Blood & Immune System

Hemopoiesis

Occurs in red bone marrow, producing RBCs. Occurs before ossification (embryonic development), takes place in liver and spleen

Red Bone Marrow

Contains blood stem cells

Yellow Bone Marrow

Unilocular adipose CT

Hemopoisis During Embryonic Development 

Takes place in liver and spleen

Hemopoietic Stem Cell

In red bone marrow divide into lymphoid or myeloid (CFU)

Lymphoid Lineage

Lymphocytes (T-cells, B-cells, and NK cells). Many subsets of T-cells and B-cells that secrete antibodies.

Colony Forming Units (CFUs)

Respond to Colony-Stimulating Factors (CSFs)

Colony-Stimulating Factors (CSFs)

Factors that stimulate differentiation of pluripotential stem cells to a particular lineage.

CSF for Erthroycyte

Erthropoietin

CSF for Megakaryocytes

Thrombopoietin

Cancer Patients

Treated with CSFs to boost the immune system. Inject factors that stimulate the production of macrophages and lymphoid cells.

Reticulocytes

Enucleated immature RBCs. Basophilic structures are organelles that have not broken down (lack a nucleus). Diagnose anemia with high reticulocyte count (indicative of hypoxia).

Hypoxia

High reticulocyte count (reticulocytosis).

Blood Sample

Plasma, Buffy coat, and RBCs

Plasma

Liquids (water), proteins, and other solutes (iron, urea, creatine, nutrients)

Plasma Proteins

Albumin, globulin, fibrinogen

Buffy Coat

Platelets & Leukocytes (WBCs)

Serum

Plasma with no fibrinogen (without clotting proteins)

Erythrocytes

Anucleate, highly flexible, and biconvex-shaped cells. Regular sized (7.5 microns).

Biconvex Shape of RBCs

Allow for movement in capillaries, increasing flexibility while also maintaining SA

Hemoglobin

Protein that binds 4 O2 molecules (4 subunits), delivers O2 to tissues. 

Heme Group

Porphyrin (Fe), where each Fe binds loosely with one O2 molecule

Allostery

Hemoglobin subunits cooperatively bind O2; the binding of one site impacts the binding of another site (increases). Favors loading in lungs and unloading in tissues.

CO2 in Hemoglobin

Binds to AA groups in hemoglobin, producing carbamate (carbaminohemoglobin)

Partial Pressures

Lungs have a high pO2, which increases affinity of hemoglobin to O2, while tissues have small difference in pO2 leading to release of O2 from hemoglobin.

Carbonic Anhydrase

Converts CO2 → bicarbonate (HCO3-). Buffers body’s pH (in blood and kidneys)

Bicarbonate

Transported in RBC or blood serum, allowing for the movement of CO2

Band 3 Antiport Protein

Integral membrane protein in RBCs. Antiports HCO3- with Cl- bidirectionally down HCO3- gradient, maintaining pH 

Bicarbonate Conversion

Converted from CO2 in tissues then converted back into CO2 in the lungs, with high concentration allowing for passive diffusion into the air

Carbonic Acid

Intermediate in conversion of CO2 to bicarbonate

Spectrin and Ankyrin

Maintain RBC shape, forming anchored webs of fibers on the inner surface of the RBC membrane. Enable bending and return to the original biconcave shape, interacting with actin.

Glycophorin C

Membrane glycoprotein that carries carbohydrate moieties that produce the ABO blood group antigens on the external surface of RBC

Blood Type

ABO antigen attached to an oligosaccharide chain projecting from glycophorin C. 

A & B

Alleles of ABO gene code a glycosyltransferase that catalyzes final step of antigen synthesis. A/B transferases differ by only 4 AA

O

Codes an inactive glycosyltransferase that cannot modify the ABO antigen precursor 

Group A

Anti-B antibodies with A antigen

Group B

Anti-A antibodies with B antigen

Group AB

No antibodies in plasma with A and B antigens

Group O

Anti-A and Anti-B antibodies with no antigens

Rh

Membrane protein of RBCs that produces a peptide antigen (Rh+ and Rh-)

Indviduals Rh- but Recieve Rh+

Build up antibodies that agglutinater transfused blood cells

Mothers Rh- but Carry Rh+ Fetus

Develop antibodies to Rh peptide via placental blood exposure 

Secondary Rh+ Pregnancy

Results in antibodies crossing the placenta and agglutinating RBCs within fetus 

Platelets

Shed by megakaryocytic cells after stimulation via thrombopoietin.

