Immunology - Basic Immunology Flashcards

(211 cards)

1
Q

what are the 3 barriers to infection?

A

skin/mucous membranes

innate immune system

adaptive immune system

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2
Q

what cells are part of the adaptive immune system?

A

B cells and T cells

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3
Q

what 2 things are unique to the adaptive immune system?

A

specific for the pathogen

memory

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4
Q

what is antigen presentation?

A

APC presents pieces of the pathogen to T cells

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5
Q

how does the immune system keep the adaptive response for the worst pathogens?

A

by using APC’s

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6
Q

what are the 5 subsets of cytokines?

A

chemokine - attracts immune cells (chemotaxis)

interleukins

TNF - can cause tumor death

transforming growth factor (TGF)

interferons - named for interfering with viral replication

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7
Q

what is the cluster of differentiation?

A

CD3, CD4, CD8 - Cell surface molecules used to identify cell types some used as receptor/cell binding

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8
Q

what are the 2 phagocytes of the innate immune system?

A

macrophages

neutrophils

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9
Q

what are the 5 cell types of the innate immune system?

A

phagocytes

complement

NK cells

Eosinophils

mast cells and basophils

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10
Q

how does the innate immune system recognize a molecule as foreign?

A

PAMPs - pathogen associated molecular patterns - present on microbes not on human cells

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11
Q

What is the main pattern recognition receptor used for recognizing a PAMP?

A

TLR - toll like receptors

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12
Q

what cells are TLRs found on?

A

macrophages

dendritic cells

mast cells

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13
Q

what happens when a TLR recognizes a PAMP?

A

the cell the TLR is on secretes cytokines to trigger an inflammatory response

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14
Q

What are 2 important PAMPs?

A

endotoxin (LPS)

peptidoglycan cell wall

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15
Q

what is endotoxin? where is it found?

A

aka LPS - lipopolysaccharide found in gram negative bacteria

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16
Q

what does LPS bind?

A

LPS binding protein - found in plasma - then the complex binds CD14 on macrophages

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17
Q

what TLR does LPS trigger?

A

TLR 4

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18
Q

when LPS binds TLR 4 what cytokines are released from the macrophage?

A

IL-1

IL-6

IL-8

TNF

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19
Q

What does CD14 bind?

A

LPS

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20
Q

what happens when peptidoglycan binds to NOD receptors?

A

cytokines released

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21
Q

what other patterns are recognized by the innate immune system?

A

mannose lipoteichoic acid on gram+ bacteria

dsRNA

unmethylated DNA

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22
Q

what is mannose?

A

a polysaccharide found on bacteria and yeast that binds MBL (mannose binding lectin) activating the lectin pathway of complement activation

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23
Q

_____ are the guardians of innate immunity

A

macrophages

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24
Q

where are macrophages produced?

