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Flashcards in Immunology Deck (236):
1

What the primary lymphoid organs?

Thymus and Bone marrow

2

What is the function of lymph nodes?

nonspecific filtration by macrophages, storage and activation of B and T cells. Ab production

3

What does the structure of a lymph node look like?

1. many afferents, one efferent
2. encapsulated w/ trabeculae
3. follicle, medullar, and paracortex

4

What is found in the follicle of a lymph node?

site of B cell localization and proliferation
- in outer cortex - primary follicles are dense and dormant. Secondary follicles have pale central germinal centers and are active

5

What is found in the medullar of a lymph node?

- medullary cords (closely packed lymphocytes and plasma cells
- medullary sinuses - communicated w/ efferent lymphatics and contain reticular cells and macrophages

6

What is found in the paracortex?

1. T cells
2. this is the region btw follicles and medulla
- contains high endothelial venules through which T and B cells enter from blood

7

What happens to the paracortex in an intense immune response?

becomes greatly enlarged

8

What happens to the paracortex in DiGeorge pts?

not well developed b/c they don't have T cells

9

What is the lymphatic drainage from the following areas of the body?
1. Upper limb, lateral breast
2. stomach
3. duodenum, jejunum
4. sigmoid colon
5. rectum (lower portion) of anal canal (above pectinate line)
6. anal canal below the pectinate line
7. testes
8. scrotum
9. thigh
10. lateral side of dorsum of foot

1. axillary
2. Celiac
3. superior mesenteric
4. colonic -- inferior mesenteric
5. internal iliac
6. superficial inguinal
7. superficial and deep plexuses --> para aortic
8. superficial inguinal
9. superficial inguinal
10. popliteal

10

What is considered to be the largest component of the immune system?

MALT - made up by GALT, NALT, BALT, genitourinary tract, appendix, tonsils, adenoids, M cells

11

What are M cells?

- found in the mucous membranes of small gut
- flattened epithelial cells lacking microvilli. there are deep pockets on the basilar side that allow Ag presentation to dendritic cells, B and T cells, and macrophages
-

12

What are Peyer's patches?

- unencapsulated lymphoid tissue
- found in lamina propria and submucosa of small gut
- B cells make IgA

13

What does the right lymphatic duct drain?

-right arm, right chest, and right half of head

14

What does the thoracic duct drain?

everything else

15

Where does the thoracic duct drain?

junction b/w lespift subclavian and internal jugular vein

16

Describe the sinusoids of the spleen?

long, vascular channels in red pulp w/ fenestrated barrel hoop basement membrane. Macrophages found nearby

17

Where are T cells found in the spleen?

Periarterial lymphatic sheath (PALS) within the white pulp

18

Where are the B cells found in the spleen?

follicles w/in the white pulp

19

What is the role of the macrophages in the spleen?

remove encapsulated bacteria

20

What happens when there is splenic dysfunction?

- decreased IgM = decreased complement activation = decreased C3b opsonization
- increases susceptibility to encapusulated organisms

21

What are some encapsulated organisms that you need to worry about when you have splenic dysfunction?

E coli, pseudomonas, strep pneumoniae, Haemophilus influenzae type B, Nessiera meningitidis, salmonella, klebsiella, cryptococcus neogformans, group B Strep

22

Where are situations that a splenic dysfunction will take place?

1. sickle cell pts
2. Trauma to spleen
3. hereditary sphereocytosis

23

What happens after postsplenectomy?

1. Howell Jolly bodies - nuclear remnants
2. Target cells
3. Thrombocytosis

24

What is important about the thymus?

1. site of T cell differentiation and maturation
2. encapsulated
3. from epithelium of 3rd branchial pouch
4. Cortex is dense w/ immature T cells
2. Medulla is pale w/ mature T cells and epithelial reticular cells containing Hassall's corpuscles.

25

What is innate immunity?

1. response to pathogens is fast and nospecific
2. no memory
3. consists of neutrophils, macrophages, dendritic cells, natural killer cells, and complement

26

What is adaptive immunity?

1. receptors that recognize pathogens undergo VDJ recombination during lymphocyte development
2. Response is slow on first exposure but memory response is faster and more robust.
3. Consists of T and B cells and circulating Abs

27

What is the MHC?

major histocompatibility complex
- encoded by human leukocyte antigen (HLA) genes
- presents Ag fragment to T cells and TCR

28

What are the genetics for MHC I?

