Lymphoid structures Flashcards
(208 cards)
1
Q
A secondary lymphoid organ that has many afferents and one or more efferents; encapsulated, with trabeculae
A
lymph node
2
Q
Functions of the lymph node
A
- nonspecific filtration by macrophages
- storage of B and T cells
- immune response activation
3
Q
Site of B-cell localization and proliferation within the lymph node.
A
Follicle
4
Q
Primary follicles in the outer cortex of the lymph node are dense and what?
A
dormant
5
Q
Secondary follicles have pale germinal centers and are [active or inactive?]
A
active
6
Q
What consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses?
A
Medulla of lymph node
7
Q
medullary sinuses communicate with
A
efferent lymphatics
8
Q
medullary sinuses contain
A
reticular cells and macrophages
9
Q
Region of cortex between follicles and medulla in the lymph node that houses T cells.
A
Paracortex
10
Q
The paracortex contains high endothelial venues through which WHAT enter from blood
A
T and B cells.
11
Q
What part of the lymph node is not well developed in pts with what syndrome?
A
DiGeorge
12
Q
Paracortex enlarges in an extreme cellular immune response, such as?
A
viral infection
13
Q
Head and neck drain to what node?
A
Cervical
14
Q
Lungs drain to what node?
A
Hilar
15
Q
Trachea and esophagus drain to what node?
A
Mediastinal
16
Q
Upper limb, breast, skin above umbilicus drain to what node?
A
Axillary
17
Q
Liver, stomach, spleen, pancreas, and upper duodenum drain to what node?
A
Celiac
18
Q
Lower duodenum, jejunum, ileum, colon to splenic flexure drain to what node?
A
Superior mesenteric
19
Q
Colon from splenic flexure to upper rectum drain to what node?
A
Inferior mesenteric
20
Q
Lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), and prostate drain to what node?
A
Internal iliac
21
Q
Testes, ovaries, kidneys, uterus drain to what node?
A
Para-aortic
22
Q
Anal canal (below pectinate line), skin below umbilicus (except popliteal territory) drain to what node?
A
Superficial inguinal
23
Q
Dorsolateral foot and posterior calf drain to what node?
A
Popliteal
24
Q
The right lymphatic duct drains
A
right side of body above diaphragm
25
The thoracic duct drains
everything below the diaphragm and the left side of the body above the diaphragm
26
into what does the thoracic duct drain?
junction of left subclavian and internal jugual veins
27
Long, vascular channels in red pulp with fenestrated "barrel hoop" basement membrane. Macrophages found nearby.
Spleen
28
Where in the spleen are T cells found?
Periarterial lymphatic sheath within the white pulp
29
Where in the spleen are B cells found?
In follicles within the white pulp
30
What do you call the area between the red pulp and white pulp of the spleen
the marginal zone
31
What types of cells are in the marginal zone?
APCs and specialized B cells.
32
What happens in the marginal zone?
APCs resent blood-bordn antigens
33
Macrophages in the spleen remove what type of bacteria?
encapsulated
34
Mechanism by wh/ splenic dysfunction --> increased susceptibility to encapsulated organisms?
decreased IgA --> decreased complement activation --> decreased C3b opsonization
35
Name the seven encapsulated bacteria
```
Strep pneumo
HiB
N meningitidis
E coli
Salmonella spp
Klebsiella pneumo
Group B strep
```
36
Postsplenectomy on peripheral blood smear
Howell-Jowell bodies (nuclear remnants), target cells, thrombocytosis
37
Encapsulated organ that is the site of T cell differentiation and maturation
Thymus
38
Thymus embryological derivation
Epithelium of third pharyngeal pouches
39
Lymphocytes within the thymus have what origin?
Mesenchymal
40
Thymic cortex is dense with what type of cells?
Immature T cells
41
Thymic medulla is pale with what type of cells and structures?
T cells and Hassall corpuscles containing epithelial reticular cells.
42
Name 6 components of innate immunity
neutrophils, macrophages, monocytes, dendtritic cells, NK cells (lymphoid origin), complement
43
Name three components of adaptive immunity
T cells, B cells, circulating antibodies
44
Innate immunity resistance is germline encoded, so it
persists through generations, does not change within and organism's lifetime
45
Adaptive immunity resistance is achieved through
variation through V(D)J recombination during lymphocyte development; microbial resistance not heritable
46
Innate immunity response to pathogens (specificity and speed?)
nonspecific; occurs rapidly (minutes to hours)
47
Adaptive immunity response to pathogens (specificity and speed?)
highly specific, refined over time; develops over long periods; memory response is faster and more robust
48
Physical barriers that aid in innate immunity?
