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NPLEX 1 > Immunology > Flashcards

Immunology Flashcards

1
Q

Primary lymphoid organs

A

Where lymphocytes are generated

Includes bone marrow and thymus

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2
Q

Which lymphocyte matures in the bone marrow?

A

B lymphocytes

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3
Q

Secondary lymphoid organs

A

Where adaptive immune responses are initiated & Ag/Ab encounter each other
Exist to bring Ag and lymphocytes together

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4
Q

Lymph node

A

a secondary lymphoid organ that has many afferents and 1 or more efferents (medulla)

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5
Q

How do naive lymphocytes exit the blood?

A

Via high endothelial venules (HEV)

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6
Q

Follicle of a LN

A

Site of B-cell localization and proliferation

In the outer cortex

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7
Q

Parts of a LN

A

Follicle, cortex (outer and paracortex), and medulla

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8
Q

Primary follicles vs. secondary follicles in LNs

A

Primary - dense and dormant

Secondary - pale central germinal centres and are active

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9
Q

What are high endothelial venules?

A
  • Specialized section of post-capillary venules
  • plump endothelial cells protrude into vessel
  • In LNs found in paracortex and some areas of cortex
  • Lymphocytes display increased adhesiveness to HEV
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10
Q

Medulla of a LN

A

Consists of medullary cords and medullary sinuses

Houses macrophages and plasma cells

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11
Q

Medullary sinuses

A

communicate with efferent lymphatics and contain reticular cells and macrophages

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12
Q

Paracortex in LNs

A

Houses T cells
Region of cortex between follicles and medulla
Contains high endothelial venules through which T and B cells enter from blood

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13
Q

What part of the LN enlarges in an extreme cellular immune response (e.g., viral infection)?

A

Paracortex

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14
Q

What art of the LN is not well developed in patients with DiGeorge syndrome?

A

Paracortex

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15
Q

What area of the body do cervical LN’s drain?

A

Head and neck

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16
Q

What area of the body do hilar LNs drain?

A

Lungs

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17
Q

What area of the body do Mediastinal LNs drain?

A

trachea and esophagus

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18
Q

What area of the body do axillary LNs drain?

A

upper limb, breast, skin above umbilicus

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19
Q

What area of the body do celiac LNs drain?

A

liver, stomach, spleen, pancreas, upper duodenum

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20
Q

What area of the body do superior mesenteric LNs drain?

A

lower duodenum, jejunum, ileum, colon to splenic flexure

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21
Q

What area of the body do inferior mesenteric LNs drain?

A

colon from splenic flexure to upper rectum

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22
Q

What area of the body do internal iliac LNs drain?

A

lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), prostate

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23
Q

What area of the body do para-aortic LNs drain?

A

testes, ovaries, kidneys, uterus

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24
Q

What area of the body do superficial inguinal LNs drain?

A

ana canal (below pectinate line), skin below umbilicus (except popliteal territory)

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25
Q

What area of the body do popliteal LNs drain?

A

dorsolateral foot, posterior calf

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26
Q

Spleen

A

collects blood born antigens and also destroys aged RBCs

divided into red pulp and white pulp

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27
Q

White pulp of the spleen

A

T cells are found in the periarterial lymphatic sheath within the white pulp
B cells are found in follicles within the white pulp

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28
Q

Red pulp of the spleen

A

where old RBCs are destroyed

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29
Q

The marginal zone btwn the red and white pulp contains what?

A

APCs and specialized B cells , and is where APCs present blood-borne antigens

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30
Q

What do macrophages in the spleen remove?

A

encapsulated bacteria

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31
Q

What occurs in the immune system when there is a splenic dysfunction (e.g., postspenectomy, sickle cell dz)?

A

decreased IgM -> decreased complement activation -> decreased C3b opsonization -> increased susceptibility to encapsulated organisms

Susceptibility to bacteria caused by encapsulated bacteria caused by failure of the immune response to these common extracellular bacteria when the enter the blood stream

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32
Q

List the pathogens that can cause splenic dysfunction

A

(SHiNE SKS)

Streptococcus pneumoniae
HiB
Neisseria meningitidis
E coli
Salmonella spp.
Klebsiella pneumoniae
group B Streptococci
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33
Q

Thymus

A

Site of T cell differentiation and maturation

Cortex is dense with immature T cells
Medulla is pale with mature T cells and Hassall corpuscles containing reticular cells

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34
Q

The thymus comes from the epithelium of….