HLA A, B, and C

29

What cells have MHC I?

expressed on all nucleated cells. not expressed on RBC

30

What does MHC I bind to?

TCR and CD8

31

How does MHC I work?

-mediates viral immunity
- pairs w/ Beta 2 microglobulin (aids in transport to cell surface)
- Ag is loaded in RER w/ mostly intracellular peptides

32

What genes are associated w/ MHC II?

HLA DR, DP, and DQ

33

What receptors does MHC II bind to?

binds TCR and CD4

34

what cells have MHC II?

expressed only on APCs

35

How does MHC II work?

Ag is loaded following release of invariant chain in an acidified endosome

36

What are the following HLA genes associated with?
1. A3
2. B27
3. DQ2/8
4. DR2
5. DR3
6. DR4
7. DR5

1. hemochromatosis
2. Psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, reiter's syndrome -- (PAIR)
3. Celiac disease
4. MS, hay fever, SLE, goodpasture's
5. DM type 1, Grave's disease
6. RA, DM type 1
7. Pernicious anemia --> B12 deficiency, Hashimoto's thyroiditis

37

How do natural killer cells work?

they use perforin and granzyme to induce apoptosis of virally infected cells and tumor cells.
- it's the only lymphocyte member of innate immune system

38

What cytokines enhance natural killer cells?

IL2, IL12, IFN-beta, and IFN -alpha

39

When are natural killer cells induced to kill?

1. when exposed to a nonspecific Ag signal on target cells
2. an absence of class I MHC on target cell surface

40

What are the surface makers for natural killer cells?

CD 16, CD 56

41

What does CD16 do?

it binds to constant region of Abs
- found on NK cells and phagocytes to help them recognize and kill Ig coated cells by Ab dependent cell mediated cytotoxicity (ADCC)

42

What are the major functions of B cells?

1. make Abs
2. used in hyperacute and humorally mediated acute and chronic organ rejection

43

What are the roles of Abs?

1. opsonize bacteria
2. neutralize viruses (IgG)
3. activated complement (IgM, IgG)
4. sensitize mast cells (IgE)

44

What are the major functions of T cells?

1. CD4 T cells help B cells make Ab and produce cytokines to activate other cells of immune system
2. CD8 cell kill virus-infected cells directly
3. involved in cell-mediated HSR (type 4)
4. Acute and chronic cellular organ rejection

45

What are all the APCs of the body

1. M cells in gut
2. Dendritic cells in the skin
3. Macrophages
4. B cells

46

What are the steps of T cell differentiation?

1. immature T cells in bone marrow travel to the thymus
2. Positive and negative selection takes place in corticomedullary junction
4. the matured cells like in the lymph nodes and wait to be activate

47

What happens during positive selection of T cells?

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

48

What happens during negative selection of T cells?

T cells expressing TCRs / high affinity for self Ag undergo apoptosis

49

What cytokines help differentiate Helper T cells to become either Th1 or Th2 cells?

1. to make Th1 cells, you need IL 12
2. to make Th2 cells, you need IL 4

50

What cells are capable of activating T and B cells?

APCs
- 2 signals are required to activate these cells

51

What are the steps of T cell activation

1. Foreign body is phagocytosed by dendritic cells
2 Forgeign Ag is presented on MHC II and recognized by TCR on T helper cells. Ag is presented on MHC I to cytoxic cells --- this is the 1st signal
3. Costimulatory signal is given by interaction of B7 and CD28 ( signal 2)
4. T helper cells activates and produces cytokines
Cytotoxic T cells activates and is able to recognize and kill virus infected cells

52

How are B cells activated?

1. First you need to get helper T cell activated so remember that process (TCR binds to Ag on MHC II, and B7 binds to CD28 for co-stimulation)
2. B cell receptor mediated endocytosis, foreign Ag is presented on MHC II and recognized by TCR on T helper cells (signal I)
3. CD 40 receptor on B cell binds CD40 ligand on Th cells (signal 2)
4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switiching, affinity maturation, and Ab production

53

What do Th1 cells do?

1. secrete IFN-gamma and IL2
2. activated macrophages and cytotoxic T cells

54

What cytokines inhibit Th1 cells?

by Il 4 and 10 from Th2 cells

55

What do Th2 cells do?

1. secrete Il 4, 5, 10, and 13
2. Recruit eosinophils for parasite defense and promote IgE production by B cells

56

What cytokines inhibt Th2 cells?

