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MOD1 > robbins ch. 6 > Flashcards

robbins ch. 6 Flashcards

1
Q

What are the major components of the innate immunity?

A
  • epithelial barrier
  • Phagocytic cells (mainly neutrophils and macrophages)
  • dendritic cells
  • NK cell
  • plasma proteins (complement)
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2
Q

what antimicrobial molecule does the epithelium produce?

A

defensins

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3
Q

Natural killer cells provide early protection against what?

A

viruses and intracellular bacteria

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4
Q

What circulating proteins of innate immunity coat microbes and promote phagocytosis?

A

Mannose-binding lectin and C-reactive protein

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5
Q

cellular receptors that recognize pamps and damps are called what?

A

pattern recognition receptors

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6
Q

TLRs signal by a common pathway that culminates in the activation of what transcription factors?

A

NF-kappaB and Interferon regulatory factors (IRFs)

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7
Q

When NF-kappaB is activated by a TLR, what happens?

A

stimulates the synthesis and secretion of cytokines and expression of adhesion molecules, both of which are critical for recruitment and activation of leukocytes

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8
Q

When IRFs are activated by a TLR, what happens?

A

stimulates the production of antiviral cytokines, type I interferons.

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9
Q

What receptors are cytossolic receptors that recognize a wide variety of substances including products from necrotic cells, ion disturbances, and some microbial products?

A

Nod-like receptors (NLRs)

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10
Q

The NLRs that signal via the inflammasome actives what enzyme to cleave what?

A

caspase-1 to cleave and produce active IL-1

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11
Q

IL-1 is a mediator of inflammation that does what?

A

rectruits leukocytes and induces fever

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12
Q

Gain of function mutations in one of the NLRs results in what?

A

periodic fever syndromes called autoinflammatory syndromes

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13
Q

Autoinflammatory syndromes respond very well to treatments with what?

A

IL-1 antagonist

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14
Q

What receptors expressed on the plasma membrane of macrophages and dendritic cells detect fungal glycans and elicit inflammatory reactions to fungi?

A

C-type lectin receptors (CLRs)

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15
Q

What receptors are located in the cytosol of most cell types and detect nucleic acids of viruses that replicate in the cytoplasm of infected cells?

A

RIG-like receptors (RLRs)

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16
Q

What do RLRs stimulate the production of?

A

antiviral cytokines

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17
Q

What do G protein coupled receptos on neutrophils, macrophages, and most other types of leukocytes recognize?

A

short bacterial peptides containing N-formylmethionyl residues

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18
Q

What does recognition by the G protein receptor on neutrophils cause?

A

chemotactic responses

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19
Q

What receptors recognize microbial sugars and induce phagocytosis of the microbes?

A

mannose receptors

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20
Q

What are the 2 main mechanisms of innate immunity?

A

inflammation and antiviral defense

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21
Q

Type I interferon

A

Anti-viral

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22
Q

Mature lymphocytes that have not encountered the antigen for which they are specific are said to be what?

A

naive

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23
Q

After naive cells are activated by recognition of antigens and other signals, they differentiate into what 2 cells?

A

effector cells and memory cells

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24
Q

The enzyme in developing lymphocytes that mediates recombination of gene segments is the product of what genes?

A

RAG-1 and RAG-2 (recombination activating genes)

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25
Q

what is the difference between germline antigen receptor genes of T and B cells and other parts of the body?

A

There are recombined in T and B cells

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26
Q

What is a valuable assay for detecting tumors derived from lymphocytes?

A

analysis of antigen receptor gene rearrangements

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27
Q

Stucture of a TCR?

A

a disulfide-linked heterodimer made up of an alpha and beta polypeptide chain each have a variable (antigen binding) region and a constant region

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28
Q

What do the alpha and beta chains of the TCR recognize?

A

peptide antigens that are presented by MHC molecules on the surface of antigen-presenting cells.

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29
Q

What TCR recognizes peptides, lipids, and small molecules without a requirement for display by MHC proteins?

A

gamma/delta

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30
Q

what T cells recognize glycolipids that are displayed by the MHC-like molecule CD1?

A

NK-T cells

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31
Q

What antibodies present on the surface of all mature, naive B cells?

A

IgM and IgD

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32
Q

What do B cells develop into after stimulation by antigen and other signals?

A

plasma cells

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33
Q

What are the invariant proteins that are also contained in the B-cell antigen receptor complex?

A

Ig-alpha (CD79a) and Ig-beta (CD79b)

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34
Q

what do B cells express that recognize complement products generated during innate immune responses?

A

type 2 complement receptor (CR2 or CD21)

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35
Q

What do B cells express that receives signals from helper T cells?

A

CD40

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36
Q

What is used by the Epstein-Barr viurs (EBV) as a receptor to enter and infect B cells?

