Mechanisms Of Self Defense Patho

Front 1

What three cell-derived chemical mediators are released by both basophils and mast cells and what are their inflammatory effects?

Back 1

histamine - increase vasodilation and vascular permeability

neutrophil chemotaxic factor -
attracts circulating neutrophils to site of injury

eosinophil chemotaxic factor -
attracts circulating eosinophils to site of injury

Front 2

Which of the cell-derived chemical mediators cause increased vasodilation & vascular permeability? Of these, which also causes pain?

Back 2

Histamine, 5-HT, Prostaglandins, & leukotrines

Prostaglandins cause pain

Front 3

Which three CD mediators are mobilized by platelet activation?

Back 3

5-HT, Platelet Activating Factor (duh), & Histamine

Front 4

Which three CD mediators are mobilized by cell injury?

Back 4

Leukotrines, PAF, & oxygen free-radicals (activated)

Front 5

Which three CD mediators come from endothelial cells (EC)?

Back 5

O2, PAF, NO, & Prostaglandins

Front 6

What are the 2 sources for lysozomal enzymes, what are their stimuli, and what effect do they have?

Back 6

Neutrophils & macrophages

Inflammatory activation

Degredation/digestion as part of phagocytosis; also some release into EC space to cause pathogen injury (also causes collateral damage)

Front 7

What is the function of PAF?

Back 7

Activates circulating platelets; promotes platelet aggregation; at med-hi [], causes vasoconstriction and at low [] causes profound increase in vasodilation & vascular permeability; also causes increased LEUKOCYTE ADHESION & CHEMOTAXIS

Front 8

Which two CD chemical mediators come from all injured cells?

Back 8

Prostaglandins & leukotrines

Front 9

Which CD chemical mediator comes from Macrophages and ECs?

Back 9

NO

Front 10

What effects does NO exert?

Back 10

Increased vasodilation; regulates inflammation endogenously by promoting decreased platelet aggregation & leukocyte adhesion

Hint 10

Stop

Front 11

What are the 3 major cytokines?

Back 11

TNF-alpha, IL-1, & IL-6

Front 12

How do the sources of TNF-alpha, IL-1, & IL-6 differ? How are they the same?

Back 12

All come from activated macrophages

IL-1 & TNF-alpha both come from injured cells

Only IL-6 come from ECs

Onlyu TNF-alpha come from NK cells and Mast cells

Front 13

What stimuli cause the relase of all three cytokines?

Back 13

Inflammatory activation or cell injury

Front 14

The systemic effects for the 3 cytokines are all the same. What are they?

Back 14

Increased CRH, fever, anorexia, & increased hepatic production of acute phase proteins (ex, CRP, MBL)

Front 15

Which of the cytokines are most similar?

Back 15

TNF-alpha & IL-1

Front 16

What are the similar local effects of IL-1 & TNF-alpha? What additional effects does TNF-alpha have?

Back 16

Increased vasodilation, vascular permeability & leukocyte adhesion

TNF-alpha also attracts and activates monocytes & neutrophils and promotes macrophage phagocytosis

Front 17

How do mast cells differ from basophils?

Back 17

Mast cells live in tissue

Front 18

What are monocytes?

Back 18

Inactivated circulating cells that when activated become active macrophages

Front 19

Where do t-cells mature?

Back 19

Thymus

Front 20

What is the common progenator of blood constiuents?

Back 20

Myeloid progenator

Front 21

What cells come from the common lymphoid progeinator?

Back 21

B-cells, t-cells, & NK cells & dendritic cells

Front 22

What is the product of megakaryocytes?

Back 22

Platelets

Front 23

What differentiates T & B lymphocytes?

Back 23

The former differentiates in the thymus while the latter in the bone marrow

Front 24

What do B & T cells differentiate to after encounter w/ an antigen?

Back 24

antibody-secreting plasma cells & effector t-cells

Front 25

What is the process that dendritic cells undergo on their way to activated macrophages?