IFN-gamma

57

Tell me about macrophage-lymphocyte interaction

Activated lymphocytes release IFN-gamma and macrophages release IL1 and TNF alpha stimulating each other

58

What do helper T cells and cytotoxic T cells have in terms of CD and what receptors do they bind to in terms of MHC?

1. Th cells have CD4 bind to MHC II
2. Tc cells have CD8 bind to MHC I

59

What are the roles of cytotoxic T cells?

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

60

How do cytotoxic T cells work?

they release cytotoxic granules containing preformed proteins
1. perforin - makes holes in membranes
2. granzyme - serine protease that activates apoptosis inside target cells
3. granulysin - antimicrobial, induces apoptosis

61

what are regulatory T cells?

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

62

What surface markers do regulatory T cell express?

1. CD3, CD4, CD25 (alpha chain of IL 2 receptor)

63

What cytokines do regulatory T cell produce?

anti-inflammatory cytokines like IL10 and TGF beta

64

What is the structure of Abs?

1. 2 light chains (lambda or kappa)
2. 2 heavy chains ( Mu, Delta, Gamma, Alpha, Epsilon)
3. Variable part of L and H chains recognize Ags
4. Heavy chain contributes to Fc and Fab fractions
5. Light chain contributes to Fab fractions

65

What holds the structure of Abs together?

Disulfide bonds - the exist within the heavy and light chains. They hold the heavy chains together. They hold the heavy and light chains together as well.

66

What is the role of the Fab portion of the Ab?

- Ag binding fragment
- determines idiotype: unique antigen binding pocket; only 1 antigenic specificity expressed per B cell

67

What is the role of the Fc portion of the Ab?

- constant chain
- carboxy terminal of Ab
- complement binding at Ch2 (IgG and IgM only)
- carbohydrate side chains
determines isotype of Ab

68

How is Ab diversity generated?

by random recombination of VJ (light chain) or VDJ (heavy chain) genes
- random combination of heavy chains w/ light chains
- somatic hypermutation (following Ag stimulation)
- Addition of nucleotides to DNA during recombination (see 1st entry in this list) by terminal deoxynucleotidy transferase
- rearrangement begins w/ break in dsDNA at recombination signal sequences (RSS) that flank the VDJ coding regions - RAG 1 and 2 recognize the RSS

69

What what happens there are mutations in the RAG genes?

inability to initiate VDJ rearrangement and an arrest of B and T cells

70

What is the normal ratio of lambda to kappa light chains?

2:1

71

What is the role of IgG

- main Ab in the delayed response to an Ag
- fixes complement and crosses the placenta (provides passive immunity to infant)
- opsonizes bacteria, neutralizes bacterial toxins and viruses

72

What is the most abundant Ab?

IgG

73

What is the role of IgA?

-prevents attachment of bacteria and viruses to mucous membranes
- does NOT fix complement
- crosses epithelial cells by transcytosis
- picks up secretory component from epithelial cells before secretion

74

What are the forms that IgA can be found in?

- in circulation = monomer
- when secreted = dimer

75

Where can IgA be found?

in secretions (tears, saliva, mucus) and early breast milk (colostrum)

76

What is the role of IgM?

- produced in the immediate response to an Ag
- Fixes complement but does NOT cross the placenta
- Ag receptor on the surface of B cells
- monomer on B cell or pentamer

77

Why does IgM exist in a pentamer form>

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

78

What is the role of IgD?

unknown; found on surface of many B cells and in serum

79

What is the role of IgE?

-binds mast cells and basophils
- cross -links when exposed to allergens, mediating immediate (type I) HSR through release of inflammatory mediators such as histamine
- mediates immunity to worms by activating eosinophils
- lowest concentration in serum

80

What is thymus independent Ag?

Ag lacking a peptide component
- can't be presented to MHC to T cells
- stimulates release of Abs and don't result in immunologic memory

81

What are examples of thymus independent Ag?

LPS from cell envelope of gram - negative bacteria and polysaccharide capsular ag

82

What are thymus dependent Ag?

Ags containing a protein component
- class switching and immunologic memory occur as a result of direct contact of B cells w/ Th cells

83

What is the role of complement?

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

84

How are the various complement pathways activated?

