Immuno--Pathologies Lect 16 & 17

Front 1

What are the four major types of hypersensitive rxns?

Back 1

Type I – immediate type hypersensitivity

Type II – cytotoxic hypersensitivity

Type III – immune complex hypersensitivity

Type IV – delayed type hypersensitivity

Front 2

Give an example of each type of sensitivity.

Back 2

Type 1: allergy, asthma (IgE mediated)

Type 2: Rh mismatch (Ig mediated C' activation)

Type 3: serum sickness, vasculitis, Ag-Ab complexes

Type 4: TB skin test, hypersensitive pneumonitis--Tdth cells

Front 3

What are the two phases of Type 1 hypersensitivity?

Back 3

Sensitization phase

Effector phase

Front 4

What happens in the sensitization phase of a Type I hypersensitivity rxn?

Back 4

Sensitization phase:

exposure to antigen (allergen)

production of IgE

binding to mast cells and basophils via Fc episilon Receptor on these cells

Front 5

What happens in the effector phase of a Type I hypersensitivity rxn?

Back 5

Effector phase:

IgE binds allergen (antigen)

crosslinking of IgE results in degranulation of the mast cell

release of pharmacologically-active mediators

Front 6

What chemicals must be released in order for IgE to crosslink on a mast cell?

Back 6

1. activation of tyrosine kinases

2. 2nd messengers. cAMP levels rise then fall. @ fall get degranulation

3. Ca+2 mobilization = influx. stimulates breakdown of arachidonic acids into: prostaglandins and especially leukotrienes

4. microtubule assembly to move granules to cell surface.

5. epinephrine and theophylline keep cAMP levels high (so no degranulation--can use as Tx)

Front 7

What determines IgE production?

Back 7

Genetics and relative dosage of an allergen

Front 8

Describe the interleukins involved in IgE activation and inhibition.

Back 8

cytokines produced by APC

IL-4, IL-5 and IL-13 (Th2) switch factor for IgE

IL-10 (Th2) INHIBITS IFN gamma(Th1), thus inhibiting IL4 production

Front 9

What does the dose of an allergen control?

Back 9

production of IgG or IgE. IgG can be used in DEsensitization. IgE causes the allergic rxn.

Front 10

What are the preformed chemical mediators of allergies?

Back 10

HISTAMINE--increase vascular permeability and smooth mm contraction

proteases: mucous secretion, generation of complement split products.

Front 11

What are NEWLY FORMED chemcial mediators of allergies?

How long do they take?

Back 11

Takes 30-60 seconds to form leukotrienes an dprostaglandins from arachodonic acid.

LEUKOTRIENES--(SRS-A=slow reactive substance of allergies/anaphylaxis). increases vascular permeability and contraction of pulmonary smooth muscles.

platelet activating factor--platelet aggregation and contraction of pulmonary smooth mm.

protaglandin D2--vasodilation, contraction of smooth muscles.

Cytokines--chemotactic and inflammatory

Front 12

What do leukotrienes do?

Back 12

increase vascular permeability and contraction of pulmonary smooth mm.

SRS-A 30-60s

Front 13

What are the symptoms of allergy and what are they dependent on?

Back 13

dependent upon SITE OF ALLERGEN EXPOSURE.

--wheal and flare rxn; pruitis, erythema

bronchoconstriction

mucous secretion

vasodilation; even shock

Front 14

What does pruritis mean? urticaria? atopy?

Back 14

pruritis (itchy)

urticaria (hives)

atopy (localized)

Front 15

What are some examples of atopy anaphylaxis?

Back 15

pruitis, urticaria

allergic rhinitis (hay fever)

asthma (atopic asthma)

eczema (atopic dermatitis)

food allergies

Front 16

What % of US pop has allergic rhinitis?

What are the symptoms?

What is the Tx?

Back 16

10%

airborne allergens with mast cells of conjunctivae and nasal mucosa--localized

localized vasodilation and increased capillary permeability
mucous production
sneezing/coughing

Tx: anti-histamines and desensitization

Front 17

How does an anti-histamine work?

