Immune Pathology I

Question 1

Chronic inflammation usually has all of the following coexist:

Answer 1

• inflammation
• tissue injury
• tissue repair

Question 2

What is well-recognized to be a risk factor for a wide range of diseases like diabetes and cancer?

Answer 2

visceral obesity

Question 3

visceral obesity can lead to the production of what in the adipocytes?

Answer 3

IL-6 and TNF-a

Question 4

when FFA are around, FFA end up binding to ?. ? when abnormally activated end up phosphorylating ? leading to ?

Answer 4

toll-like receptors
serine residues
decreased insulin sensitivity or causing insulin resistance

Question 5

elevated free fatty acids and inflammatory cytokines lead to ?

Answer 5

insulin resistance

Question 6

During chronic inflammation, parenchyma that die are replaced by ? and do not necessarily have ?

Answer 6

fibrotic tissue
normal functions

Question 7

immune-mediated inflammatory disease can be divided into ? and ?

Answer 7

autoimmune and allergic diseases

Question 8

what is autoimmune diseases?

Answer 8

when immune cells/mediators attack tissues inappropriately over long periods of time

Question 9

autoimmune diseases are mediated largely by the ?

Answer 9

adaptive immune system

Question 10

what is allergic diseases?

Answer 10

when immune cells respond excessively to exogenous allergens

Question 11

allergic diseases are typically ? mediated

Answer 11

Th2

Question 12

Chronic inflammation causes:

Answer 12

• persistent infections
• immune-mediated inflammatory disease
• prolonged exposure to toxins

Question 13

Macrophages are part of a system known as the ?

Answer 13

reticuloendothelial system

Question 14

what turns into macrophages?

Answer 14

monocytes

Question 15

after 48 hours - 1 week of inflammation, often ? are the predominant cell type in inflamed tissue

Answer 15

macrophages

Question 16

pro-inflammatory macrophage functions:

Answer 16

• lysosomal enzymes, free radicals destroy bacteria
• efficient and proficient phagocytes
• secretion of cytokine and growth factors - IL1, TNF-a
• secretion of inflammatory mediators - leukotrienes and prostaglandins
• secretion of chemotactic factors - leukotriene B4 and chemokines

Question 17

what are the two types of macrophages?

Answer 17

“classically-activated” and “alternatively-activated”

Question 18

what are the big causes of macrophages to stay “classically-activated”

Answer 18

IFN-y and recognition of PAMP and DAMP

Question 19

what do “classically-activated” macrophages do?

Answer 19

• recruit other leukocytes
• damage pathogens
• often damage “bystander” host cells

Question 20

what cause macrophages to stay “alternatively-activated”?

Answer 20

IL-4 and other cytokines

Question 21

what do “alternatively-activated” macrophages do?

Answer 21

• angiogenesis
• pro-fibrotic growth factors/cytokines
• growth factors/cytokines that stimulate repair or regeneration

Question 22

Alternatively-activated macrophages are induced by other cytokines and are important in ?

Answer 22

tissue repair and resolution of inflammation

Question 23

Classically-activated macrophages are induced by microbial products and cytokines, particularly IFN-gamma and they do what?

Answer 23

phagocytose and destroy microbes and dead tissues, increase inflammation

Question 24

explain the steps of angiogenesis

Answer 24

1. vasodilation
2. pericyte separation and endothelial migration
3. proliferation of endothelial cells behind the leading cell tip
4. pericytes/smooth muscle cells as well as basement membrane surround the “tube”

Question 25

what are particularly implicated in chronic inflammation, they are recruited to sites of chronic inflammation by macrophages that continue to respond to the inflammatory stimulus

Answer 25

Cytotoxic T-cells

Question 26

Plasma cells, macrophages, and lymphocytes can form lymphatic nodule-appearing regions in an area of chronic inflammation, Known as ?

Answer 26

tertiary lymphoid organs

Question 27

the tertiary lymphoid organs in joints, produces redundant, inflamed synovium known as ?

Answer 27

pannus

Question 28

what are the phases of healing?

Answer 28

Phase I - hemostasis Phase II - inflammation Phase III - proliferation Phase IV - maturation

Question 29

what happens in phase I (hemostasis) of healing?

Answer 29

initial vasoconstriction followed by vasodilation

Question 30

What happens in phase II (inflammation) of healing?

