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Lymphoid structures Flashcards

1
Q

A secondary lymphoid organ that has many afferents and one or more efferents; encapsulated, with trabeculae

A

lymph node

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2
Q

Functions of the lymph node

A
  1. nonspecific filtration by macrophages
  2. storage of B and T cells
  3. immune response activation
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3
Q

Site of B-cell localization and proliferation within the lymph node.

A

Follicle

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4
Q

Primary follicles in the outer cortex of the lymph node are dense and what?

A

dormant

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5
Q

Secondary follicles have pale germinal centers and are [active or inactive?]

A

active

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6
Q

What consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses?

A

Medulla of lymph node

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7
Q

medullary sinuses communicate with

A

efferent lymphatics

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8
Q

medullary sinuses contain

A

reticular cells and macrophages

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9
Q

Region of cortex between follicles and medulla in the lymph node that houses T cells.

A

Paracortex

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10
Q

The paracortex contains high endothelial venues through which WHAT enter from blood

A

T and B cells.

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11
Q

What part of the lymph node is not well developed in pts with what syndrome?

A

DiGeorge

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12
Q

Paracortex enlarges in an extreme cellular immune response, such as?

A

viral infection

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13
Q

Head and neck drain to what node?

A

Cervical

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14
Q

Lungs drain to what node?

A

Hilar

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15
Q

Trachea and esophagus drain to what node?

A

Mediastinal

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16
Q

Upper limb, breast, skin above umbilicus drain to what node?

A

Axillary

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17
Q

Liver, stomach, spleen, pancreas, and upper duodenum drain to what node?

A

Celiac

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18
Q

Lower duodenum, jejunum, ileum, colon to splenic flexure drain to what node?

A

Superior mesenteric

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19
Q

Colon from splenic flexure to upper rectum drain to what node?

A

Inferior mesenteric

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20
Q

Lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), and prostate drain to what node?

A

Internal iliac

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21
Q

Testes, ovaries, kidneys, uterus drain to what node?

A

Para-aortic

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22
Q

Anal canal (below pectinate line), skin below umbilicus (except popliteal territory) drain to what node?

A

Superficial inguinal

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23
Q

Dorsolateral foot and posterior calf drain to what node?

A

Popliteal

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24
Q

The right lymphatic duct drains

A

right side of body above diaphragm

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25
Q

The thoracic duct drains

A

everything below the diaphragm and the left side of the body above the diaphragm

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26
Q

into what does the thoracic duct drain?

A

junction of left subclavian and internal jugual veins

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27
Q

Long, vascular channels in red pulp with fenestrated “barrel hoop” basement membrane. Macrophages found nearby.

A

Spleen

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28
Q

Where in the spleen are T cells found?

A

Periarterial lymphatic sheath within the white pulp

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29
Q

Where in the spleen are B cells found?

A

In follicles within the white pulp

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30
Q

What do you call the area between the red pulp and white pulp of the spleen

A

the marginal zone

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31
Q

What types of cells are in the marginal zone?

A

APCs and specialized B cells.

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32
Q

What happens in the marginal zone?

A

APCs resent blood-bordn antigens

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33
Q

Macrophages in the spleen remove what type of bacteria?

A

encapsulated

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34
Q

Mechanism by wh/ splenic dysfunction –> increased susceptibility to encapsulated organisms?

A

decreased IgA –> decreased complement activation –> decreased C3b opsonization

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35
Q

Name the seven encapsulated bacteria

A 
Strep pneumo
HiB
N meningitidis
E coli
Salmonella spp
Klebsiella pneumo
Group B strep
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36
Q

Postsplenectomy on peripheral blood smear

A

Howell-Jowell bodies (nuclear remnants), target cells, thrombocytosis

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37
Q

Encapsulated organ that is the site of T cell differentiation and maturation

A

Thymus

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38
Q

Thymus embryological derivation

A

Epithelium of third pharyngeal pouches

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39
Q

Lymphocytes within the thymus have what origin?

A

Mesenchymal

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40
Q

Thymic cortex is dense with what type of cells?

A

Immature T cells

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41
Q

Thymic medulla is pale with what type of cells and structures?

A

T cells and Hassall corpuscles containing epithelial reticular cells.