Platelet Demarcation Channels

Develop in the outer cytoplasm of megakaryocytes via vesicular fusion. As they fuse, platelets are formed and released.

Blood Clotting

Platelets contact collagen fibers, responding with numerous cytoplasmic extensions and adherence molecules to interact with other platelets (platelet release reaction). They then contract to form a compact platelet plug (platelet contraction)

Platelets Release Reaction

Platelets contact collagen fibers, responding with numerous cytoplasmic extensions and adherence molecules to interact with other platelets

Platelet Contraction

Contract to form a compact platelet plug, leading to local vasoconstriction.

Platelets

Release cytokines leading to neutrophils and monocytes leaving the vascular system and entering interstitial regions where damage occurs.

Prothrombin

Cleaved to generate thrombin

Thrombin

Active enzyme that cleaves fibrinogen, producing fibrin

Fibrin

Cross-links with platelets plugs to form a blood clot

Order of Events for Platelets

1. Undergo platelet release reaction (self aggregate)

2. Platelets release factors that cause local vasoconstriction

3. Release chemokines that recruit neutrophils & monocytes to leave vascular and enter damaged tissues (macrophages secrete vasdcular endothelial growth factor (VEGF) stimulating angiogenesis

4. Platelets produce platelet-derived growth factor (PDGF) inducing local pericytes to differentiate into new blood vessels

Leukocytes

Granulocytes and Arganulocytes

Granulocytes

Neutrophil, eosinophil, basophil

Agranulocytes

Lymphocytes and monocytes

Lymphocytes

Adaptive immunity, B cells become plasma cells when activated and T cells perform cell-mediated immunity. Heterochromatic nucleus (large).

Neutrophils

Innate immunity against bacteria (phagocytose pathogens) with antimicrobial substances (reactive O2 species, cytotoxic proteins). Multi-lobed nucleus, pale/non-staining granules.

Eosinophil

Innate immunity against parasites (damage to the membrane). Inflammatory response. Pink granules with a bilobed nucleus (boomerang) with major basic protein.

Basophils

Allergic Reactions, releasing histamine and heparin, cause intense inflammation. Basophilic granules (a lot of them) and nucleus is not visible.

Mast Precursor Cells (Mast cells)

Inflammation, allergic reactions releasing histamine and heparin. Basophilic granules and the nucleus is clearly visible.

Monocytes (Macrophages)

Differentiate into macrophages when leaving the blood. Microbe defense, tissue morphogenesis, angiogenesis, and tissue repair. Large cells without granules. 

Macrophages (in CT)

Phagocytose invading microbe, removing damaged material, and remodeling repaired tissue. Remodel normal tissue, stimulate angiogenesis, recruit and regulate other immune cells. 

Diapedesis

Mechanism for leukocytes to leave the bloodstream and enter the CT. Transmigration through the endothelium can be paracellular or transcellular occurring in post-capillary venules.

Histamine

Increases permeability of the endothelium, promoting diapedesis, creating local edema.

Innate Immunity

Rapid response, non-specific, and no memory. Monocytes, basophils, eosinophils, neutrophils, knnown pathogens.

Adaptive Immunity

Slow, learned, specific memory (lymphocytes), unknown pathogens.

Humoral Immunity

B-cell production of antibodies that bind antigensm resulting in neutralization, lysis, phagocytosis and destruction

Cell-mediated Immuninity

T-Cell recognition of abnormal antigens on the surface of host cells (indicating viral infection or tumorigenic change) 

Humoral Response

1. Antigen-presenting cell (APC) encounters an antigen. APC presents antigen to lymphocytes, with a T-helper cell activated B-cell that recognizes the same antigen, OR a B-cell recognizes the antigen and becomes activated.

