Effector Mechanisms Of Immune Injury

Front 1

What two characteristics of the immune system can be predicted to potentially produce injury?

Back 1

1) The primary recognition receptors (TCR, Ig) are generated relatively randomly (has capacity to make self-receptors)

2) Most of the major effector mechanisms (enzymes, free radicals, etc.) are non-specific (can harm host)

Front 2

Type I hypersensitivity (anaphylactic type) (Definition)

Back 2

A rapidly developing immunologic reaction occurring within minutes after the combination of an antigen with antibody bound to mast cells (tissue) or basophils (blood) in individuals previously sensitized by prior exposure to the antigen

Front 3

Can a type 1 hypersensitivity reaction occur in response to a first-time exposure to an antigen?

Back 3

No, the individual must have been previously sensitized

Front 4

Which class of Ig is responsible for type I hypersensitivity?

Back 4

IgE

Front 5

When are IgE Ab produced in favor of IgG Ab?

Back 5

When helper T cells of the Th2 type are favored over the Th1 type

Front 6

What cytokine, secreted by Th2 cells, is responsible for B cell isotype switching to IgE?

Back 6

IL-4

Front 7

What is a basophil?

Back 7

Essentially a circulating mast cell

Front 8

How do IgE antibodies adhere to mast cells and basophils?

Back 8

Via Fc receptors, leaving the Fab portion available for binding with antigen

Front 9

What happens when an individual is re-exposed to a IgE-specific antigen?

Back 9

Degranulation of mast cells and basophils, releasing primary and secondary mediators that produce inflammation

Front 10

What is an example of a primary mediator released by mast cells and basophils?

Back 10

Histamine

Front 11

What are the characteristics of a primary mediator released by mast cells and basophils?

Back 11

Fast-acting (minutes)

Short-lived

Front 12

What are some examples of secondary mediators released from mast cells and basophils?

Back 12

Leukotrienes C4, D4, and E4 and prostaglandins (all derived from arachidonic acid)

Front 13

What are the characteristics of secondary mediators released form mast cells and basophils?

Back 13

Slow-acting (hours)

Long-lived

Front 14

What are the general effects of primary and secondary mediators released from mast cells and basophils?

Back 14

Vasodilation, increased vascular permeability, cellular infiltration, and bronchial smooth muscle spasm

ACUTE INFLAMMATORY RESPONSE

Front 15

What is the key in determining the severity of a type I hypersensitivity reaction?

Back 15

Antigen location

Front 16

Type I hypersensitivity reactions can range from ____ to ____ anaphylaxis

Back 16

Local to systemic

Front 17

Type II hypersensitivity (Definition)

Back 17

An immunological reaction mediated by antibodies directed toward antigens present on the surface of cells or other tissue components; includes complement dependent reactions, antibody dependent cell-mediated cytotoxicity (ADCC), and antibody-mediated cellular dysfunction

Front 18

What Ig isotypes are responsible for type II hypersensitivity?

Back 18

IgG, IgM, IgA

Front 19

Complement dependent reactions (Definition)

Back 19

When an antibody, most commonly IgG or IgM, attaches to a self-cell surface and activates the complement cascade

Front 20

Clinical examples of complement dependent reactions

Back 20

Tranfusion reactions

Erythroblastosis fetalis

Autoimmune hemolytic anemia

Pemphigus vulgaris

Front 21

Antibody dependent cell-mediated cytotoxicity (ADCC) (Definition)

Back 21

Cellular injury by non-sensitized effector cells (monocytes, neutrophils, eosinophils, NK cells) in response to antibody binding to self-cells

Front 22

Clinical examples of antibody dependent cell-mediated cytotoxicity

Back 22

Tumor cell destruction

Parasite destruction

Allograft rejection

Front 23

Antibody-mediated cellular dysfunction (Definition)

Back 23

A disease caused by antibodies without cell injury or inflammation

Front 24

Clinical examples of antibody-mediated cellular dysfunction

Back 24

Myasthenia Gravis

Grave's disease

Front 25

Myasthenia Gravis (Mechanism, Symptoms)

Back 25

Antibodies directed against ACh receptors on motor end plates of skeletal muscle block ACh binding, resulting in muscle weakness

Front 26

Grave's disease (Mechanism)

Back 26

Antibodies directed against TSH receptor stimulate secretion of thyroid hormones and subsequent hyperthyroidism

Front 27

Like type I hypersensitivity, the severity of type II hypersensitivity is determined by ____

Back 27

Antigen location

Front 28

Type III hypersensitivity (immune complex-mediated) (Definition)

Back 28

An immunologic reaction induced by Ag-Ab complexes that produce tissue damage as a result of their capacity to activate the complement system

Front 29

Immune complexes of what size are most pathogenic?