A

bone marrow as monocytes

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25
what is the name for macrophages that are in different tissues? 1. liver 2. CNS 3. bone
1. kupffer cells 2. microglia 3. osteoclasts
26
when does a monocyte become a macrophage?
when it enters the tissue
27
what are the 3 key functions for macrophages in innate immunity?
phagocytosis cytokine production antigen presentation
28
what happens during phagocytosis?
macrophage engulfs pathogen into phagosome that fuses with a lysosome that contains deadly enzymes killing the bacteria/virus
29
what is inside lysosomes that makes them so deadly?
Reactive oxygen species (ROS) Reactive nitrogen intermediates enzymes - proteases, nucleases, lysozymes
30
what are reactive oxygen species?
superoxides produced by NADPH oxidase via respiratory burst leading to the production of hydrogen peroxide (H2O2) and superoxide (O2-)
31
what are reactive nitrogen intermediates?
when NO is reacted with superoxide forming peroxynitrite (ONOO-) which is toxic to bacteria
32
what do lysozymes do?
hydrolyze peptidoglycan in the cell wall of bacteria
33
what pathogens block phagocytosis?
tuberculosis \*\*\* Chediak-Higashi syndrome
34
how does TB block phagocytosis?
modifies phagosome and can no longer fuse with lysosome allowing for TB to proliferate inside the macrophages and evade antibodies in the plasma
35
how does Chediak-Higashi syndrome block phagocytosis?
immune deficiency syndrome causing failure of lysosomes to fuse with phagosomes causing recurrent bacterial infections
36
someone with chediak higashi syndrome is likely to have recurrent ______ infections
bacterial
37
what are the different "states" of macrophages?
resting - debris removal; circulate through the tissues picking up dead/dying tissues activated ("primed") - more effective phagocytes/killers
38
what are the 3 major activators of macrophages via TLRs?
LPS from gram neg. bacteria Peptidoglycan from bacterial cell wall Bacterial DNA (no methylation)
39
what other things besides TLRs can activate macrophages?
IFN-gamma from T cells & NK cells
40
How do T-cells activate macrophages?
when adaptive immune system and T cells become activated they can then in turn stimulate the macrophages to become more activated
41
what component of complement are macrophages attracted to?
C5a
42
what are the key surface receptors on macrophages? what do they bind to?
CD14 - LPS on gram neg Fc-R - Fc Ab C3b-R - C3b (complement) MHCII - CD4 on TCELLS B7 - CD28 on TCELLS CD40 - CD40L on TCELLS
43
What 3 R's are needed on a macrophage for it to interact with a T cell?
MHC II B7 CD40
44
What signals on TCELLS allow for them to interact with macrophages?
CD4 CD28 CD40L
45
what cytokines do macrophages release?
IL-1 and TNF-alpha \*\*\*\* most imp other: IL-6 IL-8 IL-12
46
IL-1 and TNF-alpha both increase synthesis of what?
endothelial adhesion molecules
47
what do endothelial adhesion molecules do?
allow neutrophils to enter inflamed tissue
48
what does IL-1 do?
endogenous pyrogen - causes fever acts on hypothalamus and raises the set point for temp. of the body
49
what does TNF-alpha do?
can cause vascular leak, septic shock cachectin reduces utilization of fatty acids kills tumors in animals can cause intravascular coagulation and DIC
50
what is a cachectin?
inhibits lipoprotein lipase in fat tissue causing decreased utilization of fatty acids
51
how does TNF kill tumors in animals?
causes coagulation and thrombosis in the blood vessels that supply the tumor remember: in patients with severe infections TNF alpha can cause DIC via intravascular coagulation
52
IL-6
fever stimulates acute phase protein production in liver (CRP)
53
IL-8
attracts neutrophils
54
IL-12
promotes Th1 development (cell-mediated response)
55
how do neutrophils relate to macrophages?
they are the back up cell to macrophages
56
neutrophils are derived from where?
bone marrow
57
neutrophil granules stain what color w/ Wright stain?
pink (eosinophils = red; basophils = blue)
58
neutrophils are drawn from the blood stream to sites of inflammation by what?
macrophages and cytokines
59
how long to neutrophils circulate to become activated before they die?
5 days
60
when neutrophils enter tissues what is their job?
phagocytosis - pink staining granules are lysosomes (bactericidal enzymes)
61
when macrophages need help who do they call?
neutrophils
62
What are the steps involved in the process by which neutrophils exit the blood stream to enter sites of inflammation?
Rolling Crawling (tight binding) Transmigration Migration to site of inflammation
63
What is "Rolling"
neutrophils that are circulating in the blood start to slow down when they get near sites of inflammation and roll along the blood vessel using their selectin ligands to bind the endothelium of the blood vessel
64
what carbohydrate is known to be in the selectin ligand on neutrophils?