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42
Q

Name 6 components of innate immunity

A

neutrophils, macrophages, monocytes, dendtritic cells, NK cells (lymphoid origin), complement

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43
Q

Name three components of adaptive immunity

A

T cells, B cells, circulating antibodies

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44
Q

Innate immunity resistance is germline encoded, so it

A

persists through generations, does not change within and organism’s lifetime

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45
Q

Adaptive immunity resistance is achieved through

A

variation through V(D)J recombination during lymphocyte development; microbial resistance not heritable

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46
Q

Innate immunity response to pathogens (specificity and speed?)

A

nonspecific; occurs rapidly (minutes to hours)

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47
Q

Adaptive immunity response to pathogens (specificity and speed?)

A

highly specific, refined over time; develops over long periods; memory response is faster and more robust

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48
Q

Physical barriers that aid in innate immunity?

A

Epithelial tight junctions, mucus

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49
Q

4 secreted proteins of innate immunity

A

lysozyme, complement, CRP, defensins

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50
Q

1 secreted protein of adaptive immunity

A

immunoglobins

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51
Q

Key features in pathogen recognition in innate immunity

A

Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs).

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52
Q

Examples of PAMPs

A
  • LPS (gram-negative bacteria)
  • flagellin (bacteria)
  • ssRNA (viruses)
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53
Q

key features in pathogen recognition in adaptive immunity

A

memory cells: activated B and T cells; subsequent exposure to a previously encountered antigen –> stronger, quicker immune response

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54
Q

MHC is encode by what genes?

A

HLA

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55
Q

MHC function

A

present antigen fragments to T cells and bind TCRs

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56
Q

Where is MHC I expressed?

A

all nucleated cells (NB: not on RBCs!)

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57
Q

Where is MHC II expressed?

A

Expressed only on APCs

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58
Q

MHC I function

A

present endogenously synthesized antigens (e.g. viral) to CD8+ cytotoxic T cells

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59
Q

MHCII function

A

present exogenously synthesized proteins (e.g., bacterial proteins, viral capside proteins) to T-helper cells

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60
Q

Antigen peptides loaded onto MHC I in

A

RER after delivery via TAP peptide transporter

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61
Q

Antigen loaded following

A

release of invariant chain in an acidified endosome

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62
Q

MHC I mode of transport to cell surface

A

B2 microglobulin

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63
Q

MHC I loci

A

HLA-A, HLA-B, HLA-C

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64
Q

MHC II loci

A

HLA-DR, HLA-DP, HLA-DQ

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65
Q

With what HLA subtype is hemochromatosis associated?

A

HLA-A2

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66
Q

HLA-B27 subtype is associated with four diseases

A

PAIR

  • Psoriatic arthritis
  • Ankylosing spondylitis
  • arthritis of Inflammatory bowel disease
  • Reactive arthritis
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67
Q

With what HLA subtype is celiac disease associated?

A

HLA-DQ2 or HLA-DQ8

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68
Q

HLA-DR2 subtype is associated with 4 diseases

A
  • multiple sclerosis
  • hay fever
  • SLE
  • Goodpasture syndrome
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69
Q

Diabetes mellitus type 1 is associated with what HLA?

A

DR3 and DR4

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70
Q

SLE is associated with what HLA?

A

DR2 and DR3

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71
Q

diseases associated with HLA-DR3

A

DMT1, SLE, Graves

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72
Q

diseases associated with HLA-DR4

A

Rheumatoid arthritis, DMT1

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73
Q

diseases associated with HLA-DR5

A

Pernicious anemia –> vitamin B12, Hashimoto thyroiditis

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74
Q

How do natural killer cells induce apoptosis of virally infected cells and tumor cells??

A

Use perforin or granzymes

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75
Q

what is the only lymphocyte member of the innate immune system?

A

NK cells

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76
Q

NK activity is enhanced by 4 things

A

IL-2, IL-12, IFN-beta, IFN-alpha

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77
Q

what induces NK cells to kill

A

exposure to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.

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78
Q

NK cells also kills via antibody-dependent cell-mediated cytotoxicity - how does that work?

A

CD16 binds Fc region of bound Ig, activating the NK cell.

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79
Q

Three B cell functions

A
  1. Recognize antigen
  2. Produce antibody
  3. Maintain immunologic memory
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80
Q

How do B cells recognize antigen?

A

undergo somatic hypermutation to optimize antigen specificity

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81
Q

How do B cells produce antibody?

A

Differentiate into plasma cells to secrete specific immunoglobulins

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82
Q

How do B cells maintain immunological memory?

A

memory B cells persist and accelerate future response to antigen

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83
Q

CD4+ function

A

help B cells make antibody and produce cytokines to activate other cells of immune system

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84
Q

CD8+ function

A

kill virus-infected cells directly

85
Q

What immune cells mediate type 4 HSR?

