immunity Flashcards

Question

what is the blood cell formation process

Answer 1

Hematopoiesis

Answer 2

Hematopoiesis occurs in the bone marrow | in adults

Answer 3

``` Hematopoietic stem cells (HSCs) become… …Progenitor cells, which become… • Precursor cells that give rise to… • WBCs • RBCs • Megakaryocytes (precursor cell to platelets) ```

Answer 4

Require CYTOKINES | for differentiation!

Answer 5

1. HSCs differentiate into myeloid progenitor cells (see previous slide), which develop into proerythroblasts 2. Erythroblasts and normoblasts are formed and begin synthesizing hemoglobin 3. Further in its development, the cell ejects its nucleus and becomes a reticulocyte 4. Further maturation occurs in the blood (erythrocyte)

Answer 6

Each RBC contains 280m hemoglobin molecules that give blood its red colour

Answer 7

Hemoglobin: 4 globin proteins, each with a heme group that contains an iron core

Answer 8

Heme iron (Fe) combines with oxygen to transport it to tissues

Answer 9

A decrease in blood oxygen stimulates erythropoiesis 2. The kidneys sense this drop in blood oxygen and release erythropoietin (EPO) 3. EPO acts within the bone marrow to stimulate maturation of reticulocytes 4. Newly formed erythrocytes can now transport oxygen (attached to hemoglobin) to tissues as needed (including kidneys)

Answer 10

Adult men of all ages: ~9 mg/day

Answer 11

Pre-menopausal adult women: ~18 mg/day | • Post-menopausal women: ~9 mg/day

Answer 12

Anemia: Low RBC and/or hemoglobin concentration

Answer 13

* Eosinophils, basophils, and neutrophils | * Monocytes

Answer 14

• colony-stimulating factor (CSF) to | differentiate

Answer 15

Myeloid progenitors also give rise to megakaryocytes, which become platelets thanks to thrombopoietin (TPO)

Answer 16

: • T lymphocytes • B lymphocytes • Natural killer (NK) cells

Answer 17

HSCs are the most clinically used | type of stem cell in medicine!

Answer 18

Used to treat certain blood cancers | like leukemia

Answer 19

Leukemia: Cancer of the progenitor cells that become leukocytes Cellular constituents of the IMMUNE SYSTEM

Answer 20

The immune system includes all of the cells, tissues, and processes involved that defend against potential pathogens

Answer 21

innate ( non-specific ) defense machanism | adaptive ( specific ) defense mechanism

Answer 22

non specific skin mucouse membrane secration of skin and mucouse membrane

Answer 23

``` non specific phagocytic cells natural killers anti microbial proteins the inflammatory response ```

Answer 24

lymphocytes anti bodies macrophages and other antigen presenting cells

Answer 25

Antigens found on the surface of all cells can be detected by certain molecules (antibodies) secreted by immune cells