Sialyl-Lewis X
65
What 2 processes is Sialyl-Lewis X involved in?
neutrophils bind to endothelium during rolling sperm cells bind to eggs for fertilization
66
What do the selectin ligands on neutrophils bind to?
E-selectin or P-selectin on endothelial cells causing them to roll
67
what is "crawling"
tight binding integrin on neutrophils binds ICAM on endothelial cells
68
what is "transmigration"
neutrophils bind PECAM-1 between endothelial cells and they go across the endothelium into tissues
69
what chemokines are use to attract neutrophils to the site of inflammation?
C5a IL-8
70
neutrophils are always circulating with ______ on their surface but usually nothing is there to bind to it but with an infection \_\_\_\_&\_\_\_\_\_\_ which stimulates the expression of _____ on the surface of endothelial cells; neutrophils bind to the selectin and begin to roll along the endothelium for crawling to occur the neutrophil has to express _______ which is triggered by ____ or \_\_\_\_and then _____ can bind _____ on endothelial cells
selectin ligand IL-1 & TNF-alpha selectin integrin LPS C5a integrin ICAM
71
what is always present on endothelial cells?
ICAM
72
what stimulates the expression of selectin on the surface of endothelial cells?
IL-1 and TNF-alpha secreted by macrophages
73
what stimulates the expression of integrin
LPS C5a
74
what are the 2 groups of neutrophil granules?
small granules (specific or secondary) larger (azurophilic or primary)
75
what are the small granules (specific/secondary) of neutrophils and what do they do?
enzymes - alkaline phosphatase, collagenase, lysozyme, lactoferrin fuse with phagosomes to kill pathogens can be released in extracellular space
76
patients with certain leukemias have a low alkaline phosphatase score, what does this mean?
that they have neutrophils in their blood stream but very low levels of alkaline phosphatase (seen in CML)
77
what are the larger granules (azurophilic/primary) of neutrophils? what do they do?
contains enzymes - acid phosphatase, myeloperoxidase they only fuse with phagosomes
78
what does acid phosphatase do?
degrades protein in an acidic environment
79
what does myeloperoxidase do?
important for respiratory burst that kills bacteria
80
what are band forms of neutrophils?
immature neutrophils that have a "band like" nucleus seen in plasma during bacterial infections when the BM is being driven to produce more neutrophils
81
if a lot of band forms are present what is it called?
left shift = infection & inflammation
82
Do neutrophils present Ag?
NO
83
what do neutrophils do?
phagocytosis ONLY
84
macrophage vs neutrophil
both can do phagocytosis but only macrophages are APCs too.
85
what are the chemotaxis for neutrophils?
IL-8 from macrophages C5a from complement
86
what antibody is a major opsonin for neutrophils?
IgG is the only antibody that binds to neutrophils
87
how does IgG "tag" neutrophils?
neutrophils have R for the Fc portion of the IgG Ab
88
what is an opsonin?
substances that bind to a foreign invader and increase the likelyhood of being picked up for phagocytosis (i.e. IgG on neutrophils)
89
complement is part of the _____ immune system
innate
90
complement proteins are produced where?
in the liver
91
what is the most abundant complement protein?
C3
92
what is special about C3?
it's essential for all the pathways of complement activation
93
what is the alternative complement pathway?
a frequent, spontaneous conversion of C3 to C3b via hydrolysis
94
what does C3b bind to?
amino and hydroxyl groups that are commonly seen on the surface of pathogens
95
what happens if C3b doesn't find anything to bind to?
it is rapidly destroyed
96
how does C3b become stabilized?
binds to an amino or hydroxyl group
97
what happens once C3b becomes stabilized?
it leads to formation of MAC
98
what complement proteins form the MAC?
C5b C6 C7 C8 C9
99
How does C3b lead to the formation of MAC?
C3 is hydrolyzed to C3a and C3b then C3b cleaves C5 into C5a and C5b
100
What does the MAC do?
forms pores in bacteria leading to cell death
101
what are the 2 key roles of NK cells in innate immunity?
kill human cells infected by viruses produce INF-gamma to activate macrophages
102
What is MHC I?
surface molecule of most human cells that presents antigen to CD8 Tcells and activates adaptive immunity against intracellular pathogens
103
why do NK cells destroy human cells without MHC I?
because some viruses can prevent MHC I from coming to the surface so if it is not there then the cell must be infected with a virus and will be destroyed
104
what are the 2 important surface molecules on NK cells?
CD16 CD56
105
CD16 binds ___ of ____ antibodies.
Fc IgG (this causes enhanced activity of NK cells)
106
How do NK cells perform ADCC?
through CD16 binding of the Fc portion of IgG that NK cells perform ADCC
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what is ADCC?