1. Classical = IgG or IgM mediated --> C1 mediated to make a C4b2a C3 convertase
2. Alternative = microbe surface molecules --> C3 deposition and C3b interacts w/ Bb to make C3bBb C3 converatse. Bb comes from D
3. Lectin = mannose of other sugars on microbe surface

85

What's the function of the following complement proteins?
1. C3b
2. C3a, C5a
3. C5a
4. C5b-9

1. opsonization
2. anaphylaxis
3. neutrophil chemotaxis (LTB4, IL8)
4. MAC formation

86

What are the main opsonins?

C3b and IgG are two primary opsonins in bacterial defense; C3b also helps clear immune complexes

87

What are the inhibitors of the complement pathway?

1. DAF
2. C1 esterase inhibitor
* both help prevent complement activation on self cells

88

What happens when you have a C1 esterase inhibitor deficiency?

hereditary angioedema.
- ACE inhibitors are contraindicated

89

What happens w/ a C3 deficiency?

severe, recurrent pyogenic sinus and respiratory tract infections. Increased susceptibility to type III HSR rxns esp GN in kidneys due to complex deposition

90

What happens w/ C5-9 deficiency?

recurrent Neisseria bacteremia

91

What happens w/ a DAF (GPI anchored enzyme) deficiency?

complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)

92

What are all the cytokines secreted by the macrophage?

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

93

What is the role of IL 1?

-endogenous pyrogen
- causes fever, acute inflammation
- activates endothelium to express adhesion molecules
- induces chemokine secretion to recruit leukocytes

94

What is the role of IL 6?

- endogenous pyrogen
- also secreted by Th2 cells
- causes fever and stimulates production of acute phase proteins

95

What is the role of IL 8?

- major chemotactic factor for PMN

96

What is the role of IL 12?

- induces differentiation of T cells into Th1 cells
- activates NK cells
- also secreted by B cells

97

What is the role of TNF alpha?

- mediates septic shock
- activates endothelium
- causes leukocyte recruitment, vascular leak

98

What are cytokines secreted by all T cells?

IL 2 and IL 3

99

What is the role of IL2?

stimulates growth of helper, cytotoxic, and regulatory T cells

100

What is the role of IL 3?

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

101

What is the role of IFN gamma?

activates macrophage and Th1 cells
- suppresses Th2 cells
- has antiviral and antitumor properties
- increase MHC I and II expression and Ag presentation in all cells

102

What is the role of IL 4?

induces differentiation into Th2 cells
- promotes growth of B cells
- enhances class switching to IgE and IgG

103

What is the role of IL 5?

- promotes differentiation of B cells
- enhances class switching to IgA
- stimulates the growth and differentiation of eosinophils

104

What is the role of IL 10?

- modulates inflammatory response
- inhibits actions of activated T cells and Th1
- also secreted by regulatory T cells

105

What are interferons?

proteins that place uninfected cells in an antiviral state
- induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but not host mRNA)

106

What do IFN alpha and beta do?

inhibit viral protein synthesis
- activate NK cells to kill virus infected cells

107

What are the cell surface proteins for T cells?

TCR - binds ag-MHC complex
CD3 - associated w/ TCR for signal transduction
CD28 (binds B7 on APC)

108

What are the cell surface proteins for helper T cells?

CD4, CD40 ligand

109

What are the cell surface proteins for Tc cells?

CD8

110

What are the cells surface markers of B cells?

- Ig (binds Ag)
- CD19, 20, 21 (receptor for EBV), CD 40
- MHC II, B7

111

What are the cell surface markers for macrophages?

- CD 14, 40, 16
MHC II, B7
- Fc and C3b receptors

112

What CD binds to LPS or endotoxin of gram negative bacteria?

CD 14

113

What are the cell surface markers of NK cells?

CD 16, CD 56

114

What is anergy?

self reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic, but tolerance is less complete than in T cells

115

How do superantigens work?

- cross link the Beta region of the TCR to the MHC class II on APCs. Can activate any T cell, leading to massive release of cytokines

116

how do endotoxins/LPS work?

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

117

What are some infectious agents that can undergo antigenic variation?

- Salmonella
- Borrelia (relapsing fever)
- Neisseria gonorrhoease (pilus protein)
- Influenza (major = shift; minor = drift)
- Trypanosomes = programmed rearrangment

118

How does one acquire passive immunity?

- receive performed Abs

119

What is the onset and duration of passive immunity?

rapid onset but duration is the half life of Abs which is 3 weeks so you have to keep giving them

120

What are examples of passive immunity?

