1. Blood & Immune System Chapter 11 & 14

2. Physical characteristics of blood
Fluid connective tissue
matrix – “plasma” with dissolved proteins
cells & cell fragments – “formed elements”
temperature – 38o C
5x more viscous than H2O
pH –

3. Functions of Blood O2/CO2; nutrients/wastes; enzymes; hormones
Transportation
O2/CO2; nutrients/wastes; enzymes; hormones
Regulation
body temperature; pH & ion composition of interstitial fluid; intracellular fluid volume
Protection
defense against pathogens; restriction of fluid loss at injury sites

4. Composition of Blood 55% Plasma – liquid component of blood
45% Formed elements – cells/cellular fragments
Erythrocytes – red blood cells (RBCs)
Leukocytes – white blood cells (WBCs)
Platelets

5. Plasma

6. Formed Elements
granular
agranular

7. Hemopoiesis
Megakaryoblast

8. Erythrocytes (RBCs) around 5 million RBCs per mm3 blood
Biconcave shape, flexible cells
around 5 million RBCs per mm3 blood
average “life span” of 120 days
Cells contains cytosol, no nucleus/organelles; filled with Hemoglobin (Hb)

9. Hemoglobin
Hemoglobin allows for transport of O2 & CO2

10. As RBCs get damaged/worn out, they must be removed from circulation & replaced
About 1% of the circulating RBCs are replaced each day, at at rate of about 3 million RBCs per second
Worn out RBCs are removed by phagocytic cells in the liver, spleen & bone marrow

11. Hemoglobin recycling
“globin” proteins will be broken down into amino acids to be re-used by cells to make new proteins
Iron will be separated from “heme” & can be stored in the liver, & be re-used to make new Hb
the pigmented part of heme will get converted to biliverden & bilirubin (pigments), & most will get excreted as part of bile from the liver

12. Erythropoiesis The formation of RBCs
Occurs in bone marrow (myeloid tissue) due to hypoxia detected in kidneys

13. Blood Typing
There are many different surface antigens (transmembrane proteins) within the plasma membrane of your RBCs. These antigens (a.k.a. “agglutinogens”) are genetically determined.
Your surface antigens are recognized by your immune defense system as “self”.
The presence or absence of 3 specific antigens (A, B & Rh) determine your “blood type”
Within your plasma, you may have specific antibodies (a.k.a. “agglutinins”) against surface antigens that are not yours.
Plasma antibodies are responsible for “protecting” you from an incompatible blood type

14. Blood Typing
If the Rh antigen is also present, the person is Rh+, if they do not have the Rh antigen, they are Rh-

15. Blood Typing
When you combine the information from the AB & Rh antigens, the possible blood types will be:
A+/A-
B+/B-
AB+/AB-
O+/O-
When considering whether a transfusion will be compatible, it is most important to consider the donor’s surface antigens & the recipient’s plasma antibodies

16. Blood Typing
Unlike the AB grouping, people who are Rh- do not genetically create antibodies against Rh in their plasma.
Antibodies will only be formed after an initial exposure to Rh
This could happen during an incompatible transfusion (i.e. A+  A- ), or during pregnancy if an Rh- mom is carrying an Rh+ baby.
Rh antibody formation in a mom who is carrying an Rh+ baby will lead to “hemolytic disease of the newborn”

17. Leukocytes (WBCs)
More like “typical” cells with single nucleus, organelles
5 types of WBCs characterized as granular or agranular
all function in defense
average WBCs/mm3 of blood
variable “life” span depending on type of WBC- days (neutrophils) to decades (lymphocytes); in sick person, some WBCs live minutes to hours

18. Leukocytes (WBCs) WBCs exhibit common characteristics:
amoeboid movement
diapedesis
positive chemotaxis
phagocytosis
gliding movement of cell membrane/cytoplasm; allows WBCs to move along blood vessel walls & throughout tissues
can squeeze through epithelial cells of capillary walls to migrate into tissues
WBCs are attracted to chemicals released by invading pathogens & damaged tissues
neutrophils, monocytes, & eosinophils are phagocytic

19. Differential Count & Functions of WBCs
“WBC differential count” – normal range (in percentage) of WBCs in the peripheral circulation
differential count will vary during specific types of disorders, depending on which type of WBC responds
WBC response based on functions of specific type

