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Blood Composition &
Gas Transport & Immunity

Master the cellular components of blood, the biochemistry of oxygen and carbon dioxide transport, and the mechanisms of innate and adaptive immune responses.

MCAT Biology

What Is Blood?

Blood is a specialized connective tissue consisting of a liquid matrix called plasma (~55% of blood volume) and formed elements (~45%), including red blood cells, white blood cells, and platelets. The ratio of formed elements to total volume is called the hematocrit.

Plasma
Water, proteins (albumin, globulins, fibrinogen), electrolytes, nutrients, and waste products
Formed Elements
Erythrocytes (RBCs), leukocytes (WBCs), and thrombocytes (platelets)

Formed Elements of Blood

Erythrocyte
\(\sim 5 \text{ million}/\mu L\)
 No nucleus, biconcave Leukocyte
\(5,\!000-10,\!000/\mu L\)
 Nucleated, immune cells Thrombocyte
\(\sim 250,\!000/\mu L\)
 Cell fragments, clotting
\(\text{O}_2\) / \(\text{CO}_2\) Transport
 Immune Defense Hemostasis

Hemoglobin: The Gas Carrier

Hemoglobin (Hb) is a tetrameric protein with quaternary structure: two \(\alpha\) and two \(\beta\) subunits, each containing a heme group with an \(\text{Fe}^{2+}\) ion that reversibly binds one \(\text{O}_2\) molecule. Each Hb carries up to 4 molecules of \(\text{O}_2\).

\(\text{Fe}^{2+}\)
\(\text{Fe}^{2+}\)
\(\text{Fe}^{2+}\)
\(\text{Fe}^{2+}\)
\(\alpha_1\)
\(\alpha_2\)
\(\beta_1\)
\(\beta_2\)
 Hemoglobin Tetramer
\(4 \times \text{O}_2\) binding sites total

The Oxygen Dissociation Curve

% Hb Saturation 0 50 100
\(p\text{O}_2\) (mmHg)
 0 26 50 75 100 Normal Hb Right Shift
\(P_{50}\)
\(P_{50}\)

The Bohr Effect & \(\text{CO}_2\) Transport

Carbon dioxide is transported in three forms in the blood. The interconversion of \(\text{CO}_2\) and \(\text{H}_2\text{CO}_3\) is catalyzed by carbonic anhydrase inside erythrocytes.

1
Dissolved \(\text{CO}_2\): ~7% dissolved directly in plasma
2
Bicarbonate (\(\text{HCO}_3^-\)): ~70% converted via the reaction: \(\text{CO}_2 + \text{H}_2\text{O} \rightleftharpoons \text{H}_2\text{CO}_3 \rightleftharpoons \text{H}^+ + \text{HCO}_3^-\)
3
Carbaminohemoglobin: ~23% bound to amino groups on hemoglobin

Fetal Hemoglobin vs. Adult Hemoglobin

HbA (Adult)
\(\alpha_2\beta_2\) structure. Normal \(P_{50}\) of ~26 mmHg. Binds 2,3-BPG strongly, which reduces \(\text{O}_2\) affinity.
HbF (Fetal)
\(\alpha_2\gamma_2\) structure. Lower \(P_{50}\) (higher affinity). Binds 2,3-BPG weakly → left-shifted curve → extracts \(\text{O}_2\) from maternal blood.

Innate vs. Adaptive Immunity

Innate Immunity Adaptive Immunity
Speed Immediate (0-12 hours) Delayed (days to weeks)
Specificity Non-specific (PAMPs) Highly specific (antigens)
Memory No memory Immunological memory
Key Cells Macrophages, neutrophils, NK cells T cells, B cells
Barriers Skin, mucous membranes, complement Antibodies, cytotoxic T cells

The Leukocyte Lineup

Granulocytes Agranulocytes Neutrophil 60-70% Phagocytosis Eosinophil 2-4% Parasites, allergy Basophil <1% Histamine, allergy Lymphocyte 20-30% T, B, NK cells Monocyte 3-8% → Macrophages Mnemonic: "Never Let Monkeys Eat Bananas" Neutrophils > Lymphocytes > Monocytes > Eosinophils > Basophils (Listed in decreasing frequency in peripheral blood)

B Cells & T Cells: Adaptive Immunity

B Lymphocytes
Mature in bone marrow. Produce antibodies (humoral immunity). Differentiate into plasma cells (secrete Ab) and memory B cells.
T Lymphocytes
Mature in thymus. CD4+ (helper): activate B cells and macrophages. CD8+ (cytotoxic): directly kill infected cells. Cell-mediated immunity.
1
MHC I: present on all nucleated cells. Displays intracellular peptides to CD8+ T cells.
2
MHC II: present on APCs only (dendritic cells, macrophages, B cells). Displays extracellular peptides to CD4+ T cells.
3
Clonal selection: antigen binding activates specific lymphocyte clones → proliferation → effector + memory cells.

