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Flashcards in Immunity Deck (149):
1

3 examples of type 1 mediated reactions

asthma
hives
allergic rhinitis

2

Ig__ in type 1

Ige

3

most important cells in Type 1

mast cells, eosinophils

4

primary reaction in Type 1 is from

preformed mediators

5

secondary reaction in Type 1 is from

synthesized mediators

6

type II is

direct attack on cell/tissues by antibodies

7

6 examples of type II

hemolytic anemia
erythroblastosis fetalis
Goodpasture syndrome
Myesthenia Gravis
Rheumatic Fever
Grave's Disease

8

Type II involves

complements

9

type 3 is

damage secondary to deposition of immune complexes (igg-ag)

10

4 examples of type III

glomerulonephritis
serum sickness
polyarteritis nodosa
Arthus reaction

11

type III also involves

complements
neutrophils!

12

type IV is

t cell and macrophage mediated
delayed type hypersensitivity

13

most important cells of type IV

cytotoxic T cells
macrophages

14

hyperacute rejection

few minutes-->hour
throbmobosis and vessel attack

15

acute reject

days-->weeks
host becomes sensitized to donor tissue
cellular and antibody mediated
vasculitis, parenchymal attack and damage

16

chronic rejection

mixed mechanism with many macrophages, T cells and plasma cells
--extensive and longstanding damage and FIBROSIS to graft

17

anaphylatoxins

C3a, C5a

18

Type I mechanism

antigen-->DC processing-->DC stimulates TH2 cell-->helper T cell stimulates B cell--> can turn into plasma cell that makes IgE --> bind to FcRe on Mast cells

19

IL involved in Hay fever

IL4

20

cross linking

when Ag brings 2 IgEs close together, stimulating a signal across the mast cell membrane

21

two phases of anaphylactic rxns

immediate/initial response (5 min-1 hr)
delayed/secondary response (2hrs - days)

22

immediate response involves

IGe binding to mast cell and releasing preformed mediators

23

4 tissue events in immediate/initial responses

- vasodilation & vascular congestion (histamine mediated)
- vascular leakage= edema
- smooth muscle contraction
- glandular secretion

24

clinical response to secondary response

coughing
chest tightness
mucous after original exposure

25

3 tissue events due to secondary response

- tissue infiltraton by eosinophils, basophils, neutrophils, some T cells
- tissue injury
- mucosal damage and remodeling

26

primary mediators of secondary response

- leukotrienes
- prostaglandins
- platelet activating factor (PAF)
- cytokines

27

eosinophilic contribution

PAF acether--> LTC4 & 15 HETE
- mucous secretion & epithelial desquamation
Cationic/Neutrotoxic Protein-->Peroxidase & Arylsulphatase
- Major basic protein--> Mast cell degranulation & epithelial desquamation

28

3Localized Type 1 rxns

1) severe urticaria- massive degranulation in response to cold or heat
2) atopic keratoconjunctivitis- eye will become puffy and get corneal edema that extends into slclera
3) asthma

29

pathogenesis of asthma

1) epithelial cells killed off and have to be replaced--> myofibroblasts thicken basement membrane
2) smooth muscle cells hypertrophy
==> tissue damage and matrix remodeling

30

hemolysis through mismatched blood transfusion

type 2 rxns

31

2 mechanisms of hemolytic transfusion rxns

1) acute- premade antibodies--cells lyse due to complement very rapidly
2) delayed- no preexisting Abs- made as transfused Abs degrade by natural causes-- attacking remaining live cells

32

Mac complex

attaches to cell surface and creates pores in it

33

c3b

opsonin for Macrophages that phago the fragmented RBC

34

best Ig for hemolytic RBC

iGM (because relies on complement)

35

Good Pasture's Disease

auto-antibody against collagen Type IV in basement membrane in glomeruli (not tubule) and alveolar walls
clinical- hemoptysis and renal failure

36

where does rheumatic fever come from?

Group A beta hemolytic streptococcal infection (Ab that clear infection start attacking self-antigen)

37

subsets of rheumatic fever

endocarditis
myocarditis

38

endocarditis

vegetations form on valves with fibrin/platelet aggregates

39

myocarditis

Aschoff bodies (areas of inflammation within heart CT that become granulomatous when fully developed)

40

Grave's Disease

anti-receptor antibodies can cause autoimmune overstimulation or receptor blockade
(TSH on TSH R)

41

Myasthenia Gravis

AchR antibody binds and destroys receptor
--weakness in muscles as day progresses

42

Local Type III rxns

arthus rxn
vasculitis
glomerulonephritis
arthritis
pneumonitis

43

systemic type III rxns

serum sickness
SLE
drug rxns

44

key damage cell in Type III

neutrophil!