Back 25

Start in blood from myeloid progenitor cells -> goes into general blood circulation -> encounters potential pathogen -> enters lymphoid tissue -> activate antigen-specific T-cells

Front 26

When do granulocytes enter tissue?

Back 26

Only at sites of infection or inflammation

Front 27

Which 2 granulocytes are implicated in allergic reactions and in defense against parasites?

Back 27

Eosinophils & basophils

Front 28

Which granulocyte is recruited to phagocytose bacteria?

Back 28

Neutrophils

Front 29

Besides dendritic cells, which two leukocytes live within tissue?

Back 29

Monocytes (become macrophages) & mast cells

Front 30

Which cells are responsible for antigen presentation when activated? How is one different from the other?

Back 30

Dendritic cells & macrophages; the former is responsible for antigen presentation only in the lymph nodes (in peripheral sites, they're responsible for antigen uptake

Front 31

What is cell-mediated killing? What kind of immunity is this?

Back 31

When a killer cell can tell if a cell is abnormal or infected

Innate

Front 32

How do NK cells destroy cells?

Back 32

Release enzymes which punch holes in target cell's plasma membrane

Front 33

Which granulocyte is considered a 1st responder to inflammation?

Back 33

Neutrophils

Front 34

Which cells are complimentary to mast cells?

Back 34

Basophils

Front 35

Why are dendritic cells considered to be antigen-presenting cells?

Back 35

Because they are macropinocytic (take large "gulps" of EC fluid to sample for infections

Front 36

What are the properties of T-cells with a CD4 marker? CD8?

Back 36

First is a t-helper cell; other is a cytotoxic T-cell

Front 37

Describe the lifespan of a B-cell:

Back 37

Produced in marrow -> travel through blood stream -> when activated -> undergoes differentiation to plasma cells -> these produce antibodies

Front 38

What do helper T-cells do?

Back 38

Mediate immune response meaning they can recognize an anti-body and activate a B-cell or cyto-toxic T-cell in response to very specific pathogen

Front 39

What's the difference between NK cells and cytotoxic T-cells?

Back 39

The former isn't specific

Front 40

What three organs are part of the RES (reticuloendothelial system) but not the lymphoid system?

Back 40

Liver, skin (langerhans cells), & connective tissue

Front 41

What 2 cell types do the bulk of antigen presentation to helper-T cells?

Back 41

macrophages & dendritic cells

Front 42

What two organs/tissues are considered central lymphoid organs?

Back 42

Bone marrow & thymus

Front 43

Which lymphoid organ has direct access to blood stream and, as a result, can bypass lymphatic fluid?

Back 43

Spleen

Front 44

What do lymphatic vessels pick up?

Back 44

ECF

Front 45

What are the 4 means for detecting a pathogen that has broken through epithelia?

Back 45

1) Tissue phagocytic cells (macrophages/dendritic cells)

2) Peripheral lymphoid tissue phagocytes (via lymph)

3) Splenic phagocytic cells (via blood)

4) Circulating B lymphocytes

Front 46

After detection, which cells initiate an inflammatory response by recruiting more of them to the the area?

Back 46

Phagocytes

Front 47

After causing inflammation, what 2 routes do phagocytes use to present antigens and to what kind of cells?

Back 47

Directly in lymphoid tissue/spleen

OR

Phagocytes migrate to lymphoid tissue

T-helper cells

Front 48

What do T-helper cells do when presented with an antigen? What is this response called?

Back 48

Activates cytotoxic T-cells and B lymphocytes

Adaptive immune response

Front 49

What are the 3 areas of a lymph node and what are their primary constiuents?

Back 49

Medullary: phagocytic cells

Paracortical: t-cells

Front 50

Why do lymph nodes have multiple zones?

Back 50

To better trap antigens

Front 51

What are germinal centers in lymph nodes?

Back 51

areas of very rapid proliferation of whichever specific lymphocyte that’s been IDed

Front 52

What are the 2 functional zones of the spleen called? What function do they serve?