antibody dependent cell-mediated cytotoxicity - the process by which the innate and adaptive immune systems work together to kill a pathogen.
108
what is CD56?
aka NCAM - neural cell adhesion molecule \*\*\*\*used as a marker for NK cells expressed on surface of NK cells also found in brain and NMJ aids in binding to other cells
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what is a useful marker to identify NK cells?
CD56
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ADCC- in this process _____ which are produced by _____ of the ____ immune system coats a pathogen or cell and the pathogen is then destroyed by immune cells in a ______ process with cells from the _____ immune system like ____ & \_\_\_\_\_.
antibodies B cells adaptive non-phagocytic innate NK cells Eosinophils
111
What cells commonly use ADCC to kill a pathogen?
NK cells Eosinophils
112
What are the steps of ADCC?
Ab binds Ag on the surface of target cells CD16 on NK cells binds Fc of IgG antibody NK cell degranulates causing death of the cell
113
how do NK cells kill pathogens with ADCC?
IgG binds to pathogen-infected cells CD16 on NK binds Fc of IgG and NKC kills cell
114
how do eosinophils kill pathogens with ADCC?
IgE binds to pathogens - especially large parasites \*\* eosinophils bind Fc of IgE & toxic enzymes are released onto the parasite
115
What antibody class can bind to pathogens like a large parasite?
IgE
116
NK cells ... do/do not? 1. come from the same lineage as Tcells and Bcells 2. Have memory 3. require antigen presentation by MHC 4. mature in the thymus
1. Do - they are all lymphocytes 2. Do not 3. Do not 4. Do not
117
what is similar among eosinophils, mast cells, and basophils?
1. all contain granules with destructive enzymes 2. all can be activated/triggered by IgE antibodies 3. important for defense against parasites (helminths) 4. release of toxic substances kill parasite 5. main medical relevance is in allergic disease
118
Eosinophil granules appear what color with Wright stain? why are they this color?
red one of the contents within the granules is major basic protein which has a positive charge that picks up the negatively charged eosin dye in the Wright stain
119
what are the discharge contents (cytotoxic enzymes) that are released from eosinophils to kill parasites?
MBP = major basic protein ECP = eosinophilic cationic protein EPO = eosinophil peroxidase EDN = eosinophil-derived neurotoxin
120
what are eosinophils designed to do?
discharge contents onto parasites
121
What takes care of pathogens that are too big to be phagocytosed?
eosinophils w/ IgE
122
\_\_\_\_\_ are important in allergic disease
eosinophils
123
eosinophils are... activated by ____ antibodies stimulated by \_\_\_ from ___ cells
IgE (ADCC) IL-5 Th2
124
Patients with a helminth infection will have a high or low eosinophil count?
high
125
mast cell and basophil granules appear what color with Wright stain?
blue
126
where are basophils found?
bloodstream
127
where are mast cells found?
tissues
128
mast cells and basophils can both bind what?
Fc portion of IgE antibody
129
what happens when IgE molecules are cross-linked by a pathogen?
degranulation of the cell releasing histamine & enzymes (peroxidases & hydrolases)
130
what does histamine do to blood vessels
vasodilation
131
what are the components of innate immunity?
phagocytes - macrophages/neutrophils complement NKC eosinophils mast cells/basophils
132
what are the cellular components of adaptive immunity?
T cells B cells
133
what do CD4+ Tcells and CD8+ Tcells do?
CD4+ produces cytokines CD8+ destroys infected human cells
134
what is the function of B cells?
produce antibodies
135
how are the innate and adaptive immune systems inter-related?
cytokines from innate system activate cells in the adaptive immune system and vice versa and the innate immune system (macrophages) will present antigen to T cells to activate the adaptive immune system
136
Dendritic cells ... are called what if they are in the skin? do what?
Langerhans cells present antigen - pick up antigen from skin and mucosal membranes and migrate to the lymph nodes where they activate T cells
137
What cell type is the "go-between" the innate and adaptive immune systems?
dendritic cell - essentially calls to the adaptive system for help because the innate is being over powered while the innate system is trying to fight the pathogen the dendritic cell picks up some antigen and activates T-cells with it to come and help
138
what cells are granulocytes?
Mast cells eosinophils basophils neutrophils\*\*\* most predominant type; usually the one being tested for
139
What 2 lineages do agranulocytes come from?
lymphocytes - NKC/T cell/B cell monocytes - macrophages
140
Why is it weird that NK cells are lymphocytes?
bc they are part of the innate immune system and B/T cells are adaptive
141
multipotent hematopoietic stem cell differentiates into what 2 progenitor cells?