45

deposited complexes form

- complement cascade
- platelet activation (Hageman factor)

46

platelet activation results in

-microthrombi formation-->occlude small vessels-->potential ischemia if extensive

-hageman factor (f XII of coagulation cascade)-->activation of kinins-->vasodilation and edema

47

glomerulonephritis caused by

different streptococcus from that causing rheumatic fever

48

why do streps localize to glomeruli

charge- complexes have specific charge that allows them to cross the vascular membranes and enter blood vessel lumen

49

serum sickness

following diptheria horse antitoxin, pts develop arthritis, skin rash, and fever

formation of anti-horse Ig antibodies then form complexes that get stuck places

50

main types of cells in type IV

t cells
macrophages
APC

51

types of type Iv HS

1) Delayed type- CD4+
2) T cell mediated- CD8+
3) Rejection of transplanted organ- CD4/8/ antibodies

52

what almost always results in DTH

virally induced inflammation

53

detrimental cell products in type IV

TNFa/b
IL1
superoxides
NO
hydroxyl radicals
neuron toxins

54

beneficial cell products

TGFb
Growth & Trophic Factors
GM-CSF

55

prototype DTH

TB granuloma

56

what type of cells participate in allograph rejection

CD4 and CD8

57

hyperacute rejection

moments-48 hrs
Ab rxn at endothelium

- rapid thrombosis of vessels and organ death

58

acute rejection does NOT mean___ and is mediated by

neutrophils
- t cells

59

2 types of acute rejection

acute cellular- CD4/CD8, lymphocytes, macrophages

acute humoral-
anti-graft antibodies

60

chronic rejection

months to years
chronic vasculitis, intimal fibrosis, obliteration of lumen-->organ ischemia, interstitial mononuclear cell infiltrates-->organ atrophy

61

2 mechanisms to initiate rejection

- cellular: Tc attack cells with foreign MHCI

-humoral- Th cells recognize foreign MHCII and stim Tc and B cells-->B cells make plasma cells to make Ab

62

direct vs indirect antigen presentation

direct- APC from donor in graft
Indirect- APC is dead and host cell presents

63

acute kidney rejection

congested
swollen
hyperemic

64

chronic rejection

shrunken
scarred
severely damaged kidney

65

graft atherosclerosis

chronic graft rejection secondary toe xtensive damage to endothelium and artery wall

66

acute GVH

initially limited to endothelium of skin, GI tract, and liver

67

chronic GVJ

multiple organs show significant damage

68

positive selection

thymocyte must recognize through the TCR an MHC/peptide above a certain affinity threshold

69

negative selection

deletion happens when affinity is too high

70

3 mechanism of peripheral tolerance

1) anergy- shut off t cells via CTLA4
2) Tregs
3) clonal deletion by activation-induced cell death

71

main mechanism that shapes repertoire

negative selection

72

5 mechanisms of autoimmunty

1) molecular mimicry
2) escape of autoreactive clones
3) release of sequestered antigen
4) epitope spreading- more and more antigen released by more and more tissue damage
5) polyclonal B activation

73

PTPN22

most freq implicated
-Rheumatoid arthritis, T1DM

encodes a protein tyrosine phosphatase
-defective copy- out of control tyrosine kinases in lymphocytes-->lnger phos & activation of proteins

74

NOD2

Crohn's disease

encodes a cytoplasmic sensor of microbes
-defective copy-->poor at sensing microbes-->increase in tissue invasion by microbes-->chronic inflammation

75

cytokine receptor genes

IL2Ra (CD25) and IL7Ra
associated w/ MS

may control maintenance or dev. of tregs

76

2 mechanisms of environmental triggers of autoimmune flare ups

adjuvant effect
molecular mimicry

77

polyclonal b cell activation

increase production of autoantibodies (EBV, HIV)

78

t regs are

CD4+ CD25+

79

CD25

low affinity IL2 Receptor (alpha)
aka Tac antgien
--expression rapidly increases upon T cell activation

tends to be overexpressed in autoimmunity

80

how are CD4CD25 cells generated

-from thymus )high avidity)
-from regular t cells in periphery

**regulated by FoxP3

81

IPEX

x linked disease that is due to defect in FoxP3
--characterized by neonatal DM, enteropathy, endocrinopathy

82

what cytokines are req for tregs to suppress other cells

IL10, TGFb

83

general features of autoimmune disease

progressive- sporadic relapses/remissions

epitope spreading (tissue damage releases self antigens and exposes previously hidden epitopes)