Antibody Structure & Classes

V V Fc Fab (antigen binding) Fc region (effector function) Hinge S-S Light chain Heavy chains
IgG
Most abundant. Crosses placenta. Opsonization, complement activation.
IgM
First responder. Pentamer. Strongest complement activator.
IgA
Mucosal immunity. Found in breast milk, saliva, tears. Dimer form.
IgE
Allergic responses. Binds mast cells and basophils → histamine release.

Solving Gas Transport Problems

1
Identify the location: Are you at the lungs (high \(p\text{O}_2\), low \(p\text{CO}_2\)) or at the tissues (low \(p\text{O}_2\), high \(p\text{CO}_2\))?
2
Check for shift factors: pH, temperature, \(\text{CO}_2\), 2,3-BPG levels. Determine if the curve shifts left or right.
3
Interpret the curve: Right shift = decreased affinity = more \(\text{O}_2\) released. Left shift = increased affinity = more \(\text{O}_2\) retained.
4
Consider special cases: Fetal Hb (left shift), CO poisoning (left shift + reduced capacity), sickle cell (altered curve shape).
5
Apply the Bohr effect: \(\text{CO}_2\) → \(\text{H}^+\) → lower pH → right shift at tissues, reverse at lungs. Always connect cause to mechanism.

Example: Exercising Muscle

Scenario: A sprinter's quadriceps during intense exercise. Muscle temperature rises, \(\text{CO}_2\) production increases, pH drops from lactic acid accumulation, and 2,3-BPG rises. What happens to \(\text{O}_2\) delivery?

1
All four factors shift the curve right: increased temperature, increased \(\text{CO}_2\), decreased pH, increased 2,3-BPG.
2
Right shift = lower Hb affinity for \(\text{O}_2\) at any given \(p\text{O}_2\).
3
Result: Hb releases more \(\text{O}_2\) to the working muscle, meeting the increased metabolic demand.

Example: Carbon Monoxide Poisoning

Scenario: A patient presents with cherry-red skin after exposure to a faulty heater. Why is CO so dangerous, even when total Hb is normal?

Problem 1
CO binds the \(\text{Fe}^{2+}\) in heme with ~240x greater affinity than \(\text{O}_2\). It competitively occupies binding sites.
Problem 2
CO binding shifts the curve left, increasing remaining subunits' affinity: Hb holds onto its \(\text{O}_2\) and won't release it to tissues.

Example: Bacterial Infection Response

Bacteria Enters tissue Macrophage Phagocytosis APC Presents via MHC II CD4+ T Helper Activated B Cell Activation → Plasma cells + Ab CD8+ Cytotoxic Kill infected cells Memory Cells Formed

Common Mistakes to Avoid

✕ Confusing Shift Direction
Right shift means decreased affinity (more unloading), not increased. "Right" = "Release."
✕ Mixing Up MHC I and II
MHC I = all nucleated cells → CD8+. MHC II = APCs only → CD4+. Remember: "I goes with 8, II goes with 4" (\(1 \times 8 = 8, 2 \times 4 = 8\)).
✕ Forgetting CO's Double Effect
CO doesn't just block \(\text{O}_2\) binding: it also left-shifts the curve, preventing unloading from the remaining functional hemes.
✕ IgM vs IgG Timing
IgM is the first antibody produced (primary response). IgG dominates the secondary response and is the most abundant serum Ab.
✕ RBCs Have Mitochondria
Mature mammalian RBCs have no nucleus or organelles. They cannot do oxidative phosphorylation: only anaerobic glycolysis.

Summary Comparison

Concept Key Detail MCAT Tip
Hb Cooperativity Sigmoidal curve, T → R state Myoglobin = hyperbolic (no cooperativity)
Bohr Effect \(\text{H}^+\) / \(\text{CO}_2\) → right shift Active tissues: more \(\text{O}_2\) unloading
Fetal Hb \(\alpha_2\gamma_2\), low 2,3-BPG affinity Left shift → higher \(\text{O}_2\) affinity than HbA
\(\text{CO}_2\) Transport 70% as \(\text{HCO}_3^-\), 23% carbamino, 7% dissolved Carbonic anhydrase in RBCs
Innate vs Adaptive Non-specific/fast vs specific/memory APCs bridge both systems
MHC I vs II I: all nucleated → CD8+, II: APCs → CD4+ \(1 \times 8 = 2 \times 4 = 8\) mnemonic

Question 1 of 5

A mountain climber acclimatized to high altitude shows increased levels of 2,3-BPG. How does this affect the oxygen-hemoglobin dissociation curve?

Question 2 of 5

Which form of \(\text{CO}_2\) transport accounts for the largest fraction of \(\text{CO}_2\) carried in the blood?

Question 3 of 5

A patient with a viral infection has CD8+ cytotoxic T cells targeting infected hepatocytes. Which molecule on the infected cell is required for CD8+ T cell recognition?

Question 4 of 5

Fetal hemoglobin (HbF) has a higher oxygen affinity than adult hemoglobin (HbA). What is the primary molecular reason for this difference?

Question 5 of 5

During a secondary immune response to a previously encountered pathogen, which antibody class is produced most rapidly and in the highest quantity?