KINE 2011 - Module 2 - The Blood & The Immune System Notes
The Blood: Introduction
Blood constitutes approximately 8% of the total body weight.
Average blood volume:
5 liters in women, with a packed cell volume (hematocrit) of 42%.
5.5 liters in men, with a hematocrit of 45%.
Blood Composition
Composed of three main types of specialized cellular elements suspended in plasma:
Erythrocytes (Red blood cells): Primarily responsible for oxygen transport.
Leukocytes (White blood cells): Mobile defense units of the immune system.
Platelets (Thrombocytes): Cell fragments important for hemostasis.
Physiological Roles of Blood
Carrying: Transports oxygen, nutrients, hormones, metabolic wastes, and heat.
Regulation: Regulates body temperature and pH.
Protection: Involved in clotting and contains immunoglobulins.
The Blood: Plasma
Functions and Constituents:
Water: Acts as a transport medium and carries heat.
Electrolytes: Important for membrane excitability, fluid distribution via osmosis between ECF and ICF, and buffering pH changes.
Most abundant electrolytes: Sodium (Na+) and chloride (Cl-).
Nutrients, wastes, gases, hormones: Transported in blood; blood CO₂ plays a role in acid-base balance.
The Blood: Plasma Proteins
Plasma proteins remain in the plasma and perform valuable functions.
Act as colloids, contributing to osmotic pressure due to their size preventing diffusion through capillary walls.
Partially responsible for buffering changes in pH.
Synthesized by the liver, except for Gamma globulins, which are produced by lymphocytes.
(α and β): Non-specific (e.g. cholesterol, iron, complement, etc…)
(γ): Specific
The Blood: Erythrocytes (Red Blood Cells)
Approximately 5 billion RBCs per 1 ml of blood (5 x 10^6/mm^3).
Shape and content optimized for oxygen transport; also transports H+ and CO2 to a lesser extent.
Erythrocyte Characteristics
Biconcave disc shape:
Provides a larger surface area for oxygen diffusion across the membrane.
Thinness facilitates rapid oxygen diffusion between the exterior and interior of the cell.
Highly flexible plasma membrane, allowing passage through narrow capillaries (8 µm diameter cells through 3 µm capillaries).
Hemoglobin (Hb)
Found exclusively in red blood cells.
Iron-containing pigment that appears reddish when oxygenated and bluish when deoxygenated.
Structure:
Globin: Protein composed of 4 highly folded polypeptide chains (two α subunits and two β subunits).
Heme groups: 4 iron-containing non-protein groups, each bound to one polypeptide chain, each iron atom can reversibly bind to one oxygen (O2) molecule.
Hemoglobin Function
Primary role is to carry oxygen; each Hb molecule can transport 4 O2 molecules.
Oxygen is poorly soluble in water, so 98.5% of O2 is carried bound to Hb.
Each RBC contains over 250 million Hb molecules, enabling it to carry over a billion O2 molecules.
Hemoglobin (Hb): Additional Combinations
Also combines with:
Carbon dioxide (CO2).
Acidic hydrogen ion (H+) from ionized carbonic acid (buffering capacity).
Carbon monoxide (CO): Binds irreversibly, leading to CO poisoning if inhaled.
Nitric oxide (NO2): Vasodilator; relaxes arterioles in the lungs for efficient oxygen rounds and stabilizes blood pressure.
Erythrocyte Composition
Mature erythrocytes lack a nucleus, organelles, and ribosomes, containing primarily Hb (about 250 million molecules).
Key enzymes present:
Glycolytic enzymes: Generate energy for active transport mechanisms to maintain ionic concentrations within the cell.
Rely entirely on glycolysis for ATP formation (no mitochondria).
Erythrocyte Enzymes
Carbonic anhydrase:
Critical for CO2 transport.
Catalyzes the conversion of metabolically produced CO2 into bicarbonate ion (HCO3−).
Bicarbonate is the primary form in which CO2 is transported in the blood, in addition to being bound to Hb.
Erythrocyte Lifespan
RBCs survive approximately 120 days due to lack of nucleus/organelles.
Turnover rate: 2-3 million cells per second out of 25-30 trillion RBCs circulating.
Spleen removes most old erythrocytes from circulation.
Erythropoiesis
New RBCs are produced to replenish dying ones in a process called Erythropoiesis.
Occurs in the red bone marrow.
Pluripotent stem cells in red bone marrow differentiate into various blood cells, including RBCs and WBCs.
Erythropoiesis Process
Kidneys detect reduced oxygen-carrying capacity.