Answer 26

: • SELF (non-foreign) • NON-SELF (foreign

Answer 27

``` Type O+ (39% of Canadians) • Type O- (7% of Canadians) – UNIVERSAL DONOR • Type A+ (36% of Canadians) • Type A- (6% of Canadians) • Type B+ (7.6% of Canadians) • Type B- (1.4% of Canadians) • Type AB+ (2.5% of Canadians) – UNIVERSAL ACCEPTOR • Type AB- (0.5% of Canadians) ```

Answer 28

Blood types are based on antigens present on erythrocytes among different individuals

Answer 29

A antigen | anti-B antibody

Answer 30

B abtigen | anti-A antibody

Answer 31

both A and B antigen | neither the antibody

Answer 32

neither antigen A or B | anti-A and anti-B antibody

Answer 33

• Individuals with Type B blood carry anti-A antibodies • Anti-A antibodies recognize A antigens on the transfused blood and mark them as FOREIGN • Anti-A antibody binding to antigen causes clumping of the erythrocytes (agglutination) • Antigen-antibody complexes form and activate complement proteins in the recipient’s plasma • Causes hemolysis of erythrocytes

Answer 34

• Rh factor (Rh): Another antigen that is | commonly present on erythrocytes

Answer 35

If Rh antigen is present (~85% of Caucasians): Rh positive | • If Rh antigen is not present: Rh negative

Answer 36

Unlike anti-A or anti-B antibodies, anti-Rh antibodies are not normally present in Rh- individuals UNLESS they have been previously exposed to Rh antigen

Answer 37

Offspring are genetically different from | their mothers, so a mother may be Rh- while their fetus rh +

Answer 38

Placenta normally shields fetal blood from maternal blood (see Repro section), but exposure may occur during parturition

Answer 39

Next pregnancy: If the fetus is Rh+, eryththroblastosis fetalis can result • Hemolysis of Rh+ RBCs in the fetus

Answer 40

Antibodies are part of the adaptive (specific) immune system | • This system is built and trained to recognize and destroy specific antigens

Answer 41

Skin/mucous membranes>>>> Physical barrier for pathogens Digestive tract >>>>High acidity of stomach Inflammatory response >>>>>Histamine release, fever Phagocytosis >>>>>Cells that engulf foreign material Interferons>>>>> Produced by cells infected by viruses Complement system >>>>>Promote phagocytosis with the help of antibodies (adaptive immunity)

Answer 42

Antibodies target pathogens (bacteria, viruses, foreign RBCs), but binding alone does not destroy them • Antibodies serve as “flags” for immunological attack by: 1. Innate immune cells like macrophages and neutrophils (next couple of lectures) 2. Complement proteins present in the plasma

Answer 43

• Serves as a LINK between the innate and adaptive immune system! • Liver produces complement proteins and release them into circulation (9 inactive proteins labeled C1-C9)

Answer 44

Complement activation leads to the | eventual destruction of the pathogen

Answer 45

Classical Pathway Alternative Pathway in both cases, activation of complement proteins involves sequential modifications to the proteins to generate proteolytic enzymes

Answer 46

Involves antibody recognition followed by a cascade of complement protein modifications Starts off with… 1. Antibody binding to antigen on membrane of bacterial cell 2. C4 binds to antibody-antigen complex; activated C1 hydrolyzes C4 into C4a and C4b (C4b becomes “fixed” in the membrane) 3. C3 is then split into C3a and C3b via a C3 convertase (C4b + C2a) 4. C3b converts C5 into C5a and C5b, which attract other immune cells to the site 5. C5-C9 are inserted into the cell mb to form a membrane attack complex (MAC

Answer 47

No antibodies required! • Involves surface protein recognition by complement proteins Low levels of C3 are constantly monitoring for and binding to surface proteins If C3 binds to LPS on a bacterial cell, it is then activated

Answer 48

``` The production of C3 convertase is where both pathways converge • In both cases, cleavage of C3 results in C5 activation and subsequent MAC production • Classical pathway: • C3 convertase = C4b and C2a • Alternative pathway: • C3 convertase = C3b and factor B (another serum protein) ```