A

CR2 or CD21

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37
Q

What are the most important antigen-presenting cells for initiating T-cell responses against protein antigens?

A

Dendritic cells

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38
Q

immature dendritic cells within the epidermis are called what?

A

langerhans cells

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39
Q

What are the cells that bear Fc receptors for IfG and receptor for C3b and trap antigens bound to antibodies to present to B cells?

A

follicular dendritic cells

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40
Q

What cells function to destroy irreversibly stressed and abnormal cells such as virus infected cells and tumor cells?

A

NK cells

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41
Q

What 2 cell surface molecules are commonly used to identify NK cells?

A

CD16 and CD56

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42
Q

Describe the CD16 on NK cells and what it is used for?

A

Fc receptor for IgG; gives NK cells the ability to lyse IgG coated target cells. known as antibody-dependent cell-mediated cytotoxicity (ADCC)

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43
Q

What family of receptors is the best characterized ACTIVATING receptors on NK cells?

A

NKG2D family

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44
Q

What do NK cell inhibitory receptors recognize?

A

self class I MHC molecules which are expressed on all healthy cells

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45
Q

What do NK cells secrete?

A

IFN-gamma which activates macrophages

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46
Q

What cytokines regulate NK cells?

A

IL-2, IL-15, and IL-12

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47
Q

what do IL-2 and IL-15 do to NK cells?

A

stimulate proliferation

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48
Q

What does IL-12 do to NK cells?

A

activates killing and secretion of IFN-gamma

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49
Q

The Thymus and Bone marrow are consider what type of organs?

A

Generative lymphoid organs because T and B lymphocytes mature and become competent to respond to antigens

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50
Q

What are the peripheral lymphoid organs?

A
  • lymph nodes
  • spleen
  • the mucosal and cutaneous lymphoid tissues
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51
Q

In the morphology of the lymph node, the B cells are located where?

T cells?

A

Follicles in the Cortex

paracortex adjacent to the follicle

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52
Q

If the B cells in a follicle have recently responded to an antigen, this follicle may contain a central region called what?

A

germinal center

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53
Q

In the spleen, T lymphocytes are concentrated where?

B cells?

A

periarteriolar lymphoid sheaths surrounding small arterioles

follicles

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54
Q

Why do T lymphocytes need to recirculate and B cells can remain in lymphoid organs and the bone marrow?

A

T cells have to go find the antigens or the infections while B cells secrete antibodies that can be carried by the blood to distant tissues

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55
Q

In humans, the MHC molecules are called what?

A

human leukocyte antigens (HLA)

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56
Q

The genes encoding HLA molecules are clustered on a small segments of what chromosome

A

chromosome 6

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57
Q

Where are Class I MHC molecules expressed?

A

all nucleated cells and platelets

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58
Q

Describe the structure of the class I MHC molecule

A

heterodimer; polymorphic alpha or heavy chain linked to nonpolymorphic beta-2-microglobulin

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59
Q

The alpha chain of the class I MHC molcule are encoded by what 3 genes?

A

HLA-A, HLA-B, and HLA-C

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60
Q

the nonplymorphic alpha-3 domain of class I MHC molecules has a binding site for what?

A

CD8

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61
Q

Class II MHC molecules are encoded in a region called what? which has what 3 subregions?

A

HLA-D; HLA-DP, HLA-DQ, and HLA-DR

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62
Q

Describe the structure of the class II MHC molecule

A

heterodimer; polymorphic alpha and beta chains both which have 2 domains.

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63
Q

Where is the peptide binding cleft in the class II MHC molecule?

A

formed by an interaction of the alpha 1 and beta 1 domains

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64
Q

Class II MHC molecules present what antigens?

A

those that are internalized into vesicles and are typically derived from extracellular microbes and soluble proteins

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65
Q

what cells express class II MHC molecules?

A

macrophages, B lymphocytes, and dendritic cells

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66
Q

What are the innate immunity cytokines?

A
  • TNF
  • IL-1
  • IL-12
  • Type 1 IFNs
  • IFN-gamma
  • chemokines
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67
Q

in adaptive immune responses, cytokines are produced principally by what?

A

CD4+ T lymphocytes activated by antigen

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68
Q

what are the main cytokines of the adaptive immune system?

A
  • IL-2
  • IL-4
  • IL-5
  • IL-17
  • IFN-gamma
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69
Q

What cytokines serve mainly to limit and terminate immune responses?

A

TGF-beta and IL-10

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70
Q

Some cytokines stimulate hematopoiesis and are called what?

A

colony-stimulating factors (CSFs)

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71
Q

2 examples of CSFs

A

GM-CSF and IL-7

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72
Q

Therapy for rheumatoid arthritis?

A

TNF antagonist

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73
Q

What are the microbial mimics given in an immunization called?