Back 52

Red Pulp: traps aging RBCs

White Pulp: clustered around arterioles; contain lymphocytes

Front 53

What mediate transmission bet immune cells?

Back 53

Cytokines

Front 54

What are the two lines of innate defense?

Back 54

Epithelial barriers (physical & chemical

Inflammatory response

Front 55

What are the hallmark signs of acute inflammation?

Back 55

swelling (edema), redness (erythema), heat, & pain (algesia)

Front 56

What 2 main purposes does the inflammatory response have in the immune response?

Back 56

Isolates area of injury

Helps to deliver WBCs to injury by enlarging blood vessels -> endothelial cells further apart -> leaks -> phagocytes able to enter

Front 57

What are the 4 main steps in the inflammatory response?

Back 57

1) Histamine released by damaged tissue, increasing bloodflow to area of injury

2) Histamines cause capillaries to leak, releaseing phagocytes & clotting factors into wound

3) Phagocytes engulf debris and dead cells

4) Platelets move out of capillary to seal wounded area.

Front 58

What 2 types of events occur in inflammatory process?

Back 58

Vascular changes/events & Cellular events

Front 59

What are the 2 main components of Vascular Events and their mechanisms? What is the 3rd delayed event?

Back 59

Vasodilation (heat & redness) & increased permeability of microvasculature (more space in Endoth cells -> more plasma proteins leak out -> loss of IC fluid volume -> increase in osmotic pressure -> edema)

Vascular stasis (blood more viscous -> reduced flow in vessel

Front 60

What are the 4 cellular events in inflamm. response, what cells are affected, and when do they occur?

Back 60

1)Circulating WBCs are stimulated to migrate to site of injury

2) These then adhere to the endothelial lining at the site of injury

3)They then squeeze themselves in between endothelial cells and undergo transmigration (cells that are squeezing through those endothelial cells) and get outside of the vessel; once outside, they start to detect pathogens in the ECF since bacteria in particular

4)They then undergo hemotaxis (move in the direction of the bacteria because the bacteria release a chemical signal) and then destroy the bacteria; these are generally phagocytes (neutrophils)

WBCs

Can occur same time as vascular

Front 61

4 overlapping pathways for inflammatory response?

Back 61

1) Injured tissue releases cytokines that activate macrophages

2) Injury activates Mast Cells (mast cells release pro-inflammatory mediators)


3) Macrophages detect/ingest pathogen then release pro-inflammatory mediators

4) Activated macrophages stimulate Mast cells to release pro-inflammatory mediators)

Front 62

What kind of response is there for pathogens that get by epithelial border but don't cause tissue injury?

Back 62

pathogen alone can activate an inflam response via phagocytosis and the subsequent release of cytokines

Front 63

1st cells that initiate inflammatory response?

Back 63

Tissue mast cells and tissue macrophages

Front 64

Which cytokine can activate mast cells?

Back 64

IL-1

Front 65

What are the 2 mediators released by mast cells?

Back 65

First is via degranulation (similar to exocytosis); secretory granules inside are released when activated; a big component released is Histamine (a very potent vasodilator and vastly increases permeability)

Second is release of newly synthesized Leukotrienes and prostaglandins, which is a delayed response (these are arachodonic acid products)

Front 66

Activation pathways for mast cells?

Back 66

direct injury; IL-1; IgE-mediated mechanisms (anti-body); activated complement system (composed of plasma proteins that is a very important part of innate immunity and can initiate inflammatory response through activation of mast cells)

Front 67

Circulating equivalent for mast cells?

Back 67

Basophils

Front 68

What effect does vasodilation have in inflam response that is beneficial?

Back 68

Increases fluid allowed in microvasculature which contains lots of leukocytes

Front 69

What causes release of albumin into IS space by endothelial cells?

Back 69

More permeable -> retraction of cells -> bigger gaps -> leaks

Front 70

When does vascular stasis occur?

Back 70

When a critical mass of neutrophils and eosinophils have migrated to site of injury

Front 71

What function does leukocytic adhesion have?