86
Q

What mediates acute and chronic cellular organ rejection?

87
Q

Where does positive selection of T cells occur?

A

Thymic cortex

88
Q

What cells are CD4+ and CD8+?

A

Immature T cells in the cortex

89
Q

What is positive selection?

A

T cells expressing TCRs capable of binding surface self MHC molecules survive.

90
Q

Where does negative selection of T cells occur?

A

Thymic medulla

91
Q

What is negative selection?

A

T cells expressing TCRs with high affinity for self antigens undergo apoptosis

92
Q

What are the three types of APCs?

A

B cells,
macrophages,
dendritic cells

93
Q

Describe the four steps of naive helper T cell activation

A
  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
Q

Describe the four steps of naive cytotoxic T cell activation

A
  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
Q

Describe the steps of B cell activation and class switching

A
  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
Q

What do Th1 cells secrete?

97
Q

What do Th2 cells secrete?

A

IL4, IL5, IL6, IL10, IL13

98
Q

What does Th1 secretion of IFN-gamma do?

A

Activates macrophages and cytotoxic T lymphocytes (CTLs)

99
Q

What does Th2 activity do?

A

Recruits eos for parasite defense and promotes IgE production from B cells

100
Q

What inhibits Th1?

A

IL4 and IL10 from Th2

101
Q

What inhibits Th2?

A

IFN-gamma from Th1

102
Q

What is the macrophage-lymphocyte interaction?

A

Macrophages release IL12, which stimulates T cells to differentiate into Th1 cells, which then release IFN-gamma to stimulate macrophages.

103
Q

What is the function of CTLs?

A

Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis

104
Q

How do CTLs induce apoptosis

A

Release cytotoxic granules containing preformed proteins

105
Q

what are the three preformed proteins in CTL secreted cytotoxic granules?

A

perforin
granzyme B
granulysin

106
Q

what does perforin do?

A

helps to deliver the content of granules into the target cells

107
Q

What does granzyme B do?

A

a serine protease, activates apoptosis inside target cell

108
Q

what does granulysin do?

A

antimicrobial, induces apoptosis

109
Q

What cells help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions?

A

Regulatory T cells

110
Q

Regulatory T cells can be identified by expression of what four cell surface markers

A

CD3, CD4, CD25 (alpha chain of IL-2 receptor), and transcription factor FOXP3

111
Q

Activated regulatory T cells produce what two anti-inflammatory cytokines?

A

IL-10 and TGF-beta

112
Q

What part of the antibody recognizes antigens?

A

variable part of light and heavy cahins

113
Q

What part of IgM and IgG fixes complement?

A

Fc portion

114
Q

The heavy chain contributes to what fractions of the antibody?

A

Fc and Fab

115
Q

The light chain contributes to what fractions of the antibody?

116
Q

What is Fab?

A

Antigen-binding fragment, determines idiotype; unique antigen binding pocket; only 1 antigenic specificity expressed by B cell

117
Q

What is Fc (4Cs +D)?

A 
Constant, 
carboxy terminal, 
complement binding
carbohydrate side chains
Determines isotype (IgM, IgD, etc)
118
Q

what are the four things contributing to antibody diversity?

A
  • 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
Q

Mature B cells express what immunoglobulins on their surfaces?

A

IgM and IgD

120
Q

Mature B cells may differentiate in germinal centers of lymph nodes by WHAT?

A

isotype switching into plasma cells that secrete IgA, IgE or IgG

121
Q

What is isotype switching?

A

gene rearrangement; mediated by cytokines and CD40L

122
Q

What is the main antibody in secondary (delayed) response to an antigen?

123
Q

What is the most abundant immunoglobulin in serum?

124
Q

What are the four functions of IgG?

A
  • fixes complement
  • crosses the placenta
  • opsonizes bacteria
  • neutralizes bacterial toxins and viruses
125
Q

What Ig prevents attachment of bacteria and viruses to mucous membranes?

126
Q

What is the form of IgA in circulation and when secreted?

A

monomer in circulation and dimer when secreted

127
Q

how does IgA cross epithelial cells

A

transcytosis

128
Q

what is IgA in breast milk called?

129
Q

Where does IgA pick up the secretory component before secretion?

A

epithelial cells

130
Q

Which Ig is produced in the primary (immediate) response to an antigen?

131
Q

What does IgM do?

A

Fixes complement, but does not cross placenta; immediate response; antigen receptor on surface of B cells?