A

adjuvants

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74
Q

What are the principal costimulators for T cells that are expressed on antigen presenting cells?

A

B7 proteins (CD80 and CD86)

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75
Q

What on T cells recognize CD80 or CD86?

A

CD28

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76
Q

what is one of the earliest responses of CD4+ helper T cells?

A
  • secretion of IL-2

- expression of high-affinity receptors for IL-2

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77
Q

what does IL-2 do?

A

growth factor that act on T lymphocytes and stimulates their proliferation, leading to an increases in the number of antigen-specific lymphocytes

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78
Q

The functions of helper T cells are mediated by what?

A

CD40L and cytokines

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79
Q

Cells of the Th1 subset secrete what cytokine?

A

IFN-gamma

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80
Q

What does IFN-gamma from Th1 cells do?

A

macrophage activation and stimulations of IgG

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81
Q

What cytokines induce the Th1 subset?

A

IFN-gamma and IL-12

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82
Q

Th1 protects against what?

A

intracellular microbes

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83
Q

What do Th2 secrete?

A

IL-4, IL-5, and IL-13

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84
Q

What cytokine induces Th2 subset?

A

IL-4

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85
Q

What does IL-4 from Th2 do?

A

B cells to IgE secreting plasma cells

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86
Q

What does IL-5 from Th2 do?

A

activates eosinophils

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87
Q

What do Th2 protect against?

A

helminthic parasites

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88
Q

Th2 cells induce what pathway of macrophage activation?

A

alternative which is associated with tissue repair and fibrosis

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89
Q

Th17 produce what cytokines?

A

IL-17 and IL-22

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90
Q

What cytokines induce Th17?

A

TGF-beta, IL-6, IL-1, and IL-23

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91
Q

what does IL-17 from Th17 do?

A

recruit neutrophils and monocytes

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92
Q

what does Th17 protect against?

A

extracellular bacteria and fungi

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93
Q

Polysaccharides and lipids stimulate secretion mainly of what antibody?

A

IgM

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94
Q

Isotype switching is induced by what cytokines?

A

IFN-gamma and IL-4

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95
Q

Isotype switching and affinity maturation occur mainly where?

A

germinal centers

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96
Q

Which antibody opsonizes microbes?

A

IgG

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97
Q

What antibodies activate the complement system by the classical pathway?

A

IgG and IgM

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98
Q

What antibody is secreted from mucosal epithelia and neutralizes microbes in the lumens of the respiratory and GI tracts?

A

IgA

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99
Q

What antibody is actively transported across the placenta and protects the newborn until the immune system becomes mature?

A

IgG

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100
Q

Name the hypersensitivity: immediate, caused by Th2 cells, IgE antibodies and mast cells.

A

Type 1

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101
Q

Name the hypersenstivity: antibody-mediated, secreted IgG and IgM injure cells by promoting their phagocytosis or lysis and injure tissues by inducing inflammation

A

Type 2

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102
Q

Name the hypersensitivity: immune complex mediated. IgG and IgM bind antigens usually in the circulation, and the antigen-antibody complexes deposit in tissues and induce inflammation

A

type 3

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103
Q

Name the hypersensitivity: cell-mediated. sensitized T lymphocytes (Th1, Th17, and CTLs) are the cause of the tissue damage.

A

Type 4

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104
Q

Type I hypersensitivity reactions are often also called what?

A

allergy

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105
Q

What are the well defined phases of many local type I hypersensitivity reactions?

A

Immediate reaction and Late-phase reaction

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106
Q

What chemokines, drugs, and physical stimuli cause secretion of mast cell granules?

A
  • IL-8
  • Codeine, morphine, and melittin (bee venom)
  • heat, cold, sunlight
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107
Q

How are basophils different from mast cells?

A

they are not normally present in tissues but rather circulate in the blood in extremely small numbers

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108
Q

What is the high affinity receptor for IgE found on mast cells and basophils?

A

Fc-epsilon-RI

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109
Q

Preformed mediators contained within mast cell granules are the first to be released and can be divided into what 3 categories?

A
  • Vasoactive amines
  • Enzymes
  • Proteoglycans
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110
Q

What is the most important mast cell derived amine?

A

Histamine

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111
Q

What does histamine do?

A

causes intense smooth muscle contraction, increased vascular permeability, and increased mucus secretion by nasal, bronchial, and gastric glands

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112
Q

What are the preformed enzymes in mast cell granules?

A

neutral proteases (chymase, tryptase) and several acid hydrolases

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113
Q

What do the preformed enzymes do?

A

cause tissue damage and lead to the generation of kinins and activated components of complement (C3a) and generate kinins

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114
Q

What are the preformed proteoglycans in mast cell granules?

A

heparin (anti-coagulant) and chondroitin sulfate

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115
Q

What do the preformed proteoglycans of mast cell granules do?