- IgA in breast milk, antitoxin, humanized monoclonal antibody

121

How does one acquire active immunity?

- exposure to foreign antigen

122

What is the onset and duration of active immunity?

- slow onset but long lasting protection due to memory

123

What are examples of active immunity?

natural infections, vaccines, toxoid

124

In what clinical exposures are preformed antibodies givens?

- tetanus toxin
- botulinum toxin
- HBV
- rabies virus
- premature babies get RSV passive vaccine during winter months

125

What are live attenuated vaccine?

- microorganism loses its pathogenicity but retains capacity fro transient growth within inoculated host

126

What kind of response doe a live attenuated vaccine induce?

cellular response

127

What are the pros/cons of a live attenuated vaccine?

1. pros- induces strong often life-long immunity
2. con - may revert to virulent form so don't give to ICPs

128

What are examples of live attenuated vaccine?

-MMR, polio (sabin - oral), varicella, yellow fever, intrasnasal flu

129

What are killed vaccines?

pathogen is inactivated by heat or chemicals
- maintains epitope structure on surface antigens
- is a thymus dependent Ag

130

What kind of response does a killer vaccine induce?

humoral immunity

131

What are pros and cons of a killed vaccine?

1. pro - stable and safer than live vaccines
2. con - weaker immune response; booster shots usually required

132

What are examples of killed vaccines?

cholera, Hep A, polio (salk), rabies, IM flu

133

What are egg based vaccines?

flu, yellow fever

134

What is a type 1 HSR rxn?

- free Ag cross links IgE on presensitized mast cells and basophils triggering release of vasoactive amines that act at postcapillary venules.
- rxn develops rapidly after antigen exposure b/c of preformed Abs
- anaphylactic and atopic
- wheal and flare

135

What is a type 2 HSR rxn?

- cytotoxic (antibody mediated) IgM, IgG bind to fixed antigen on enemy cell leading to cellular destruction.
- opsonization leads to phagocytosis or complement activation
- complement mediated lysis
- ADCC usually due to NK cells

136

What is a why to determine if a type 2 HSR rxn took place?

Direct and indirect Coomb's

137

What is a type 3 HSR rxn?

Immune complex - Ag-Ab (IgG) complexes activate complement which attracts PMNs. PMNs release lysosomal enzymes

138

What is serum sickness?

- immune complex disease (type III) in which Abs to the foreign proteins are produced (takes 5 days). Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage). More common than Arthus rxn

139

What is most serum sickness caused by?

drugs acting as a hapten.

140

What are symptoms of serum sickness?

fever, urticaria, arthralagia, proteinuria, LAD, 5-10 days after antigen exposure

141

What is an Arthus rxn?

a local subacute Ab mediated HSR (type III) rxn. Intradermal injection of Ag induces complexes in the skin. Characterized by edema, necrosis and activation of complement

142

What is a type IV HSR?

delayed (T cell mediated) - sensitized T lymphocyes encounter antigen and then release lymphokines (leads to macrophage activation.; no Abs involved)

143

What are examples of type I HSR?

anaphylaxis; allergic and atopic disorders (rhinits, hay fever, ecezma, hives, asthma)

144

What are examples of type II HSR?

AIHA, pernicious anemia, ITP, erythroblastosis fetalis, acute hemolytics transfusion reactions, rheumatic fever, Good pastures, Bullous pemphigoid, pemphigus vulgaris, graves, myasthenia gravis

145

What are examples of type III HSR?

SLE, polyarthritis nodosa, PSGN, serum sickness, Arthus rxn, RA

146

What are examples of type IV HSR?

MS, GBS, graft verus host disease, PPD, contact dermatitis

147

What happens when you have an allergic rxn to blood transfusions?

- type I HSR; rxn aganist plasma proteins in transfused blood
- urticaria, pruritus, wheezing, fever
- treat w/ antihistamines

148

What happens when you have an anphylactic rxn to blood transfusions?

- severe rxn
- IgA deficient pts must receive blood products that lack IgA
- dyspnea, bronchospasm, hypotension, respiratory arrest, shock

149

What happens when you have a febrile non-hemolytic tranfusion rxn?

- type II HSR, host Abs against donor HLA antigens and leukoctyes.
- fever, headaches, chills, flushing

150

What happens when you have an acute hemolytic transfusion rxn?