A

3rd pharyngeal pouches

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35
Q

Components of the innate immune system

A

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

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36
Q

Components of the adaptive immune system

A

T cells, B cells, circulating antibodies

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37
Q

Innate immune systems response to pathogens

A 
Nonspecific
Occurs rapidly (minutes to hours)
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38
Q

Adaptive immune system response to pathogens

A

Highly specific, refined over time

Develops over long periods; memory response is faster and more robust

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39
Q

Innate immunity physical barriers

A

Epithelial tight junctions, mucus

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40
Q

Adaptive immunity physical barriers

A

none

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41
Q

Proteins secreted by Innate immunity

A

lysozyme, complement, CRP, defensins

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42
Q

Proteins secreted by adaptive immunity

A

immunoglobulins

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43
Q

Key features in pathogen recognition by innate immunity

A

TLRs: pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs)
- signalling induces innate immune responses and inflammation

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44
Q

Examples of PAMPs

A

LPS (gram negative bacteria), flagellin (bacteria), ssRNA (viruses)

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45
Q

Key features in pathogen recognition by adaptive immunity

A

Memory cells: activated B and T cells; subsequent exposure to previously encountered antigen -> stronger, quicker immune response

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46
Q

Types of adaptive immune responses

A

Humoral and cell mediated

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47
Q

Humoral responses

A

Adaptive immunity
mediated by Abs
Produced by bone marrow derived B lymphocytes

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48
Q

Cell-mediated responses

A

Adaptive immunity

mediated by thymus derived T lymphocytes

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49
Q

Genes responsible for recognizing a graft as being foreign are termed …?

A

Histocompatibility genes

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50
Q

MHC are encoded by…

A

HLA genes

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51
Q

MHC present antigen fragments to…

A

T cells and bind TLRs

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52
Q

MHC I loci

A

HLA-A, HLA-B, HLA-C

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53
Q

MHC II loci

A

HLA-DR, HLA-DP, HLA-DQ

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54
Q

MHC I molecules present Ags derived from the ______ to _______ cells

A

cytosol; CD8+ T cells

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55
Q

MHC II molecules present Ags derived from ______ to _______ cells

A

outside the cell; CD4+ T cells

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56
Q

MHC I function

A

present ENDOGENOUSLY synthesized ANTIGENS (e.g., viral) to CD8+ T cells

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57
Q

MHC II function

A

present EXOGENOUSLY synthesized PROTEINS (e.g., bacteria) to CD4+ T cells

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58
Q

MHC I Ag loading

A

Ag peptides loaded onto MHC I in RER after delivery via TAP peptide transporter

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59
Q

MHC II Ag loading

A

Ag loaded following release of invariant chain in an acidified endosome

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60
Q

MHC I mode of transport to cell surface

A

beta 2-microglobulin

61
Q

HLA- A3 subtype associated dzs

A

Hemochromatosis

62
Q

HLA- B27 subtype associated dzs

A

Psoriatic arthritis, ankylosing spondylitis, arthritis of inflammatory bowel dz, reactive arthritis

63
Q

HLA- DQ2/DQ8 subtype associated dzs

64
Q

HLA- DR2 subtype associated dzs

A

MS, hay fever, SLE, Goodpasture syndrome

65
Q

HLA- DR3 subtype associated dzs

A

DM type 1, SLE, Grave’s dz

66
Q

HLA- DR4 subtype associated dzs

A

Rheumatoid arthritis, DM type 1

67
Q

HLA- DR5 subtype associated dzs

A

Pernicious anemia -> vit B12 deficiency, Hashimoto thyroiditis

68
Q

NK cells

A 
Use perforin and granzymes to induce apoptosis of virally infected cells and tumour cells 
Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface
69
Q

Which cells are the only lymphocyte member of the innate immune system?

70
Q

NK cells activity are enhanced by which cytokines?

A

IL-2, IL-12, IFN-b, and IFN-a

71
Q

B cell functions (3 main ones)

A

Recognize Ag - undergo somatic hypermutation to optimize Ag specificity
Produce Ab - differentiate into plasma cells to secrete specific immunoglobins
Maintain immunologic memory - memory B cells persist and accelerate future response to Ag

72
Q

T cell functions

A

CD4+ T cells help B cells make Ab and produce cytokines to activate other cells of immune system
CD8+ T cells kill virus infected cells directly
Delayed cell-mediated hypersensitivity (TypeIV)
Acute and chronic cellular organ rejection

73
Q

Describe the process of T cell differentiation

A

T cell precursor starts in the bone marrow
T cell precursor travels to the cortex in the thymus where it becomes a CD4+ and CD8+ T cell
T cell divides in the medulla of the thymus into a CD4+ T cell and a CD8+ T cell
In the LN the cytotoxic CD8+ T cell kills virus infected, neoplastic, and donor graft cells
In the LN the Helper CD4+ T cell differentiates further from cytokines (Th1 cell, Th2 cell, Th17 cell, Threg cell)

74
Q

How many signals are required for T cell activation, B cell activation, and class switching?