132
Q

What is the form of IgM on B cells and when secreted?

A

Monomer on B cell but pentamer when secreted

133
Q

What is the significance of the pentamer shape of IgM when secreted?

A

Allows it to efficiently trap free antigens out of tissue while humoral response evolves

134
Q

What does IgE do?

A

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
Q

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

A

Thymus-independent antigens

136
Q

Give one example of a vaccine with a thymus-independent antigen

A

Pneumococcal polysaccharide caccine

137
Q

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)

A

Thymus-dependent antigens

138
Q

what is an example of a vaccine with a thymus-dependent antigen?

A

diphtheria vaccine

139
Q

What specific cytokines induce acute-phase reactants?

A

IL6, IL1, TNF-alpha, IFN-gamma

140
Q

What are acute phase reactants?

A

factors whose serum concentrations change significantly in response to inflammation; produced by the liver in both acute and chronic inflammatory states

141
Q

Name five “positive” acute-phase reactants (upregulated)

A

Serum amyloid A, CRP, ferritin, fibrinogen, hepcidin

142
Q

Name two “negative” acute-phase reactants (downregulated)

A

Albumin and transferrin

143
Q

What is a consequence of prolonged elevation of serum amyloid A?

A

amyloidosis

144
Q

what is c-reactive protein?

A

opsonin; fixes complement and facilitates phagocytosis

145
Q

What is ferritin?

A

binds and sequesters iron to inhibit microbial iron scavenging

146
Q

What is fibrinogen?

A

Coagulation factor; promotes endothelial repair; correlates with ESR

147
Q

What is hepcidin?

A

Prevents release of iron bound by ferritin; too much hepcidin –> anemia of chronic disease

148
Q

Why is albumin downregulated in response to inflammation?

A

Reduction conserves amino acids for positive reactants

149
Q

Why is transferrin downregulated in response to inflammation?

A

internalized by macrophages to sequester iron

150
Q

System of interacting plasma proteins that play a role in innate immunity and inflammation

A

Complement!

151
Q

against what does MAC defend?

A

gram negs!

152
Q

What mediates the classic complement pathway?

A

IgG and IgM

153
Q

What activates the alternative complement pathway?

A

microbe suface molecules

154
Q

what activates the lectin complement pathway?

A

mannose or other sugars on microbe surfaces

155
Q

What is the function of C3b?

A

opsonization (c3b binds bacteria)

156
Q

C3a, C4a, and C5a all promote what?

A

anaphylaxis

157
Q

C5a –> ?

A

neutrophil chemotaxis

158
Q

What is the function of C5b-9?

A

cytolysis by membrane attack complex (MAC)

159
Q

What are the two primary opsonins in bacterial defense?

A

C3b and IgG (C3b also helps clear immune complexes)

160
Q

What helps prevent complement activation on self cells?

A

Decay-accelerating factor (DAF, CD55) and C1 esterase inhibitor

161
Q

C1 esterase inhibitor deficiency

A

Causes hereditary angioedema. ACE inhibitors are contraindicated.

162
Q

C3 deficiency

A

Increases risk of severe, recurrent progeny sinus and RTIs; inc. susceptibility to type 3 HSR

163
Q

C5-C9 deficiencies

A

Increase susceptibility to recurrent Neisseria bacteremia

164
Q

DAF (GPI anchored enzyme) deficiency

A

Causes complement-mediated lysis of RBCS and paroxysmal nocturnal hemoglobinuria (PNH)

165
Q

Hot T-bone stEAK

A 
IL1 = fever
IL2= stimulates T cells
IL3 = stimulates bone marrow
IL4= stimulates IgE production
IL6= stimulates aKute phase protein production
166
Q

An endogenous pyrogen, also called osteoclast-activating factor. Causes fever, acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes

167
Q

IL1 does what?

A
  • fever & acute inflammation
  • endothelium –> adhesion
  • chemokine –> leukocytes
168
Q

An endogenous pyrogen. Also secreted by Th2 cells. Causes favor and stimulates production of acute phase proteins

169
Q

IL6 does what?

A

secreted by Th2 and macrophages;
fever
acute phase reactants

170
Q

Major chemotactic factor for neutrophils

171
Q
  • Induces differentiation of T cells into Th1 cells.
  • Activates NK cells
  • Also secreted by B cells
172
Q
  • Mediates septic shock
  • Activates endothelium
  • Causes leukocyte recruitment, vascular leak
173
Q

What cytokines are secreted by macrophages?

