Immune Dysfunction - Hsn Reactions

Front 1

Type I, II, and III HSN all have what in common?

Back 1

Require the active production of antibody by plasma cells

Front 2

Antibody type involved in Type I HSN:

Back 2

IgE secreted by Bcells in response to antigen/IL-4 environment from Th cells

Front 3

Main factor released by Mast cell degranulation in Type I HSN upon subsequent Ag exposure:

Back 3

Histamine

Front 4

Effect of Histamine:

Back 4

Increased vascular permeability

Front 5

Major chemotactic factors released by mast cell degran in Type I HSN recruits:

Back 5

Eosinophils

Front 6

IL that activates eosinophils:

Back 6

IL-5

Front 7

3 Primary mediators released by mast cell degranulation:

Back 7

-Histamine
-Proteases
-Chemotactic factors

Front 8

Main effect of primary mediators of mast cell degranulation?

Back 8

-Bronchial Sm musc Contraction
-Vascular Dilation

Front 9

3 Secondary mediators released in mast cell degranulation:

Back 9

-Cytokines
-Leukotrienes
-Prostaglandin

Front 10

Why do 2ndary mediators take longer to be released?

Back 10

They require gene transcription and expression

Front 11

Clinical example of disease of type I hsn:

Back 11

Bronchial asthma

Front 12

2 types of txmt for Bronchial asthma/what is each for?

Back 12

-PDE inhibitors - to relax bronchial smooth muscle
-Corticosteroids for inflammation (late phase)

Front 13

Treatment for Anaphylaxis?

Back 13

Txmt: Epinephrine

Front 14

Type II HSN is also called:

Back 14

Antibody-mediated

Front 15

What are the antibodies involved in Type 2 HSN directed against??

Back 15

Antigens that are INTEGRAL components of the target cell!

Front 16

What are 3 distinct antibody-dependent mechanisms of type II HSN?

Back 16

a. Complement dependent
b. ADCC
c. Ab-mediated cell dysfunction

Front 17

What are 2 ways that Complement reactions can kill cells in type II HSN (a)?

Back 17

-Directly cause lysis
-Opsonization/phagocytosis

Front 18

What does the interaction of complement with the target cell surface in type II hsn result in?

Back 18

Cell lysis and death or phagocytosis

Front 19

Where are the antigens involved in type II hsn reactions typically located?

Back 19

In basement membranes or in blood cell membranes

Front 20

What are 3 clinical examples of disorders of Type II mediated hypersensitivity where Ag is in RBC membranes?

Back 20

-Warm Ab Autoimmune HA
-Hemolytic Transfusion rxns
-Hemolytic Disease of the Newborn

Front 21

What is the Ig that mediates WAIHA?

Back 21

IgG

Front 22

What syndrome of Type II complement-mediated Ab-depend hypersensitivity targets Ag in the glomerular/alveolar basement membranes?

Back 22

Goodpastures syndrome

Front 23

How does ADCC type II HSN work?

Back 23

-Antibodies directly bind cell surfaces
-Fc receptors on killer cells bind the Ab-cell complexes

Front 24

What is the most important killing cell that works in ADCC?

Back 24

NK cells

Front 25

What is the main distinction between type a/b Type II HSN?

Back 25

Complement is only involved in type II a

Front 26

What are 2 clinical examples of Type II HSN where there is antibody-mediated Cell Dysfunction?

Back 26

-Graves disease
-Myasthenia gravis

Front 27

What is the antibody in Graves disease and what is it directed against?

Back 27

TSI - thyroid stimulating antibody; directed against the TSH receptor

Front 28

What is the antibody in Myasthenia gravis directed against and what is its effect?

Back 28

-Ab is against the NMJ receptor for Acetylcholine; result is inhibition of neurotransmission and destruction of the receptors.

Front 29

What are the 2 main effects of the TSI in Grave's disease?

Back 29

-Hyperplasia of the thyroid gland
-Overproduction of T3/T4 - hyperthyroidism

Front 30

What are 6 other Type 2 HSN disorders in addition to Graves and Myasthenia gravis?