common myeloid progenitor common lymphoid progenitor
142
common myeloid progenitor can become what 3 things?
megakaryocyte --\> thrombocytes erythrocytes myeloblast --\> granulocytes
143
what does the common lymphoid progenitor cell differentiate into?
NK cell (large granular lymphocyte) small lymphocyte = B lymphocyte & T lymphocyte
144
what do B lymphocytes become?
plasma cell
145
what do plasma cells produce?
antibodies
146
what are the phases of the bacterial growth curve?
lag growth stationary death
147
what happens in the lag phase of the bacterial growth curve?
culture has been inoculated with a certain # of bacteria but there is no growth in the # of bacteria there can be growth in size - increasing the number of proteins, taking up some of the nutrients but they haven't yet started to divide
148
what is lymph? where does it end up?
interstitial fluid from tissues that drains into the lymphatic system, circulates through lymph nodes and eventually drains into subclavian veins
149
why is It important for lymph to circulate through the lymph nodes?
important for activating the immune system in response to pathogens that may be present in the tissue the lymph came from
150
what are primary lymphoid organs? where are they located?
sites of lymphocyte formation - B & T cells bone marrow thymus
151
what are secondary lymphoid organs? where can they be found?
site where B & T cells proliferate in response to infection lymph nodes spleen peyer's patches tonsils
152
what are the layers of a lymph node?
cortex (outermost) paracortex medulla
153
how do lymph nodes work to activate an immune response?
infection in a tissue --\> lymph drains from the site of infection towards the lymph node --\> dendritic cells in the lymph carry processed Ag on MHC I/II to present to the B & T cells when the lymph reaches the lymph node there is also free Ag in the lymph that gets picked up by APC's waiting in the lymph node many B & T cells waiting for matching Ag =\> this results in an adaptive immune response
154
what is the first layer of the lymph node that the lymph encounters? what happens there?
follicle of the cortex; B-cell activation
155
where does all of the immune system action in the cortex of a lymph node happen?
lymphoid follicle
156
what special cells are in the follicle of the cortex in the lymph node that help activate B cells?
follicular dendritic cells
157
how do follicular dendritic cells differ from tissue dendritic cells?
they are residents of the lymph node
158
how do follicular dendritic cells help to activate B cells?
they have surface R's that bind complement-Ag complexes this makes it easy for the B cells to cross link and become activated
159
What are follicular dendritic cells a reservoir for?
HIV early after infection large amounts of HIV particles seen in FDCs
160
what cell is an important part of the pathophysiology of HIV?
follicular dendritic cells
161
what are the 2 types of lymphoid follicles?
primary follicles - inactive, contain follicular dendritic cells and B cells secondary follicles - "germinal center"
162
what are secondary lymphoid follicles?
what you see during inflammation and infection aka germinal centers
163
what takes place in germinal centers?
B cell growth and differentiation B cell class-switching --\> secrete different types of Ab's nearby helper T cells can bind Ag and stimulate more growth from the B cells
164
what are the 2 key features of the paracortex layer of a lymph node?
contain T cells that can be activated by dendritic cells presenting Ag contain high endothelial venues
165
what are vessels of the paracortex that allow B and T cells into the node?
high endothelial venules
166
what are high endothelial venules? where can you find them?
venules that come after the capillaries in the lymph nodes, peyers patches, and tonsils they have spaces between cells of their endothelium so the B and T cells can squeeze through to exit the blood stream and enter the lymph nodes
167
how to B and T cells that come from the bone marrow and thymus exit the blood stream to localize into the lymph nodes throughout the body?
gaps between cells of high endothelial venules
168
what layer of lymph nodes becomes engorged during an immune response to give a person "swollen glands"?
paracortex
169
the paracortex layer of lymph nodes will be underdeveloped in patients with what?
T-cell deficiency disorders (i.e. - DiGeorge)
170
why is the paracortex underdeveloped in rare T-cell deficiency disorders?
there are no T cells to make up that portion of the lymph node
171
what part of the lymph node do T-cells live?
paracortex
172
the medulla of the lymph node has what 2 parts?
sinuses aka cavities chords - tissue between cavities
173
what is the function of medullary sinuses of a lymph node?
house macrophages that filter lymph and phagocytose any invaders
174
what is the function of medullary chords of a lymph node?
