IMSE 311: Immunity

Immunology

Study of host’s reactions when foreign substances are introduced into the body

Immunity

Condition of being resistant to infection

Antigens (Ag)

Foreign substances that induce a host response

Chinese and Turkish People

• Inhalation of powders from smallpox scabs

• 1500’s

Edward Jenner

• Immunity from smallpox through cowpox injection

• Late 1700’s

Louis Pasteur

• Developed the first attenuated vaccine

• “Father of Immunology”

• 1800’s

Attenuation

It means to make a pathogen less virulent

Elie Metchnikoff

• Discovered phagocytosis by injecting foreign Ag into a transparent starfish

• "Cellular Immunity”

Emil von Behring

• Noncellular portion of the blood (serum) from previously infected animals could neutralize toxins

• “Humoral Immunity”

Robert Koch

• Tuberculosis

• 1900’s

Jules Bordet

• Complement Pathway

• 1900’s

Karl Landsteiner

• Blood Groups

• 1900’s

Kohler and Milstein

• Principle of monoclonal Ab production

• 1900’s

Suzumu Tonegawa

• Ab Diversity

• 1900’s

Ian Frazer

• Human Papillomavirus (HPV) vaccine

• 2000’s

Ipilimumab

• Stage IV Melanoma

• 2000’s

Active Immunity

• Immunity that occurs when Ag is introduced into the body to produce Ab and memory cells

  • Pros: Long-lasting

  • Cons: Takes time to develop

2

How many weeks does it takes for the body to produce Ab in response to Foreign Ag?

Passive Immunity

• Immunity that occurs when pre-formed Ab are introduced into an individual

  • Pros: Immediate protection

  • Cons: Short-lived and no memory cells

2 Years Old

Age wherein Ab in the body are fully developed

Natural Active Immunity

Type of immunity where foreign Ag is introduced through infection

Natural Passive Immunity

Type of Immunity where Ab is transferred from one organism to another

Artificial Active Immunity

Type of immunity you get from vaccine shots

(note: vaccines contain attenuated pathogens)

Artificial Passive Immunity

Type of immunity through injection of Ab into the body

(like booster shots)

Innate Immunity

• “Natural Immunity”

• Defenses against infection that are ready for immediate action when a host is attacked by a pathogen

• Nonadaptive / nonspecific

• No prior exposure required

• Influenced by:

  • nutrition

  • age

  • fatigue

  • stress

  • genes

External Defense System

Physical, chemical, and biological barriers that prevent most pathogens from entering the body

Skin

Several layers of tightly packed epithelial cells that contain a protein called “keratin”, making it impermeable to most pathogens

Lactic Acid (in sweat)

Skin secretion that discourages growth of microorganisms

Fatty Acid (in sebaceous glands)

Skin secretion that maintains skin pH of approx. 5.6

Surfactants

Small proteins in mucus secretions that bind to microorganisms to help move pathogens out

Flushing of Urine

Removes many potential pathogens from the genitourinary tract

Lactic Acid

Keeps the vagina at a pH of about 5

Hydrochloric Acid

Keeps the stomach acid at the pH as low as 1

Lysozyme

Enzyme found in many bodily secretions that attacks the cell walls of microorganisms, especially those that are gram-positive

Lactobacillus acidophilus

Microbiota that is responsible for the acidity of the vagina

Hematopoietic Stem Cell

All blood cells arise from this type of cell

Heterophile Antibody

Ab which can work on other diseases

• Edward Jenner’s discovery of smallpox immunity through cowpox

Pelger-Huet Anomaly

An abnormality in neutrophils wherein it only contains 2 lobes

Diapedesis

Movement of WBCs outside of blood vessels

Chemotaxis

Movement of free WBCs to the site of inflammation (towards a chemical signal, “chemotaxins”)

• “Chemo na taxi”

Selectins

A cell-surface adhesion molecule that helps WBCs to hold onto the blood vessel walls

• They weaken during trauma or blood vessel injury, causing an increase in circulating WBCs in the blood

Red Bone Marrow

Bone marrow that produces blood cells and contains hematopoietic stem cells

Yellow Bone Marrow

Bone marrow that is primarily composed of adipose tissue

Internal Defense System

The cellular and humoral factors that destroy foreign Ag

Neutrophils (NEUT)

• 50 - 75% (most abundant) (50 - 70% in the book)

• 10 - 15 μm

• “Segmented Neutrophil”, 3 - 5 lobes

• Function: Phagocytosis, kills bacteria

• Granules:

  • Primary / Azurophilic: for anti-bacterial activity

  • Secondary / Specific: for oxidative burst

Lymphocytes (LYMPH)

• 20 - 40%

• 7 - 10 μm

• Function: Adaptive immunity

• Differentiates further into: (bone marrow and thymus)

  • B cells

  • T cells

  • NK cells

Monocytes (MONO)

• 4 - 10% (2 - 10% in the book)

• 12 - 22 μm (largest cell in the blood) (12 - 20μm in the book)

• Function: Precursors of macrophage

• “Scavenger cells”

• Irregularly folded or horseshoe-shaped nucleus that occupies almost half of entire cell volume

• Digestive vacuoles may also be observed in the cytoplasm

Eosinophils (EO)