Kidneys secrete erythropoietin (EPO) into the blood when less O2 is delivered.
Erythropoietin stimulates erythropoiesis in the bone marrow.
Additional circulating erythrocytes increase the O2-carrying capacity.
Increased O2-carrying capacity relieves the initial stimulus, reducing erythropoietin secretion.
The Blood: Blood Types
Blood types depend on surface antigens on erythrocytes.
Lymphocytes produce antibodies against foreign antigens.
Antigen: A large, complex molecule that triggers a specific immune response.
Antibodies: Bind with specific antigens, leading to their destruction.
Blood Type Antibodies
Naturally occurring antibodies against foreign RBC antigens appear in human plasma after 6 months of age.
Most common blood antigen system.
Blood Type Transfusion Reaction
Example: A transfusion reaction resulting from type B blood being transfused into a recipient with type A blood.
Rhesus (Rh) Blood Group
CDE system: 50 blood-group antigens with 5 primary antigen groups (D, C, E, c, e) → Fisher-Race system.
Someone with the C antigen will NOT have the c one. (Same pattern follows for the other antigens) – remember there are two alleles!
There is no d antigen; sometimes ‘d’ is used to denote the absence of the D antigen.
The D antigen is commonly found and is the most antigenic, thus the most important.
Rh Factor
The terms Rh factor, Rh positive (Rh+) or Rh negative (Rh-), refer to the D antigen.
People with the Rh factor have Rh-positive blood (D).
People lacking the Rh factor are Rh-negative (d).
No naturally occurring antibodies develop against the Rh factor.
Anti-Rh antibodies are produced only by Rh-negative people if exposed to Rh-positive blood through transfusion or placental exposure during pregnancy.
The notion of universal blood donors (O) and recipients (AB) can be misleading due to other blood antigen systems.
The Blood: Leukocytes
White blood cells (WBCs).
Mobile units of the body’s immune system.
Composed of leukocytes, their derivatives, plasma proteins, and immune organs.
Leukocytes: Immune System Role
Recognizes and neutralizes or destroys foreign materials.
Defends against disease-producing microbes (e.g., bacteria and viruses).
Functions as a cleanup crew, removing worn-out cells and tissue debris.
Identifies and destroys cancer cells.
Leukocyte Characteristics
Colorless due to lack of hemoglobin (stained for microscopy).
Vary in structure, function, and number (unlike uniform RBCs; size > RBCs).
Five major types of circulating leukocytes:
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
The Blood: Granulocytes
Polymorphonuclear (PMNs) granulocytes.
Neutrophils:
Phagocytic specialists that engulf and destroy bacteria intracellularly.
Release neutrophil extracellular traps (NETs) containing bacteria-killing chemicals.
Granulocytes: Eosinophils
Killing of antibody-coated parasites through release of granule contents.
Eosinophilia (increase in circulating eosinophils) is associated with:
Allergic conditions such as asthma and hay fever.
Internal parasite infestations, such as worms.
Attach to worm and secrete substances to kill it.
Granulocytes: Basophils
Chemotactic factor production.
Least numerous and poorly understood of the leukocytes.
Synthesize and store:
Histamine: Essential in allergic reactions.
Heparin: Speeds up removal of fat particles from blood after a fatty meal.
The Blood: Mononuclear Cells
Mononuclear agranulocytes.
Monocytes:
Phagocytosis, antigen presentation, cytokine production, and cytotoxicity.
Emerge from bone marrow while immature; circulate for 1-2 days; settle in various tissues.
Mature and enlarge into macrophages.
Lifespan ranges from months to years, but dies sooner during phagocytosis; ingest limited foreign material before succumbing.
Tissue Resident Macrophages
First to sense invading microorganisms → secrete cytokines/chemokines → recruit neutrophils and other leukocytes.
Mononuclear Cells: Lymphocytes
Two types:
Large granular lymphocytes → Natural Killer (NK) cells
Effector cells of the innate immune response.
Effective against virally infected cells.
Release lytic granules to kill infected cells.
Produce cytokines to limit viral replication.
Lymphocytes: Adaptive Immune Response
Small lymphocytes of the adaptive immune response:
Cytokine production, antigen recognition, antibody production, memory, cytotoxicity.
Two types:
B Lymphocytes: Humoral immunity; produce antibodies as plasma cells.
T Lymphocytes: Cell-mediated immunity; do not produce antibodies; directly destroy specific target cells.
T Lymphocytes
T Lymphocytes: cell-mediated immunity
Do not produce antibodies
Directly destroy specific target cells by releasing chemicals that punch holes in the victim cell
Target cells include body cells invaded by viruses and cancer cells
Leukocyte Production
All blood cells originate from the same undifferentiated pluripotent hematopoietic stem cells in red bone marrow.
