Immuno FA - part I 96-108 Flashcards

1
Q

Primary lymphoid organs and function

A

Bone marrow—immune cell production, B cell maturation ƒ Thymus—T cell maturation

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2
Q

Secondary lymphoid organs and function

A

Spleen, lymph nodes, tonsils, Peyer patches ƒ Allow immune cells to interact with antigen

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3
Q

What happens in a lymphoid follicle? Loc where in a lymph node?

A

Site of B-cell localization and proliferation. , in outer cortex

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4
Q

Diff between primary and 2ndary follicle?

A

1° follicles are dense and dormant. 2° follicles have pale central germinal centers and are active

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5
Q

What do medullary sinuses contain?

A

reticular cells and macrophages.

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6
Q

What is in the paracortex?

A

T cells

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7
Q

What disease has under developed paracortex?

A

DiGeorge syndrome

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8
Q

What part of the lymph node enlarges during viral infections?

A

Paracortex - Paracortex enlarges in an extreme cellular immune response (eg, EBV and other viral infections Ž paracortical hyperplasia Ž lymphadenopathy).

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9
Q

What is contained in the white pulp of a spleen?

A

ƒ T cells are found in the periarteriolar lymphatic sheath (PALS) within the white pulp (white arrows in A). ƒ B cells are found in follicles within the white pulp.

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10
Q

What’s in the marginal zone?

A

ƒ The marginal zone, in between the red pulp and white pulp, contains macrophages and specialized B cells, and is where antigen presenting cells (APCs) capture blood-borne antigens for recognition by lymphocytes.

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11
Q

Which bacteria are cleared by the spleen? ex/

A

encapsulated bacteria - Pseudomonas aeruginosa, Streptococcus pneumoniae A, Haemophilus influenzae type b, Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella pneumoniae, and group B Strep (S. agalacticae)

Please SHiNE my SKiS

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12
Q

How does splenic dysfunction lead to inc susceptibility to encapsulated organisms?

A

dec IgM –> dec complement activation –> dec C3b opsonization

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13
Q

Blood finding post splenectomy?

A

ƒHowell-Jolly bodies (nuclear remnants) ƒ Target cells ƒ Thrombocytosis (loss of sequestration and removal) ƒ Lymphocytosis (loss of sequestration)

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14
Q

Which vaccines do splenectomy patients need?

A

ƒ N meningitidis ƒ S pneumoniae ƒ H influenzae

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15
Q

Embryonic origin of thymic lymphocytes and epithelium?

A

Thymus epithelium is derived from Third pharyngeal pouch (endoderm), whereas thymic lymphocytes are of mesodermal origin

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16
Q

What is in the cortex and medulla of the thymus?

A

Cortex is dense with immature T cells;

Medulla is pale with Mature T cells and Hassall corpuscles containing epithelial reticular cells

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17
Q

Neoplasm of thymus assoc with which diseases?

A

Associated with myasthenia gravis, superior vena cava syndrome, pure red cell aplasia, Good syndrome.

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18
Q

How to innate immune cells recognize pathogens?

A

Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and lead to activation of NF-κB.

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19
Q

Ex of PAMPs?

A

Examples of PAMPs include LPS (gram ⊝ bacteria), flagellin (bacteria), nucleic acids (viruses), dectin1 (fungi)

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20
Q

MHCs are encoded by which genes?

A

HLA genes

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21
Q

Fxn of MHC?

A

Present antigen fragments to T cells and bind T-cell receptors (TCRs).

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22
Q

Loci of MHC I and MHC II?

A

HLA-A, HLA-B, HLA-C MHC I loci have 1 letter HLA-DP, HLA-DQ, HLA-DR MHC II loci have 2 letters

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23
Q

What binds to MHC I and II?

A

MHC I - TCR and CD8 MHC II - TCR and CD4

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24
Q

Structure of MHC I and II?

A

MHC I - 1 long chain, 1 short chain MHC II - 2 equal-length chains (2 α, 2 β)

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25
Q

Where is MHC I and II expressed?

A

MHC I - All nucleated cells, APCs, platelets (except RBCs) MHC II - APCs

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26
Q

Function of MHC I and MHC II?

A

MHC I - Present endogenous antigens (eg, viral or cytosolic proteins) to CD8+ cytotoxic T cells

MHC I - In - endogenous

MHC II - Present exogenous antigens (eg, bacterial proteins) to CD4+ helper T cells

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27
Q

How are antigens loaded on to MHC I and MHC II?

A

MHC I - Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing) MHC II - Antigen loaded following release of invariant chain in an acidified endosome

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28
Q

Proteins associated by MHC I and MHC II?

A

MHC I - B2 microglobulin MHC II - invariant chain

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29
Q

Disease assoc w/ HLA subtype A3

A

Hemochromatosis HA3mochromatosis.

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30
Q

Disease assoc w/ HLA subtype B8

A

Addison disease, myasthenia gravis, Graves disease Don’t Be late(8), Addison, or else you’ll send my patient to the grave.

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31
Q

Disease assoc w/ HLA subtype B27

A

Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis PAIR. Also known as seronegative arthropathies.

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32
Q

Disease assoc w/ HLA subtype C

A

Psoriasis

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33
Q

Disease assoc w/ HLA subtype DQ2/DQ8

A

Celiac disease I ate (8) too (2) much gluten at Dairy Queen.

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34
Q

Disease assoc w/ HLA subtype DR2

A

Multiple sclerosis, hay fever, SLE, Goodpasture syndrome Multiple hay pastures are TWO dirty (DR2).

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35
Q

Disease assoc w/ HLA subtype DR3

A

DM type 1, SLE, Graves disease, Hashimoto thyroiditis, Addison disease 2-3, S-L-E.

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36
Q

Disease assoc w/ HLA subtype DR4

A

Rheumatoid arthritis, DM type 1, Addison disease There are 4 walls in 1 “rheum” (room).

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37
Q

Disease assoc w/ HLA subtype DR5

A

Hashimoto thyroiditis Hashimoto is an odd Dr (DR3, DR5).

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38
Q

How do NK cells induce apoptosis?

A

using perforins and granzymes or by antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound IgG, activating the NK cell).

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39
Q

NK cell activity activated by ?

A

enhanced by IL-2, IL-12, IFN-α, and IFN-β.

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40
Q

How is NK cell induced to kill?

A

Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of MHC I on target cell surface.

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41
Q

Functions of B cells

A

Humoral immunity. Recognize antigen—undergo somatic hypermutation to optimize antigen specificity. Produce antibody—differentiate into plasma cells to secrete specific immunoglobulins. Maintain immunologic memory—memory B cells persist and accelerate future response to antigen.

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42
Q

Functions of T cells

A

Cell-mediated immunity.
CD4+ T cells help B cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes.
CD8+ T cells directly kill virus-infected cells.
Delayed cell-mediated hypersensitivity (type IV).
Acute and chronic cellular organ rejection.

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43
Q

Explain where/how positive selection in the thymus happens

A

Thymic cortex. T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive.

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44
Q

Explain where/how negative selection in the thymus happens?

A

Thymic medulla. T cells expressing TCRs with high affinity for self antigens undergo apoptosis or become regulatory T cells

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45
Q

Issue with tissue restricted self antigen expression def?

A

Deficiency leads to autoimmune polyendocrine syndrome-1.

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46
Q

How are self antigen expressed in the thymus?

A

action of autoimmune regulator (AIRE)

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47
Q

What do Th1 cell secrete?

A

IFN-γ, IL-2

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48
Q

Function of Th1 cell?

A

Activates macrophages and cytotoxic T cells to kill phagocytosed microbes

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49
Q

Stimulation/Inhibition of Th1 cell?

A

Th1:

(+) by IFN-γ, IL-12

IFNy - from Th1 cells, so self stimulation
IL12 - from mac, T cells –> Th1 thru IL 12

(-) by IL-4, IL-10 (from Th2 cell)
Th2 (-) Th1

50
Q

Th2 cells secrete?

A

IL-4, IL-5, IL-6, IL-10, IL-13

51
Q

Function of Th2 cells?

A

Activates eosinophils and promotes production of IgE for parasite defense

52
Q

Stimulation/Inhibition of Th2 cell?

A

(+) by IL-2, IL-4 (-) by IFN-γ

53
Q

Secreted by Th17 cell?

A

IL-17, 1L-21, IL-22

54
Q

Fxn of Th17 cell?

A

Immunity against extracellular microbes, through induction of neutrophilic inflammation

55
Q

Stimulation/Inhibition of Th17 cell?

A

T17:
(+) by TGF-β, IL-1, IL-6

TGF-B - from Treg?
IL-1 & IL-6 - start of neutrophilic inflammation –> (+) T17
(-) by IFN-γ, IL -4

IFN-y - from Th1
IL 4 - from Th2

56
Q

Immunodef of Th17 leads to?

A

Hyper IgE syndrome

57
Q

Treg secretes?

A

TGF-β, IL-10, IL-35

58
Q

Fxn of Treg?

A

Prevents autoimmunity by maintaining tolerance to self antigens

59
Q

Stimulation/Inhibition of Tregs?

A

(+) by TGF-β, IL-2 (-) by IL-6

60
Q

Immunodef of Treg?

A

IPEX

61
Q

How do T cells and macrophages interact?

A

Th1 cells secrete IFN-γ, which enhances the ability of monocytes and macrophages to kill microbes they ingest. This function is also enhanced by interaction of T cell CD40L with CD40 on macrophages.

62
Q

Fxn of Tc cells?

A

Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis. Release cytotoxic granules containing preformed proteins (eg, perforin, granzyme B). Cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells.

63
Q

Fxn of Treg cells?

A

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

64
Q

Genetic def of FOXP3 leads to?

A

IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome

65
Q

Sx of IPEX?

A

Characterized by enteropathy, endocrinopathy, nail dystrophy, dermatitis, and/or other autoimmune dermatologic conditions. Associated with diabetes in male infants.

Sx/ severe watery diarrhea, mult exczematous rashes, born w/ hyperglycemia

66
Q

Give Ex of APCs?

A

B cells, dendritic cells, Langerhans cells, macrophages

67
Q

List the two signal req for T cell activation after an APC presents an Ag?

A

T-cell activation (signal 1): antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell. Endogenous or cross-presented antigen is presented on MHC I to Tc (CD8+) cell. Proliferation and survival (signal 2): costimulatory signal via interaction of B7 protein (CD80/86) on dendritic cell and CD28 on naïve T cell.

68
Q

Two signal req for B cell activation/class switching?

A

B-cell receptor–mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell. CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell.

69
Q

Fab region of Ab - what parts and fxn?

A

Fab (containing the variable/hypervariable regions) consisting of both light (L) and heavy (H) chains ;recognizes antigens.

70
Q

Fc region of Ab - what parts and fxn?

A

Fc region of IgM and IgG fixes complement, and where macrophages bind. only heavy chain

71
Q

What region of Ab determines idiotype?

A

Fab region

72
Q

Each B cell expresses specficity for how many Ag?

A

1 Ag

73
Q

What region of Ab determines isotype?

A

Fc region

74
Q

4 Cs of Fc region?

A

Fc: ƒ Constant ƒ Carboxy terminal ƒ Complement binding ƒ Carbohydrate side chains

75
Q

How do we form diverse Ab without an Ag binding?

A
  1. Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes 2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT) 3. Random combination of heavy chains with light chains
76
Q

How do we make Ab specific to an Ag?

A
  1. Somatic hypermutation and affinity maturation (variable region) 5. Isotype switching (constant region)
77
Q

What Ab do B cells express prior to activation?

A

All isotypes can exist as monomers. Mature, naïve B cells prior to activation express IgM and IgD on their surfaces.

78
Q

When do B cells produce other Ab?

A

They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement; induced by cytokines and CD40L) into plasma cells that secrete IgA, IgE, or IgG.

79
Q

What is the main Ab that responds to Ag - primary and secondary response?

A

primary - IgM secondary - IgG

80
Q

Most abundant isotype in serum?

A

IgG

81
Q

Fxn of IgG?

A

Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses.

82
Q

Which isotype of Ab crosses through the placenta? What type of immunity does it convey?

A

IgG ; passive immunity

83
Q

How does IgA help fight bacteria and virus infection?

A

Prevents attachment of bacteria and viruses to mucous membranes;

84
Q

What forms of IgA are there?

A

Monomer (in circulation) or dimer (with J chain when secreted)

85
Q

IgA is formed where (ex/) in the GI tract, fxn there?

A

Produced in GI tract (eg, by Peyer patches) and protects against gut infections (eg, Giardia).

86
Q

Where is IgA released?

A

Released into secretions (tears, saliva, mucus) and breast milk.

87
Q

Where does IgA pick up its secretory component? Fxn?

A

Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases

88
Q

Which two Ig fix complement?

A

IgM, IgG

89
Q

Forms of IgM?

A

Monomer on B cell, pentamer with J chain when secreted

90
Q

What types of cells does IgE bind to ?

A

mast cells and basophils

91
Q

What does IgE do in an allergic rxn?

A

cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine

92
Q

Which Ig is in lowest conc in serum?

A

IgE

93
Q

Difference between thymus independent and dependent antigens?

A

Independent Ag lacks a peptide component and can’t be presented by MHC to T cells, dependent Ag have a protein component

94
Q

Complement derived membrane attack complex defends against what organisms?

A

MAC defends against G - bacteria

95
Q

Function of C3b?

A

Binds to lipopolysaccharides on bacteria (as an opsonin), also helps clear immune complexes

96
Q

Function of different complement proteins

A

C3b—opsonization. C3a, C4a, C5a—anaphylaxis. C5a—neutrophil chemotaxis C5b-9—cytolysis by MAC.

97
Q

Major opsonins in bacterial defense?

A

C3b and IgG

98
Q

What inhibits complement activation on self cells?

A

DAF (decay accelerating factor CD55) and C1 esterase inhibtor

99
Q

what do opsonins do?

A

enhance phagocytosis

100
Q

Early complement deficiencies (C1-C4) - inc risk of what?

A

inc risk of severe, recurrent pyogenic sinus and respiratory tract infections. Increased risk of SLE.

101
Q

Terminal complement deficiencies (C5–C9) - inc risk of ?

A

susceptibility to recurrent Neisseria bacteremia.

102
Q

cause of hereditary angioedema? what drug causes angioedema due to similar mech?

A

C1 esterase inhibitor deficiency Causes hereditary angioedema due to unregulated activation of kallikrein –> inc bradykinin. ACE inhibitors are contraindicated (also inc bradykinin).

103
Q

How to detect c1 esterase inhibitor def/

A

dec C4 levels

104
Q

Tx for hereditary angioedema?

A

Danazol

105
Q

Disease with issue forming glycosylphosphatidylinositol (GPI) anchors for complement inhibitors?

A

PNH (Paroxysmal nocturnal hemoglobinuria)

106
Q

ex of complement inhibitors

A

decay-acclerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59)

107
Q

gene defective in PNH?

A

PIGA

108
Q

Drug vs PNH? Mech?

A

Eculizumab - vs. C5

109
Q

Fxn IL 1 - secreted by?

A

From macrophages

  • Causes fever, acute inflammation.
  • Activates endothelium to express adhesion molecules.
  • Induces chemokine secretion to recruit WBCs.
  • Also known as osteoclast-activating factor.
110
Q

IL 2 - secreted by? Fxn? Rx that is an analogue of it?

A

From all T cells

  • Stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells.
  • Aldesleukin - Renal Cell CA, Malignant melanoma
111
Q

IL 3 - secreted by? Fxn?
Rx that functions like GM- CSF?

A

From all T cells

  • Supports growth and differentiation of bone marrow stem cells.
  • ​Functions like GM-CSF. Stimulates the myeloid cell line - formation of granulocytes,etc
    IL 3 –> M
  • Filgrastim - fxn like GM-CSF
112
Q

IL 4 - secreted by? Fxn?

A

From Th2 cells

  • Induces differentiation of T cells into Th (helper) 2 cells.
  • Promotes growth of B cells.
  • Enhances class switching to IgE and IgG.

IL4 = Goes 4 Ever ==>IgG, IgE

Ain’t too proud 2 BEG 4 help. 2 - Th2 cells B - B cells EG - IgE IgG

113
Q

IL 5 - secreted by? Fxn?

A

From Th2 cells

  • growth and differentiation of B cells.
  • Enhances class switching to IgA.
  • Stimulates growth and differentiation of eosinophils
114
Q

IL 6 - secreted by? Fxn?

A

From Macrophages

  • Causes fever
  • ​stimulates production of acute phase proteins.
115
Q

IL 7 -

A

stimulates the lymphoid precursor line

116
Q

IL 8 - secreted by? fxn?

A

by macrophages
Major chemotactic factor for neutrophils

117
Q

Interleukin-10 - secreted by? fxn?

A

IL10
Secreted by Th2 and Treg cells

  • Attenuates inflammatory response.
  • Decreases expression of MHC class II and Th1 cytokines.
  • Inhibits activated macrophages and dendritic cells.
118
Q

Tumor necrosis factor-α - secreted by? fxn?

A

TNF alpha:

from macrophages

  • Activates endothelium.
  • Causes WBC recruitment, vascular leak.
  • Causes cachexia in malignancy.
  • Maintains granulomas in TB.
  • IL1, IL6 and TNF a all mediate fever, sepsis
119
Q

Interferon-γ - secreted by? fxn?

A

From NK and Th1 cells (1 = I (INF))

  • Secreted by NK cells and T cells in response to antigen or IL-12 from macrophages;
  • stimulates macrophages to kill phagocytosed pathogens.
  • Inhibits differentiation of Th2 cells.
  • Also activates NK cells to kill virus-infected cells.
  • Increases MHC expression and antigen presentation by all cells
120
Q

IL 12 - secreted by? fxn?

A

by macrophages

  • Induces differentiation of T cells into Th1 cells.
  • ​Activates NK cells.
121
Q

Which two cytokines attenuate immune response

A

TGF-B & IL10
TGF-β and IL-10 both attenuate the immune response.

122
Q

What is produced by Macrophages? (IL, etc)

A

IL 1 - fever, inflammation
IL 6 - fever, APP
IL 8 - neutrophils
IL12 - T –> Th1, (+) NK
TNF alpha - endothelium (+)’n, cachexia, granulomas in TB