma, tissues, or within cells
96
Complement proteins collaborate as a
cascade (waterfall)
97
Complement system is activated by
microbes & antibodies
98
Byproducts of complement activation stimulate
inflammatory reactions.
99
3 Pathways of Complement Activation:
The classical pathway
The alternative pathway
The lectin pathway
100
The classical pathway is activated by
certain isotypes of antibodies bound to antigens;
101
The alternative pathway is activated by
microbial cell surfaces in the absence of antibody
102
The lectin pathway is activated by
mannose-binding protein that binds to surface carbohydrates on microbes
103
What pathway is always at work
Alternative pathway
104
Which proteins make up the classical pathway
C1, C2, C3, C4, C5, C6, C7, C8, C9
105
How do proteins become activated
When they are cleaved
106
What is the protein C1 made of
C1q (X6)
C1r (X2)
C1s (X2)
107
C1q units bind to
The Fc unit of an antibody that’s attached to an antigen
108
C1r and C1s are called
Serine proteases
109
C1 is found in
Calcium
110
How is the Cq molecule activated
When antibodies attached to C1q attach to antigens, it twists the C1 revealing the C1s and C1r. C1r cleaves C1s which activates the C1 molecule.
111
What does an active C1 molecule do
It cleaves C4 into C4a and C4b
C4a floats away and C4b attaches to the antigen.
It cleaves C2 into C2a and C2b
C2a floats away and C2b attaches to the antigen along with C4b
112
C2b and C4b on the antigen form
C4b2b known as C3 convertase.
113
What does C3 convertase do
It cleaves C3 into C3b and C3a
114
C1 generates ...... C3 covertase
10
115
A single C3 convertase can cleave ...... C3 proteins per second
A thousand
116
C3 convertase stays active for... minutes
2
117
C3b is called
Opsonin
118
What does C3b do
It binds to the C3 covertase (C4b2b) and turns it into C4b2b3b which is called a C5 convertase.
119
What does C5 convertase do
It cleaves C5 into C5a and C5b
120
What does C5b do
It binds to C6, C7 and C8 which all penetrate with the antigens cell membrane joined by C9 proteins which form a channel through the membrane
121
What is the membrane attack complex and how does it work
C5, C6, C7 and C8 along with C9. It creates a hole in the bacterial cell membrane
122
MAC
Membrane attack complex
123
How is the lectin binding pathway different from the classical pathway
Instead of a C1 protein attaching to and antibody antigen complex, lectin binding pathway uses a protein called mannose lectin binding proteins which attaches to mannose, a sugar found on many bacterial surfaces, it is shaped like C1 and does the same job.
124
How does the alternative pathway work
Even when there isn’t C3 convertase, C3 still is cleaved, there are some C3b in the body, C3b attaches to pathogens, to which factor B (which is always in the blood) attaches. When factor B attaches to C3b, this allows it to be cleft by factor D which is always active. Factor b
b is cleft into Bb and Ba which floats away. Bb is still attached to C3b which creates C3 convertase and then it’s the same.
125
How is the alternative pathway regulated
C1 Inhibitor disassociate Bb from C3b and factor H (cofactor of factor i ) turns C3b into inactive C3b (iC3b) which just acts as an opsonin with no enzymic activity.
126
All pathway end with
MAC
127
What do C3a and C5a cells act like?
Chemotaxins
| Anaphylatoxins
128
What do anaphylatoxins do
Help mast cells and basophils degranulation to release pro inflammatory molecule like histamine and heparin
129
What do chemotaxins do
Attract neutrophils, eosinophils, monocytes and macrophages
130
Lack of C1, C2, C3 and C4 causes
Lupus like disease
Chronic renal disease
Recurring infection
131
Deficiency in C5, C6. C7, C8 causes
Repeated neisseria infection and high risk of gonorrehea
132
What antibodies help complement activation
IgM is more efficient than IgG
IgG1 and IgG3 are more efficient than other subtypes
IgG2 has some ability to activate complement but IgG4 doesn’t
133
Functions of complement
Opsonization and phagocytosis
Stimulation of inflammatory reactions
Complement-mediated cytolysis
134
Phagocytosis-enhancing components are called
opsonins
135
Examples of opsonins
C3b, C4b
136
Anaphylatoxins greek meaning
against protection.
137
What anaphylatoxins stimulate leukocyte recruitment
C5a, C4a , C3a (lesser extent)
138
How does the MAC look like under EM
The complex itself forms a ring-shaped multimer of complement proteins with a central hole through which cytoplasmic contents can escape.
139
MACs can also form on infected host cells, although the complement system must first overcome....
regulatory mechanisms designed to protect host cells from complement attack.
140
Lack of C1q, C2, and C4 causes
erythematosus
| systemic lupus
141
Lack of C3 causes
frequent serious pyogenic bacterial infections
142
Deficiencies in the terminal complement
| components cause
Increased meningococcal infections
143
Deficiency of C1 inhibitors
hereditary angioedema
144
Factor H deficiency
Glomerulonephritis caused by inadequate clearance of immune complexes and renal deposition of complement byproduct
145
Factor H or MCP mutation
Hemolytic-uremic syndrome
146
Factor B and Factor D deficiencies, X-linked recessive properdin deficiency causes
Increased susceptibility to meningococcal infections
147
Deficiency in DAF causes
Paroxysmal nocturnal hemoglobinuria
148
DAF
Deccay acceleration factor
149
How does C1 inhibitor work
It prevents C1r2s2 from becoming proteolytically active
150
C1 INH interacts with.... and its function....
C1r, C1s
| Serine protease inhibitor, binds to C1r, C1s and dissociates them from c1q
151
Factor I interacts with.... and its function....
C4b, C3b serine protease, cleaves C3b and C4b by using factor H, MCP, C4BP or CR1 as cofactors
152
Factor H interacts with.... and its function....
Binds C3b and displaces Bb cofactors for factor I mediated cleavage of C4b
153
MCP
Membrane cofactor protein
154
Protectin
CD59
155
Protectin interacts with.... and it’s function....
C7, C8
| Blocks C9 binding and prevents formation of MAC
156
DAF interacts with..... and it’s function.....
C4b2a, C3bBb
| Displaces c2a from C4b and Bb from C3b (dissociation of C3 conterverse)
157
MCP
Membrane cofactor protein
| CD46
158
MCP interacts with.... and it’s function.....
C4b
| Binds C4b and displaces C2 cofactor for factor I mediated cleavage of C4b