Answer 30

Neutrophils, macrophages kill microbes

Question 31

what happens near the end of phase II of healing?

Answer 31

macrophages transition from classically to alternatively activated

Question 32

what happens in phase III (proliferation) of healing

Answer 32

Recruitment of fibroblasts which produce a network of collagen, proteoglycans (ground substance) and fibronectin (forms framework for tissue)

Question 33

what happens in phase IV (maturation) of healing?

Answer 33

Remodeling of connective tissue, regression of "unnecessary" angiogenesis

Question 34

what are the steps in repair by scar formation?

Answer 34

- Injury to a tissue, such as muscle (which has limited regenerative capacity), first induces inflammation which clears dead cells and microbes - Followed by the formation of vascularized granulation tissue and then the deposition of extracellular matrix to form the scar

Question 35

what is a granuloma?

Answer 35

an attempt by lymphocytes and macrophages to "wall off" an inflammatory stimulus

Question 36

what are macrophages that resemble epithelial cells?

Answer 36

Epithelioid macrophage

Question 37

what are giant cells?

Answer 37

macrophages that develop into large “supercells” – they perform most of the “walling-off” function of a granuloma

Question 38

what is the pathological hallmark of tuberculosis

Answer 38

caseating granuloma

Question 39

what are hypersensitivity reactions?

Answer 39

An excessive and/of pathogenic immune response to either foreign or self-antigens

Question 40

what are the 4 types of hypersensitivity reactions?

Answer 40

Type I – IgE-mediated hypersensitivity (also called immediate hypersensitivity) Type II – antibody-mediated cytotoxic reactions Type III – immune-complex reactions Type IV - "delayed reactions" also known as T-cell mediated reactions

Question 41

What primes mast cells in Type I hypersensitivity?

Answer 41

IgE and Th2 cytokines.

Question 42

What are the immediate effects of mast cell degranulation in the skin?

Answer 42

Edema and urticaria.

Question 43

What are the immediate effects in the airways for type I hypersensitivity?

Answer 43

Edema, mucous secretion, and smooth muscle contraction.

Question 44

When does the late-phase response occur in Type I hypersensitivity?

Answer 44

2–24 hours after the initial allergen exposure.

Question 45

What cells are recruited during the late-phase response?

Answer 45

Eosinophils, basophils, neutrophils, and T cells.

Question 46

What do eosinophils secrete that can damage tissue?

Answer 46

Proteolytic enzymes, major basic protein, and eosinophilic cationic protein.

Question 47

What are complications of the late-phase response in asthma?

Answer 47

Epithelial damage and intense bronchoconstriction leading to difficult-to-reverse airway obstruction.

Question 48

What are complications of the late-phase response in anaphylaxis?

Answer 48

Long-lasting edema and vasodilation leading to shock.

Question 49

What are the targets of antibodies in Type II hypersensitivity?

Answer 49

Cell components and matrix components.

Question 50

What happens when antibodies bind to self or absorbed antigens?

Answer 50

Inflammation, cellular destruction, and matrix destruction.

Question 51

Name two diseases caused by receptor effects in Type II reactions.

Answer 51

Graves disease (activation) and myasthenia gravis (inhibition).

Question 52

What role do Fc receptors on neutrophils play in Type II reactions?

Answer 52

They recognize bound antibodies and trigger inflammation.

Question 53

What causes tissue damage in Type III hypersensitivity?

Answer 53

Immune complexes deposited in tissue elicit inflammation.

Question 54

Where are immune complexes typically deposited?

Answer 54

Blood vessel walls, glomeruli, and synovial membranes.

Question 55

What kind of antibodies form immune complexes?

Answer 55

IgG or IgM.

Question 56

What kind of tissue damage is seen in Type III hypersensitivity?

Answer 56

Fibrinoid necrosis with immune complex and complement deposits.

Question 57

How does Type IV hypersensitivity differ from the others?

Answer 57

It is T-cell mediated rather than antibody-mediated.

Question 58

What are the four subtypes of Type IV hypersensitivity?

Answer 58

IVa (Th1/granulomas), IVb (Th2/eosinophils), IVc (cytotoxic T-cells), IVd (Th17/neutrophils).

Question 59

How long does it take for most Type IV hypersensitivity responses to develop?

Answer 59

Months to years, except in acute exposures.

Question 60

Give an example of an acute Type IV reaction.

Answer 60

Contact dermatitis from poison ivy.