A

IL1, IL6, IL8, IL12, TNF-alpha

174
Q

What cytokines are secreted by ALL t cells?

A

IL2 and IL3

175
Q

Stimulates growth of helper, cytotoxic, and regulatory T cells

176
Q

Supports the growth and differentiation of bone marrow stem cells. Functions like GM-CSF

177
Q

What cytokine is produced by Th1 cells only?

A

interferon-gamma

178
Q

Has antiviral and antitumor properties. Activates NK cells to kill virus-infected cells. Increases MHC expression and antigen presentation in all cells

A

interferon-gamma

179
Q

What cytokines are produced by Th2 cells only?

A

IL4, IL5, IL10

180
Q
  • Induces differentiation into Th2 cells
  • Promotes growth of B cells
  • Enhances class switching to IgE and IgG
181
Q
  • Promotes differentiation of B cells
  • Enhances class switching to IgA
  • Stimulates growth and differentiation of eos
182
Q
  • Modulates inflammatory reposne
  • Inhibits actions of activated T cells and Th1
  • Also secreted by regulatory T cells
183
Q

has similar actions to IL10 because it is involved in inhibiting inflammation

184
Q

Interferon alpha and beta protect against

185
Q

Glycoproteins synthesized by viral-infected cells that act locally on uninfected cells, “priming them” for viral defense

A

Interferon alpha and beta

186
Q

When a virus infects a cell that has been primed by IFN-alpha or beta, the viral nucleic acid material activates

A
  • RNAase L –> degradation of viral/host mRNA
  • Protein kinase –> inhibition of viral/host protein synthesis
  • Effectively results in apoptosis, thereby interrupting viral amplification
187
Q

What cell surface proteins are on all T cells?

A
  • TCR (binds antigen-MHC complex)
  • CD3 (associated with TCR for signal transduction)
  • CD28 (binds B7 on APC)
188
Q

What cell surface proteins are unique to Th?

A

CD4, CD40L

189
Q

What cell surface protein is unique to Tc?

190
Q

What 7 cell surface proteins are on B cells?

A

Ig (binds antigen),
CD19, CD20, CD21 (EBV receptor),
CD40, MHCII, B7
(you can drink Beer at the Bar when you are 21)

191
Q

What 6 cell surface proteins are on macrophages

A

CD14, CD40
MHCII, B7
Fc and C3b receptors (enhanced phagocytosis)

192
Q

What 2 cell surface proteins are on NK cells

A

CD16 (binds Fc of IgG)

CD56 (unique marker for NK)

193
Q

What is it called when T cells become nonreactive without costimulatory molecule?

A

Anergy (don’t they always need two signals?)

194
Q

What two bugs have superantigens?

A

Strep pyogenes and Staph aureus

195
Q

How do superantigens lead to massive release of cytokines?

A

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
Q

What is the effect of endotoxins/LPS (gram negs) on the immune system?

A

directly stimulate macrophages by binding to endotoxin receptor CD14 (only on macrophages!); Th cells are NOT involved

197
Q

Name three bacteria notable for antigenic variation

A 
Salmonella (2 flageller variants),
Borrelia (relapsing fever),
Neisseria gonorrhoeae (pilus protein)
198
Q

Name a virus notable for antigenic variation

A

Influenza (major = shift, minor = drift)

199
Q

Name a parasite notable for antigenic variation

A

Trypanosomes (programmed rearrangment)

200
Q

Mechanisms for antigenic variation

A

DNA rearrangement and RNA segment reassortment

201
Q

What exposures require giving the pt preformed antibodies?

A 
Tetanus
Botulinum
HBV
Rabies
(to be healed rapidly!)
202
Q

Combined passive and active immunization can be given for

A

Hep B and rabies

203
Q

immunoglobulin that crosses the placenta?

204
Q

Immunoglobulin in breast milk?

205
Q

What is a live attenuated vaccine?

A

Microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host. Mainly induces a cellular response.

206
Q

What are some examples of live attenuated vaccines?

A 
MMR, 
Polio (Sabin, oral), 
influenza (intranasal), 
varicella, 
yellow fever
207
Q

What is an inactivated or killed vaccine?

A

Pathogen is inactivated by heat of chemicals; maintaining epitope structure on surface antigens is important for immune response. Humoral immunity induced

208
Q

What are some examples of inactivated or killed vaccines?

A 
Cholera, 
Hep A,
Polio (Salk, IV),
influenza (injection),
rabies

FA Immuno (2 decks)

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