84

TH1 autoimmune disorder contains

macrophage rich inflammation

85

TH17 autoimmune disorder contains

neutrophil rich

86

type 1 diabetes mellitus

t cells reacting to beta cells in islets

often preceeded by dev of anti-insulin antibodies

major targets include insulin and GAD

87

clinical manifestations of lupus

Malar Rash
Libman Sacks
Retinal Damage (vasculitis-->arterial occusion)

88

Malar Rash

liquefactive degeneration of the basal layer of the epidermis and edema at the dermo-epidermal junction
igg deposits

89

Libman Sacks

sterile, inflmmation-free valve vegtations associated with SLE

90

immunological pathology of SLE

failed self tolerance-cant eliminate b cells, CD4 cells
abnormal rxn of TLr to self DNA/RNA rather than viral RNA (mediated by IFN1)

91

environmental factors that influence sLe

UV exposure
sex hormones (esp during reproductive years)
drugs

92

rheumatoid arthritis

chronic systemic inflammatory disease affecting many organs but main target is joint (non-suppurative proliferative/inflam synovitis)

93

microscopic of RA

synovial hypertrophy with formation of villi

subsynovial tissue containg dense lymphoid aggregate

94

environmental associatins with RA

infectious agents, but one agent has not been specifically implicated

citrullinated proteins (arginine-->citruline)- can be seen in lung of smokers

95

immunological factors of RA

CD4+ t cells with TH17 and TH1 appear early

96

80% of patients with RA have

rheumatoid factor-typically igm

autoanitbodies to Fc portion of IgG

NOT cause of disease but marker of disease

97

anti-CCP

antibody to citrullinated peptides

produced at sites of inflammation

98

clinical success with RA and

TNFa antagonists

99

primary vs secondary ids

primary-genetically determined
secondary-acquired

100

xlinked primary iDs

xla
hyper igm
scids
wiskott-aldrich syndrome

101

autosomal primary ids

dominant -
C1 inhibitor deficiency

recessive-
digeorge syndrome
scids

102

molecular primary ids

isolated iga deficiency
common variable immunodeficinecy

103

secondary ids

iatrogenic
hiv

104

humoral deficiencies

- XLA
- common variable immunodeficinecy
- isolated iga deficiency
- hyper igm syndorme

105

XLA

failure of b cell precursors to develop into mature b cells--> decrease to absent b cells-->deficiency of igg

t cells are still intact so increase risk of autoimmune

106

what are pts with xla susceptible to?

bacterial infection
-- haemophilus, strept, staph
enteroviral
--echovirus, poliovirus, coxsackie
severe intenstinal giardiasis (parasite normally resisted by iga)
--giardia lamblia

107

etiology of xla

mutation on Btk gene on x chrome-->req for signal transduction necessary for ig light-chain rearrangement and b cell maturation-->mutation removes maturation signal

108

treatment xla

ivig

109

common variable immunodef

- hypogammaglobulinemia
- normal number of b cells, but cant turn into plasma

110

differentiating brutons and CVI

- CVI affects both geneders equally
-CVI has later onset

111

isolated iga def

low levels iga-->increase risk resp and gi and uti

112

hyper igm syndrome

defect in Th cells ability to deliver activiating signals to b cells for class switching

most are xlinked with mutation in gene encoding CD40L (CD154)

113

cellular deficiencies

digeorge syndrome

114

digeorge syndrome

- failure of 3rd and 4th pharyngeal pouches to develop during embryogenesis (no thymus, no pth)
- loss of t cell mediated immunity

115

clinical manifestations digeorge

tetany (no PTH-->noCa2+), congenital heart defects, abnormal facia appearance

116

genetic manifestation of digeorge

22q11 deletion

117

infections associated with t cell defects

bacterial sepsis
viruses- cmv, epistein-barr, severe varicella, chronic respiratory and intestina infection
fungi/parasites- candida

118

overlap syndromes

SCID
Wiskott-Aldrich Syndrome
Complement Deficiencies

119

SCID cellualr level

-lymphopenia (low absent T/B cells)
-hypogammaglobulinemia

120

etiology of scid is

variable!
cytokine recepto def: impacts t cell dev (x linked)
ADA def (autosomal recessive) -- cant remove excess purines (accum of toxic derivatives)

121

WAS genetics

x linked recessive mutation of XP11.23 Was protein
--from a family of membrane receptor signal proteins