• 1 - 3% (1 - 4% in the book)

• 12 - 15 μm (10 - 15μm in the book)

• Function: kills large parasites

• Bi-lobed, eccentric nucleus (away from the center)

• Granules: reddish-orange in color (takes up acid eosin dye)

Basophils (BASO)

• < 1% (least numerous)

• 10 - 15 μm (smallest of the granulocytes)

• Function: Inducing and maintaining allergic reactions

• Obscured nucleus

• Granules: densely staining deep-bluish-purple granules that contains:

  • Histamine

  • Heparin

Macrophages

• 25 - 80 μm

• Function:

  • Presents phagocytosed antigens to T lymphocytes (initiates specific immunity)

  • Anti-tumor

• Slow mobility / immobile

Kupffer Cell

Macrophage in the liver

Microglial Cell

Macrophage in the brain

Osteoclast

Macrophage in the bones

Alveolar Macrophage / Dust Cell

Macrophage in the lungs

Histiocyte

Macrophage in the connective tissues

Hofbauer Cell

Macrophage in the placenta

Littoral Cell

Macrophage in the spleen

Mesangial Cell

Macrophage in the kidneys

Type A Lining Cell

Macrophage in the synovial

Mast Cells

• 20 μm (larger than BASOs)

• Function: (versatility)

  • Major conduit between innate and adaptive immunity

  • Allergic reactions

  • Antigen-presenting cells (APCs)

• Resembles basophil (also contains histamine and heparin)

• Life Span: 9 - 18 months

Dendritic Cells

• Covered with long, membranous extensions that resemble nerve cell dendrites

• Most potent phagocytic cell

• Most effective APC in the body

Acute Phase Reactants

Normal serum constituents that rapidly increase or decrease in concentration because of infection, injury, or trauma to the tissues

• positive acute-phase reactants (increases)

• negative acute-phase reactants (decreases)

Liver Parenchymal Cells / Hepatocytes

Which cell primarily produces acute-phase reactants in response to an increase in cytokines?

C-Reactive Protein (CRP)

• Acute-Phase Reactant

• Most widely used indicator of acute inflammation but not preferred because it doesn’t say where the inflammation is located

• Capable of:

  • Opsonization (coating of foreign particles to trap)

  • Agglutination

  • Precipitation

  • Activation of complement by classical pathway

Serum Amyloid A (SAA)

• Acute-Phase Reactant

• Acts as a chemical messenger, similar to a cytokine

• Found to increase significantly more in bacterial infections than in viral infections

• Contributes to cleaning up remnants of pathogens (waste) because of high affinity for high-density lipoprotein (HDL) cholesterol

  • SAA deficient > lipid buildup > “plaque” > “Arteriosclerosis”

Cytokines

• “Messenger cells”

• Intercellular signaling polypeptides

Mannose-Binding Protein (MBP)

• Acute-Phase Reactant

• Also known as “Mannose-Binding Lectin”

• Acts as an “opsonin”

• Widely distributed on mucosal surfaces

• Lack of MBP has been associated w/ recurrent yeast/fungal infections

Mannose

Main carbohydrate component of fungi

Alpha 1 - Antitrypsin (AAT)

• Acute-Phase Reactant

• General plasma inhibitor of proteases released from leukocytes

• Limits the harmful side effects of inflammation

• AAT deficient > uninhibited proteases > “Premature Emphysema”

Haptoglobin

• Acute-Phase Reactant

• Binds irreversibly to free hemoglobin released by intravascular hemolysis

• Antioxidant

• Helps in protecting the kidneys from damage

  • Haptoglobin deficiency > unregulated free HGB > oxidative damage > masks protein behavior > “Chronic Kidney Disease” (CKD)

Fibrinogen (Factor I)

• Acute-Phase Reactant

• Most abundant coagulation factor in plasma

• Cleaved by thrombin (Factor IIa) to form fibrils that make up a fibrin clot

  • Formation of a clot creates a barrier that helps prevent the spread of microorganisms further into the body

Ceruloplasmin

• Acute-Phase Reactant

• Principal copper-transporting protein in human plasma

• “Wilson’s disease” > copper buildup > Ceruloplasmin depletion > “Kayser Fleischer Ring” (blindness, symptom of Wilson’s disease)

Adaptive Immunity

• “Specific Immunity”

• Has the ability to memorize an antigen

T Cell / T Lymphocytes

• 61 - 80% of LYMPH

• Differentiate in Thymus

• Function:

  • Cytokine production

  • Cell-mediated Immunity (tumor + virus-infected cells)

• CD3 (found in all T Cells), CD4, and CD8

B Cell / B Lymphocytes

• 10 - 20% of LYMPH

• Differentiate in Bone Marrow

• Function: Produces highly specific Ab

• CD19, CD20, and CD21

Natural Killer (NK) Cells

• 10 - 15% of LYMPH

• Differentiate in Bone Marrow

• Function: Kill target cells without prior exposure to them (like cancer cells)

• CD16 and CD56

Cluster of Differentiation (CD) Marker

Helps to identify LYMPH subtypes because they are difficult to distinguish visually

Ficoll-Hypaque

Liquid solution used in CD marking to isolate specific WBCs

400 x g for 30 minutes

Centrifugation parameter for CD marking