Immunology Final

Front 1

DTH Phase 1: Sensitization Phase

Back 1

Macrophages present Ag on MHC class II to CD4+ TH cells
release cytokines & call in more TH1 cells & commit TH cells to the type 1 lineage

Front 2

DTH Phase 2: Effector Phase

Back 2

Th1: IFN-γ, TNF-B, IL-2, IL-3, GM-CSF, MIF
Macrophages then mediate the DTH response.

Front 3

INF-gamma

Back 3

Pro-Inflammatory
Activates Macrophages:

-->Macrophage to become effector, increases # of MHC class II for more efficient presentation of pathogen

-->Up regulates TNF receptors,

-->up-regulates Oxygen radical production

-->Up regulates Nitric Oxide

Front 4

IL-2:

Back 4

Pro-Inflammatory, & turns on nearby CD8+ TC

Front 5

IL-3

Back 5

turns on monocytes production in bone marrow, b/c need more macrophages to get rid of pathogen

Front 6

GM-CSF

Back 6

growth factor that turns on monocytes production

Front 7

TNF-beta

Back 7

mediates macrophage activation, local tissue destruction and alters adhesion molecules on local blood vessel endothelium to facilitate extravasation of other cells (eg neutrophiles)

Front 8

IL-3 and GM-CSF

Back 8

enhance monocyte production by the bone marrow

Front 9

activated macrophages can

Back 9

respiratory burst
produce nitric oxide
phagocytose cellular debris
secrete cytokines - esp. TNF-alpha
Continue to present antigen on MHC II and to stimulate helper T cells

Front 10

TNF-alpha

Back 10

Made by: Monocytes, Macrophages and others including activated T cells, NK cells, neutrophils, and fibroblasts

Functions: Strong mediator of inflammatory & immune functions; known to regulate growth and differentiation of a wide variety of cell types

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w/out INF-gamma macrophages

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won’t activate & won’t clear pathogen/infections

IFN-γ is needed to clear DTH, w/out you could die, can’t clear pathogen

Macrophages take care of intracellular pathogens, w/out IFN-γ you can’t clear intracellular pathogens

Front 12

Langhans Cells

Back 12

multinucleated giant cells

Front 13

Langerhan cells

Back 13

are dendritic cells in the skin

landeRhan are dendRitic

Front 14

Chronic Granulomatous Disease

Back 14

Chronic DTH
auto immune condition macrophages that have fused together (Multinucleated Giant Cells) and granulomas with lymphocytes surrounding

Front 15

Epitheloid cells

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activated macrophages which fuse to become multinucleated giant cells

Front 16

Chronic DTH

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longer than 72 hours, granulomas form, Disregulated DTH

Front 17

What distinguishes a type I hypersensitive response form a normal Humoral response?

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cells secrete IgE in response to the activation of allergen specific TH2 cells --> Mast cells and basophils possess receptors for the Fc region of IgE (Fcε-R1)  they can bind (the base) of IgE with high affinity

Front 18

IL-4 & IL-13 made by? do what?

Back 18

made by Th2

increases IgE production from B cells,

promote class switching to IgE

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Antigen induces ThI response can never cause?

Back 19

allergies

Front 20

Histamine

Back 20

increases vascular permeability; smooth muscle contraction, contraction of intestinal & bronchial smooth muscles, increased permeability of venules (from capillaries to veins), and increased mucus secretion by goblet cells

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Leukotriens & prostaglandins

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from mast cell degranulation & enzymatic breakdown of phospholipids in plasma membrane --> takes longer to become apparent

Front 22

Leukotriens

Back 22

mediate bronchoconstriction, increased vascular permeability, and mucus production

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Prostaglandins

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bronchoconstrition, vasodilation

Front 24

For an antigen to be an allergen it must ?

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elicit a TH2 response only, not TH1

Front 25

Addition of increasing amounts of IFN-γ leads to decreased

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IgE

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IFN-γ can prevent

Back 26

class switching --> Pro-Inflammatory pushes away from hypersensitive type I response (IL-4 & IL-13)

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Association w/urban dwelling, higher socioeconomic, had lower ?