A

package and store the amines in the granules

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116
Q

What are the major lipid mediators of immediate hypersensitivity?

A

arachidonic acid derived products

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117
Q

What enzyme converts membrane phospholipids to arachidonic acid?

A

Phospholipase A2

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118
Q

Leukotrienes and protaglandins are produced by what enzymes, respectively from AA?

A

5-lipoxygenase and cyclooxygenase

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119
Q

What are the most potent vasoactive and spasmogenic agents known?

A

Leukotrienes C4 and D4

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120
Q

What leukotriene is highly chemotactic for neutrophils, eosinophils, and monocytes

A

B4

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121
Q

What is the most abundant mediator produced in mast cells by the COX pathway?

A

PGD2

122
Q

What does PDG2 do?

A

intense bronchospasm and increased mucus secretion

123
Q

What is a lipid mediator produced by some mast cells but not derived from AA?

A

PAF

124
Q

What does PAF do?

A
  • platelet aggregation
  • release of histamine
  • bronchospasm
  • increased vascular permeability
  • vasodilation
125
Q

What are often an abundant leukocyte population in the late phase reaction of a type I hypersensitivity?

A

eosinophils

126
Q

What recruits eosinophils?

A

eotaxin

127
Q

What is the most potent eosinophil-activating cytokine known?

A

Th2 cytokine IL-5

128
Q

What are the 2 eosinophil proteins that damage tissue?

A

Major basic protein and eosinophil cationic protein

129
Q

An increased propensity to develop immediate hypersensitivity reactions is called what?

A

atopy

130
Q

Atopic individuals tend to have higher levels of what compared to the general population?

A

Serum IgE and IL-4 producing Th2 cells

131
Q

Studies of patients with asthma reveal linkage to polymorphisms in several genes on what chromosome?

A

5 and also 6, close to HLA complex

132
Q

When an immediate hypersensitivity reaction is triggered by non-antigenic stimuli such as temperature extremes and exercise, Th2 and IgE are not involved and these are called what?

A

nonatopic allergy

133
Q

4 examples of disorders caused by immediate hypersensitivty (type 1)?

A
  • Anaphylaxis
  • Bronchial asthma
  • Allergic rhinitis
  • food allergies
134
Q

What is anaphylaxis characterized by?

A
  • vascular shock
  • widespread edema
  • difficulty breathing
135
Q

The membrane attack complex formed from complement is effective in killing what?

A

cell that have thin cell walls such as Neisseria bacteria

136
Q

Name the Disease: antibodies reactive with acetylcholine receptors in the motor end plates of skeletal muscles block neuromuscular transmission and therefore cause muscle weakness

A

myasthenia gravis

137
Q

Name the disease: antibodies against the thyroid-stimulating hormone receptor on thyroid epithelial cells stimulate the cells, resulting in hyperthyroidism

A

Graves Disease

138
Q

What are the common sites of immune complex deposition for type III hypersensitivity?

A

kidney, joints, and small blood vessels

139
Q

What are the 3 phases of systemic immune complex disease?

A
  • Formation of immune complexes
  • Deposition of immune complexes
  • inflammation and tissue injury
140
Q

The cell-mediated type of hypersensitivity (type IV) is caused by what?

A

inflammation resulting from cytokines produced by CD4+ T cells and cell killing by CD8+ T cells

141
Q

What is the prototype of T-cell mediated inflammation?

A

delayed-type hypersensitivity (DTH)

142
Q

Th1 cells produce inflammation by what cells?

A

macrophages

143
Q

Th17 cells produce inflammation by what cells?

A

neutrophils

144
Q

What is the classic example of DTH?

A

tuberculin reaction

145
Q

Tuberculin reaction is produced by the intracutaneous injection of what?

A

purified protein derivative (PPD)

146
Q

Morphologically, DTH is characterized by what?

A

accumulation of mononuclear cells, mainly CD4+ T cells and macrophages, around venules, producing perivascular “cuffing”

147
Q

Sustained activation of a DTH reaction turns macrophages into what and forms a what?

A

epitheloid cells; granuloma

148
Q

Granulomatous inflammation is typically associated with what?

A

strong Th1-cell activation and high level production of cytokines such as IFN-gamma

149
Q

Autoreactive T cells react against CNS myelin

A

multiple sclerosis

150
Q

diversity of antibodies directed against DNA, platelets, red cells, and protein-phospholipid complexes resulting in widespread lesions throughout the body

A

SLE

151
Q

antibodies to basement membranes of lung and kidney inducing lesions in these organs

A

Goodpasture syndrome

152
Q

What protein stimulates expression of some peripheral tissue-restricted self antigens in the thymus and is thus critical for deletion of immature T cells specific for these antigens?

A

AIRE

153
Q

mutations in AIRE gene are the cause of what?