2. B-cell undergoes clonal expansion (mitosis)

3. Daughter cells mature into plasma cells and produce an antibody specific to the antigen.

4. Antibodies tag antigens and inactivate and/or facilitate their removal

Somatic Hypermutation

Occurs in variable region of each B-cell Ig gene

V-D-J Recombination

Immunoglobulin genes have unique specialized regions where they can draw from different combinations of exons, heavy chain recombination (variable, diversity, joining)

B-Cell

Combines one or more random segments from each VDJ region, plus the constant region, to produce the heavy chain (variability among population)

Activation-Induced Cytidine Deaminase (AID)

Affects DNA after B-cell activation by converting cytidine into uridine in the hypervariable region of the Ig gene. Creates a base pair mismatch, the cell attempts to remove U from the DNA. Creates point mutations that can create Igs with higher binding affinity. Tightening of affinity for that specific B-cell, with increased interactions, stronger binding. Converts light and heavy chain DNA throughout life.

Igs Binding Affinity

Higher binding affinity cells produce memory B-cells so that future encounters with the antigen will activate clones with better binding antibodies.

Class Switching

AID creates sites where recombination can take place, allowing portions of the constant region genome to be excised. Allows for the same antigen-binding regions to be paired with different constant regions. Occurs within specific plasma cell clones, creating various plasma cells responsible for different isotype production.

Class Switching

Plasma cells can modify the constant region while maintaining the antibody specific variable region

Immunoglobin Isotype

Five characteristic constant regions distinguish the Igs, with the presence of carb groups cannote different binding properties. Different effects to same antigen.

Cell-Mediated Response

1. A virus-infected cell expresses antigens on its surface and presents them to cytotoxic T-cells (T-helper cells activated by APC activate cytotoxic T-cells

2. Cytotoxic T-cell with receptor for antigen replicated massively (clonal expansion)

3. Cytotoxic T-cells seek out abnormal cells expressing antigen

4. Kill affected cells by lysis or apoptosis.

Naive T-Cell

Recentely released from thymus, not yet activated, able to differentiate to other T-cells

Memory T-Cell

Inactive daughter cell of an activated T-cell that resides in tissues, waiting to be reactivated by the reappearance of the pathogen.

Cytotoxic T-Cell

Express CD8 on cell membrane, recognize MHC I. If T-cell receptor binds to the epitope on MHC I, beocmes activated. Rapidly kill target cell through lysis or apoptosis. Produce a few memory T cells that can be reactivated if pathogen reappaers.

T-Cell Receptors

Variable regions that are encoded by VDJ and VJ regions that can be recombined before birth.

Heterodimeric Receptor

Forms from alpha and beta chains, each with variable & constant regions (t-cell)

Helper T-Cell

Express CD4 on the cell membrane, which recognizes MHC II, and gets activated by it. Activate and recruit B-cells to initiate humoral immune response. Activate macrophages and cytotoxic T-cells to initiate a cellular immune response. Produce a few memory T-cells that can be reactivated if the pathogen reappears.

MHC I

Glycoproteins are expressed on the cell surface of all nucleated cells in the body (absent on RBCs). Displays tiny portions of cells protiens to the exterior envirnoment constantly recycling which are presented. Cytotoxic T-cell have MHC I binding sitres on their T-cell receptor. If antigen from, virus or malformed host amterial bind to T-cell receptor, cytotoxic moleculea are secreted.

MHC II

Glycoprotein is expressed on only antigen-presenting cells (macrophages, dendritic cells, B-cells). Cells with this display portions of foreign, phagocytosed proteins and migrate to lymphatic tissue (lymph nodes). Helper T-cell cells have binding sites on T-cell receptors. If foreign antigen binds to T-cell receptor, helper T will activate humoral immune response by stimulating B cells.

Stave Cells

Modified endothelial cells entering the splenic sinuses. Thin spaces between these cells capture RBCs with irregular shapes so they can be consumed by phagocytic cells.