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free IgE, b/c it was already bound to mast & basophils

they had higher allergies

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asthma & atopy are less common in ?

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children of animal farmers
children with siblings
households with dogs

Front 29

TNF-alpha & IL-1 can cause?

Back 29

are found in Type I rx
anaphylaxis
increased expression of CAM on venular endothelial cells

Front 30

Histamine & Heparin

Back 30

increase vascular permeability leakier

Front 31

Proteases in type I hypersensitivity

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increase secretion of mucus,

generating split products of complement --> activating complement

Front 32

IL-4 & IL-9

Back 32

enhance mast cell production

Front 33

IL-5 & IL-9

Back 33

enhance Eosinophil maturation, activation, and accumulation

Front 34

IL-3

Back 34

made by T cells & mast cells
mast cell growth factor

Front 35

IL-5

Back 35

Secreted By: TH2
Targets/Effects: Eosinophil activation and generation

Front 36

IL-6

Back 36

Sources: T cells, B cells, several nonlymphoid cells, including macrophages
proliferation and antibody secretion of B cell lineage

Front 37

IL-10

Back 37

Type I Hypersensitivity
made by Th ?2?
Stimulates or enhances proliferation of B cells
antigaonizes Th1

Front 38

Type II Hypersensitivity Effector Mechanisms

Back 38

Cells are exposed to high levels of pre-formed Antibody that causes
Complement Activation
Antibody Dependent Cellular Cytotoxicity (ADCC)
Opsonization: using Ab to opsonize target which leads to lysis

Front 39

Type II Hypersensitivity examples

Back 39

Transfusion reaction
Rh syndrome
Drug-induced hemolytic anemia

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Hemolytic disease of the newborn

Back 40

Mom is Rh negative & Fetus is Rh+

Rhogam: Mother takes Rhogam, an Ab that attaches to Rh+,

Front 41

Drug-induced hemolytic anemia

Back 41

type II Hypersensitivity
drugs bind to erythrocyte proteins and create novel epitopes
an individual may make an IgG response to the novel epitopes
IgG antibody may mediate complement-mediated lysis of red cells - leading to hemolytic anemia

Front 42

Immune complexes are normally removed from circulation ?

Back 42

C3b binding to receptors on erythrocytes
then cleared primarily by splean, 2nd liver

Front 43

High levels of immune complexes may ?

Back 43

adverse effects as a result of complement activation and localized inflammation b/c they deposit in blood vessel, joints, Glomerulus of Kidneys

Front 44

Localized Type III reaction

Back 44

Inject Ag (insect bite/sting)
pre-formed IgM/IgG (can co-occur w/type I if IgE is preformed)
Ab-Ag complex activates Classical Complement
C3a & C5a anaphylatoxins that cause localized mast cell degranulation

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how are anaphlatoxins generated in hypersenesitivity 1 & 3?

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I: proteases cleave C3 & C5 to generate anaphlatoxins C3a & C5a

3: Classical pathway C3 convertase & C5 convertase

Front 46

Generalized Type III reactions

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Ag injected intravenously into an individual with high levels of antibody to the antigen --> masive complement activation
Serum Sickness

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Type III Hypersensitivity which is an Auto Immune disease driven by immune complex deposition

Back 47

Lupus

Front 48

Free-Martin

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vascular anastomoses between bovine twins
Nonidentical twin cows sharing the same uterus

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Immunologically privileged sites

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Brain
EYE
testis
uterus (fetus)
Hamster Cheek pouch

Front 50

TGF-Beta & IL-10 do what?

Back 50

down regulate inflammatory responses
silence TH1 driven (regulated), TC cell mediated, NK cell responses

Front 51

AIRE
Autoimmune regulator element

Back 51

expressed in the thymus
causes expression of Pro found in periphery
educate/ expose these Thymocytes to different proteins. Mutations in the gene encoding AIRE result in autoimmunity.