A

autoimmune polyendocrinopathy

154
Q

If a maturing CD4+ T cell sees a self antigen in the thymus and doesn’t die, it turns into what?

A

regulatory T cells

155
Q

When lymphocytes that recognize self antigens and are rendered functionally unresponsive it is called what?

A

anergy

156
Q

What are the 2 costimulatory molecules that are inhibitory and can cause anergy?

A

CTLA-4 and PD-1

157
Q

What has higher affinity for B7 molecules, CD28 or CTLA-4?

A

CTLA-4

158
Q

What are the best defined regulatory T cells?

A

CD4+ cells that express high levels of CD25, the alpha chain of the IL-2 receptor, and FOX3P

159
Q

In humans, mutations of FOX3P cause what?

A

IPEX

160
Q

The inhibitory activity of Treg cells may be mediated in part by the secretion of what?

A

IL-10 and TGF-beta

161
Q

Treg cells express CTLA-4 and reduced ability of APCs to activate T cells via what?

A

CD28

162
Q

T cells that recognize self antigens may express what pro-apoptotic member of the Bcl family?

A

BIM without antiapoptotic Bcl-2 and Bcl-x

163
Q

Death receptor Fas

A

CD95

164
Q

mutation of the FAS gene leads to what in humans?

A

autoimmune lymphoproliferative Syndrome (ALPS)

165
Q

What are the immune privileged sites?

A

Testis, Eye, brain

166
Q

polymorphisms in what gene are associated with rheumatoid arthritis, type I diabetes, and several other autoimmune diseases?

A

PTPN22 which encodes tyrosine phosphatatase

167
Q

Polymorphisms in what gene are associated with Crohn Disease?

A

NOD2

168
Q

polymorphisms in what genes are associated with multiple sclerosis?

A

IL-2 receptor (CD25) and IL-7 receptor

169
Q

SLE predominantly affects what gender?

A

women during reproductive years

170
Q

Antinuclear antibodies (ANAs) can be grouped into what 4 categories?

A
  • antibodies to DNA
  • antibodies to histones
  • antibodies to nonhistone proteins bound to RNA
  • antibodies to nucleolar antigens
171
Q

What are the 4 patterns of staining for ANAs

A
  • Diffuse
  • speckled
  • Anti-centromeric
  • Nucleolar
172
Q

Antibodies to what are virtually diagnostic of SLE?

A

double stranded DNA and the so-called Smith (Sm) antigen

173
Q

Lupus patients may have a false positive test for what?

A

syphilis

174
Q

What drugs can induce an SLE-like response in humans?

A
  • hydralazine
  • procainamde
  • D-penicillamine
175
Q

Any phagocytic leukocyte that has engulfed the denatured nucleus of an injured cell is called what?

A

LE cell

176
Q

Typically the presentation of SLE is a young woman with some but not necessarily all of what of the following features?

A
  • butterfly rash over the face
  • fever
  • pain but no deformity in one or more peripheral joints
  • pleutitic chest pain
  • photosensitivity
177
Q

Chronic Discoid Lupus Erythrmatosus is a disease in which the skin manifestations may mimic SLE, but systemic manifestations are rare. It is characterized by what?

A

-Presence of skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy. Usually face and scalp

178
Q

How do you distinguish Subacute Cutaneous Lupus Erythematosus from Chronic discoid lupus erythematosus?

A
  • The skin rash tends to be widespread, superficial and non scarring
  • Strong association with antibodies to the SS-A antigen and with the HLA-DR3 genotype
179
Q

Name the Disease: chronic disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands

A

Sjogren syndrome

180
Q

Keratoconjuctivitis sicca

A

dry eyes

181
Q

xerostomia

A

dry mouth

182
Q

About 75% of Sjogren syndrome patients have what?

A

rheumatoid factor (an antibody reactive with self IgG)

183
Q

What are the most important antibodies found in Sjogren syndrome patients?

A

ones directed against two ribonucleoprotein antigens, SS-A (Ro) and SS-B (La)

184
Q

What cytoskeletal protein is possibly implicated in Sjogren syndrome?

A

alpha-fodrin

185
Q

Most common people to get Sjogren?

A

women between 50 and 60

186
Q

Keratoconjunctivitis causes what symtoms?

A

blurring of vision, burning, and itching and thick secretions accumulate in conjunctival sac

187
Q

Xerostomia results in what symptoms?

A
  • Difficulty swallowing solid foods
  • decrease in ability to taste
  • cracks and fissures in the mouth
  • dryness of the buccal mucosa
188
Q

Enlargement of what gland is seen in half the patients of Sjogren?

A

parotid

189
Q

What is essential for the diagnosis of Sjogren syndrome?

A

Biopsy of the lip to examine minor salivary glands

190
Q

Systemic Sclerosis (Scleroderma) is characterized by what 3 things?