Answer 49

``` Formation of MAC (resulting in hemolysis) 2. Chemotaxis: 3. Opsonization: 4. Stimulation of histamine release: ```

Answer 50

2. Chemotaxis: Free complement fragments attract phagocytic cells to site of infection

Answer 51

3. Opsonization: Complement proteins | recruit phagocytic cells to eat bacteria

Answer 52

4. Stimulation of histamine release: Free complement fragments induce mast cells and basophils to release histamine

Answer 53

– Respiratory secretions | – Resident macrophages

Answer 54

Alveolar macrophages are phagocytic cells; they recognize bacterial antigens and can either… – Engulf bacteria (phagocytosis) and destroy them via lysosomal enzymes – Recruit other innate immune cells to the site via chemotaxis

Answer 55

– IL-1β (Interleukin-1) | – TNF-α (Tumour necrosis factor)

Answer 56

Increase vascular permeability • Increase vasodilation • Increase expression of endothelial adhesion proteins

Answer 57

CHEMOKINES: CXCL8 | – Help attract other immune cells to the site of infection

Answer 58

Histamine released by mast cells and basophils further increase vasodilation and vascular permeability

Answer 59

– Prostaglandins released by damaged cells to intensify the effects of histamine

Answer 60

Leukotrienes released by mast cells and basophils further increase vascular permeability

Answer 61

Complement proteins, in addition to their direct role in killing bacteria, also stimulate histamine release, attract neutrophils by chemotaxis, and promote phagocytosis

Answer 62

As the battle continues, neutrophils arrive on the scene thanks to chemokines secreted by macrophages (chemotaxis)

Answer 63

Monocytes (macrophage and dendritic cell | precursors) arrive later

Answer 64

Neutrophils and monocytes from the blood enter the tissue at the site of infection thanks to extravasation (also called diapedesis)

Answer 65

Inflammation is characterized by classic or cardinal signs

Answer 66

Rubor (redness): Increased vasodilation – Calor (heat): Increased vasodilation (fever covered in next slide) – Tumor (swelling): Increased vascular permeability – Dolor (pain): Increased cytokine release stimulates pain receptors – Functio laesa (loss of function): Tissue health is suboptimal; not in homeostasis

Answer 67

Anti-inflammatory medications such as ibuprofen (a nonsteroidal anti-inflammatory drug [NSAID]) BLOCK the formation of prostaglandins

Answer 68

Prednisone, acting like cortisol, suppresses the immune system by BLOCKING the formation of prostaglandins AND leukotrienes

Answer 69

Reduced vascular permeability = fewer immune cells | at the site of infection = infection persists

Answer 70

FEVER: Monocytes and macrophages, upon interaction with bacteria, secrete cytokines that act as pyrogens • Pyrogens affect the preoptic area of the hypothalamus, raising body temperature

Answer 71

``` At worst, high fevers can lead to organ damage and spread of infection. At best, fevers are uncomfortable and temporary, and assist with recovery from infection. ```

Answer 72

neutrophils eosinophils basophils

Answer 73

lymphocytes | monocytes

Answer 74

Contains granules that stain blue with hematoxylin dye • Has a bilobed nucleus • Low #’s in circulation; <1% of WBCs

Answer 75

FUNCTIONS: – Releases histamine (vasodilator) – Releases heparin (slows down blood clotting)

Answer 76

• MAST CELLS: similar to basophils, but located in | tissues instead of the blood

Answer 77

Neutrophils • Contains granules that stain very slightly pink with eosin • Has a multilobed nucleus • Most abundant leukocyte; 54-62% of WBCs

Answer 78

– First responders to infections – Phagocytose bacteria; ~5-20 bacterial cells during their short lifespan (1-2 days)

Answer 79

* Contains granules that stain bright red with eosin * Has a multilobed nucleus * ~1-3% of WBCs

Answer 80

FUNCTIONS: – Defend against parasites – Also help against viral infections, allergic responses, and certain types of bacteria – Higher number of eosinophils correlates with increased severity of asthma

Answer 81

• Agranulocyte: no granules; 2-3x larger than an RBC • Has a kidney-shaped nucleus • ~3-9% of WBCs; but only stay in the blood for ~8 hrs before differentiating

Answer 82

– Monocytes are precursors to: • Tissue resident macrophages • Dendritic cells

Answer 83

All tissues; spleen, lymph nodes, bone marrow

Answer 84

Kupffer cells: Liver • Microglia: Brain • Alveolar macrophages: Lungs

Answer 85

``` Phagocytose bacteria (100 bacterial cells per lifespan) AND act as antigen-presenting cells ```

Answer 86

Dendritic cells: Antigen-presenting cells

Answer 87

“tissue clean up crew | Remove debris: Old RBCs, dead neutrophils, cells undergoing apoptosis

Answer 88

Agranulocyte: no granules; only slightly larger than an RBC • Has an “eccentric” nucleus • ~25-33% of WBCs; ~5% circulating, the rest in tissues until they encounter pathogens

Answer 89

– T lymphocytes (adaptive immune system) – B lymphocytes (adaptive immune system) – Natural killer cells (innate immune system)

Answer 90

Protect against viral infections and some types of cancer • Unlike B and T lymphocytes, natural killer cells respond very quickly (within a few to several hours) upon stimulation

Answer 91

Destroys target cells by cell:cell contact through | granzymes

Answer 92

• Can release interferons (IFNs) and other cytokines to warn uninfected cells AND/OR enhance immune response mediated by other cell types

Answer 93

B and T Lymphocytes | • Part of the adaptive immune system (both humoral and immune-mediated immunity)

Answer 94

• A subset of WBCs are conditioned to respond and attack | pathogens

Answer 95

• While some of their comrades remain at the site of infection, other macrophages/dendritic cells transport antigens to a lymph node . Neutrophils release free antigen into the bloodstream, where these molecules can eventually reach a lymph node

Answer 96

• Lymph nodes are part of the lymphatic system (next lecture) and are home to B lymphocytes and T lymphocytes

Answer 97

Mature lymphocytes that have not yet encountered antigen

Answer 98

Lymphocytes must be trained and cloned to mount an immune response to a specific antigen

Answer 99

Immature B lymphocytes stay and mature in the bone marrow | • Immature T lymphocytes leave and mature in the thymus (gone in adults)

Answer 100

Immunocompetence: Ability to carry out adaptive immune | responses

Answer 101

Gain antigen receptors on their membranes before moving to lymphoid organs

Answer 102

• Two major types of mature, immunocompetent | T cells thus exit the thymus: – Helper T cells (CD4+ T cells) – Cytotoxic T cells (CD8+ T cells)

Answer 103

• Mature T cells now have antigen receptors that can respond to antigen presented by antigen presenting cells

Answer 104

• Initially, when a pathogen first enters the body, there are only a few lymphocytes that have the correct antigen receptor to respond to that antigen

Answer 105

(cell mediated immunity Antigen presenting cells (macrophages, dendritic cells, etc.) are “professional” cells that can present antigen on a complex called MHC II (major histocompatibility complex)

Answer 106

Antigen presented by MHC II molecules on antigen presented cells will activate CD4+ T lymphocytes (helper T cells)

Answer 107

Some immunocompetent helper T cells in the lymph node will have antigen receptors that can recognize the “presented” antigen

Answer 108

ACTIVATION: Results in the clonal selection of that helper T cell that correctly responded to the antigen

Answer 109

``` For proper activation and clonal selection to occur, the antigen receptor (T cell receptor) and a co-receptor (CD4) must BOTH bind to the MHC II molecule ```

Answer 110

Active helper T cells respond by secreting cytokines that enhance the immune response of cytotoxic T cells and activation of B cells

Answer 111

Not every immunocompetent helper T cell that leaves the thymus will recognize our specific antigen • The ones that do will become activated, will proliferate, and become “effector” versions (help!!) or “memory” versions that can easily become effectors if infection occurs again

Answer 112

• RECAP: Antigen presenting cells (macrophages, dendritic cells, etc.) have MHC II molecules on their membrane that they can use to activate helper T cells • ALL nucleated cells also have MHC I molecules on their membrane too • If a tissue cell (not an APC) is infected with a virus, it can present antigen on MHC I molecules on its membrane By presenting antigen in this way, the infected tissue cell acts like a martyr, signaling to cytotoxic T cells that it should be destroyed

Answer 113

• Cytotoxic T cell activation occurs in a similar manner to | helper T cell activation

Answer 114

If a mature, immunocompetent cytotoxic T cell encounters a target cell with a foreign antigen that it can recognize on the MHC I molecule, the T cell will kill it • Similar to helper T cells, cytotoxic T cell activation requires a co-receptor to bind to MHC I → CD8

Answer 115

• Similar to helper T cells, cytotoxic T cell activation requires a co-receptor to bind to MHC I → CD8

Answer 116

Once activated, cytotoxic T cells release perforin to make pores in the cell membrane • Following pore creation, granzymes(protease enzymes) are released into the cell to destroy it from the inside • Cytotoxic T cells can also stimulate apoptosis in the affected cell

Answer 117

Unlike cytotoxic T cells that leave lymph nodes to seek out and destroy foreign antigens, B cells stay put

Answer 118

When B cells mature and gain immunocompetence in bone marrow, they move to lymph nodes where they can produce certain types of antibodies

Answer 119

• When certain naïve B cells are exposed to a particular antigen which binds to their B cell receptor, they undergo clonal selection