Back 17

blocks histamine binding--does NOT block release of histamine and does NOT block IgE.

Front 18

How does desensitization work?

Back 18

stimulate the immune response to produce IgG instead of IgE

Front 19

What are the two major branches of asthma and what are their causes?

Back 19

allergic and intrinsic asthma.

Allergic: airborne allergins (dust, pollen, insect parts), blood borne allergens (viral Ag), degranulation of mast cells due to IgE cross linking. lower respiratory tract usually.

Intrinsic has nothing to do w/ IgE. not immune stimulated. Instead exercise induced, warm to cold climates, other cmpds producing granulation--not IgE.

Front 20

What % of the US poplulation has allergic asthma?

What can allergic asthma lead to?

Back 20

5%

airway edema and mucous secretion, with subsequent exposures gets worse. Can even lead to airway obstruction.

Usually hypersensitive to allergens

Front 21

Where are cytokine genes found in asthmatics?

Back 21

5q23-33 (IL-3, 4, 5, 9, 13)

IgE switch, eosinophil recruitment, mast cell proliferation.

Front 22

What are some hypotheses for the increasing incidence of asthma?

Back 22

increasing in cases AND severity

maybe due to:

complex genetic disease (see previous slide)

environmental factors (cockroach implicated)

Front 23

How are allergies Dx?

Back 23

skin test--scratch or intradermal. could cause severe rxn.

radioimmunoassays--need purified allergens. detect allergen specific IgE.

Front 24

What are the treatments for allergies?

Back 24

Anti-histamine – for atopic allergies

Epinephrine – for quick response--relaxes smooth muscle contraction and causes vasoconstriction

Anti-inflammatory
glucocorticoids and leukotriene modifiers

Desensitization – stimulate “blocking” IgG
doesn’t always work

Front 25

What is the initial rxn in Type II sensitivity?

Back 25

Ab mediated cytotoxicity

C' activation and ADCC.

Abs bind cell surface and activate C' then lysis

Front 26

What would happen if you inject type B blood into a type A individual?

Back 26

Type A person has anti-B abs, therefore will cause C' and lysis

Front 27

Besides checking for type of blood what other test should always be done?

Back 27

cross matching blood. detect the presence of Abs in donor and/or recipient

person may have had a transfusion etc and may produce Abs that would lead to rejection of blood.

Front 28

Do O blood types have Ags? Do they have Abs?

Back 28

Type O blood has anti-a AND anti B Abs, but neither Ag.

Universal Donor!

they DO have sugars, just none corresponding to Ag

Front 29

What is erythroblastosis fetalis?

How does this happen?

How can this be prevented or treated?

Back 29

hemolytic disease of the newborn (HDN). Caused when Rh - mother has a Rh +; no complications w/ this pregnancy.

However the mother should be treated w/ RhoGAM w/in 24-48 hrs of delivery so that she will not harm her next fetus.

Other more invasive options are to remove mothers plasma and replace the Abs OR give fetus Rh- blood every 10-21 days until delivery.

Front 30

How does a Type III hypersensitivity rxn work?

Where do they localize?

What can this cause?

Back 30

Immune complex disease: Ex. serum sickness and lupus

large Ab-Ab complexes are formed; mostly IgG, some IgM

Localized in the KIDNEY, blood vessel walls, choroid plexus of the brain.

When localized in the kidney can lead to accumulation and complications

Front 31

What is an example of a localized type III reaction?

Where does the immune complex form?

Back 31

arthus rxn= local inflammation

insect bite: remember must have had first exposure in order to exhibit inflammation.

where ag is deposited is where the immune complex will form

Front 32

What is an example of a generalized type III rxn?

What happens when Ag is in excess?

Back 32

complexes circulate and get concentrated by phagocytosis--Ex. kidney

if Ag in excess--don't get clearance of complexes by phagocytosis

Front 33

Do you see large immune complex formation in serum sickness on the first or second injection of foreign serum?

Back 33

second injection see rash, arthritis, edema, glomerulonephritis.