A
  • chronic inflammation thought to be the result of autoimmunity
  • widespread damage to small blood vessels
  • progressive interstitial and perivascular fibrosis in the skin and multiple organs
191
Q

What are the 2 categories of systemic sclerosis?

A
  • Diffuse scleroderma

- limited scleroderma

192
Q

Diffuse scleroderma is characterized by what?

A

widespread skin involvement at onset, with rapid progression and early visceral involvement

193
Q

Limited scleroderma is characterized by what?

A

involvement is often confined to fingers, forearms, and face. Visceral involvement occurs late

194
Q

Some patients with Limited scleroderma develop a combination of calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. This is called what?

A

CREST syndrome

195
Q

The cause of systemic sclerosis is not known but the disease likely results from what three interrelated processes?

A
  • autoimmune responses
  • vascular damage
  • collagen deposition
196
Q

The CD4+ cells found on the skin of systemic sclerosis patients produce what cytokines that can stimulate transcription of genes that encode collagen and other ECM proteins (fibronectin) in fibroblasts.

A

TGF-beta and IL-13

197
Q

What is the distinctive feature of systemic sclerosis?

A

striking cutaneous changes notably skin thickening

198
Q

Raynaud phenomenon is what?

A

severe vasoconstiction of extremities

199
Q

What is the most life threatening aspect of systemic sclerosis?

A

malignant hypertension with subsequent development of fatal renal failure

200
Q

Mixture of the features of SLE, systemic sclerosis, and polymyositis?

A

Mixed connective Tissue Disease

201
Q

What does mixed connective tissue disease typically present with?

A
  • synovitis of fingers
  • Raynaud phenomenon
  • mild myositis
202
Q

Grafts exchanged between individuals of the same species?

A

allografts

203
Q

Grafts from one species to another?

A

Xenografts

204
Q

What is the APC in the direct pathway of allorecognition?

A

DONOR dendritic cells

205
Q

What is the mechanism of killing in the direct pathway of allorecognition?

A

CD4+ and CD8+

206
Q

What is the APC for the indirect pathway of allorecognition?

A

HOST

207
Q

What is the result of the indirect pathway of allorecognition?

A

delayed hypersensitivity

208
Q

what is the mechansim of killing in the indirect pathway of allorecognition?

A

T-cell cytokine production and inflammation. CD8+ CTLs CANNOT kill graft cells

209
Q

What is seen in acute cellular rejection? also called acute T cell-mediated rejection

A
  • Clinical and biochemical signs of the organ failure
  • Cytokines secreted by activated CD4+ T cells
  • Increased vascular permeability and local accumulation of mononuclear cells
210
Q

Most common glomerular disease associated with SLE?

A

Diffuse lupus nephritis (class IV) also most common

211
Q

What organs are not affected in drug induced lupus Erythematosus?

A

Kidneys and CNS

212
Q

Early Sjogren syndrome shows what pathology?

A

Mixture of polyclonal T and B cells

213
Q

Over time what can emerge in Sjogren syndrome?

A

A dominant B-cell clone-> marginal Zone Lymphoma

214
Q

Other clinical features of systemic sclerosis

A
  • Dysphagia from esophageal fibrosis (hypomotility)
  • Respiratory diffuculty
  • Myocardial fibrosis-> arrhthmias/cardiac failure
  • Renal: mild proteinuria/malignant hypertension
215
Q

IgG4 related Disease often affects who?

A

middle-aged and older men

216
Q

Enlargement and fibrosis of salivary and lacrimal glands

A

Mikulicz syndrome

217
Q

IgG4 related Disease is characterized by what?

A
  • Tissues are infiltrated by IgG4 antibody-producing plasma cells and lymphocytes (mainly T cells)
  • Storiform Fibrosis
  • Obliterative phlebitis
  • usually increased serum IgG4
218
Q

What happens in chronic rejection?

A
  • Lymphocytes react against alloantigens in the vessel wall

- secrete cytokines that induce local inflammation

219
Q

What occurs when PREFORMED antidonor antibodies are present in the circulation of the recipient?

A

hyperacute rejection

220
Q

Hyperacute refection can develop in persons with what/

A
  • previous transplant
  • prior blood transfusions
  • multiparous women
221
Q

What is it called when Antidonor antibodies are produced after transplantation?

A

Acute antibody-mediated rejection

222
Q

Acute antibody-mediated rejection initially targets what/

A

graft vasculature

223
Q

Which allele matching shows substantial benefit in kidney transplants?

A

HLA-A, B, and DR

224
Q

In immunosuppressive therapy, what does mycophenolate mofetil do?

A

inhibits lymphocyte proliferation

225
Q

in immunosuppressive therapy, What does Tacrolimus (FK506) do?