Back 71

prevents leukocytes from getting swept up into general circulation

Front 72

What happens after leukocytes adhere to EnC?

Back 72

Transmigrate to IS where they "sniff" out pathogens -> phagocytize pathogens -> extra fluid swept up into lymphatic circulation

Front 73

What are the constiuents of plasma protein systems?

Back 73

enzymes that become activated, resulting in a chain rxn

Front 74

How is 5-HT released?

Back 74

Cytokines/tissue injury -> activation of platelets -> 5-HT release (similar axn to H1)

Front 75

Besides activating more platelets, what else do PAF do?

Back 75

Mediate many other inflam responses (adhesion, etc.)

Front 76

Where do Lysozomal enzymes act, and where they do they reside?

Back 76

They can act either IC or EC:

IC: They sit in macrophages and allow them to digest pathogens when phagotycized

EC: released to kill neighboring pathogens (results in collateral damage)

Front 77

What is opsonization and what system is it related to?

Back 77

Tagging of pathogens to make them more attractive to phagocytes

Complement System activation

Front 78

What are the 3 ways to activate the complement system?

Back 78

1 – The presence of a pathogen

2 – As part of a systemic inflammatory response

3 – Can be activated by adaptive immunity (antibody-mediated)

Front 79

What is the most potent activator of clotting cascade?

Back 79

Exposed collagen

Front 80

What are the 3 outputs of the complement system?

Back 80

1) More inflammation

2) Opsonization

3) Creates memmbrane attack complex

Front 81

What does Kinin system activation cause?

Back 81

Activation of Complement System

Front 82

Steps from presence of pathogen to Complement activation?

Back 82

Macrophage activation -> inflammation -> migration of neutrophils -> activates Kinin system

Front 83

Tissue injury pathways?

Back 83

Clotting cascade activation (blood clotting & pain) -> Kinin cascade activation (pain & clotting) -> Complement activation -> inflammation

Front 84

Three pathways of complement activation?

Back 84

Classical, MB (mannose-binding lecithin), and Alternative pathways

Front 85

Classic pathway mechanism? How does binding occur?

Back 85

Classic pathway involves the binding of the first protein of a complement system to the pathogen surface, which can then cause the cascade;

binding can happen directly,

via CRP (a systemic marker of inflammation) which is then bound to pathogen surface,

and the antibody-antigen complex, where a specific (i.e. B-cell) response can turn on the complement system which is part of an adaptive response

Front 86

MB-L pathway mechanism?

Back 86

C1q binds to mannose-binding lecithin -> bound to pathogen surface

Front 87

Alternative pathway mechanism?

Back 87

complement system bypasses the first two complement proteins, causing C3 to bind directly to pathogen surface

Front 88

Crucial step in all 3 pathways for Complement system?

Back 88

C3 convertase

Front 89

What are inactive circulating kinins called?

Back 89

Kininogens

Front 90

What is kallikrein? What are the two ways of producing?

Back 90

Liberate kinins from kininogens

Neutrophil activation & Factor XII activation

Front 91

Ultimate purpose of clotting cascade?

Back 91

To convert fibrinogen to fibrin, which forms clots

Front 92

What is thrombin?

Back 92

pro-inflammatory contributor

Front 93

Main player in clotting cascade?

Back 93

Factor XII

Front 94

Clotting cascade activation?

Back 94

Activated platelets, tissue damage, or both

Front 95

When does a Systemic inflammatory response occur? What is this response called?

Back 95

when you have enough of the inflammation mediators (especially cytokines) to bind systemically to different tissues

Acute-phase response

Front 96

Which cytokine is a major mediator of sepsis when high levels occur for global effects?

Back 96

TNF-alpha

Front 97

Where does a large effect from an acute-phase response occur?

Back 97

Bone marrow

Front 98

What happens to cortisol levels during an acute-phase response?

Back 98

Increases

Front 99

What happens to hepatic protein production during APR?

Back 99

Rate of production of ARP proteins (CRP & MBL) increases; that of other proteins decreases

Front 100

What kind of nuclear material is always present in viral ifx?