Back 29

Small or intermediate

Front 30

Why are small or intermediate immune complexes more pathogenic than large immune complexes?

Back 30

They are not as efficiently removed by phagocytic cells

Front 31

What conditions promote the formation of small or intermediate immune complexes?

Back 31

Slight antigen excess

Front 32

What are two potential causes of slight antigen excess?

Back 32

1) The antigen is a self-antigen

2) Underwhelming immune response

Front 33

Beyond antigen excess, what is another possible cause of an increase in immune complexes?

Back 33

Failure of the mononuclear phagocytic system to effectively eliminate immune complexes, whether due to dysfunction or overload

Front 34

Where are immune complexes most likely to deposit?

Back 34

Vascular filtration beds (glomerular basement membranes, synovial membranes, serosal surfaces, arachnoid granulations, lacrimal glands, and salivary glands)

Front 35

What are the three phases of systemic immune complex disease?

Back 35

1) Formation of Ag-Ab complexes in the circulation (5 days)

2) Deposition of the immune complexes in various tissues, facilitated by the increase in vascular permeability that occurs when cytokines are released by inflammatory cells after interaction with immune complexes via C3b or Fc receptors

3) Initiation of an inflammatory response in dispersed sites throughout the body (10 days)

Front 36

Examples of systemic immune complex diseases

Back 36

Acute and chronic serum sickness

Acute poststreptococcal glomerulonephritis

Systemic lupus erythematosus

Front 37

Why is it difficult to diagnose a specific systemic immune complex disease?

Back 37

They have overlapping symptoms

Front 38

Arthus reaction (Definition)

Back 38

A local immune complex disease that results from acute immune complex vasculitis

Front 39

How can an Arthus reaction be produced experimentally?

Back 39

Intracutaneous injection of an antigen in a subject that already has circulating antibodies to the injected antigen

Front 40

When does an Arthus reaction reach its peak?

Back 40

4 to 10 hours after antigen injection

Front 41

Unlike the other effector mechanisms of immune injury, type III hypersensitivity is not dependent on ____

Back 41

Antigen location

Front 42

Type IV hypersensitivity (cell-mediated) (Definition)

Back 42

An immunological reaction initiated by specifically sensitized T lymphocytes; includes classic delayed-type hypersensitivity reactions initiated by helper T cells and direct cell cytotoxicity mediated by cytotoxic T cells

Front 43

In order for a delayed-type hypersensitivity reaction (type IV) to occur, an individual must be ____ to the antigen

Back 43

Sensitized

Front 44

What are the steps in a delayed-type hypersensitivity reaction (type IV)?

Back 44

1) Patient is re-exposed to antigen

2) Memory Th1 cells bind the antigen and secrete cytokines (e.g. IL-12, IFN-γ, IL-2, TNF-α)

3) Activated macrophages attempt to remove the offending antigen

4) Granulomas form

Front 45

What are some examples of delayed-type hypersensitivity reactions (type IV)?

Back 45

A positive tuberculin skin test

Cutaneous exposure to poison ivy or oak

Front 46

What is T cell-mediated cytotoxicity (Type IV)?

Back 46

The killing of antigen-bearing cells by sensitized cytotoxic T cells

Front 47

Cytokine storm (Definition)

Back 47

The systemic release of cytokines

Front 48

What can cause a cytokine storm?

Back 48

Severe physiological injury

Front 49

What are the effects of systemic cytokine release?

Back 49

Systemic vasodilation and subsequent hypotension

Widespread endothelial injury and activation, causing leukocyte adhesion and alveolar capillary damage

Activation of the coagulation pathway

Front 50

The various effects of a cytokine storm combine to cause...

Back 50

Widespread hypoperfusion that may lead to multisystem organ failure