A

inhibits T cell functions

226
Q

What does IVIG do?

A

suppresses inflammation

227
Q

What is plasmapheresis used for?

A

Used in cases of severe antibody-mediated rejection

228
Q

What virus is common due to immunosuppressive therapy in kidney transplants?

A

Polyoma virus

229
Q

What latent viruses can become reactivated when given immunosuppressive therapy?

A
  • EBV-induced lymphomas
  • HPV induced squamous cell carcinoma
  • Kaposi sarcoma (HHV8)
230
Q

What is hematopoietic stem cell transplantation used for?

A
  • hematologic malignancies
  • Bone marrow failure syndromes (aplastic anemia)
  • Inherited stem cell defects (sickle cell, thalassemia, and immunodeficient states)
231
Q

How are hematopoietic stem cells harvested?

A

give CSF and harvest from peripheral blood

-also can be obtained from umbilical cord blood of newborn infants

232
Q

What occurs when transplant cells recognize alloantigens in the host and attack host tissues?

A

Graft-vs-Host Disease (GVHD)

233
Q

When is GVHD most common?

A

bone marrow (HSC ) tansplantation

234
Q

what is needed to minimize GVHD?

A

HLA matching

235
Q

The majority of clinical manifestations of Acute GVHD come from what organs?

A
  • immune system
  • skin
  • liver
  • intestines
236
Q

What is a way to eliminate GVHD?

A

knock out Donor T cells before transfusion

237
Q

What are the consequences of knocking out Donor T cells?

A
  • Recurrence of tumor in leukemia patients
  • Increased incidence of graft failures
  • increased rates of EBV-related B-cell lymphoma
238
Q

Infants with SCID present with what?

A
  • Prominent Thrush (oral candidiasis)
  • Extensive diaper rash
  • failure to thrive
239
Q

Some infants with SCID can develop a GVHD type rash how?

A

maternal T cells are transferred across the placenta and attack the fetus

240
Q

SCID patients are extremely susceptible to what infections?

A
  • Candida albicans
  • pneumocystic jiroveci
  • pseudomonas,
  • CMV
  • Varicella
241
Q

Death of SCID patients occurs within the first year of life unless they get what?

A

HSC (BMT) transplantation or maybe gene therapy

242
Q

SCID is most commonly what type of inheritance?

A

X linked

243
Q

Failure of B-cell precursors to develop into mature B cells is what?

A

X Linked (Bruton) Agammaglobulinemia

244
Q

What infections are common for X-linked Agammaglobulinemia?

A

Respiratory tract- haemophilus influenzae, Streptococcus pneumoniae, staphylococcus aureus

Viruses in blood or mucus- enterovirus, poliovirus, coxsackievirus

Giardia Lamblia (intestinal protozoan)

245
Q

When do you see symptoms of X-linked Agammaglobulinemia?

A

after 6 months once maternal IGs are depleted

246
Q

about 35% of patients with X-linked Agammaglobulinemia will develop what autoimmune disease?

A

Arthritis and dermaomyositis

247
Q

How do you treat X-linked Agammaglobulinemia?

A

IVIG

248
Q

T-cell deficiency that develops from failure of development of 3rd an 4th pharyngeal pouches

A

DiGeorge Syndrome (Thymic hypoplasia)

249
Q

What does DiGeorge Syndrome give rise to?

A

-Thymus-> loss of T cell mediated immunity, poor defense against certain fungal and viral infections

Parathyroids->Hypocalcemia –>tetany

  • Some C cells of thyroid aren’t formed
  • Ultimobranchial body–> congenital defects of the heart and great vessels
  • Abnormal appearance of mouth, ears, and facies
250
Q

DiGeorge syndrome is considered a component of what deletion?

A

22q11 deletion syndrome

251
Q

Hyper-IgM syndrome is caused by what?

A

defect in ability of helper T cells to deliver activating signals to B cells and macrophages

252
Q

Hyper-IgM syndrome is what inheritance?

A

X-linked (70%) or autosomal recessive

253
Q

What type of infections are common with Hyper-IgM syndrome?

A

pyogenic infections

254
Q

Hyper-IgM syndrome patients susceptible to Pneumocystis jiroveci pneumonia have what mutations?

A

CD40L

255
Q

Occasionally IgM antibodies react with blood cells to cause what?

A
  • autoimmune hemolytic anemia
  • thrombocytopenia
  • neutropenia
256
Q

Common Variable Immunodeficiency (CVID) affects what antibody classes?

A

usually all but sometimes only IgG

257
Q

How do you differentiate CVID from X-linked agammaglobulinemia?

A

normal B cells numbers but they just aren’t able to differentiate into plasma cells

258
Q

Isolated IgA deficiency is seen in association with what infections?

A
  • Toxoplasmosis
  • Measles
  • other viral infections
259
Q

Symptomatic patients with isolated IgA deficiency will have what?

A
  • Recurrents Sinopulmonary infectons
  • Diarrhea
  • High frequency of respiratory tract allergy and autoimmune diseases
260
Q

What the issue with blood transfusion in isolated IgA deficiency?

A

if it’s IgA containing blood the IgA behaves like a foreign substance and they can develop severy/fatal anaphylactic reactions

261
Q

Immunodeficiency can be Associated with systemic diseases such as what?

A
  • Wiskott-Aldrich syndrome

- Ataxia Telangiectasia

262
Q

Wiskott-Aldrich Syndrome inheritance?

A

X-linked

263
Q

highlights of Wiskott-Aldrich?

A

Thrombocytopenia, eczema, recurrent infection –> early death

264
Q

Treatment of Wiskott Aldrich?

A

HSC transplantation

265
Q

inheritance of Ataxia Telangiectasia?

A

Autosomal recessive

266
Q

highlights of Ataxia telangiectasia?

A
  • abnormal gait
  • vascular malformations
  • neuro deficits
  • increased incidence of tumors
  • immunodeficiency
267
Q

Where is HIV-1 most common?

A
  • US
  • Europe
  • Central Africa
268
Q

where is HIV-2 common?

A

West Africa and India

269
Q

HIV virus core contains what protein?

A

Major Capsid protein p24

270
Q

What is used to diagnose HIV infection?

A

ELIZA test

271
Q

HIV core contains what viral enzymes?

A
  • protease
  • Reverse transcriptase
  • Integrase
272
Q

what is the HIV core surrounded by?

A

Matrix protein called p17

273
Q

What studs the viral envelope of HIV and is critical for HIV infections of cells?

A

gp120 and gp41

274
Q

HIV first infects what cells that have what marker?

A
  • T cells, dendritic cells, and macrophages

- CD4

275
Q

What on HIV cells binds to CD4?

A

gp120

276
Q

After CD4 and gp120 bind, they both bind to what?

A

chemokine receptor

277
Q

What is used for HIV membrane penetration?

A

gp41

278
Q

What helps distinguish what strain of HIV?

A

which chemokine receptor is used

279
Q

R5 strain uses what receptor?

A

CCR5

280
Q

R5 strain preferentially infects cells of what lineage?

A

monocyte/macrophage (M-tropic)

281
Q

What HIV strain uses CXCR4 receptor

A

X4

282
Q

X4 strain preferentially infects what cells?

A

T cells (T-tropic)

283
Q

What strain can infect both types of cells?

A

R5X4

284
Q

Why does HIV have a hard time infecting naive T cells?

A

they contain an enzyme that mutates the HIV genome

285
Q

Stimulated cells with an HIV infection leads to what?

A

release of NF-kappaB to nucleus –>increased HIV DNA transcription

286
Q

HIV-1 uses what gene to infect and multiply in terminally differentiated non-dividing macrophages?

A

vpr gene

287
Q

Dendritic cells pick up HIV and present it to CD4+ T cells via what?

A

Lectin-like receptor

288
Q

Clinical presentation of the initial spread of HIV and host response

A

Acute retroviral syndrome

289
Q

Acute Retroviral syndrome typically occurs when?

A

3-6 weeks after infection

290
Q

When does Actue retroviral syndrome resolve?

A

after 2-4 weeks

291
Q

Symptoms of acute retroviral syndrome?

A
  • sore throat
  • Myalgias
  • fever
  • weight loss
  • fatigue
  • rash
  • cervical adenopathy
  • diarrhea
  • vomiting
292
Q

what is used to predict the rate of progression of HIV?

A

viral load

293
Q

During the clinical Latency period of HIV, what are the possible clinical symptoms?

A
  • Oral candidiasis (thrush)
  • vaginal candidiasis
  • herpes Zoster
  • maybe tuberculosis
  • autoimmune thrombocytopenia
294
Q

What does HIV down modulate on infected cells?

A

Class I MHC

295
Q

Combination of 3-4 drugs that block different steps of HIV life cycle

A

HAART

296
Q

What are the adverse side effects of HAART?

A
  • lipoatrophy (loss of facial fat)
  • Lipoaccumulation (excess fat deposition centrally)
  • elevated lipids
  • insulin resistance
  • peripheral neuropathy
  • premature cardiovascular kidney and liver disease
297
Q

What can develop from HAART?

A

immune reconstitution inflammatory syndrome

298
Q

AL from Ig light chains is major fibril protein in what?

A

multiple myeloma

299
Q

AA from SAA is major fibril protein in what?

A

chronic inflammatory diseases

300
Q

Abeta2m from class I MHC beta2 microglobulin is major fibril protein in what?

A

chronic renal disease

MOD1 (8 decks)

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