122

WAS presentation

thrombocytopenia (dec platelets)
eczema
immune defiency

123

WAS at cellular level

- low igm, normal igg, high iga & ige

- do not make antibodies to polysacch antigens and poor antibodies to protein antigens

-progressive t lymph depeletion

124

Rx WAS

- bone marrow transplant to cure
- platelet transfusion support before that

125

compliment deficiencies

C2 def.
C3 def.
C5-9 def.
C1 inhibitor

126

C2 def

does not result in an increased risk of infection (alternative C pathway compensates), but there is an increased risk of SLE like autoimmune disease

most common

127

C3 deficiency

-required for function both classic and alt pathways
-increased risk of serious bacterial infection

128

C5- 9 Deficiency

cannot form MAC involved in lysis of organisms
-increased suceptibility to Neisseria infection, as this bacteria's thin cell walls make it susceptible to MAC

129

C1 inhibitory deficiency

hereditary angioedema
- episodic edema of skin and mucosa surfaces due to stressor trauma

stressor trauma-->unregulated C1 Hageman factor, kallikrein and Plasmin-->mast cell degran and vasoactive peptide release

130

Iatrogenic disorders due to

Chemotherapy, immunosuppressive therapy
--bone marrow becomes less cellular and more fatty

underlying medical conditions
-cancer, diabetes, renal disease, infection

131

HIV structure

spherical and contains an electron-dense, cone-shaped core surrounded by a lipid envelope derived from the host cell membrane

132

virus core contains

1) major capsid protein p24
2) nucleocapid protein p7/p9
3) two copies of genomic RNA
4) three viral enzymes

133

three viral proteins of HIV

protease
reverse transcriptase
integrase

134

p24

most readily detected viral antigen and is target for antibodies that are used for the diagnosis of HIV infection in the widely used enzyme-linked immunosorbent assay

135

2 glycoproteins on viral envelope

gp120, gp41
critical for hib infection of cells

136

HIV genome

RNA--> gag, pol, env
-->translated into large precursor protein that are cleaved by viral protease--> mature proteins

137

targets of highly effective anti-hiv1 drugs

protease

inhibit formation of mature viral proteins-->not curative, but suppress viral load

138

primary infection of HIV

virus enters blood or mucosal tissues-->infects t cells, DC, and MO-->carry it to lymphoid tissue-->viremia

139

mechanism of infection of HIV

gp120 binds CD4 R and chemokine coreceptors on t cell, monocyte macrophage, or DC-->confirmational change in gp41 that allows fusion of virus with host cell-->viral core enters cytoplasm of host cell--> lipid envelope surrounds capsids derived from host membrane-->viral particles bud

140

mechanisms of ID in HIV

-direct, cytopathic effect of replicating virus
-colonization of lymphoid tissue leading to progress destruction
-chronic activation of uninfected cells leading to activation induced cell death
-klling of infected cells by cytotoxic t lymphocytes

141

3 phases of HIV infection

1) acute retroviral syndrome
2) middle, chronic phase
3) clinical AIDS

142

acute retroviral syndrome

- infection of CD4+ t cells (expresse CCR5)
- mucosal infection--> dissemination of virus & dev of host immune response
-CD8+ t cells- initial containment (kill Cd4) -->drop in viremia
==> end of acute phase reflects equil. between virus and host response (patient can be stable for several years)

143

middle chronic phase

asymptomatic--" clinical latency period"

-replicate and destroy cells in lymph nodes and spleen
-majority of circulating CD4+ t cells do not have disease, but since ones made in lymph nodes are being destroyed, level of t cells is steadily declining

144

clinical AIDs

-breakdown of host defense, dramatic increase in plasma virus, severe
-long-lasting fever, fatigue, weight loss, diarrhea
- after a period of time, opportunistic infections, secondary neoplasms, clinical neurologic disease emerge

145

when and how does HIV evade host immune system?

chronic phase

- virus has glycan shield -prevents antibody binding
-pt mutations, insertions, deletions-->alter position of sugars--> ever-changing disguise

146

when is seroconverstion first detected?

3-7 weeks post-exposure

147

considered to have aids when

<200 cells/ul

148

category B conditions

- oroopharyngeal candida (thrush)
- vulvovaginal candidiasis (yeast infecton)
- pelvic inflammatory disease
-hairy, leukoplakia, oral-cancer
-idiopathic thrombocytopenic purpura
-peripheral neuropathy
-herpes zoster (shingles)

149

category C indicator conditiosn

-active CMV in lungs
-mycobacterium avium-intracellulare infection of lymph nodes in
-toxoplasmosis of brain
-lung infection with pneumocystis carinii
-kaposi sarcoma lesion