20. Differential Count & Functions of WBCs
Neutrophils %
Lymphocytes – 20-30%
Monocytes – 4-8%
Eosinophils – 2-4%
Basophils - <1%
function in acute bacterial infections; phagocytic
function in “immunity” – specific resistance to disease
function in chronic bacterial infections; migrate into tissues to become “wandering macrophages”
active against parasites & elevated in allergic reactions; destroy antibody-coated antigens by phagocytosis
release chemicals (histamine, heparin) during tissue inflammation

21. Platelets (Thrombocytes)
Cellular fragments (cell membrane “packet” filled with cytoplasm) from large Megakaryocytes found within bone marrow
around 350,000 platelets/mm3
platelets circulate for 9-12 days before being removed from circulation
platelets function in “hemostasis” – the processes that stop bleeding from damaged blood vessels

22. Hemostasis There are three overlapping processes of hemostasis:
Vascular spasm – damage to BV wall causes the smooth muscle within the wall to spasm vasoconstriction & decreased blood loss through vessel; begins within a few seconds of injury, lasts about 30 minutes
Platelet plug formation – damaged BV endothelium gets sticky & circulating platelets stick to the endothelium & each other, creating a platelet plug; begins within 15 seconds of BV damage; may be enough to stop bleeding completely within a small BV (i.e. capillary)
Coagulation – blood clotting; complex series of steps resulting in the conversion of fibrinogen  fibrin

23. Overview of Coagulation
initiated by both “extrinsic” (tissue) & “intrinsic” (platelet) factors
both pathways result in activation of Factor X (10)
activation of Factor X begins the “common pathway”
all 3 pathways require the presence of Ca2+ & vitamin K

24. Coagulation Extrinsic pathway –
begins with damage to surrounding tissues & BV endothelium which cause the release of “tissue factors”
eventually results in the formation of an enzyme (“Factor X activator”) capable of activating Factor X
shorter, quicker pathway for initiation of coagulation
Intrinsic pathway –
begins with the release of “platelet factors”
eventually results in the formation of “Factor X activator”
more complicated, slower pathway of coagulation

25. Coagulation Common pathway –
begins with the activation of Factor X, by the production of Factor X activator from either the extrinsic or intrinsic pathway
the activation of Factor X results in the formation of the enzyme Prothrombinase
Prothrombinase converts Prothrombin (a clotting protein)  Thrombin (an enzyme)
Thrombin converts Fibrinogen (soluble protein)  Fibrin (insoluble protein strands that create the actual clot)

26. Clot Retraction, Repair & Removal
Once the clot has begun to form, the fibrin threads & trapped platelets cause the edges of the damaged vessel to pull together causing “clot retraction”
Repair to the damage vessel & surrounding tissues occur as fibroblasts invade the area & endothelial cells regenerate
Eventually the clot gets removed by the enzyme “plasmin” in a process known as “fibrinolysis”
A clot which remains present in an intact vessel is known as a “thrombus”. Thrombi can block blood flow & pieces can dislodge creating an “embolism”

27. Immunity ( Chap 14, p )

28. Humans have two major types of defense mechanisms: Non-specific defenses & Specific defenses
do not distinguish between one threat and another
are present at birth
include: physical barriers (e.g. skin), phagocytic cells, inflammation, fevers, etc.

29. Specific defenses
protect against specifically identified threats (i.e. may defend against one particular bacterial infection but not a different one)
many specific defenses develop after birth upon exposure to an antigen (Ag); an antigen can be a pathogen (disease-causing organism), foreign protein (e.g. toxin), abnormal or infected body cell, foreign tissue transplant
specific defenses produce a state of long-term protection known as “Immunity”

30. Immunity ( Chap 14, p )
Immunity = specific resistance to disease
depends on coordinated activity of T & B lymphocytes
T cells- involved in “cell-mediated (aka cellular) immunity”; defense against abnormal cells & intracellular pathogens
B cells- involved in “antibody-mediated (aka humoral) immunity”; defense against pathogens (Ag’s) in body fluids (blood/lymph)

31. Overview of Immunity
Fig )

32. Immunity is either “innate” or “acquired”
Innate Immunity
present at birth
independent of previous exposure to Ag
genetically determined
species dependent

33. Acquired Immunity
arises throughout life by active or passive means

34. Active immunity – development of resistance (i. e
Active immunity – development of resistance (i.e. antibody (Ab) production) to specific disease secondary to exposure to specific Ag (pathogen)
naturally acquired active immunity – natural exposure results in immune response & development of long term immunity
induced (artificial) active immunity – deliberate “artificial” exposure to Ag (i.e. vaccine/immunization)