Epithelial tight junctions, mucus
49
4 secreted proteins of innate immunity
lysozyme, complement, CRP, defensins
50
1 secreted protein of adaptive immunity
immunoglobins
51
Key features in pathogen recognition in innate immunity
Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs).
52
Examples of PAMPs
- LPS (gram-negative bacteria)
- flagellin (bacteria)
- ssRNA (viruses)
53
key features in pathogen recognition in adaptive immunity
memory cells: activated B and T cells; subsequent exposure to a previously encountered antigen --> stronger, quicker immune response
54
MHC is encode by what genes?
HLA
55
MHC function
present antigen fragments to T cells and bind TCRs
56
Where is MHC I expressed?
all nucleated cells (NB: not on RBCs!)
57
Where is MHC II expressed?
Expressed only on APCs
58
MHC I function
present endogenously synthesized antigens (e.g. viral) to CD8+ cytotoxic T cells
59
MHCII function
present exogenously synthesized proteins (e.g., bacterial proteins, viral capside proteins) to T-helper cells
60
Antigen peptides loaded onto MHC I in
RER after delivery via TAP peptide transporter
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Antigen loaded following
release of invariant chain in an acidified endosome
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MHC I mode of transport to cell surface
B2 microglobulin
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MHC I loci
HLA-A, HLA-B, HLA-C
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MHC II loci
HLA-DR, HLA-DP, HLA-DQ
65
With what HLA subtype is hemochromatosis associated?
HLA-A2
66
HLA-B27 subtype is associated with four diseases
PAIR
- Psoriatic arthritis
- Ankylosing spondylitis
- arthritis of Inflammatory bowel disease
- Reactive arthritis
67
With what HLA subtype is celiac disease associated?
HLA-DQ2 or HLA-DQ8
68
HLA-DR2 subtype is associated with 4 diseases
- multiple sclerosis
- hay fever
- SLE
- Goodpasture syndrome
69
Diabetes mellitus type 1 is associated with what HLA?
DR3 and DR4
70
SLE is associated with what HLA?
DR2 and DR3
71
diseases associated with HLA-DR3
DMT1, SLE, Graves
72
diseases associated with HLA-DR4
Rheumatoid arthritis, DMT1
73
diseases associated with HLA-DR5
Pernicious anemia --> vitamin B12, Hashimoto thyroiditis
74
How do natural killer cells induce apoptosis of virally infected cells and tumor cells??
Use perforin or granzymes
75
what is the only lymphocyte member of the innate immune system?
NK cells
76
NK activity is enhanced by 4 things
IL-2, IL-12, IFN-beta, IFN-alpha
77
what induces NK cells to kill
exposure to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.
78
NK cells also kills via antibody-dependent cell-mediated cytotoxicity - how does that work?
CD16 binds Fc region of bound Ig, activating the NK cell.
79
Three B cell functions
1. Recognize antigen
2. Produce antibody
3. Maintain immunologic memory
80
How do B cells recognize antigen?
undergo somatic hypermutation to optimize antigen specificity
81
How do B cells produce antibody?
Differentiate into plasma cells to secrete specific immunoglobulins
82
How do B cells maintain immunological memory?
memory B cells persist and accelerate future response to antigen
83
CD4+ function
help B cells make antibody and produce cytokines to activate other cells of immune system
84
CD8+ function
kill virus-infected cells directly
85
What immune cells mediate type 4 HSR?
T cells!
86
What mediates acute and chronic cellular organ rejection?
T cells!
87
Where does positive selection of T cells occur?
Thymic cortex
88
What cells are CD4+ and CD8+?
Immature T cells in the cortex
89
What is positive selection?
T cells expressing TCRs capable of binding surface self MHC molecules survive.
90
Where does negative selection of T cells occur?
Thymic medulla
91
What is negative selection?
T cells expressing TCRs with high affinity for self antigens undergo apoptosis
92
What are the three types of APCs?