Granulocytes and monocytes are produced only in bone marrow.
Lymphocyte Production
Most new lymphocytes are produced via cell division by lymphocytes already in lymphoid tissues like lymph nodes, spleen, and tonsils.
Total number of white cells and percentage of each type may vary considerably to meet changing defense needs.
The Immune System: Introduction
Immunity is the body’s ability to protect itself by resisting or eliminating harmful foreign invaders or abnormal cells.
Immune system activities:
Defends against invading pathogens.
Removes “worn-out” cells and tissue damaged by trauma.
Identifies and destroys abnormal or mutant cells (immune surveillance).
Mounts inappropriate immune responses, leading to allergies or autoimmune diseases.
Immunity: Pathogenic Microbes
Bacteria
Non-nucleated, single-celled microorganisms.
Cause tissue damage by releasing enzymes or toxins (e.g., Chlamydia, Streptococcus, E. coli, Salmonella).
Viruses
Consist of DNA or RNA enclosed by a protein coat.
Cannot carry out metabolism or reproduce without invading a host cell (e.g., SARS-CoV-2, HIV, HCV, Influenza, Ebola, Polio).
Immunity: Other Pathogens
Fungi (e.g., Aspergillus, Candida).
Protozoan parasites (e.g., plasmodium → malaria).
Helminth parasites (worms).
Virulence: The pathogen's inherent ability to cause disease.
Immunity: External Defenses
External defenses include:
Skin: Epithelial cells joined by tight junctions, fatty acids, antimicrobial peptides, normal microbiota.
Gut: Longitudinal flow of air or fluid, low pH, antimicrobial enzymes, antimicrobial peptides, normal microbiota.
Lungs: Movement of mucus by cilia, pulmonary surfactant, antimicrobial peptides.
Eyes/nose/oral cavity: Tears, nasal cilia, antimicrobial enzymes in tears and saliva, antimicrobial peptides.
Immunity: Internal Defenses
Lymphoid Tissue: Tissues that produce, store, or process lymphocytes, including:
Bone marrow
Thymus
Lymph nodes
Spleen
Tonsils
Adenoids
Appendix
Peyer’s patches or gut-associated lymphoid tissue (GALT)
Strategically located to intercept invading microorganisms.
Immunity: Functions of Lymphoid Tissue
Bone marrow: Origin of all blood cells; site of maturational processing for B lymphocytes
Lymph nodes, tonsils, adenoids, appendix, gut-associated lymphoid tissue (GALT):
Exchange lymphocytes with the lymph (remove, store, produce, and add them)
Resident lymphocytes produce antibodies and activated T cells, which are released into the lymph
Resident macrophages remove microbes and other particulate debris from the lymph
Spleen:
Exchanges lymphocytes with the blood (removes, stores, produces, and adds them)
Resident lymphocytes produce antibodies and activated T cells, which are released into the blood.
Resident macrophages remove microbes and other particulate debris, most notably worn-out red blood cells, from the blood
Stores a small percentage of red blood cells, which can be added to the blood by splenic contraction as needed
Thymus: Site of maturational processing for T lymphocytes; Secretes the hormone thymosin
Overview of the Immune Response
Innate immunity: Epithelial barriers, phagocytes, complement, NK cells and ILCs, dendritic cells, mast cells
Adaptive immunity: B lymphocytes (plasma cells producing antibodies), T lymphocytes (effector T cells)
Immunity: Immune Responses
Two immune responses: Innate and Adaptive
Innate responses nonselectively defend against foreign material
First line of defense, “non-specific”, rapid but limited response
Defenses include: Inflammation, Interferons, Natural killer cells (NK), Complement system, Dendritic cells
Immunity: Adaptive Responses
Adaptive responses selectively target particular invaders
Antibody-mediated immunity (Humoral): Production of antibodies by plasma cells (B-lymphocyte derivatives)
Cell-mediated immunity: Production of activated T lymphocytes that directly attack unwanted cells
Immunity: Innate vs. Adaptive Immunity
* Innate Response: Acts early in infection
* Adaptive Response: Acts later in infection
Immunity: Innate Immunity - Inflammation
Innate, nonspecific response to tissue injury
Recruitment of phagocytes to the invaded or injured area
Isolate, destroy, or inactivate the invaders
Remove debris
Prepare for subsequent healing and repair
Inflammation Process
Inflammatory response is similar regardless of the triggering event (pathogens or sterile)
Initiated by resident tissue macrophages → release cytokines and chemokines
Mast cells are activated → release histamine
Localized vasodilation
Increased capillary permeability
Localized edema
Walling-off the inflamed area
Inflammation: Leukocyte Activity
Emigration (recruitment) of leukocytes (neutrophils and monocytes)
Leukocyte proliferation
Marking of bacteria for destruction by opsonins (complement)
Leukocytic destruction of bacteria
Innate Immunity: Cytokines
Kill microbes directly
Several chemicals (i.e., interleukin (IL)-1 and 6, TNF) bring about a diverse array of effects
EP (endogenous pyrogen) induces fever in the body
Decrease plasma concentration of iron
Stimulate release of acute phase proteins (e.g., CRP)
Trigger clotting and anticlotting systems
Innate Immunity: Tissue Repair
Ultimate goal: Tissue repair.