Back 30

Good Peanut Butter Tastes Very Awesome

Front 31

What are the Type II HSN disorders represented by Good Peanut Butter Tastes Very Awesome?

Back 31

-Goodpastures
-Pernicious anemia
-Bullous pemphigoid
-Thrombotic phenomena
-Vasculitides
-Acute rheumatic fever

Front 32

Antibody specificity in:
-Goodpastures
-Pernicious anemia
-Acute rheumatic fever

Back 32

G = Type 4 collagen in BM
P = Anti-IF
RF = Antistreptococcal Ab that cross reacts w/ heart

Front 33

Type III HSN is aka:

Back 33

Immune complex

Front 34

Major difference of type III HSN from type II:

Back 34

Antigen in type III is NOT an integral component of target cells; it is CIRCULATING.

Front 35

What do Ag-Ab that are good sized normally do?

Back 35

Get eaten by MPS system cells

Front 36

What if the Ag-Ab complexes are insoluble aggregates?

Back 36

They deposit on serosal surfaces or in vessel walls.

Front 37

What happens when insoluble immune complexes in type III Hsn deposit in places?

Back 37

They activate COMPLEMENT which is highly chemotactic for NEUTROPHILS

Front 38

What happens when the neutrophils come flooding in to attack the immune complex depositions?

Back 38

They release their lysosomal enzymes and cause lots of TISSUE DAMAGE

Front 39

What are 4 substances that neutrophils release in type III hypersensitivity?

Back 39

-Lysosomal enzymes
-Prostaglandins
-Kinins
-Free radicals!

Front 40

What other major important pathway is activated in type III hypersensitivity?

Back 40

Hageman factor 12 is activated
-Complement
-Clotting cascade
-Kinin system

Front 41

Which pathway of coag is activated by Fx 12? Result?

Back 41

Intrinsic - nearby small vessels thrombose

Front 42

What does Kinin activation lead to?

Back 42

-Vasodilation (Bradykinin)
-Edema

Front 43

What does platelet aggregation in type III HSN lead to?

Back 43

More microthrombus formation and release of dense granule contents - Vasoactive amines!

Front 44

What are 3 general conditions that result from deposition of immune complexes in small vessels and type III HSN?

Back 44

-Vasculitis
-Glomerulonephritis
-Arthritis

Front 45

What SIZE of immune complex is more likely to be deposited in vessel walls? Why?

Back 45

SMALLER - less likely to precipitate locally and be removed by the MPS

Front 46

5 clinical examples of Type III hypersensitivity:

Back 46

-Serum sickness
-Arthus reaction
-SLE
-Polyarteritis nodosa
-Glomerular diseases

Front 47

What was Serum sickness characterized by?

Back 47

Deposition of immune complexes in multiple sites - heart/joints/kidneys

Front 48

What causes serum sickness?

Back 48

Injections of large amounts of foreign protein (horse serum)

Front 49

What is the most common cause of serum sickness if it is seen today, and how is it treated?

Back 49

Cause: Antibiotics - Penicillin
Treat: Corticosteroids

Front 50

What is Arthus reaction?

Back 50

A LOCALIZED immune complex reaction

Front 51

What is Arthus reaction caused by?

Back 51

Introduction of an exogenous antigen in the presence of a EXCESS of PREFORMED antibodies

Front 52

Type IV HSN is aka?

Back 52

Cell-mediated hypersensitivity

Front 53

What are 2 subtypes of Type IV cell mediated HSN?

Back 53

1. Delayed type
2. CTL mediated

Front 54

What are the cells that act in DTH type IV HSN?

Back 54

-CD4+ Thelper cells
-Macrophages

Front 55

What is the 1st step in DTH?

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APC processing and presentation of antigen to CD4+ cell

Front 56

What does the CD4+ Th cell do in response to Ag presentation?

Back 56

Secrete cytokines to stimulate inflammation and get rid of the antigen, and REMEMBER the antigen

Front 57

What cytokine especially is produced by CD4 Thelpers on subsequent exposure to the same antigen? What does it do?