Front 52

Characteristics of “regulatory” T

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high output of IL-10

TGF-β

CD4+

CD25

Foxp3

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CD25

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IL-2 receptor alpha chain, which is up regulated in activated T cells

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C3a, C5a, & C5b67 are also chemotactic factor for

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Neutrophils

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Neutrophils which release lytic enzymes when bound to

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C3b- generated by Classical complement in Type III hypersenesitivity & proteases in Type I

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Mutations in Foxp3 cause ?

Back 56

autoimmunity, this is a sign of disregulation
Foxp3 must somehow be involved with immune regulation

Front 57

How do regulatory T cells regulate?

Back 57

IL-10 & TGF-β
cause APC to down express MHC II

Front 58

TH3 produce less ____ then Tr1

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IL-10

Don't produce any FoxP3

Front 59

TH3 cell characteristics

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CD4+

CD25+

Interact with MHC class II presentation of APC

Involved with direct cell to cell contact they are touchy feely to turn cells off

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Th1 cells
Secrete what?
This promotes who?
& these mediate what?

Back 60

Th1 secretes INF-gamma
INF gamma activates Macrophages
Macrophages mediate inflamation

Th1 also secretes IL-2 that causes CTL proliferation and differentiation of the Ag-activated CTL-P into effector CTLs w/CD28-B7

Front 61

What 3 things to CTL-P need to become effector CTL?

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1. An Ag-specific signal transmitted by TCR complex upon recognition of MHC I complexed to a "licensed" APC (usually a dendritic cell).

2. Costimulatory signal transmitted by CD28-B7

3. Signal induced by IL-2 binding to IL-2R resulting in proliferation and differentiation of the Ag-activated CTL-P into effector CTLs.

Front 62

CTL-A4 is the ?

Back 62

CD28 antagonist
it won't let CTL-P become effector CTL

Front 63

Fox P3 is expressed in cells that are

Back 63

Tregulator1: turning down immune response

Front 64

IL-10

Back 64

suppressive cytokine
involved more with humoral than cellular
suppresses inflammation

Front 65

TR1 is predominantly in the ?

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Intestines

Front 66

Danger theory

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danger & damage than self/non-self

signals are endogenous, coming from within the cells that they are secreting

controlling signals are endogenous

can’t turn off autoimunity

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Janeway’s theory

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danger” signals are PAMPs, not endogenous molecules

Front 68

Humoral Auto immune diseases

Back 68

pernicious anemia
Graves’ disease
myasthenia gravis
autoimmune hemolytic anemia

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autoimmune hemolytic anemia

Back 69

Autoimmune disorder: Humoral

Antibodies to red cell antigens --> complement-mediated lysis of red cells.

Front 70

Graves Disease

Back 70

Autoimmune Disorder

antibody to thyroid TSH receptor

Ab binds to receptor, hyperactivates it leads to hyperthyroid

Front 71

Pernicious Anemia

Back 71

Autoimmune Disorder

antibody to intrinsic factor

Intrinsic factor is needed for Vit B-12 absorption

Front 72

Myasthenia Gravis

Back 72

Autoimmune Disorder

Blocking of surface receptors on muscle for Acety Choline from nerve

Blocks muscle Activation
Problems swallowing

Front 73

Cell-mediated autoimmune diseases

Back 73

type I (insulin-dependent) diabetes (IDDM)

multiple sclerosis

Hashimoto’s thyroiditis

inflammatory bowel disease

Front 74

SLE: Systemic Lupus Erthymatosis

Back 74

Complement-mediated inflammation
Type of autoimmune hemolytic anemia

characterized by the production of non-organ-specific autoantibodies,

antinuclear Ab (ANA),

Ab anti-double-stranded DNA

anti-phospholipid antibodies

Ab against glomularus

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Molecular Mimicry

Back 75

infection causes autoimmune cells to proliferate, too many to regulation properly

Heart-Ab after infection with Streptococcus - which has antigens that cross-react with cardiac myosin.

Trypanosoma cruzi - heart & never

hepatitis B encephalitogenic myelin

Front 76

Multiple sclerosis

Back 76

chronic inflammatory demyelinating disease of the central nervous system

CD4+ T lymphocyte population with B and T cells and macrophages associated with myelin destruction

peripheral blood lymphocytes in patients with MS show an increased frequency of activated myelin-reactive cells

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IDDM- Type I diabetes

Back 77

lymphocytic infiltration of tissue, destruction of tissue cells, accompanied by autoantibody production.