Back 100

double-stranded RNA

Front 101

What does interferon do?

Back 101

Signals viral infections

Front 102

What effects do interferon have?

Back 102

Producing cell: stimulates host cell that degrade viral RNA & block viral protein production)

EC: activates NK cells to attack infected cells and causes the NKs to produce interferon-gamma

Front 103

What does interferon-gamma do?

Back 103

Increases effects of interferon- alpha & -beta

Front 104

Where do you find MHC I molecules? MHC II?

Back 104

All cells in body (except for RBCs)

Antigen presenting cells (macrophages, dendritic cells, B cells)

Front 105

What cells recognize MHC I cells? MHC II?

Back 105

cytotoxic-T cells & NK cells

helper T-cells

Front 106

Which MHC cells are involved in adaptive immune response?

Back 106

MHC II

Front 107

What do MHC I cells ix?

Back 107

virus infected, non-self, or abnormal self cells

Front 108

How is adaptive immune response activated?

Back 108

by recognizing non-self and missing-self antigens

Front 109

What type of immunity are B-cells involved in and what do they create?

Back 109

Humoral immunity

Antibodies (Ig)

Front 110

Where does generation of clonal diversity occur?

Back 110

central lymphoid organs

Front 111

B-cell differentiation?

Back 111

Triggered by matching antigen -> engulfs antigen and displays fragments bound to unique MHC -> combo of MHC & antigen attract mature matching helper-T -> T releases cytokines -> B cells multiply & mature into plasma cells -> released into blood

Front 112

Antigen Presenting Cell in naive lymphocytes?

Back 112

Dendritic cells

Front 113

Where do B-cells recognize antigens? T-cells?

Back 113

Outside cells of the body

Inside infected cells of the body

Front 114

Requirements for clonal selection of t-cells?

Back 114

Must be reactive and specific to MHC or peptide molecules

Front 115

Major function of all IgG subtypes:

Back 115

Diffusion into extravascular sites

Front 116

Ig subtypes that activate complement systems?

Back 116

IgM & IgG3

Front 117

Function of IgE?

Back 117

Sensitization of mast cells

Front 118

Ig neutralizers?

Back 118

IgGs & IgA

Front 119

Ig for transport across epithelium?

Back 119

IgA (dimer)

Front 120

Ig for opsonization? & sensitization for killing by NK cells?

Back 120

IgG1 (lesser extent, IgG3

Front 121

Arachidonic acid metabolites in inflammation?

Back 121

COX (prostaglandins [prostacyclin & thromboxane)

Lipoxygenase (lipoxin A & B)

Front 122

Negative selection in clonal selection:

Back 122

Forces lymphocytes to try to bind to self-peptides; those with high affinity die

Front 123

Plasma cells are created when:

Back 123

B-cells phagocytize a pathogen -> B-cell becomes APC -> antigenic peptides loaded into MHC II on EC surface -> helper-T binds to MHC II/antigen site -> B-cells activated -> plasma cells

Front 124

Killer T's work by:

Back 124

punching holes in infected cell, causing apoptosis

Front 125

Killer T's only recognize antigens coupled to:

Back 125

MHC I molecules

Front 126

Helper T's and B's only recognize antigens coupled to:

Back 126

MHC II molecules

Front 127

Class switching occurs in ______. The resulting cells can now interact with different _______ molecules but retain the same binding affinity for antigens.

Back 127

mature B-cells

effector

Front 128

Effector cells:

Back 128

have been activated by their cognate antigen, and are actively involved in eliminating a pathogen

Front 129

Exogenous antigens are usually presented by"

Back 129

Dendritic cells

Front 130

IgE cells cause Type I rxns because:

Back 130

They are marked by B-cells, which make large amts of IgE specific antibody, resulting in a memory rxn on subsequent exposure

Front 131

What does MBL do?

Back 131

recognizes carb patterns as 1st line of defense

Front 132

What does CRP do?

Back 132

assists in complement binding