- Tyep II HSR,
intravascular hemolysis (ABO blood group incompatibility)
extravascular hemolysis (host Ab rxn against foreign antigen on donor RBCs)
- fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinema (intravascular), jaundice

151

What infectious agents are you predisposed to get if you have no T cells?

- sepsis from bacteria
- CMV, EBV, VZV, chronic infection w/ respiratory/GI viruses
- Candida, PCP

152

What infectious agents are you predisposed to get if you have no B cells?

1. encapsulated bacterial infections
2. enteroviral, encephalitis, poliovirus (live vaccine contraindicated)
3. GI giardiasis (no IgA)

153

What infectious agents are you predisposed to get if you have no granulocytes?

1. staph, burkholderia cepacia, serratia, nocardia
2. candida, aspergillus

154

What infectious agents are you predisposed to get if you have no complement?

1. neisseria ( no MAC)

155

What are the encapsulated bacteria? (SHiN SKiS)

1. Steptococcus pneumoniae
2. Hamephilius infuenzae type B
3. Neisseria meningitidis
4. Salmonella
5. Klebsiella pneumoniae
6. group B Strep

156

What are B cells disorders?

1. X linked (Bruton's) agammaglobulinemia
2. Selective IgA deficiency
3. Common variable immunodeficiency

157

What is X linked Brutons agammaglobulinema?

- defect in BTK, a tyrosine kinase gene -> no B cell maturation
- more common in boys

158

What is the presentation of x linked bruton's agammaglobulinema?

recurrent bacterial infections after 6 months (decreased maternal IgG) as a result of opsonization defect

159

What are the immune findings for Bruton's agammaglobulinema?

1. normal pro- B
2. decreased maturation
3. decreased number of B cells
4. decrease IgG of all classes

160

What is selective IgA deficiency?

most common primary immunodeficiency
- most people are Asx
- can get sinopulmonary infections, GI infections, autoimmune disease, Anaphylaxis to IgA containing blood products

161

What are the immune findings for IgA deficiency?

- IgA < 7mg/dL w/ normal IgG, IgM, and IgG vaccine titers
- false positive Beta hCG tests due to presence of hereophile antibody

162

What is CVID?

defect in B cell maturation; many causes
- can be acquired in 20s and 30s
- increased risk of autoimmune disease; lymphoma, sinopulmonary infections
- normal number of B cells, decreased plasma cells and Igs

163

What are T cell disorders?

Digeorge syndrome, IL12 receptor deficiency, Hyper IgE syndrome, chronic mucocutaneous candidiasis

164

What is DiGeorge syndrome?

-thymic aplasia
- 22q11 deletion
- failure to develop 3rd and 4th pharyngeal pouches

165

What is the presentation of DiGeorge Syndrome?

- tetant (hypocalcemia)
- recurrent viral/fungal infections
congential heart and great vessel defects
- absent thymic shadow on CXR

166

What is IL 12 receptor deficiency?

decreased Th1 response
- disseminated mycobacterial infections
- decreased IFN gamma

167

What is Job's syndrome -- hyper IgE syndrome?

Th1 cells fail to produce IFN gamma --> inability of PMNs to respond to chemotactic stimuli

168

What is the clinical presentation of Job's syndrome?

1. coarse facies
2. cold (noninflamed) staphylococcal abscesses
3. retained primary teeth
4. increased IgE
5. dermatology problems (ecezma)

169

What is chronic mucocutaneous candidasis?

T cell dysfunction causing candida albicans infections of skin and mucous membranes

170

What are B and T cell disorders?

1. severe combined immunodeficiency (SCID)
2. Ataxis telangiectasia
3. Hyper IgM syndrome
4. Wiskott Aldrich syndrome

171

What is SCID?

several types: defective Il 2 receptor (most common X linked), adenosine deaminase deficiency

172

What is the clinical presentation of SCID?

- failure to thrive
- chronic diarrhea, thrush
- recurrent viral, bacterial, fungal, and protozoal infections
- absence of thymic shadow, germinal centers (lymph node biopsy) and B cells (peripheral blood smear)

173

What is the treatment for SCID?

bone marrow transplant

174

What are the immune findings for SCID?

- decreased T cell recombinant excision circles
- absence of thymic shadow, germinal centers, and T cells (flow cytometry)

175

What is Ataxia telangiectasia?