CD8 T cells play biggest role, Ab are involved also

Front 78

Hashimoto’s thyroiditis

Back 78

Tc inflitration in Thyroid

Front 79

Most autoimmune diseases associated with class __ MHC

Back 79

class II MHC genes - indicates trouble at the MHC, CD4+ helper T-cell interaction

Something in thymic development is causing problems in negative selection

Front 80

Therapies for PsA and other autoimmune disorders

Back 80

TNF-alpha inhibitors

Front 81

CCR5 & Autoimmune Diseases

Back 81

liver disease
IBD
Multiple sclerosis
Type I diabetes
Grave’s disease

Front 82

CCR5delta32 deletion

Back 82

suspected of aiding in survival of bubonic plague (also amoung the most studied for being a factor in HIV) & small pox but makes more suceptable to West Nile

Front 83

CCR5 & Infectious diseases

Back 83

Hepatitus C
A variety of viral infections and viral infections in general
Certain parasitic infections
HIV (either resistance or suseptability depending on which allele)

Front 84

Individuals naturally express varying levels of cytokines indicates

Back 84

polymorphisms in cytokine genes.

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TNFα

Back 85

– Identified as an important part of Psoriatic Arthritis (PsA)
– Studies tried to link TNFα polymorphisms with PsA – NOT a link
– HOWEVER, TNFa2308 and TNFa +252 were found to influence the severity of PsA joint erosions
– Therapies for PsA and other autoimmune disorders include TNFα inhibitors

Front 86

TNF alpha inhibitors

Back 86

Enbrel,

Remicade

Humira

Front 87

Remicade

Back 87

Ab that binds TNFalpha

is part mouse/human chimerical Ab

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Humira

Back 88

similar to Remicade, but fully human Ab that binds TNF alpha

some people are hypersenitive to mouse part of Remicade

Front 89

Genetics of Autoimmune Diseases

Back 89

MHC polymorphisms

Specific Mutations

Ability for MHC to present/not present certain peptides

Non MHC poly: If you make more/less of a cytokine

Front 90

CCR5

Back 90

Lance: we need to know what binds to this receptor & why it's important

Front 91

Autograft

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to another site on the same individual

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Isograft

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to a genetically identical individual

Iso=Identical

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Allograft

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to a different individual of the same species

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Xenograft

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to a different speices

Front 95

hyperacute rejection

Back 95

Occurs quickly, recipient has preformed Ab against tissue

This is common in xenografts-btw species

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how would complement split products then attract ? & then ?

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Lance: we need to finish this card

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Why can't we use pig organs?

Back 97

Humans recognize epitopes containing terminal galactose residues as foreign.

pigs contain enzyme α-1,3-galatosyltransferase - transfers terminal galactose residues

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Acute graft rejection

Back 98

2 stages
First set rejection
Second set rejection

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First set rejection

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- Infliltration w/
- Celeular event that _____
o Starving graft

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Second set rejection

Back 100

- Occurs faster
- Completely nercotic
- Based on subsequent exposure to Ag

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Acute graft rejection is mediated by

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T cells, mostly CD4+

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Chronic rejection

Back 102

develops months or years after tissue transplant

- arises as a result of tissue repair as well as immune mechanisms

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a major problem in tissue transplantation

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Chronic rejection
1/2 of renal grafts that make through 1st are still working 9 years later

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renal and cardiac allografts chronic rejection is caused by

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arteriosclerosis in the graft

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lung allografts chronic rejection is caused by

Back 105

bronchiolitis obliteran

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Hyperacute rejection incidence

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< 1%

Front 107

Hyperacute rejection Time of onset

Back 107

min-days after transplant

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Hyperacute rejection Histopathology

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Thrombosis

Platelet & Neutrophil accumulation

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Hyperacute rejection mediators

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Ab

complement

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Acute Rejection Incidence

Back 110

50%

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Acute Rejection Time of onset