Back 57

IL-2 - stimulates macrophages to phagocytose the antigen.

Front 58

What are 2 clinical examples of DTH cell-mediated HSN involving CD4+ Thelpers and macrophages?

Back 58

-Tuberculin reaction (PPD)
-Contact dermatitis

Front 59

How does the PPD test work in positive patients?

Back 59

1. First TB exposure produced Th1 cells with MEMORY
2. Intracutaneous shot of PPD causes activation and proliferation of the Th1 cells

Front 60

What is induration?

Back 60

Firming of the site of the PPD shot due to fibrin formation

Front 61

What is the other type of cell-mediated HSN?

Back 61

CTL-mediated

Front 62

Other than involving CD8+ CTLs instead of CD4 Th's, what is the major difference between the 2 types of cell mediated type IV HSN?

Back 62

CD4 Th1 mediated involves cytokines; CD8 CTL does NOT involve cytokines

Front 63

What are the 2 mechanisms of direct killing by CTL's in that type of cell-mediated HSN?

Back 63

-Fas-fasL mediated
-Perforin/granzyme mediated

Front 64

What do Granzymes trigger?

Back 64

Apoptosis

Front 65

What does Fas-FasL interaction trigger?

Back 65

Apoptosis as well

Front 66

What type of target cells are generally killed in Type IV CTL mediated hypersensitivity?

Back 66

-Tumor cells
-Virus infected cells

Front 67

What MHC presents the antigen of target cells to CTLs?

Back 67

MHC I

Front 68

What are the 3 EARLY histologic findings in Cell-mediated hypersensitivity?

Back 68

-Perivascular cuffing of Tcells
-Edema
-Fibrin deposition (induration)

Front 69

What are the LATER events of Cell-mediated histology?

Back 69

Granuloma formation

Front 70

What is a Granuloma a type of?

Back 70

Chronic inflammation

Front 71

What IS a granuloma?

Back 71

A nodular collection of EPITHELIOID cells surrounded by a rim of lymphocytes

Front 72

What are Epithelioid cells?

Back 72

Special macrophages that have been activated to transform into Epithelioid cells.

Front 73

What starts off the formation of a Granuloma?

Back 73

Presentation of antigen by an APC (macrophage) to a naive but Ag-specific CD4+ Th cell.

Front 74

What interleukin does the APC secrete as it presents the Ag to the Th cell?

Back 74

IL-12

Front 75

What effect does IL-12 have?

Back 75

It helps convert the CD4+ Th cell into an active Th1

Front 76

What are 2 interleukins secreted by the activated Th1 cell? What effect does each have

Back 76

-IL-2: stim autoproliferation of Th1 cells
-IFN-y: activates macrophages to transform into Epithelioid and Giant cells

Front 77

How do more monocytes get recruited to add to the formation of a granuloma?

Back 77

By endothelial cell changes in the vasculature in response to TNF-a secreted by Th1 cell

Front 78

Do granulomas develop from a PPD skin test?

Back 78

I don't think so.

Front 79

But what do Granulomas develop in?

Back 79

A number of infections

Front 80

What are 4 infections in which granulomatous inflammation is characteristic?

Back 80

-Mycobacterial (TB/leprae)
-Fungal - Blast/Histo/Cocci
-Treponema pallidum (syph)
-Bartonela henselae (cat scr)

Front 81

What disease of unknown etiology is characterized by granulomatous inflammation?

Back 81

Sarcoidosis

Front 82

What is the predominant difference in granulomas seen in TB vs sarcoidosis?

Back 82

TB - caseating

Sarcoid - noncaseating

Front 83

What is caseation?

Back 83

Death of macrophages in the center of a granuloma due to the actions of peripheral lymphocytes.

Front 84

What are 2 types of Giant cells based on morphologic appearance?

Back 84

-Langhans
-Foreign body giant cells

Front 85

What do Langhans giant cells look like and what are they classic in?

Back 85

Nuclei in HORSESHOE pattern at the PERIPHERY of cell
-Tuberculosis

Front 86

What do Foreign body Giant cells look like?

Back 86

Nuclei are just scattered everywhere.