B cells,
macrophages,
dendritic cells
93
Describe the four steps of naive helper T cell activation
1. DC eats foreign body
2. DC presents foreign body on MHCII.
3. Costimulatory sig: B7 (DC) binds CD28 (Th)
4. Th produces cytokines
94
Describe the four steps of naive cytotoxic T cell activation
1. DC eats foreign body
2. DC presents foreign body on MHCI
3. Costimulatory sig: B7 (DC) binds CD28 (Tc)
4. Tc recognizes and kills virus-infected cell
95
Describe the steps of B cell activation and class switching
1. B cell endocytoses foreign body
2. B cells presents foreign body on MHCII, which is recognized by activated Th.
3. CD40 (B) binds CD40L (T)
4. Th secretes cytokines that determine Ig glass switching of B cell
5. B cell activates and undergoes class switching, affinity maturation, & antibody production.
96
What do Th1 cells secrete?
IFN-gamma
97
What do Th2 cells secrete?
IL4, IL5, IL6, IL10, IL13
98
What does Th1 secretion of IFN-gamma do?
Activates macrophages and cytotoxic T lymphocytes (CTLs)
99
What does Th2 activity do?
Recruits eos for parasite defense and promotes IgE production from B cells
100
What inhibits Th1?
IL4 and IL10 from Th2
101
What inhibits Th2?
IFN-gamma from Th1
102
What is the macrophage-lymphocyte interaction?
Macrophages release IL12, which stimulates T cells to differentiate into Th1 cells, which then release IFN-gamma to stimulate macrophages.
103
What is the function of CTLs?
Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis
104
How do CTLs induce apoptosis
Release cytotoxic granules containing preformed proteins
105
what are the three preformed proteins in CTL secreted cytotoxic granules?
perforin
granzyme B
granulysin
106
what does perforin do?
helps to deliver the content of granules into the target cells
107
What does granzyme B do?
a serine protease, activates apoptosis inside target cell
108
what does granulysin do?
antimicrobial, induces apoptosis
109
What cells help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions?
Regulatory T cells
110
Regulatory T cells can be identified by expression of what four cell surface markers
CD3, CD4, CD25 (alpha chain of IL-2 receptor), and transcription factor FOXP3
111
Activated regulatory T cells produce what two anti-inflammatory cytokines?
IL-10 and TGF-beta
112
What part of the antibody recognizes antigens?
variable part of light and heavy cahins
113
What part of IgM and IgG fixes complement?
Fc portion
114
The heavy chain contributes to what fractions of the antibody?
Fc and Fab
115
The light chain contributes to what fractions of the antibody?
Fab
116
What is Fab?
Antigen-binding fragment, determines idiotype; unique antigen binding pocket; only 1 antigenic specificity expressed by B cell
117
What is Fc (4Cs +D)?
```
Constant,
carboxy terminal,
complement binding
carbohydrate side chains
Determines isotype (IgM, IgD, etc)
```
118
what are the four things contributing to antibody diversity?
- random recombination of VJ (light chain) and V(D)J (heavy chain) genes
- random combination of heavy and light chains
- somatic hypermutation (following antigen stimulation)
- addition of nucleotides to DNA during recombination by terminal deoxynucletidyl transferase
119
Mature B cells express what immunoglobulins on their surfaces?
IgM and IgD
120
Mature B cells may differentiate in germinal centers of lymph nodes by WHAT?
isotype switching into plasma cells that secrete IgA, IgE or IgG
121
What is isotype switching?
gene rearrangement; mediated by cytokines and CD40L
122
What is the main antibody in secondary (delayed) response to an antigen?
IgG
123
What is the most abundant immunoglobulin in serum?
IgG
124
What are the four functions of IgG?
- fixes complement
- crosses the placenta
- opsonizes bacteria
- neutralizes bacterial toxins and viruses
125
What Ig prevents attachment of bacteria and viruses to mucous membranes?
IgA
126
What is the form of IgA in circulation and when secreted?
monomer in circulation and dimer when secreted
127
how does IgA cross epithelial cells
transcytosis
128
what is IgA in breast milk called?
colostrum
129
Where does IgA pick up the secretory component before secretion?
epithelial cells
130
Which Ig is produced in the primary (immediate) response to an antigen?
IgM
131
What does IgM do?
Fixes complement, but does not cross placenta; immediate response; antigen receptor on surface of B cells?
132
What is the form of IgM on B cells and when secreted?