Back 111

w/in first year

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Acute Rejection Mediators

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escalating leukocytic infiltration, edema, necrosis

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Chronic Rejection Time of onset

Back 113

usually 5-10 years

can happen w/in weeks

Front 114

RAG 1 / RAG 2 Mutations

Back 114

associated with SCID
(severe combined immuno deficiency)
~ RAG associated with recombination,
~ influencing both T & B cell

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Rag1 hypomorphic mutation

Back 115

mech: Too much RAG 1, not enough RAG 2

~ Result in T cell imbalance: increase in TCR delta gamma T cells

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TCR delta gamma T cells

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should be less than 10% of T cells

do not require MHC presentation

increased cytomagalovirus

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don’t make enough Rag 2 can lead to

Back 117

an increase of CMV

an autoimmune reaction to blood cells leading to anemia

Front 118

Hyperacute rejection of kidney graft by the #'s

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1. Preexisiting Ab in recipent

2. Ab bind Ag on graft & activate complement

3. Complement split products attract neutrophils which release lytic enzymes

4. Neutrophil lytic enzymens destroy endothelial cells; Platelets adhere to injured tissue, causing vascular blockage

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What is the major difference btw Acute & Chronic rejection?

Back 119

Mediators

Front 120

Mediators in Acute

Back 120

T cells mediated

Th --> IL2, INFgamma --> bring in macrophage & CTL

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Mediators in Chronic tissue rejection

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Ab, Cytokines, & tissue growth factors

Front 122

important determinants of graft accceptance or rejection

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MHC

We screen for this

Front 123

which is more important in tissue transplant MHC I or II

Back 123

MHC II b/c it presents to CD4+ T that activate cell mediated & humoral responces

Front 124

acute graft rejection immunosuppressive drugs
- azathioprine, mycophenolate

Back 124

inhibitors of purine biosynthesis
inhibit T cell proliferation across the board

Front 125

acute graft rejection immunosuppressive drugs
cyclosporin A, tacrolimus (FK506)

Back 125

- prevent production of IL-2 by activated T cells
IL-2 promotes T cell proliferation

Front 126

acute graft rejection immunosuppressive drugs
Sirolimus (rapamycin)

Back 126

blocks IL-2 receptor signal transduction

Front 127

immunosuppressive antibodies

Back 127

Ab anti-CD3 (OKT3)

knocks out all TCR signaling

Front 128

drugs turn off T cells but do not induce tolerance

Back 128

Anti CD40 ligand

CTLA 4 Ab: competes w/B7 to bind w/CD28

Front 129

Antigenic Variation Pathogens

Back 129

o Influenza type A
o Trypanosoma (sleeping Sickness) Parasite
o Plasmodium parasitic protozoa
o Neisseria gonorrhea Bacteria

Front 130

pathogens that Interfere with MHC class I presentation

Back 130

o Herpes Simplex Virus (HSV
o Human Cytolomega Virus (HCMV)
o Adenovirus
o human herpesvirus
o Kaposi's sarcoma-associated herpesvirus (KSHV)

Front 131

what does tap do?

Back 131

- Transports angitgen to load on MHC class 1

Front 132

w/out Tap

Back 132

o Down regulates MHC Class I Expression b/c
w/out peptide β2 Microglobulin won’t stick and whole thing will fall apart

Front 133

viruses that interfere with TAP

Back 133

Herpes Simplex Virus (HSV)

Front 134

Impairment of complement activity

Back 134

Vaccinia virus

Herpes simplex virus

Herpesviruses

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Latency

Back 135

The most notorious- Herpes Simplex Virus

Herpes zoster (chickenpox)

EBV

Front 136

immunosupressive drugs that down play IL2

Back 136

Sirolimus (rapamycin

cyclosporin A, tacrolimus (FK506)

Front 137

o Influenza type A

Back 137

 NA: neuraminidase
 HA: hemagglutinin

Front 138

Herpes Simplex Virus

Back 138

inhibit tap

expresses a protein (C-1) that binds C3b and therefore stops coplt destruction of cell