75
Q

Name the APCs?

A

B cells, macrophages, dendritic cells

76
Q

Naive T cell activation stages

A
  1. Foreign body is phagocytosed by dendritic cell
  2. Foreign Ag is presented on MHC II and recognized by TCR (T cell receptor) on Th (helper) cell. Ag is presented on MHC I to Tc (cytotoxic) cells (signal 1)
  3. “Costimulatory signal” is given by interaction of B7 and CD28 (signal 2)
  4. Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus infected cells
77
Q

B cell activation and class switching stages

A
  1. Helper T cell activation
  2. B cell receptor-mediated endocytosis; foreign Ag is presented on MHC II and recognized by TCR on Th cell (signal 1)
  3. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)
  4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and Ab production
78
Q

Which APC is the only one able to activate naive T cells?

A

Dendritic cells

79
Q

Helper T cell - Th1 Cell

A

Secretes IFN-y
Activates macrophages and cytotoxic T cells
Inhibited by IL-4 and IL-10 (from Th2 cell)

80
Q

Helper T cell - Th2 cell

A

Secretes IL-4, IL-5, IL-6, IL-13
Recruits eosinophils for parasite defence and promotes IgE production by B cells
Inhibited by IFN-y (from Th1 cell)

81
Q

Macrophages release IL-12 which stimulates what?

A

Stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-y to stimulate macrophages

82
Q

Cytotoxic T cells

A

Kill virus infected, neoplastic, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins (perforin and granzyme B)

83
Q

Regulatory T cells

A

Help maintain specific immune tolerance by suppressing CD4 and CD8 T cell effector functions

84
Q

How are regulatory T cells identified?

A

Expression of cell surface markers CD3, CD4, CD25 (alpha chain of IL-2), and transcription factor FOXP3

85
Q

Activated regulatory T cells produce which anti-inflammatory cytokines?

A

IL-10 and TGF-beta

86
Q

Which part of the Ab recognizes Ag?

A

Light and heavy chains

87
Q

The Fc region of an Ab is made from which chain type?

88
Q

The Fab region of an Ab is made from which chain type?

A

Both - heavy and light

89
Q

Fab region of Ab

A

Ag binding fragment

Determines idiotype: unique Ag binding pocket; only 1 antigenic specificity expressed per B cell

90
Q

Fc region of Ab

A 
Constant
Carboxyl terminal
Complement binding
Carbohydrate side chains
Determines isotype (IgM, IgD, etc.)
91
Q

Ab diversity is generated by…

A 
Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
Random combination of heavy chains with light chains
Somatic hypermutation (following Ag stimulation)
Addition of nucleotides to DNA during recombination bu terminal deoxynucleotidyl transferase
92
Q

Which immunoglobulins do mature B cells express on their surfaces?

A

IgM and IgD

93
Q

IgG

A

Main Ab in secondary (delayed) response to an Ag.
Most abundant isotype in serum.
Fixes complement, crosses placental (provides infants with passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses

94
Q

IgA

A

Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement.
Monomer in circulation or dimer when secreted
Crosses epithelial cells by transcytosis

95
Q

Which Ab is mostly produces overall?

96
Q

Which Ab is released in our secretions (tears, saliva, mucus)?

97
Q

Which Ab is in colostrum?

98
Q

IgM

A

Produces in primary (immediate) response to Ag. Fixes complement but does not cross the placenta

99
Q

Which Ab crosses the placenta?

100
Q

Which Ab is the Ag receptor on B cells?

A

IgM and IgD

Monomer on B cells or pentamer when secreted

101
Q

IgD

A

Unclear function. Found on the surface of many B cells and in serum.

102
Q

IgE

A

Binds mast cells and basophils; cross links when exposed to allergen, mediating immediate (type 1) hypersensitivity through release of inflammatory mediators such as histamine

103
Q

How does IgE mediate immunity to worms?

A

By activating eosinophils

104
Q

Which Ab is in the lowest concentration in serum?