contain plasma cells secreting antibodies
175
What does the spleen do?
filters BLOOD ONLY all blood elements can enter - no high endothelial venules/selective entry
176
where in the body is the spleen located?
LUQ
177
what happens when blood gets to the spleen?
it enters from the splenic artery and then percolates through the white pulp and then through the red pulp then out through the splenic vein
178
what 3 structures are found in the white pulp of the spleen?
follicles PALS marginal zone
179
what is the most important structure in the red pulp of the spleen?
sinusoids
180
what happens in the white pulp of the spleen?
blood is exposed to B and T cells which can be activated if Ag is present macrophages for phagocytosis
181
what happens in the red pulp?
blood gets filtered through the sinusoids 30-40% of all platelets are stored
182
why are the sinusoids in the red pulp of the spleen important?
they get rid of old RBCs - why the red pulp is red
183
the marginal zone of the white pulp in the spleen is important for what?
house macrophages to remove debris house DCs to process Ag
184
follicles of the white pulp in the spleen contain what?
B cells - similar to follicles of the lymph nodes
185
Where are T-cells found in the spleen?
periarteriolar lymphocyte sheath PALS
186
periarteriolar lymphocyte sheath
PALS part of the white pulp in the spleen that houses T-cells for them to respond to Ag's present in the blood
187
red pulp is lined by vascular \_\_\_\_\_\_\_\_.
sinusoids
188
sinusoids of the spleen have an open \_\_\_\_\_\_\_.
endothelium; allows cells to pass in and out
189
sinusoids of the spleen exit into _____ \_\_\_\_\_\_.
splenic chords
190
splenic chords contain \_\_\_\_\_\_.
macrophages
191
what is unique about the macrophages in the sinusoids of the spleen?
their main job is to get rid of dead and dying RBCs; this is how hold RBC's exit the circulation
192
barrel hoop membrane
thin basement membrane that surrounds the cells of the sinusoids
193
splenic dysfunction puts you at risk for what kinds of infections?
bloodstream infections from encapsulated organisms
194
why is there an increased risk of infection from encapsulated organisms associated with splenic dysfunction?
loss of marginal zone macrophages results in decreased phagocytosis of encapsulated organisms loss of opsonization results in decreased: IgM and IgG against capsules IgG opsonization complement against encapsulated bacteria C3b opsonization
195
if encapsulated organisms can resist phagocytosis, how do we get rid of them?
macrophage phagocytosis & complement organism is tagged with IgG --\> activate complement which can directly kill the bacteria complement also creates C3b which attracts macrophages to phagocytose the bacteria
196
why is there less IgM and IgG as a result of splenic dysfunction?
loss of splenic B cells
197
what bugs cause infection in ppl with splenic dysfunction?
Strep. pneumo H. flu type B Neisseria meningitidis *less common:* S. pyogenes E. coli salmonella *RBC infections* - malaria, babesia
198
what is the most common pathogen to cause sepsis in a patient with splenic dysfunction
strep pneumo death in \>50% of patients
199
what are 2 common reasons for splenic dysfunction?
splenectomy functional asplenia
200
what are the reasons someone might have a splenectomy?
trauma ITP hereditary spherocytosis
201
Why would a splenectomy treat ITP?
ITP causes increased phagocytosis of platelets which happens in the spleen so if it is removed they won't be destroyed and the platelet count will rise
202
Why would a splenectomy treat hereditary spherocytosis?
less destruction of RBCs minimizes anemia
203
people with what kind of anemia will have functional asplenia?
sickle cell anemia they have so many abnormal red cells that their spleen is often damaged from trying to consume and remove all of them and as a result they are functionally asplenic and at risk for encapsulated bacterial infections
204
what are the characteristic peripheral blood smear findings in a patient that has had a splenectomy?
Howell-Jolly bodies Target cells
205
Howell-Jolly bodies
some RBCs leave the marrow with nuclear remnants still present inside the cell which are normally cleared by the spleen no spleen = nuclear remnants not cleared
206
what causes target cells
too much surface area/membrane or too little volume of the RBC
207
target cells are indicative of what 3 things?
splenic dysfunction liver disease (too much surface area of RBC) hemoglobin disorders (too little volume in RBC)
208
why do you get target cells post-splenectomy?
there is always a small amount that are usually cleared by the spleen so the number of target cells will increase
209
splenectomy is associated with what blood disorder?
thrombocytosis - failure of spleen to remove and store platelets
210
T cells can only recognize what?
Peptides presented by an APC
211
p