Latent

Front 139

cytolomega Virus

Back 139

degrades MHC class I heavy chain (alpha chain)
mimics MHC class I & tells NK that it’s all good
High Rag1 low 2 increase CMV infectrions

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Adenovirus

Back 140

MHC class I molecules in the ER and inhibit transport to PM
deletion of this leads to greater tissue damage by inflammatory response

Front 141

human herpesvirus

Back 141

tags MHC class I in ER --> lysosome

Front 142

these promote endocytosis of MHC class I

Back 142

Kaposi's sarcoma-associated herpesvirus (KSHV)- K3 K5

HIV-1 Nef protein

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Kaposi's sarcoma-associated herpesvirus (KSHV)

Back 143

promotes endocytosis of MHC class 1

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HA: hemagglutinin

NA: neuraminidase

Back 144

HA: used to bind host's salicilic acid residues

NA: viral budding from host cells

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Cell Mediated - Early cytokines

Back 145

INF-β

TNF-Beta

IL-1

Front 146

IL-1

Back 146

mediator of inflammation
fever
attracks inflammatory cells

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INF-beta

Back 147

stimulates NK cells

Front 148

Trypanosoma

Back 148

parasite vectored by the tsetse fly
Variable Surface Glycoprotein -Shifts if loseing
autoantibodies heat nerve

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what's good to fight parasites

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Nutrophils, eosinophils, B cells, Ab (IgE are the most efficient b/c it can cause degranulation of Mast cell, eosinophils & basophils)

Front 150

these can shift during infection

Back 150

Trypanosoma

Neisseria gonorrhea

Plasmodium

Front 151

Neisseria gonorrhea

Back 151

Shifts by pilin gene conversion

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Pathogens that bind cytokines

Back 152

Vaccinia
Cowpox
Myxoma virus (a rabbit poxvirus
Shope fibroma virus (a rabbit poxvirus)
EBV

Front 153

Vaccinia and cowpox both

Back 153

bind IL-1

Front 154

Myxoma virus (a rabbit poxvirus

Back 154

binds IFN-gamma

Front 155

Shope fibroma virus (rabbit pox)

Back 155

binds and inactivates TNF (proinflammatory)
- Decreases Apoptosis
- Decreases Inflamation
- This affects the innate & adaptive (can’t get to infection

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EBV

Back 156

IL-10 homolog

Front 157

Pathogens that impair complement

Back 157

Vaccinia virus
Herpes simplex virus
Herpesvirus

Front 158

Vaccinia virus

Back 158

VCP-binds C4b needed for C3 convertase
stops classical & lectin

Front 159

Herpes simplex virus

Back 159

binds C3b ->entirely block Lytic Pathway
inhibits Tap --> can't load on MHC I
Latency

Front 160

Herpesvirus

Back 160

gE & gI -binds IgG
- blocks classic complement
- blocks phagocytosis
in ER tags MHC I --> lysosome

Front 161

Combined immune deficiencies

Back 161

- X-linked SCID
- ADA deficiency
- Wiskott-Aldrich syndrome
- Reticular dysgenesis
- Bare lymphocyte syndrome

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X-linked SCID

Back 162

don't have gamma subunit for
IL-2, & 7(activates B cells)

Front 163

Adenosine deaminase (ADA) deficiency

Back 163

disrupts B and T cell function.
stops ribonucleotide reductase--> destoys dividing cells

Front 164

- Wiskott-Aldrich syndrome

Back 164

mutation in the WASP (Wiskott-Aldrich Syndrome Protein)
cytoskeleton and with cellular signal transduction pathways.
eczema
- thrombocytopenia
- susceptibility to bacterial infections
- absence of DTH reactivity
- variable T cell function

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- Reticular dysgenesis

Back 165

The most severe immune deficiency - total absence of any form of immunity
failure to differentiat lymphoid and myeloid lineages.

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- Bare lymphocyte syndrome

Back 166

3 types Deficiency of MHC expression.
Type I - loss of class I MHC expression
Type II - loss of class II MHC expression
Type III - loss of both class I and class II MHC expression