105
Q

Thymus-independent Ags

A

Ags lacking a peptide component
Weakly or nonimmunogenic
Vaccines often require boosters

106
Q

Which Ag type cannot be presented by MHC to T cells?

A

Thymus-independent antigens

107
Q

Thymus-dependent Ags

A

Ags containing a protein component. Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction)

108
Q

Acute phase reactants

A

Factors whose serum concentrations change significantly in response to inflammation

109
Q

When and where are acute phase reactants produced?

A

Liver in both acute and chronic inflammatory states

110
Q

What cytokines induce acute-phase reactants?

A

IL-6, IL-1, TNF-a, and IFN-y

111
Q

serum amyloid A (Upregulated)

A

prolonged elevation can lead to amyloidosis

112
Q

C-reactive protein (Upregulated)

A

Opsonin; fixes complement and facilitates phagocytosis

Measured clinically as a sign of ongoing inflammation

113
Q

ferritin (Upregulated)

A

binds and sequesters iron to inhibit microbial iron scavenging

114
Q

fibrinogen (Upregulated)

A

coagulation factor; promotes endothelial repair; correlates with ESR

115
Q

hepcidin (Upregulated)

A

prevents release of iron bound by ferritin -> anemia of chronic dz

116
Q

albumin (downregulated)

A

reduction conserves amino acids for positive reactants

117
Q

transferrin (downregulated)

A

internalized by macrophages to sequester iron

118
Q

What kind of pathogens do MACs defend agains?

A

gram-negative bacteria

119
Q

Classic pathway of complement

A

IgG and IgM mediated

120
Q

Alternative pathway of complement

A

microbe surface molecules

121
Q

Lectin pathway of complement

A

mannose or other sugars on microbe surface

122
Q

C3b

A

opsonization

123
Q

C3a, C4a, C5a

A

anaphylaxis

124
Q

C5a

A

neutrophil chemotaxis

125
Q

C5b-9

A

cytosine by MAC

126
Q

Opsonins

A

C3b and IgG are the two primary opsonins in bacterial defence

127
Q

Which complement protein helps clear immune complexes?

128
Q

What are the names of the inhibitors that help prevent complement activation on self cells (e.g., RBCs)

A

Decay-Accelerating factos (DAF aka CD55) and C1 esterase

129
Q

C1 esterase inhibitor deficiency

A

causes hereditary angioedema. ACE inhibitors are CI

130
Q

C3 deficiency

A

Increases risk of severe, recurrent pyogenic sinus and respiratory tract infections; increases susceptibility to type III hypersensitivity reactions

131
Q

C5-C9 deficiencies

A

increases susceptibility to recurrent Neisseria bacteremia

132
Q

DAF deficiency

A

causes complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria

133
Q

What cytokines are secreted by macrophages?

A

IL-1, IL-6, IL-8, IL-12, TNF-alpha

134
Q

What cytokines are secreted by T cells?

A

IL-2, IL-3

135
Q

What cytokines are secreted from Th1 cells?

136
Q

What cytokines are from Th2 cells?

A

IL-4, IL-5, IL-10

137
Q

IL-1

A

Endogenous pyrogen.
Causes fever and acute inflammation
Activated endothelium to express adhesion molecules
Induces chemokine secretion to recruit leukocytes

138
Q

IL-2

A

stimulates growth of all T cells

139
Q

IL - 3

A

supports the growth and differentiation of bone marrow stem cells

140
Q

IL-4

A 
Stimulates IgE production and IgG through class switching 
induces differentiation into Th2 cells
Promotes growth of B cells
141
Q

IL-5

A

Enhances class switching to IgA
Promotes differentiation of B cells
Stimulates the growth and differentiation of eosinophils

142
Q

IL-6

A

Causes fever and stimulates production of acute phase proteins
Also secreted by Th2 cells

143
Q

IL-8

A

Major chemotactic factor for neutrophils

144
Q

IL-10

A

Moderates inflammation response
Inhibits actions of activated T cells and Th1
Also secreted by regulatory T cells

145
Q

What cytokine has similar actions to IL-10 bc it is involved in inhibiting inflammation?

146
Q

IL-12

A

Induces differentiation of T cells into Th1 cells
Activates NK cells
Also secreted by B cells

147
Q

TNF-alpha

A

Mediates septic shock
Activates endothelium
Causes leukocyte recruitment, vascular leak

148
Q

IFN-y

A

has antiviral and anti tumour properties
activates NK cells to kill virus infected cells
increases MHC expression and Ag presentation in all cells

NPLEX 1 (10 decks)

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