Cell division replaces lost cells with the same kind of cells
In non-regenerative tissue (nerve and muscle): Lost cells are replaced with scar tissue
Prolonged chronic inflammation is unwanted.
Alzheimer’s disease, atherosclerosis, asthma, diabetes, cancer
Interferons have antiviral effects and limit viral spread
Innate Immunity: The Complement System
Nonspecific response
Composed of plasma proteins that are produced by the liver and circulate in inactive form
Three mechanisms of activation:
Spontaneous activation on microbial surfaces
Binding to carbohydrate chains present on surfaces of microorganisms
Activation by antibody binding to antigens on pathogens
Causes destruction of pathogen by two mechanisms:
Forms membrane attack complexes (MAC) that punch holes in the pathogen
Enhances the uptake of the pathogen by phagocytes (opsonization)
Dendritic Cell (DC)
Tissue resident cells with a unique star-shaped morphology
Immature DC in tissue have very high ability to internalize particles (macropinocytosis)
Professional APC
Encounter with pathogen causes maturation of DC → Mature DC
Immunity: From Innate to Adaptive Immunity
Immature dendritic cells reside in peripheral tissues
Dendritic cells migrate via lymphatic vessels to regional lymph nodes
Mature dendritic cells activate naive T cells in lymphoid organs such as lymph nodes
Immunity: Adaptive Immunity
Two classes of adaptive immunity:
Antibody-mediated or humoral immunity: Involves production of antibodies by B lymphocyte derivatives known as plasma cells
Cell-mediated immunity: Involves production of activated T lymphocytes that directly attack unwanted cells
Antigen:
Large, foreign, unique complex molecule
Induces (elicits) an immune response against itself
In general, the more complex a molecule is, the greater its antigenicity
Mostly protein in nature
Adaptive Immunity: Clonal Selection Theory
Specificity: Billions of lymphocytes recognizing different antigens
Lymphocytes with receptors that recognize the specific Ag will proliferate (clonal expansion or clonal selection)
The adaptive immune system acquires immunological memory towards foreign Ag → acquired or protective immunity
Immunity: B Lymphocytes
Secreted antibodies → mediators of humoral immunity
Membrane-bound on B cell surface → function as antigen receptors → Initiate B cell activation proliferation and differentiation of antigen-specific B cells → plasma cells → secretion of soluble form of the antibody (same specificity as the mb bound)
Immunity: Antibodies - Basic Functions
Binding antigens
Activate complement system
Neutralization:
Binding and neutralizing bacterial toxins
Inhibiting bacterial access to host cells
Inhibiting viral entry into host cells
Enhancing phagocytosis of pathogens (opsonization)
Immunity: T Lymphocytes
Carry out cell-mediated immunity
Do not secrete antibodies; directly bind to targets
Killer T cells release chemicals that destroy targeted cells
Clonal and antigen specific; acquire receptors/mature in the thymus
T cells are activated for foreign attack only when the attack is on the surface of a cell that carries foreign antigens presented on self-antigens
Immunity: T cells and its Targets
T-cell receptor (antigen receptor) → peptide fragments (antigen) bound to self proteins called Major Histocompatibility Complex (MHC) → displayed on the surface of APCs
Immunity: Two types of T Cells: CD4+ Cells
CD4 cells (mostly helper T cells: Th)
Modulate activities of other immune cells and secrete chemicals that amplify the activity of other immune cells
Immunity: Two types of T Cells: CD8+ Cells
CD8 cells (cytotoxic, or killer T cells: Tc)
Destroy host cells harboring anything foreign (viral infected cell; cancer cell)
Bind to the viral antigen and self-antigen on the surface of the infected cell
May kill cell directly or through enzymes that cause the cell to self-destruct