Answer 120

humoral immunity

Answer 121

– Plasma cells (effector cells) that serve as antibody factories (short-lived) – Memory B cells (continue to proliferate; long lived)

Answer 122

Upon re-exposure to the same antigen, memory B cells rapidly expand to produce more plasma cells and memory B cells

Answer 123

• Helper T cells also aid in B cell activation, AND B cells can reciprocate by acting like APCs (antigen presentation via MHC II)

Answer 124

Antibodies block or neutralize bacterial toxins and can prevent viral attachment to body cells

Answer 125

Antibodies cause “clumping” of pathogens (see Immune lecture 1)

Answer 126

Antibodies cross-link soluble antigens into complexes that are too large to stay in solution

Answer 127

Initiate the classical pathway of the complement system (see Immune lecture 1)

Answer 128

Coat” the microbe for easier recognition and phagocytosis by phagocytes

Answer 129

• Due to the presence of long-lasting antibodies and lymphocytes thanks to clonal selection of lymphocytes

Answer 130

Primary responses mediated by the immune system tend to be slower and less intense than secondary responses

Answer 131

``` Natural infection • IgG antibodies received through placental circulation or breast milk • Vaccination • Immune serum: gamma globulin (antibody) transfer ```

Answer 132

naturally: infaction , contact with the pathogen | passive : antibodies passes from the mother to the fetus via pacenta or passes through her milk

Answer 133

passive injection of an immune serum | active :vaccine dead or attenuated pathogens

Answer 134

When lymphocytes undergo maturation, they are trained to recognize self-antigens in a process called self-tolerance The non-reactive lymphocytes get to stay, while reactive lymphocytes are weeded out

Answer 135

Autoimmune disorders: this mechanism fails, leading to the development of autoantibodies

Answer 136

Allergies are abnormal responses by B lymphocytes or T | lymphocytes

Answer 137

– APCs present antigen to helper T cells that eventually help recruit eosinophils to the site – Helper T cells also stimulate B lymphocytes, which become plasma cells that secrete IgE antibody

Answer 138

IgE binds to mast cells and basophils which release | histamine & other cytokines

Answer 139

– Cell-mediated T lymphocyte response; symptoms are caused by the release of cytokines – Antihistamines provide no relief

Answer 140

: If the antibodies/chemicals/cytokines produced by the immune system are in large quantities, they may reach systemic circulation and cause anaphylactic shock

Answer 141

Anaphylactic shock causes extreme vasodilation, low blood pressure/volume, and bronchoconstriction Epinephrine injection allows for near immediate relief of these life-threatening symptoms

Answer 142

• Epinephrine, acting as a hormone, travels to adrenergic receptors on the blood vessels, heart, and bronchioles

Answer 143

IgG and IgM are types of antibodies; IgG is most abundant in the blood, and IgM antibodies cause issues during mismatched blood transfusions.

Answer 144

Drain excess interstitial fluid • Return filtered plasma proteins to the blood • Carry out immune responses • Transport dietary lipids

Answer 145

Interstitial fluid (water + salts, nutrients, and wastes) is formed from filtration out of blood tissue capillaries

Answer 146

Lymphatic capillaries within tissues have a porous junctions within their endothelial cells, allowing them to soak up: • Excess interstitial fluid + proteins • Microbes, antigens & immune cells • Lipids

Answer 147

• Lymph fluid picked up from interstitial space is transported to lymph nodes • Lymph fluid containing APCs or free antigen will subsequently activate lymphocytes in lymph node (Immune lecture 2) • Lymph fluid will continue to lymphatic duct where it will drain into a major vein

Answer 148

• Lymphatic capillaries act like a “sponge” to soak up interstitial fluid (lymph fluid) • Series of one-way valves move the fluid through circulation • “Squeezed” through movement!

Answer 149

Prolonged periods of sitting can cause blood to pool in the veins • Excess blood in lower limbs = more fluid leaking out into interstitial space • Without movement, lymphatic circulation cannot bring fluid back up to the heart • Harmless for short periods of time!

Answer 150

Tonsils: Trap and destroy pathogens that enter the throat • Thymus: Site of maturation for T lymphocytes (before adulthood) • Spleen: Filters blood and removes bacteria and viruses as well as worn out RBCs • Peyer’s patches: Prevent bacteria from penetrating through the intestinal wall • Appendix: Functions similarly to other intestinal lymphoid tissue

Answer 151

• All homeostatic processes can take place in the circulatory system because it is a CLOSED SYSTEM

Answer 152

Sequence of responses that results in wound repair

Answer 153

The goal of hemostasis is to stop the bleeding that results from a break in a blood vessel via coagulation thanks to the action of platelets

Answer 154

This often happens concurrently with the activation of local innate defense mechanisms (resident macrophages) to protect against potential infection

Answer 155

Hemostasis (stopping of bleeding) helps | us maintain circulatory homeostasis

Answer 156

Formed from the breakdown of megakaryocytes in a process called thrombopoiesis

Answer 157

Platelets enter main circulation | •

Answer 158

Disc shaped, no nucleus

Answer 159

Stop blood loss from damaged blood vessels and promote coagulation

Answer 160

In the absence of injury… • Circulating platelets are inactive • Intact endothelial cells release a type of prostaglandin and nitric oxide; both inhibit platelet aggregation

Answer 161

Vascular spasm causes vasoconstriction 2. Exposed collagen fibers causes platelets to stick, forming a plug 3. Coagulation: Fibrin is formed, trapping the platelets and some RBCs, forming a clot 4. Clot dissolves once tissue damage is repaired

Answer 162

Vascular spasm occurs by… • Damaged endothelial cells release a cytokine that signals to surrounding smooth muscle to contract • If the smooth muscle is damaged, they will intrinsically contract as well • Pain receptors stimulated by inflammatory cytokines cause contraction

Answer 163

Platelet adhesion: VWF is now exposed and binds to platelets | • “Stuck” platelets now secrete ADP, thromboxane A (TxA2), and serotonin to recruit other platelets to the site

Answer 164

The platelet plug is strengthened by an insoluble mesh of protein called fibrin, which together with the platelet plug form a blood clot

Answer 165

Fibrin is converted from fibrinogen through a series of enzymatic activation of blood factors

Answer 166

Conversion may occur through: • Intrinsic pathway (damaged vessel wall) • Extrinsic pathway (extravascular damage)

Answer 167

Most blood coagulation factors (proteins) are produced in the liver, and are inactive within circulation

Answer 168