Ex. bite, treat w/ horse Ab. 2nd bite then do not treat w/ horse Ab b/c human body saw that once as Ag and developed Ab against it. Treat w/ human Ab if possible, if not cow Ab etc. to avoid serum sickness.

Front 34

Give 5 examples of immune complexes that contribute to pathology.

Back 34

SLE

rheumatoid arthritis

penicillin rxn

malaria

mononucleosis

Front 35

What is vasculitis?

What is the mechanism of pathology?

What happens when Ag in excess?

Back 35

inflammation and damage to blood vessels
immunopathogenic mechanisms

thought to cause the pathology

Ag excess get complexes deposited on blood vessels. leads to local or systemic (hep B, serum sickness, cutaneous vasculitis are exs.)

Front 36

What type of immune rxns occur in Type III immune complexes?

Back 36

complement ADCC (neutrophil can release immune factors AND granules)

Front 37

What is type IV hypersensitivity?

Back 37

Delayed type hypersensitivity

DTH response:
1. CD4+ T cell (Tdth) – cytokines stimulate inflammation (Th1 type cytokines)

2. influx of inflammatory cells (especially macrophages)

3. initial symptoms seen after ~24 hours and peaks between 48-72 hours

4. not always detrimental…can be useful to fight certain infections--
especially intracellular pathogens

Front 38

What is the Tuberculin rxn?

Back 38

inject PPD (purified protein derivative from M. tuberculosis)

if EXPOSED, MEMORY Tdth cells present and become activated. confirm w/ chest x-ray

Front 39

What can DTH be used to monitor? How?

Back 39

monitor immune status of AIDS patient

use previously exposed Ags and inject under the skin and look at response

Front 40

What induces DTH response?

Back 40

intracellular bacteria, fungi, parasites

viruses, contact Ag

Front 41

Where do primary immunodeficiencies come from? secondary?

Back 41

primary=inherited defects

secondary= due to infections, aging, malignancies

Front 42

What is SCID?

What causes it?

What is the treatment?

Back 42

Severe combined immunodeficiency (SCID)

2 causes:
1 defect in g-chain of IL-2 receptor (CD132)

Shared by IL-2, -7, -11, and 15

lymphocyte development is abnormal

2. Autosomal mutants
defect in RAG1, 2 or other enzymes that prevent development of NORMAL B and T cells

defect in alpha chain of IL2 receptor (CD25)

Treatment is by bone marrow transplant

Front 43

What is Bare lymphocyte syndrome due to?

Back 43

Bare lymphocyte syndrome:

MHC deficiency due to
defect in MHC class II transactivator protein gene (= lack of MHC II)

OR

TAP gene defect (= lack of MHC class I)

Causes immunosupression

Front 44

What syndrome is caused by congenital thymic aplasia/hypoplasia?

What happens?

What is the treatment?

Back 44

Di George syndrome

defect in fetal development in the 6-10th wk.

due to unknown causes

Tx: thymic graft from early fetus--13-14wk--to prevent graft vs. host disease.

Front 45

Which is the most common of all the primary immunodeficiencies?

Back 45

IgA deficiency

Front 46

Why are nude mice important?

Back 46

good experimental models of immunodeficiency (athymic).

Front 47

What are SCID mice?

Back 47

RAG 1 or RAG 2 mutants

put human cells into mouse SCID/Hu mouse

Front 48

What is HIV and infection of?

Back 48

CD4+ tcells

eventually lose Th cells

become more susceptible to opportunistic infections
N

Note: graph= initial spike in HIV and dip in CD4 in acute phase. Chronic phase: CD4 rise then continual fall as HIV increases.

Front 49

Why can you irradiate to get rid of HIV and then do a bone marrow transplant to regain T cells?

Back 49

because HIV infects macrophages too. macrophages are resistant to radiation. So, if you did a bone marrow transplant at that point the HIV in the macrophages would attack the activated T cells and you'd be worse off

Front 50

What is normal CD4 level?

Back 50

1000ug/ml

Front 51

What is the CD4 count in HIV?

Back 51

<200ug/ml