Immunology
Lecture 1
First Lines of Defense
First line of defense = non-specific
1. Physical defenses
1.1 Physical barrier defenses – non specific responses
- Skin – barrier to entry
- Tight junc@ons + gap junc@ons between epidermis layers and epithelial layers
§ Forma@on of close cell to cell contact to prevent microbial entry
- 3 layers
§ Epidermis
• Kera@n
• Frequent shedding
§ Dermis
• Hair follicles, sweat glands, nerves, blood vessels
§ Hypodermis
• FaLy @ssue
• Blood and lymph vessels
- 3kg weight and 25m2 area
- