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► Med - Step 1 > Immunology - First Aid > Flashcards

Immunology - First Aid Flashcards

1
Q

LN Follicle is the site of…

A

B-cell localization and proliferation.

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2
Q

In the outer cortex, primary follicles are…

A

dense and dormant.

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3
Q

Secondary follicles have…

A

pale central germinal centers.

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4
Q

The LN medulla consists of…

A

medullary cords (closely packed lymphocytes and plasma cells and medullary sinuses).

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5
Q

Medullary sinuses communicate with…

A

efferent lympmhatics and contain reticular cells and macrophages.

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6
Q

The LN paracortex houses…

A

T cells. It is the region of the cortex between the follicles and medulla.

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7
Q

The paracortex contains high endothelial venules through which…

A

T and B cells enter from the blood.

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8
Q

The paracortex is not well developed in…

A

pts with DiGeorge syndrome.

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9
Q

The paracortex enlarges in…

A

an extreme cellular immune response (ex. viral infection).

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10
Q

Cervical LNs drain…

A

the head and neck.

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11
Q

Hilar LNs drain…

A

the lungs.

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12
Q

Mediastinal LNs drain…

A

the trachea and esophagus.

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13
Q

Axillary LNs drain…

A

the upper limb, breast, and skin above the umbilicus.

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14
Q

Celiac LNs drain…

A

the liver, stomach, spleen, pancreas and upper duodenum.

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15
Q

Superior mesenteric LNs drain…

A

the lower duodenum, jejunum, ileum, and colon to the splenic flexure.

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16
Q

Inferior mesenteric LNs drain…

A

the colon from the splenic flexure to the upper rectum.

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17
Q

Internal iliac LNs drain…

A

the lower rectum to teh anal canal (above pectinate), bladder, vagina and prostate.

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18
Q

The para-aortic LNs drain…

A

testes, ovaries, kidneys and uterus.

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19
Q

The superficial inguinal LNs drain…

A

the anal canal (below pectinate), and skin below the umbilicus (except popliteal).

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20
Q

The popliteal LNs drain…

A

the dorsolateral foot and posterior calf.

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21
Q

The right lymphatic duct drains…

A

the right side of the body above the diaphragm.

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22
Q

The thoracic duct drains…

A

everything else into the junction of the left subclavian and internal jugular veins.

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23
Q

The sinusoids of the spleen are…

A

long, vascular channels in the red pulp with fenestrated “barrel hoop” basement membrane.

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24
Q

In the spleen, T cells are found in…

A

the periarterial lymphatic sheath within the white pulp.

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25
Q

In the spleen, B cells are found in…

A

follicles within the white pulp.

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26
Q

The marginal zone of the spleen is in between the…

A

red pulp and white pulp, contains APCs and specialized B cells, and is where APCs present blood-borne antigens.

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27
Q

Macrophages in the spleen act to…

A

remove encapsulated bacteria.

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28
Q

Splenic dysfunction (postsplenectomy, sickle cell) leads to…

A

decreased IgM which leads to decreased complement activation, which leads to decreased C3b opsonization which leads to increased susceptiblity to encapsulated organisms.

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29
Q

Encapsulated organisms

A

SHiNE SKis

  1. Strep pneumo
  2. H. influenzae
  3. N. meningitidis
  4. E. coli
  5. Salmonella
  6. Klebsiella
  7. group B Strep
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30
Q

Postsplenectomy Findings

A
  1. Howell-Jolly bodies (nuclear remnants)
  2. target cells
  3. thrombocytosis
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31
Q

The thymus is the…

A

site of T-cell differentiation and maturation. It is encapsulated.

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32
Q

The thymus comes from the…

A

epithelium of the 3rd pharyngeal pouches. Contains lymphocytes of mesenchymal origin.

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33
Q

The thymus cortex is…

A

dense with immature T cells.

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34
Q

The thymus medulla is…

A

pale with mature T cells and Hassall corpuscles containing epithelial reticular cells.

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35
Q

Components of Innate Immunity

A
  • neutrophils
  • macrophages
  • monocytes
  • dendritic cells
  • NK cells
  • complement
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36
Q

Components of Adaptive immunity

A
  • T cells
  • B cells
  • circulating antibodies
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37
Q

Innate immunity resistance

A
  • germline encoded

- resistance persists through generations, does not change within an organism’s lifetime

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38
Q

Adaptive immunity resistance

A
  • variation through VDJ recombination during lymphocyte development
  • microbial resistance not heritable
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39
Q

Innate immunity response to pathogens

A
  • nonspecific

- occurs rapidly (mins to hrs)

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40
Q

Adaptive immunity response to pathogens

A
  • hihgly specific, refined over time

- develops over long periods; memory response is faster and more robust

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41
Q

Physical barriers of the innate immune resposne

A
  • epithelial tight junctions

- mucus

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42
Q

Innate immunity secreted proteins

A

lysozyme
complement
CRP
defensins

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43
Q

Adaptive immunity secreted proteins

A

immunoglobulins

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44
Q

Innate immunity key features in pathogen recognition

A

-TLRs: pattern recognition receptors that recgonize PAMPs

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45
Q

examples of PAMPs include…

A

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

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46
Q

Adaptive immunity key features in pathogen recognition

A

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

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47
Q

MHC is encoded by…

A

HLA genes and presents antigen fragments to T cells and binds TCRs.

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48
Q

MHC I loci

A

HLA-A
HLA-B
HLA-C

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49
Q

MHC II loci

A

HLA-DR
HLA-DP
HLA-DQ

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50
Q

MHC I Binding

A

TCR and CD8

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51
Q

MHC II Binding

A

TCR and CD4

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52
Q

MHC I Expression

A

expressed on all nucleated cells; not expressed on RBCs

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53
Q

MHC II expression

A

only on APCs

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54
Q

MHC I Function

A

present endogenously synthesized antigens (viral) to CD8 cytotoxic T cells

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55
Q

MHC II Function

A

present exogenously synthesized protesin (bacterial proteins, viral capsid proteins) to T helper cells

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56
Q

MHC I Antigen loading

A

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

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57
Q

MHC II Antigen loading

A

antigen loaded following release of invariant chain in an acidified endosome

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58
Q

MHC I mode of transport to cell surface

A

Beta-2-microglobulin

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59
Q

HLA-A3 association

A

hemochromatosis

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60
Q

HLA-B27 association

A

Psoriatic arthritis
Ankylosing spondylitis
arthritis of IBD
Reactive arthritis

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61
Q

HLA-DQ2/DQ8 association

A

celiac disease

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62
Q

HLA-DR2 association

A

MS
hay fever
SLE
Goodpasture

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63
Q

HLA-DR3 association

A

T1DM
SLE
Graves

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64
Q

HLA-DR4 association

A

Rheumatoid arthritis

T1DM

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65
Q

HLA-DR5 association

A 
Pernicious anemia (leading to B12 deficiency)
Hashimoto
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66
Q

NK cells use…

A

perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.

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67
Q

Activity of NK cells is enhanced by…

A

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

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68
Q

NK cells are induced to kill when exposed to…

A

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

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69
Q

NK cells also kill via…

A

antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating the NK cell).

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70
Q

Major functions of B cells (3)

A
  1. recognize antigen
  2. produce antibody
  3. maintain immunologic memory
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71
Q

To recognize antigen, B cells…

A

undergo somatic hypermutaiton to optimize antigen specificity.

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72
Q

To proudce antibody, B cells differentiate into…

A

plasma cells to secrete specific Igs.

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73
Q

To maintain immunologic memory, memory B cells…

A

persist and accelerate future response to Ag.

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74
Q

CD4 T cells function to…

A

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

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75
Q

CD8 T cells function to…

A

kill virus-infected cells directly.

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76
Q

Other T cell functions

A
  • delayed cell-mediated hypersensitivity (type IV)

- acute and chronic cellular organ rejection

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77
Q

Positive selection occurs in the…

A

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

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78
Q

Negative selection occurs in the…

A

medulla. T cells expressing TCRs with high affinity for self antigen undergo apoptosis.

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79
Q

Antigen presenting cells (3)

A
  1. B cells
  2. macrophages
  3. dendritic cells
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80
Q

Two signals are required for (3):

A
  1. T cell activation
  2. B cell activation
  3. class switching
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81
Q

Naive T cell activation (4 steps)

A
  1. Foreign body is phagocytosed by the dendritic cell.
  2. Foreign Ag is presented on MHC II and recognized by TCR 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/kill virus-infected cells.
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82
Q

B cell activation and class switching (4 steps)

A
  1. Helper T cell activation
  2. B cell receptor-mediated endocytosis; foreing antigen 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 antibody production.
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83
Q

Th1 cell secretes…

A

IFN-gamma.

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84
Q

Th1 cell activates…

A

macrophages and cytotoxic T lymphocytes.

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85
Q

Th1 cell is inhibited by…

A

IL-4 and IL-10 (from the Th2 cell).

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86
Q

Th2 cell secretes…

A

IL-4, IL-5, IL-6, and IL-13.

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87
Q

Th2 cell recruits…

A

eosinophils for parasite defense and promotes IgE production by B cells.

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88
Q

Th2 cell is inhibited by…

A

IFN-gamma (from the Th1 cell).

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89
Q

Macrophage-lymphocyte interaction

A

Macrophages release IL-12 which stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-gamma to stimulate macrophages.

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90
Q

Cytotoxic T cells kill..

A

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

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91
Q

Cytotoxic T cells release…

A

cytotoxic granules containing preformed proteins:

  1. perforin that helps deliver content of granules into target cell
  2. granzyme B = a serine protease that activates apoptosis inside a target cell
  3. antimicrobial that induces apoptosis
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92
Q

Regulatory T cells help maintain specific immune tolerance by…

A

suppressing CD4 and CD8 T-cell effector functions.

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93
Q

Regulatory T cells are identified by expression of…

A

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

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94
Q

The part of antibody that recognizes antigen is…

A

variable part of L and H chains.

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95
Q

Fc portion of IgM and IgG acts to…

A

fix complement.

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96
Q

Heavy chain contributes to…

A

Fc and Fab fractions.

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97
Q

Light chain contributes to…

A

Fab fraction only.

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98
Q

Fab is the…

A

antigen binding fragment.

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99
Q

Fab determines…

A

the idiotype: it is a unique antigen-binding pocket. Only 1 antigenic specificity is expressed per B cell.

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100
Q

Fc is the…

A

constant region with a carboxy terminal. It binds complement and has carbohydrate side chains.

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101
Q

Fc region determines…

A

isotype (IgM, IgD, etc.)

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102
Q

Antibody diversity is generated by (4):

A
  1. random recombination of VJ (light chain) or VDJ (heavy chain) genes
  2. random combination of heavy chains
  3. somatic hypermutation (following Ag stimulation)
  4. addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
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103
Q

Mature lymphocytes express…

A

IgM and IgD on their surfaces.

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104
Q

Mature B lymphocytes may differentiate in…

A

germinal centers of LNs by isotype switching (gene rearrangement; mediated by cytokines and CD40 ligand) into plasma cells that secrete IgA, IgE or IgG.

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105
Q

IgG is the main antibody in…

A

secondary (delayed) response to an antigen. It is the most abundant isotype in the serum.

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106
Q

Actions of IgG

A
  • fixes complement
  • crosses placenta to provide infants w/ passive immunity
  • opsonizes bacteria
  • neutralizes bacterial toxins and viruses
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107
Q

IgA prevents…

A

attachment of bacteria and viruses to the mucous membranes. It does NOT fix complement.

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108
Q

IgA crosses epithelial cells by…

A

transyctosis. It is a monomer in circulation and a dimer when secreted.

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109
Q

IgA is the most..

A

produced antibody overall but is released into secretions (tears, saliva, mucus) and early breast milk (colustrum).

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110
Q

IgA picks up a…

A

secretory component from epithelial cells before secretion.

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111
Q

IgM is produced in…

A

the primary (immediate) response to an antigen. It fixes complement but does not cross the placenta.

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112
Q

Antigen receptor for IgM is on…

A

surface of B cells.

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113
Q

Form of IgM

A

monomer on B cell or pentamer when secreted; the pentamer shape allows it to efficiently trap free Ags out of tissue while the humoral response evolves.

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114
Q

IgD is found…

A

on the surface of many B cells and in the serum.

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115
Q

IgE binds…

A

mast cells and basophils. Has the lowest concentration in serum.

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116
Q

When exposed to an allergen, IgE will..

A

cross-linke mediating immediate (type I) hypersensitivity through the release of inflammatory mediators such as histamine.

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117
Q

IgE mediates immunity to…

A

worms by activating eosinophils.

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118
Q

Thymus-independent antigens are…

A

antigens lacking a peptide component (ex. lipopolysaccharides from gram-negative bacteria).

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119
Q

Thymus-independent antigens cannot be…

A

presented by MHC to T cells. They are weakly or non-immunogenic.

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120
Q

Vaccines for thymus-independent antigens often require…

A

boosters. (ex. pneumococcal polysaccharide vaccine).

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121
Q

Thymus-dependent antigens are…

A

antigens containing a protein component (ex. diphtheria vaccine).

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122
Q

As a result of direct contact between B cells with thymus-dependent antigens and Th cells, there is…

A

class switching and immunologic memory.

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123
Q

Acute phase reactants are…

A

factors whose serum concentrations change significantly in response to inflammation.

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124
Q

Acute phase reactants are produced by the…

A

liver in both acute and chronic inflammatory states.

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125
Q

Acute phase reactants are induced by…

A

IL-6, IL-1, TNF-alpha and IFN-gamma.

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126
Q

Positive Acute phase reactants

A
  • serum amyloid A
  • C-reactive protein
  • ferritin
  • fibrinogen
  • hepcidin
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127
Q

Negative acute phase reactants

A
  • albumin

- transferrin

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128
Q

Serum amyloid A

A

prolonged elevation can lead to amyloidosis

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129
Q

C-reactive protein

A

opsonin; fixes complement and facilitates phagocytosis

measured clinically as a sign of ongoing inflammation

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130
Q

Ferritin

A

binds and sequesters iron to inhibit microbial iron scavenging

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131
Q

Fibrinogen

A

coagulation factor; promotes endothelial repair; correlates with ESR

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132
Q

Hepcidin

A

prevents release of iron bound by ferritin leading to anemia of chronic disease

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133
Q

Albumin

A

reduction during acute phase reaction acts to conserve amino acids for positive reactants

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134
Q

Transferrin is downregulated in the acute phase to be…

A

internalized by macrophages to sequester iron.

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135
Q

Complement is a system of…

A

interacting plasma proteins that play a role in innate immunity and inflammation. MAC defends against gram-negative bacteria.

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136
Q

Activation of the Complement pathways

A

Classic pathway - IgG or IgM mediated
Alternative pathway - microbe surface molecules
Lectin pathway - mannose or other sugars on microbe surface

137
Q

Functions of complement

A

C3b - opsonization
C3a, C4a, C5a - anaphylaxis
C5a - neutrophil chemotaxis
C5b-9 - cytolysis by membrane attack complex

138
Q

The two primary opsonins in bacterial defense are…

A

C3b and IgG. C3b also helps clear immune complexes.

139
Q

Complement activation on self cells is prevented by…

A

decay-accelerating factor (DAF aka CD55) and C1 esterase inhibitor.

140
Q

C1 esterase inhibitor deficiency causes…

A

hereditary angioedema. ACE inhibitors are contraindicated.

141
Q

C3 deficiency increases risk of…

A

severe, recurrent pyogenic sinus and respiratory tract infections. It increases susceptibility to type III HSRs.

142
Q

C5-C9 deficiencies increase…

A

susceptibility to recurrent Neisseria bacteremia.

143
Q

DAF deficiency causes…

A

complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria.

144
Q

Cytokines secreted by macrophages

A 
IL-1
IL-6
IL-8
IL-12
TNF-alpha
145
Q

IL-1 is an…

A

endogenous pyrogen (aka osteoclast-activating factor).

146
Q

IL-1 causes…

A

fever and acute inflammation. It activated endothelium to express adhesion molecules and induces chemokine secretion to recruit leukocytes.

147
Q

IL-6 is an…

A

endogenous pyrogen that causes fever and stimulates production of acute phase reactants.

148
Q

IL-8 is the major…

A

chemotactic factor for neutrophils.

149
Q

IL-12 induces…

A

differnetiation of T cells into Th1 cells and activates NK cells.

150
Q

TNF-alpha mediates…

A

septic shock, activates the endothelium and causes leukocyte recruitment, vascular leak.

151
Q

Cytokines secreted by all T cells

A
  • IL-2

- IL-3

152
Q

IL-2 stimulates…

A

growth of helper, cytotoxic and regulatory T cells

153
Q

IL-3 supports the…

A

growth and differentiation of bone marrow stem cells. It functions like GM-CSF.

154
Q

Cytokine secreted by Th1 cells…

A

IFN-gamma.

155
Q

IFN-gamma has…

A

antiviral and antitumor properties. IT activates NK cells to kill virus-infected cells. It increases MHC expression and antigen presentation in all cells.

156
Q

Cytokines secreted from Th2 cells

A

IL-4
IL-5
IL-10

157
Q

IL-4 induces…

A

differentiation into Th2 cells. It promotes growth of B cells and enhances class switching to IgE and IgM.

158
Q

IL-5 promotes…

A

differentiation of B cells. It enhances class switching to IgA. Stimulates growth and differentiation of eosinophils.

159
Q

IL-10 modulates…

A

inflammatory response. It inhibits the actions of activated T cells and Th1.

160
Q

Interferon alpha and beta are a part of the…

A

innate host defense against both RNA and DNA viruses.

161
Q

Interferons are…

A

glycoproteins synthesized by viral-infected cells that act locally on uninfected cells “priming” thme for viral defense.

162
Q

When a virus infects a cell “primed” by interferons, the viral dsRNA activates:

A
  1. RNAase L (leading to degradation of viral/host mRNA
  2. protein kinase (leading to inhibition of viral/host protein synthesis)

*This essentially results in apoptosis, thereby interrupting viral amplification.

163
Q

T cell surface proteins

A
  1. TCR (binds antigen-MHC complex)
  2. CD3 (associated with TCR for signal transduction)
  3. CD28 (binds B7 on APC)
164
Q

Helper T cell surface proteins

A

CD4

CD40 ligand

165
Q

Cytotoxic T cell surface protein

A

CD8

166
Q

B cells surface proteins

A
  • Ig (binds antigens)
  • CD19, CD20, CD21 (receptor for EBV), CD40
  • MHC II, B7
167
Q

Macrophage surface proteins

A
  • CD14, CD40
  • MHC II, B7
  • Fc and C3b receptors (enhanced phagocytosis)
168
Q

NK cell surface proteins

A
  • CD16 (binds Fc of IgG)

- CD56 (unique marker for NK)

169
Q

Anergy is when…

A

self-reactive T cells become nonreactive without a costimulatory molecule.

170
Q

Superantigens (from S. pyogenes and S. aureus) act to…

A

cross-link the beta region of the T-cell receptor to the MHC class II on APCs. They can activate any T cell leading to a massive release of cytokines.

171
Q

Endotoxins/lipopolysaccharide (gram-negative bacteria) directly stimulate…

A

macrophages by binding to endotoxin receptor CD14; Th cells are not involved.

172
Q

Classic examples of Antigenic variation (5)

A
  1. Salmonella (2 flagellar variants)
  2. Borrelia (relapsing fever)
  3. Neisseria gonorrhae (pilus protein)
  4. influenza virus (major shift, minor drift)
  5. Trypanosomes (programmed rearrangement)
173
Q

Some mechanisms for variation include…

A

DNA rearrangement and RNA segment reassortment.

174
Q

Examples of passive immunity

A
  • IgA in breast milk
  • maternal IgG crossing placenta
  • antitoxin
  • humanized monoclonal antibody
175
Q

Examples of active immunity

A

natural infection
vaccines
toxoid

176
Q

Pts are given preformed antibodies (passive immunity) after exposure to…

A

tetanus toxin, botulinum toxin, HBV or Rabies.

177
Q

Combined passive and active immunizations can be given for…

A

hep B or rabies exposure.

178
Q

Live attenuated vaccine

A

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

179
Q

Pros of live attenuated vaccine

A

induces strong, lifelong immunity

180
Q

Cons of live attenuated vaccine

A

may revert to virulent form, often contraindicated in pregnancy and immune deficiency

181
Q

Examples of live attenuated vaccine

A
  • mumps
  • measles
  • rubella
  • polio (Sabin)
  • influenza (intranasal)
  • varicella
  • yellow fever
182
Q

Inactivated or killed vaccine

A

pathogen is inactivated by heat or chemicals; maintaining epitope structure on surface Ag is important; humoral immunity is induced.

183
Q

Pros of inactivated/killed vaccine

A

stable and safer than live vaccines

184
Q

Cons of inactivated/killed vaccine

A

weaker immune response, boosters usually required

185
Q

Examples of inactivated/killed vaccine

A
  • cholera
  • hep A
  • polio (salk)
  • influenza (injection)
  • rabies
186
Q

Type I Hypersensitivity is…

A

anaphylactic and atopic. Free antigen cross-links IgE on presensitized mast cells and basophils, triggering immediate release of vasoactive amines that act at postcapillary venules.

187
Q

In Type I HSR, the rxn develops…

A

rapidly after Ag exposure because of preformed Ab. The delayed response follows due to production of arachidonic acid metabolites (leukotrienes).

188
Q

Type I HSR test

A

skin test specific for IgE

189
Q

Type II HSR is…

A

cytotoxic (antibody mediated) - IgM, IgG bind to fixed Ag on “enemy” cell, leading to cellular destruction.

190
Q

3 mechanisms of Type II HSR

A
  1. opsonization leading to phagocytosis or complement activation
  2. complement-mediated lysis
  3. antibody-dependnet cell-mediated cytotoxicity, usually due to NK cells or macrophages
191
Q

In Type II HSR, antibody and complement lead to…

A

MAC.

192
Q

Test for Type II HSR

A

direct and indirect Coombs

193
Q

Direct Coombs

A

detects antibodies that have adhered to pt’s RBCs

ex. test an Rh+ infant of an Rh- mother

194
Q

Indirect Coombs

A

detects antibodies that can adhere to other RBCs

ex. test an Rh- woman for Rh+ antibodies

195
Q

Type III HSR is…

A

immune complex - antigen-antibody (IgG) complexes activate complement which attracts neutrophils; neutrophils release lysosomal enzymes.

196
Q

Serum sickness is…

A

an immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes 5 days). IMmune complexes forma and are deposited in membranes where they fix complement (leading to tissue damage).

197
Q

Most serum sickness is now caused by…

A

drugs acting as haptens. Fever, urticaria, arthralgias, proteinuria, lymphaadenopathy 5-10 days after exposure.

198
Q

Arthus rxn is a…

A

local, subacute antibody-mediated HSR type III. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin.

199
Q

Arthus rxn is characterized by…

A

edema, necrosis, and activation of complement.

200
Q

Test for Arthus rxn (or Type III HSRs)

A

immunofluorescent staining

201
Q

Type IV HSR is a…

A

delayed (T cell mediated) type. Sensitized T lymphocytes encoutner antigen and then release lymphokines which leads to macrophase activation.

NO antibody involved.

202
Q

Test of Type IV HSR

A

patch test, PPD

203
Q

Examples of Type I HSR

A
  1. anaphylaxis (bee sting, food/drug allergy)

2. allergic/atopic disorders (rhinitis, hay fever, eczema, hives, asthma)

204
Q

Presentation of Type I HSR

A

immediate, anaphylactic, atopic

205
Q

Presentation of Type II HSR (8)

A
  1. autoimmune hemolytic anemia
  2. pernicious anemia
  3. ITP
  4. erythroblastosis fetalis
  5. rheumatic fever
  6. goodpasture syndrome
  7. bullous pemphigoid
  8. pemphigus vulgaris
206
Q

Presentation of Type II HSR

A

disease tends to be specific to tissue or site where antigen is found

207
Q

Type III HSR examples (5)

A
  1. SLE
  2. polyarteritis nodosa
  3. poststreptococcal glomerulonephritis
  4. serum sickness
  5. arthus rxn
208
Q

Type III HSR presentation

A

associated with vasculitits and systemic manifestations

209
Q

Type IV HSR examples (5)

A
  1. MS
  2. Guillain-Barre
  3. GVHD
  4. PPD (test for TB)
  5. Contact dermatitis (poison ivy, nickel allergy)
210
Q

Allergic rxn to blood tranfusion pathogenesis

A

Typer I HSR against plasma proteins in transfused blood.

211
Q

Allergic rxn to blood transfusion presentation

A

urticaria, pruritis, wheezing, fever. Treat with antihistamines.

212
Q

Anaphylactic rxn to blood transfusion pathogenesis

A

severe allergic rxn; IgA-deficient individuals must receive blood products that lack IgA

213
Q

Anaphylactic rxn to blood transfusion presentation

A

dyspnea, bronchospasm, hypotension, respiratory arrest, shock

214
Q

Febrile nonhemolytic transfusion rxn pathogenesis

A

Type II HSR. Host antibodies agaisnt donor HLA Ags and leukocytes.

215
Q

Febrile nonhemolytic transfusion rxn presentation

A

fever, HAs, chills, flushing

216
Q

Acute hemolytic transfusion rxn pathogenesis

A

Type II HSR. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host Ab rxn against foreign antigen on donor RBCs).

217
Q

Acute hemolytic trasnfusion rxn presentation

A

fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), and jaundice (extravascular hemolysis).

218
Q

Anti-Ach receptor

A

myasthenia gravis

219
Q

Anti-basement membrane

A

goodpasture syndrome

220
Q

anti-cardiolipin, lupus antigocagulant

A

SLE, antiphospholipid syndrome

221
Q

anticentromere

A

limited sclerosderma (CREST syndrome)

222
Q

anti-desmoglein

A

pemphigus vulgaris

223
Q

Anti-dsDNA, anti-Smith

A

SLE

224
Q

anti-glutamate decarboxylase

A

T1DM

225
Q

anti-hemidesmosome

A

bullous pemphigoid

226
Q

antihistone

A

drug-induced lupus

227
Q

anti-Jo-1, anti-SRP, anti-Mi-2

A

polymyositis, dermatomyositis

228
Q

antimicrosomal, antithyroglobulin

A

Hashimoto thyroiditis

229
Q

antimitochondrial

A

primary biliary cirrhosis

230
Q

antinuclear antibodies

A

SLE (nonspecific)

231
Q

anti-Scl-70 (anti-DNA topoisomerase I)

A

scleroderma (diffuse)

232
Q

anti-smooth muscle

A

autoimmune hepatitis

233
Q

anti-SSA, anti-SSB (anti-Ro, anti-La)

A

Sjogren syndrome

234
Q

Anti-TSH receptor

A

graves

235
Q

Anti-U1 RNP (ribonucleoprotein)

A

mixed CT disease

236
Q

c-ANCA (PR3-ANCA)

A

granulomatosis with polyangiitis (Wegener)

237
Q

IgA antiendomysial, IgA anti-tissue transglutaminase

A

celiac disease

238
Q

p-ANCA (MPO-ANCA)

A

microscopic polyangiitis, Churg-Strauss

239
Q

Rheumatoid factor (antibody, most commonly IgM, specific to IgG Fc region), anti-CCP

A

Rheumatoid arthritis

240
Q

Patients with no T cells are susceptible to bacterial…

A

sepsis.

241
Q

Pts with no T cells viral susceptibility

A 
CMV
EBV
JCV
VZV
chronic infx with respiratory/GI viruses
242
Q

PTs with no T cells fungal/parasitic susceptibility

A

Candida, PCP

243
Q

Pts with No B cells bacterial susceptibility

A

Encapsulated bacteria

244
Q

Pts with No B cells viral susceptibility

A

Enteroviral encephalitis, poliovirus (live vaccine contraindicated)

245
Q

Pts with No B cells fungal/parasitic susceptibility

A

Giardia (no IgA)

246
Q

Pts w/ no granulocytes bacterial susceptibilty

A

Staph
Burkholderia cepacia
Serratia
Nocardia

247
Q

Pts with no granulocytes fungal/parasitic susceptibility

A

Candida

Aspergillus

248
Q

Pts with no complement bacterial susceptibility

A

Neisseria (no MAC)

249
Q

B-cell deficiencies are tend to produce…

A

recurrent bacteiral infxns while T-cell deficiencies tend to produce more fungal and viral infections.

250
Q

X-linked (Bruton) agammaglobulinemia defect

A

Defect in BTK, a tyrosine kinase gene leading to no B cell maturation.

251
Q

X-linked agammaglobulinemia presentation

A

recurrent bacterial and enteroviral infxns after 6 months (decreased maternal IgG).

252
Q

Findings of X-linked agammaglobulinemia

A
  • normal CD19+ B cell count
  • decreased pro-B
  • decreased Ig of all classes
  • absent LNs and tonsils
253
Q

Selective IgA deficiency presentaiton

A
  • usually asymptomatic
  • can see airway and GI infections
  • autoimmune disease
  • atopy
  • anaphylaxis to IgA-containing products
254
Q

Findings of IgA deficiency

A

-IgA

255
Q

Common variable immunodeficiency defect

A

defect in B-cell differentiation

256
Q

Common variable immunodeficiency presentation

A

-can be acquired in 20-30s; increased risk of autoimmune disease, bronchiechtasis, lymphoma, sinopulmonary infxns

257
Q

Findings of common variable immunodeficieincy

A
  • decreased plasma cells

- decreased immunoglobulins

258
Q

DiGeorge syndrome (Thymic aplasia) defect

A
  • 22q11 deletion

- failure to develop 3rd and 4th pharyngeal pouches (leading to an absent thymus and parathyroids)

259
Q

Digeorge Syndrome presentation

A
  • tetany (hypocalcemia)
  • recurrent viral/fungal infxns (T-cell deficiency)
  • conotruncal abnormalities (tetralogy of fallot and truncus arteriorsus)
260
Q

Findings of DiGeorge

A
  • decreased T cells
  • decreased PTH
  • decreased calcium
  • absent thymic shadow on CXR
  • 22q11 deletion detected by FISH
261
Q

IL-12 recptor deficiency defect

A

decreased Th1 response; autosomal recessive

262
Q

IL-12 receptor deficiency presentation

A

disseminated mycobacteiral and fungal infxns; may present after administration of BCG vaccine

263
Q

Findings of IL-12 receptor deficiency

A

decreased IFN-gamma

264
Q

Autosomal dominant hyper-IgE syndrome (Job syndrome) defect

A

-deficiency of Th17 cells due to STAT3 mutation leading to impaired recrutiment of neutrophils to the site of infxn

265
Q

Autosomal dominant hyper-IgE syndrome presentation

A
  • coarse Facies
  • cold staphylococcal abscesses
  • retained primary teeth
  • dermatolgic problems (eczema)
266
Q

Findings of autosomal dominant hyper-IgE syndrome

A
  • increased IgE

- decreased IFN-gamma

267
Q

Chronic mucocutaneous candidiasis defect

A

T-cell dysfunction

268
Q

Chronic mucocutaneous candidiasis presnetation

A

noninvasive candida infections of the skin and mucous membranes

269
Q

Findings of chronic mucocutaneous candidiasis

A
  • absent invitro T-cell proliferation in response to candida

- absent cutaneous rxn to candida antigens

270
Q

Severe combined immunodeficiency (SCID) defect

A

several types including defective IL-2R gamma chain (most common, X-linked), adenosine deaminase deficiency (autosomal recessive)

271
Q

SCID presentation

A
  • FTT
  • diarrhea
  • thrush
  • recurrent viral, bacterial, fungal and protzoal infxns
272
Q

SCID treatment

A

bone marrow transplant

273
Q

Findings of SCID

A
  • decreased T cell receptor excision circles (TRECs)
  • absense of thymic shadow
  • absence of germinal centers (LN biopsy)
  • absence of T cells (flow cytometry)
274
Q

Ataxia-telangiectasia defect

A

defects in ATM gene leading to DNA double strand breaks leading to cell cycle arrest

275
Q

Ataxia-telangiectasia presentation

A 
cerebellar defects (ataxia)
spider angiomas (telangiectasia)
IgA deficiency
276
Q

Ataxia-telangiectasia findings

A
  • increased AFP
  • decreased IgA, IgG, IgE
  • lymphopenia
  • cerebellar atrophy
277
Q

Hyper-IgM syndrome defect

A

most commonly due to defective CD40L on Th cells (class switching defect); X-linked

278
Q

Presentation of Hyper-IgM syndrome

A

severe pyogenic infections early in life; opportunistic infxn with Pneumocystis, Cryptosporidium, CMV.

279
Q

Findings of Hyper-IgM syndrome

A
  • increased IgM

- decreased IgG, IgA, IgE

280
Q

Wiskott-Aldrich syndrome defect

A
  • mutation in WAS gene (x-linked recessive)

- T cells unable to reorganize actin skeleton

281
Q

Presentation of Wiskott-Aldrich

A
  • Thrombocytopeic purpura
  • eczema (esp. trunk)
  • recurrent infections
  • increased risk of atuoimmune disease and malignancy
282
Q

Findings of Wiskott-Alrdrich

A
  • decreased/normal IgG, IgM
  • increased IgE, IgA
  • fewre and smaller platelets
283
Q

Leukocyte adhesion deficiency (LAD) type I Defect

A

defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; AR

284
Q

LAD type I presentation

A

recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord

285
Q

LAD type I findings

A
  • increased neutrophils

- absence of neutrophils at infection sites

286
Q

Chediak-Higashi syndrome defect

A

defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; AR

287
Q

Chekiak-Higashi syndrome presentation

A

recurrent pyogenic infxns by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis

288
Q

Chediak-higashi findings

A
  • giant granules in neutrophils and platelets
  • pancytopenia
  • mild coagulation defects
289
Q

Chronic granulomatous disease defect

A

defect of NADPH oxidase leading to decreased ROS and absent respiratory burst in neutrophils; X-linked

290
Q

Chronic granulomatous disease presentation

A

increased susceptiblity to catalase positive organisms

291
Q

Findings of chronic granulomatous disease

A
  • abnormal dihydrorhodamine test

- nitroblue tetrazolium dye reduction test is negative

292
Q

Hyperacute (w/i minutes) transplant rejection pathogenesis

A

pre-existing recipient antibodies react to donor antigen (type II HSR) and activate complement

293
Q

Hyper acute rejection features

A

widespread thrombosis of graft vessesl leading to ischemia/necrosis.

(graft must be removed)

294
Q

Acute rejection (wks to months) pathogenesis

A

Cellular: CTLs activated against donor MHCs

Humoral: similar to hyperacute, excpt antibodies develop after transplant

295
Q

Acute rejection features

A
  • vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
  • prevent/reverse with immunosuppressants
296
Q

Chronic (months to years) rejection pathogenesis

A

recipient T cells perceive donor MHC as recipient MHC and react against donor antigens presented; both cellular and humoral components

297
Q

Chronic rejection features

A
  • irreversible; t-cell and antibody mediated damage
  • Heart: atherosclerosis
  • Lungs: bronchiolitis obliterans
  • Liver: vanishing bile ducts
  • Kidney: vascular fibrosis, glomerulopathy
298
Q

GVHD pathogenesis

A

grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with “foreign” proteins leading to severe organ dysfunction

299
Q

Features of GVHD

A
  • maculopapular rash, jaundie, diarrhea, hepatosplenomegaly
  • usually in bone marrow and liver transplants (rich in lymphocytes)
  • potentially beneficial in BMT for leukemia (graft vs. tumor)
300
Q

Cyclosporine MOA

A

calcineurin inhibitor; binds cyclphilin; blocks T-cell activation by preventing IL-2 transcription

301
Q

Use of cyclosporine

A

transplant rejection prophylaxis
psoriasis
RA

302
Q

Toxicity of Cyclosporine

A
  • Nephrotoxicity**
  • HTN
  • hyperlipidemia
  • hyperglycemia
  • tremor
  • hirsutism
  • gingival hyperplasia
303
Q

Tacrolimus MOA

A

calcineurin inhibitor; binds FK506 binding protein; blocks T cell activation by preventing IL-2 transcription

304
Q

Use of Tacrolimus

A

transplant rejection prophylaxis

305
Q

Toxicity of Tacrolimus

A
  • increased risk of diabetes and neurotoxicity

- nephrotoxic**

306
Q

Sirolimus MOA

A

mTOR inhibitor; binds FKBP

blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction

307
Q

Use of Sirolimus

A

kidney transplant rejection prophylaxis

308
Q

Toxicity of Sirolimus

A
  • anemia
  • thrombocytopenia
  • leukiopenia
  • insulin resistance
  • hyperlipidemia
  • NON-nephrotoxic
309
Q

Basiliximab MOA

A

monoclonal antibody; blocks IL-2R

310
Q

Basiliximab Use

A

kidney transplant rejection prophylaxis

311
Q

Basiliximab Toxicity

A

edema
HTN
tremor

312
Q

Azathioprine MOA

A

antimetabolite precursor of 6-MP; inhibits lymphocyte proliferation by blocking nucleotide synthesis

313
Q

Azathioprine use

A
  • transplant rejection prophylaxis
  • RA
  • Crohn disease
  • glomerulonephritis
314
Q

Azathioprine toxicity

A
  • leukopenia
  • anemia
  • thrombocytopenia
315
Q

Glucocorticoids MOA

A

inhibit NF-kappaB; suppress both B and T cell fxn by decreasing transcription of many cytokines

316
Q

Use of Glucocorticoids

A
  • transplant rejection prophylaxis (immune suppression)

- inflammation

317
Q

Toxicity of Glucocorticoid

A
  • hyperglycemia
  • osteoporosis
  • central obesity
  • muscle breakdown
  • psychosis
  • acne
  • HTN
  • cataracts
  • peptic ulcers
318
Q

Glucocorticoids can cause iatrogenic…

A

Cushing Syndrome.

319
Q

Epoeitin alfa (erythropoietin) is used for…

A

anemias esp. in renal failure.

320
Q

Thrombopoietin is used in…

A

thrombocytopenia.

321
Q

Oprelvekin (IL-11) is used in…

A

thrombocytopenia.

322
Q

Filgrastim (granulocyte colony-stimulating-factor) is used in…

A

recovery of bone marrow.

323
Q

Sagramostim (granulocyte-macrophage colongy-stimulating factor) is used in…

A

recovery of bone marrow.

324
Q

Aldesleukin (IL-2) is used in…

A

renal cell carcinoma and metastatic melanoma.

325
Q

IFN-alpha is used in…

A

Hep B/C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC, and malignant melanoma

326
Q

IFN-beta is used in..

A

MS.

327
Q

IFN-gamma is used in…

A

chronic granulomatous disease

328
Q

Alemtuzumab targets…

A

CD52 and is used for CLL.

329
Q

Bevacizumab targets…

A

VEGF and is used in colorectal cancer and RCC.

330
Q

Cetuximab targets…

A

EGFR and is used in Stage IV colorectal cancer and head/neck cancer.

331
Q

Rituximab targets…

A

CD20 and is used in B-cell non-hodgkin lymphoma, RA, and ITP

332
Q

Trastuzumab targets…

A

HER2/neu and is used in breast cancer and gastric cancer.

333
Q

Infliximab and adalimumab target…

A

TNF-alpha and are used in IBD, RA, ankylosing spondyliits and psoriasis.

334
Q

Natalizumab targets…

A

alpha4-integrin and is used in MS and Crohn disease.

335
Q

Abciximab targets…

A

glycoprotein IIb/IIIa and is used as an anti-platelet agent for prevention of ischemic complications in pts undergoing percutaneous coronary intervention.

336
Q

Denosumab targets…

A

RANKL and is used in osteoporosis to inhibit osteoclast maturation.

337
Q

Digoxin immune Fab targets…

A

digoxin and is used for digoxin toxicity.

338
Q

Omalizumab targets…

A

IgE and is used for allergic asthma; it prevents IgE binding to FcepsilonRI.

339
Q

Palvizumab targets…

A

RSV F protein and is used for RSV prophylaxis for high-risk infants.

► Med - Step 1 (31 decks)

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