Monomer on B cell but pentamer when secreted
133
What is the significance of the pentamer shape of IgM when secreted?
Allows it to efficiently trap free antigens out of tissue while humoral response evolves
134
What does IgE do?
Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) HSR through release of inflammatory mediators, such as histamine. Mediated immunity to worms by activating eos.
135
Antigens lacking a peptide component (eg LPS from gram negs); cannot be presented by MHC to T cells; weakly or nonimmunogenic; vaccines often require boosters
Thymus-independent antigens
136
Give one example of a vaccine with a thymus-independent antigen
Pneumococcal polysaccharide caccine
137
Antigens containing a protein component; class-switching and immunologic memo occur as a result of direct contact of B cells with Th (CD40 to CD40L)
Thymus-dependent antigens
138
what is an example of a vaccine with a thymus-dependent antigen?
diphtheria vaccine
139
What specific cytokines induce acute-phase reactants?
IL6, IL1, TNF-alpha, IFN-gamma
140
What are acute phase reactants?
factors whose serum concentrations change significantly in response to inflammation; produced by the liver in both acute and chronic inflammatory states
141
Name five "positive" acute-phase reactants (upregulated)
Serum amyloid A, CRP, ferritin, fibrinogen, hepcidin
142
Name two "negative" acute-phase reactants (downregulated)
Albumin and transferrin
143
What is a consequence of prolonged elevation of serum amyloid A?
amyloidosis
144
what is c-reactive protein?
opsonin; fixes complement and facilitates phagocytosis
145
What is ferritin?
binds and sequesters iron to inhibit microbial iron scavenging
146
What is fibrinogen?
Coagulation factor; promotes endothelial repair; correlates with ESR
147
What is hepcidin?
Prevents release of iron bound by ferritin; too much hepcidin --> anemia of chronic disease
148
Why is albumin downregulated in response to inflammation?
Reduction conserves amino acids for positive reactants
149
Why is transferrin downregulated in response to inflammation?
internalized by macrophages to sequester iron
150
System of interacting plasma proteins that play a role in innate immunity and inflammation
Complement!
151
against what does MAC defend?
gram negs!
152
What mediates the classic complement pathway?
IgG and IgM
153
What activates the alternative complement pathway?
microbe suface molecules
154
what activates the lectin complement pathway?
mannose or other sugars on microbe surfaces
155
What is the function of C3b?
opsonization (c3b binds bacteria)
156
C3a, C4a, and C5a all promote what?
anaphylaxis
157
C5a --> ?
neutrophil chemotaxis
158
What is the function of C5b-9?
cytolysis by membrane attack complex (MAC)
159
What are the two primary opsonins in bacterial defense?
C3b and IgG (C3b also helps clear immune complexes)
160
What helps prevent complement activation on self cells?
Decay-accelerating factor (DAF, CD55) and C1 esterase inhibitor
161
C1 esterase inhibitor deficiency
Causes hereditary angioedema. ACE inhibitors are contraindicated.
162
C3 deficiency
Increases risk of severe, recurrent progeny sinus and RTIs; inc. susceptibility to type 3 HSR
163
C5-C9 deficiencies
Increase susceptibility to recurrent Neisseria bacteremia
164
DAF (GPI anchored enzyme) deficiency
Causes complement-mediated lysis of RBCS and paroxysmal nocturnal hemoglobinuria (PNH)
165
Hot T-bone stEAK
```
IL1 = fever
IL2= stimulates T cells
IL3 = stimulates bone marrow
IL4= stimulates IgE production
IL6= stimulates aKute phase protein production
```
166
An endogenous pyrogen, also called osteoclast-activating factor. Causes fever, acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes
IL1
167
IL1 does what?
- fever & acute inflammation
- endothelium --> adhesion
- chemokine --> leukocytes
168
An endogenous pyrogen. Also secreted by Th2 cells. Causes favor and stimulates production of acute phase proteins
IL6
169
IL6 does what?
secreted by Th2 and macrophages;
fever
acute phase reactants
170
Major chemotactic factor for neutrophils
IL8
171
- Induces differentiation of T cells into Th1 cells.
- Activates NK cells
- Also secreted by B cells
IL12
172
- Mediates septic shock
- Activates endothelium
- Causes leukocyte recruitment, vascular leak
TNF-alpha
173
What cytokines are secreted by macrophages?