35. Passive immunity – development of immunity due to transfer of “pre-made” antibodies
naturally acquired passive immunity – Ab’s transferred from mom  baby across placenta or in breast-milk
induced (artificial) passive immunity – administration of Ab’s to fight disease after exposure to pathogen

36. Properties of Immunity
Immunity has four general properties:
Specificity
Versatility
Memory
Tolerance
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

37. Properties of Immunity
Specificity – T & B cells have specific receptors that will allow them to only recognize & target a specific Ag; this process is known as “antigen recognition”
Versatility – millions of different lymphocyte populations, each with specific Ag recognizing receptors; allows for “anticipation” of potential Ag’s
Memory – after initial exposure, long term acquired immunity occurs through the production of memory cells; secondary exposure results in stronger faster response to previously recognized Ag
Tolerance – immune cells recognize self-antigens & “tolerate” (ignore) them, only going after foreign (non-self) Ag’s

38. Overview of the immune response
The purpose of the immune response is to inactivate or destroy pathogens, abnormal cells & foreign molecules (such as toxins)
In order for the response to occur, lymphocytes must be “activated” by the process of antigen recognition
T cells are usually activated first, & then B cells. T cells mainly rely on activation by phagocytic cells collectively known as “antigen presenting cells (APC’s)”
Once activated, T cells both attack the invader, & stimulate the activation of B cells
Activated B cells mature into “plasma cells” which produce specific antibodies designed to inactivate the harmful antigen.

40. Cell Mediated (a.k.a. Cellular) Immunity
In order for T cells to respond, they must first be activated by exposure to an antigen which is bound to membrane receptors of phagocytic antigen presenting cells (APC’s) (“antigen recognition”)
These membrane receptors on cells are called “MHC proteins” (major histocompatibility complex proteins), & are genetically determined (i.e. differ among individuals)
Antigens bound to MHC proteins “tell” the T lymphocyte what the specific foreign invader is (i.e. a specific bacteria) so that the lymphocytes can mount a cellular defense

41. Cell Mediated (a.k.a. Cellular) Immunity
Once a T cell is activated by the presentation of the combined MHC/Ag, it will clone (by mitosis) & differentiate into:
cytotoxic T cells – seek out the specific pathogen/infected cell that contains the targeted Ag & destroys it by secreting various chemicals
helper T cells – necessary for coordination of both specific & non-specific defenses, as well as for stimulating both cell-mediated & antibody-mediated immunity.
In cell-mediated immunity they release chemicals (cytokines) that strengthen the activity of cytotoxic T cells.
In antibody-mediated immunity they release cytokines that stimulate activated B cell division & differentiation into plasma cells

42. Cell Mediated (a.k.a. Cellular) Immunity
memory T cells – remain “in reserve” so if same Ag appears, these cells can immediately differentiate into cytotoxic & helper T cells, causing a swift secondary response to the invasion
suppressor T cells – activated more slowly than the other T cells; inhibit the response of the immune cells to prevent potential “autoimmune” response

43. Activated T cells clone & differentiate into: Cytotoxic T cells
Helper T cells
Memory T cells
Suppressor T cells
Direct physical &
chemical attack
ANTIGENS
bacteria
viruses
SPECIFIC DEFENSES
(Immune response)
CELL MEDIATED IMMUNITY
APC’s phagocytize Ag & activate T cells
Antigens
bacteria
viruses

44. Antibody Mediated (Humoral) Immunity
B cells must also be activated before they can respond to an invading Ag
The body has millions of different B cell populations, each B cell has its own particular antibody (Ab) molecule within its cell membrane
When the corresponding Ag invades the interstitial fluid surrounding the B cell, the Ag binds to the Ab & is taken into the cell, eventually being displayed on the B cell’s MHC protein. The B cell is now “sensitized”
Helper T cells (that had been previously activated to the same Ag) then attach to the sensitized B cells & activate them by secreting chemicals (cytokines)
Cytokine secretion results in B cell cloning & differentiation into plasma cells & memory cells

45. Antibody Mediated (Humoral) Immunity
Plasma cells produce millions of copies of antibodies which are released into the blood & lymph
Antibodies seek out & bind to the Ag forming an “Ab-Ag complex”, eventually leading to the elimination of the antigen by various means
Memory cells remain in reserve to respond to any subsequent exposure by the same Ag. Upon secondary exposure, memory B cells quickly differentiate into Ab producing plasma cells

46. Antibody Mediated (Humoral) Immunity

47. Antibody Mediated (Humoral) Immunity

48. Review of Immune Response