- defects in the ATM gene - codes for DNA repair enzymes
- increased risk of lymphoma and severe leukemia
- poor smooth pursuit
- increased AFP

176

What is the clinical presentation of ataxia telangiectasia?

- cerebellar defects (ataxia)
- spider angiomas (telangiectasia) after age 5
- IgA deficiency

177

What is Wiskott Aldrich synrome?

- x linked: in WAS gene on X chromosome -> T cells unable to recognize actin cytoskeleton

178

What is the clinical presentation of Wisktt Aldrich syndrome?

- thrombocytopenic purpura
- infections
- eczema

179

What are the immune findings for Wiskott Aldrish syndrome?

- increased IgE, IgA
- decreased IgM
thrombocytopenia

180

What are some phagocyte dysfunction disorders?

- Leukocyte adhesion deficiency - type 1
- Chediak-Higashi syndrome
- Chronic granulomatous disease

181

What is leukocyte adhesion deficiency?

- defect in LFA-1 integrin (CD18) protein on phagocytes
-neutrophilia b/c they can't migrate into intersititum

182

What is the clinical presentation of leukocyte adhesion deficiency?

- recurrent bacterial infxn,
absent pus formation
delayed separation of umbilical cord

183

What is Chediak Higashi Syndrome?

- AR
- defect in lysosomal trafficking regulator gene (LYST)
- microtubule dysfunction in phagosome-lysosome fusion
- giant granules in neutrophils

184

What is the clinical presentation of Chediak Higashi Syndrome?

- recurrent pyogenic infections by staph and strep
- partial albinism
- peripheral neuropathy and other CNS problesm

185

What is chronic granulomatous diease?

lack of NADPH oxidase --> decreased ROS and absent respiratory burst in neutrophils

186

What is the clinical presentation of chronic granulomatous disease?

increased susceptibility to catalase-positive organism

187

What is the immune findings of chronic granluomatous diease?

- abnormal dihydrorhodamin (DHR) flow cytometry test
- nitroblue tetrazolium dye reduction test

188

What is an autograft?

grafts from your own body

189

What is an syngeneic graft?

graft from identical twin or clone

190

what is an allograft?

from nonidentical individuals of same species

191

what is a xenograft?

from different species

192

What is a hyperacute transplant rejection?

- w/in minutes
- Ab mediated (type II) b/c of presence of preformed anti-donor antibodies in transplant recipient
- occludes graft vessels causing ischemia and necrosis

193

What is acute transplant rejection?

- weeks later
- cell mediated due to CTL reacting against foreign MHCs
- reversible w/ immunosuppressants
- vasculitis of giant vessels w/ dense interstitial lymphocytic infiltrate

194

What is chronic transplant rejection?

- months to years
- CLass I MHCnonself is perceived by CTLS as class I MHC self presenting a nonself antigen
- irreversible T cell and Ab mediated vascular damage
- fibrosis of graft tissue and blood vessels

195

What is graft vs host rejection?

- Grafted immunocompetent T cells proliferate in the irradiated immunocompromised disease hose and reject cells w/ foreign proteins resulting in sever organ dysfunction

196

What are the features of graft vs host?

- maculopapular rash
- jaundice
- hepatosplenomegaly
- diarrhea
- usually in bone marrow and liver transplant
- potentially beneficial in bone marrow transplant

197

What is the MOA of cyclosporine?

binds to cyclophilins
complex blocks the differentiation and activation of T cells by inhibiting calcineurin thus preventing production of IL2 and its receptor

198

ADE of cyclosporine?

Nephrotoxicity, gingivial hyperplasia, hirsutism
HTN, HLD, hyperglycemia, Tremor

199

What can the nephrotoxicity of cyclosporine be prevented w/

diuresis w/ mannitol

200

MOA of Tacrolimus

- binds to FK binding protein, inhibits calcineurin and secretion of IL2 and other cytokines

201

ADE of tacrolimus

Nephrotoxicity
HTN, HLD, hyperglycemia, tremor

202

MOA of Sirolimus

- inhibits mTOR by binding to FK binding protein
- inhibits T cell proliferation in response to IL2

203

ADE of sirolimus

-HLD, thrombocytopenia, leukopenia

204

MOA of azathioprine

antimetabolite precurore of 6MP that interferes w/ metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes

205

ADE of azathioprine

Bone marrow suppression
Active metabolic 6MP is metabolized by xanthine oxidase thus toxic effects may be increased by allopurinol