IL1, IL6, IL8, IL12, TNF-alpha
174
What cytokines are secreted by ALL t cells?
IL2 and IL3
175
Stimulates growth of helper, cytotoxic, and regulatory T cells
IL2
176
Supports the growth and differentiation of bone marrow stem cells. Functions like GM-CSF
IL3
177
What cytokine is produced by Th1 cells only?
interferon-gamma
178
Has antiviral and antitumor properties. Activates NK cells to kill virus-infected cells. Increases MHC expression and antigen presentation in all cells
interferon-gamma
179
What cytokines are produced by Th2 cells only?
IL4, IL5, IL10
180
- Induces differentiation into Th2 cells
- Promotes growth of B cells
- Enhances class switching to IgE and IgG
IL4
181
- Promotes differentiation of B cells
- Enhances class switching to IgA
- Stimulates growth and differentiation of eos
IL5
182
- Modulates inflammatory reposne
- Inhibits actions of activated T cells and Th1
- Also secreted by regulatory T cells
IL10
183
has similar actions to IL10 because it is involved in inhibiting inflammation
TGF-beta
184
Interferon alpha and beta protect against
viruses
185
Glycoproteins synthesized by viral-infected cells that act locally on uninfected cells, "priming them" for viral defense
Interferon alpha and beta
186
When a virus infects a cell that has been primed by IFN-alpha or beta, the viral nucleic acid material activates
- RNAase L --> degradation of viral/host mRNA
- Protein kinase --> inhibition of viral/host protein synthesis
- Effectively results in apoptosis, thereby interrupting viral amplification
187
What cell surface proteins are on all T cells?
- TCR (binds antigen-MHC complex)
- CD3 (associated with TCR for signal transduction)
- CD28 (binds B7 on APC)
188
What cell surface proteins are unique to Th?
CD4, CD40L
189
What cell surface protein is unique to Tc?
CD8
190
What 7 cell surface proteins are on B cells?
Ig (binds antigen),
CD19, CD20, CD21 (EBV receptor),
CD40, MHCII, B7
(you can drink Beer at the Bar when you are 21)
191
What 6 cell surface proteins are on macrophages
CD14, CD40
MHCII, B7
Fc and C3b receptors (enhanced phagocytosis)
192
What 2 cell surface proteins are on NK cells
CD16 (binds Fc of IgG)
| CD56 (unique marker for NK)
193
What is it called when T cells become nonreactive without costimulatory molecule?
Anergy (don't they always need two signals?)
194
What two bugs have superantigens?
Strep pyogenes and Staph aureus
195
How do superantigens lead to massive release of cytokines?
Cross link the beta region of the T-cell receptor to the MHC class II on APCs Can activate any T cell, leading to massive release of cytokines.
196
What is the effect of endotoxins/LPS (gram negs) on the immune system?
directly stimulate macrophages by binding to endotoxin receptor CD14 (only on macrophages!); Th cells are NOT involved
197
Name three bacteria notable for antigenic variation
```
Salmonella (2 flageller variants),
Borrelia (relapsing fever),
Neisseria gonorrhoeae (pilus protein)
```
198
Name a virus notable for antigenic variation
Influenza (major = shift, minor = drift)
199
Name a parasite notable for antigenic variation
Trypanosomes (programmed rearrangment)
200
Mechanisms for antigenic variation
DNA rearrangement and RNA segment reassortment
201
What exposures require giving the pt preformed antibodies?
```
Tetanus
Botulinum
HBV
Rabies
(to be healed rapidly!)
```
202
Combined passive and active immunization can be given for
Hep B and rabies
203
immunoglobulin that crosses the placenta?
IgG
204
Immunoglobulin in breast milk?
IgA
205
What is a live attenuated vaccine?
Microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host. Mainly induces a cellular response.
206
What are some examples of live attenuated vaccines?
```
MMR,
Polio (Sabin, oral),
influenza (intranasal),
varicella,
yellow fever
```
207
What is an inactivated or killed vaccine?
Pathogen is inactivated by heat of chemicals; maintaining epitope structure on surface antigens is important for immune response. Humoral immunity induced
208
What are some examples of inactivated or killed vaccines?
```
Cholera,
Hep A,
Polio (Salk, IV),
influenza (injection),
rabies
```