``` • Damage to the endothelial cells reveals collagen, which activates Factor XII • Factor XII activates Factor XI • Factor XI activates Factor IX • Factor IX activates Factor X ```

Answer 169

• Damaged extravascular cells release Tissue Factor (TF) into the bloodstream • TF activates Factor VII • TF-Factor VIIa activates Factor X

Answer 170

Expedited pathway that leads to the activation of | the factor needed to produce fibrin

Answer 171

Common pathway: • Factor X is needed to convert prothrombin into thrombin • Prothrombin is a Vitamin k dependent glycoprotein; Vit K deficiency = bleeding tendencies • Thrombin converts fibrinogen to fibrin

Answer 172

Fibrinolysis • Once tissue has repaired, Factor XIIa AND/OR tissue plasminogen activator (tPA) convert plasminogen to plasmin in the bloodstream • Plasmin breaks down (lyses) fibrin proteins (fibrin degradation products; FDPs) • Clot is dissolved and blood can flow normally within this repaired blood vessel

Answer 173

Thrombosis: Inappropriate formation of blood clots which can eventually occlude a blood vessel • Clot is now called a thrombus

Answer 174

Caused by endothelial injury, abnormal blood | flow, or hypercoagulability, Atherosclerosis, high BP, high blood glucose

Answer 175

If the clot forms in a coronary artery, in the brain, the lung, or if a clot moves from a peripheral vessel to these organs… • Heart attack, stroke, or pulmonary embolism can result

Answer 176

* Heparin * Inhibits the activity of thrombin * Warfarin * Inhibits activation of vitamin K (factors VII, IX, and X) * Aspirin * Inhibits release of TxA2