206

MOA of muromonab

mab that binds CD3 on surface of T cells.
- blocks cellular interaction w/ CD3 protein responsible for T cell signal transduction

207

ADE of muromonab

cytokine release syndrome, HSR rxn

208

thalidomide uses

immunosuppression, anti-angiogenic

209

MOA mycophenolate

inhibits IMP DH preventing production of guanine

210

What is aldesleukin

IL 2 used in Renal cell carcinoma and metastic melanoma

211

What is Epotein Alfa

erythropoietin for anemias (especially in renal failure)

212

what is filgrastim and sargramostime

granulocyte colony stimulating factor - to help bone marrow recover

213

What is alpha-interferon used for

Hep B and C, Kaposi's sarcoma, leukemias, malignant melanoma

214

What is beta interferon used for?

MS

215

What is gamma IFN used for

chronic granulomatous disease

216

What is oprelvekin

recombinant IL12 for thrombocytopenia

217

What is digoxin immune Fab

targets digoxin; antidote for digoxin intoxication

218

MOA of inflixmab, adalimumab, enteracept

anti TNF alpha
- used for Crohn's , RA, psoriatic arthritis

219

MOA of abciximab

targets glycoprotein IIb/IIIa to prevent cardiac ischemia in unstable angina and in pts treated w/ percutaneous coronary intervention

220

MOA of trastuzumab?

targets HER2

221

MOA of rituximab?

targers CD20; B cell non-Hodgkin's lymphoma

222

MOA of omalizumab

targets IgE; additional line of treatment for severe asthma

223

What diseases do the following autoAb associate w/?
1. Antinuclear
2. Anti-dsDNA, anti-Smith
3. Anti-histone
4. Rheumatoid factor, anti CCP
5. Anti-centromere

1. SLE - nonspecific
2. SLE - renal dz
3. Drug induced lupus
4. RA
5. CREST scleroderma

224

What diseases do the following autoAb associate w/?
1. Anti-Scl70: DNA topo I
2. Antimitochondrial
3. IgA antiendomysial, antiTGminase
4. Anti-basement membrane
5. Anti-desmoglein

1. Scleroderma diffuse
2. Primary biliary cirrhosis
3. Celiac dz
4. Goodpastures
5. Pemphigus vulgaris

225

What diseases do the following autoAb associate w/?
1. Antimicrosomal, antithyroglobulin
2. Anti-Jo1, anti SRP, anti-Mi2
3. Anti SSA (anti-Ro)
4. Anti-SSB (anti-La)
5. Anti- U1 RNP (ribonucleoprotein)

1. Hashimoto's thyroiditis
2. Polymyositis, dermatomyositis
3. Sjogren's syndrome
4. Sjogren's syndrome
5. Mixed CT disease

226

What diseases do the following autoAb associate w/?
1. Anti-smooth muscle
2. Anti-glutamate decarboxylase
3. C-ANCA
4. p-ANCA
5. MPO-ANCA

1. autoimmune hepatitis
2. Type 1 DM
3. Granulomatosis w/ polyangitis (wegner's)
4. Microscopic polyangitis, Churg-Strauss syndrome
5. pauci-immune cresentic GN

227

What disease do the following autoAb associate w/?
1. Anti-ACH receptor
2. Anti-cardiolipin, lupus anticoagulant
3. Anti-hemidesmosome
4. Anti-TSH receptor

1. Mysathenia gravis
2. SLE, antiphosplipid syndrome
3. Bullous pemphigoid
4. Grave's dz

228

MOA of Basiliximab

blocks IL2-R, mab
- used for kidney transplant rejection prophylaxis

229

ADE of basiliximab

edema, HTN, tremor

230

MOA of glucocorticoids

Inhibits NFkB
- suppresses both B and T cell function and decreases transcription of cytokines

231

ADE glucorticoids

hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, peptic ulcers

232

MOA of Alemtuzumab

Ab against CD52, used in CLL

233

MOA of cetuximab

Ab aginst EGFR, use in stage 4 CRC, head and neck cancer

234

MOA of Natalizumab

Ab against alpha-4 integrin, used in MS and Crohn's disease
- risk of PML in pts w/ JC virus

235

MOA of denosumab

Mab against RANKL
- used to treat osteoporosis (inhibits osteoclast maturation - mimics osteoprotegrin)

236

MOA of Palivizumab

Mab against RSV F protein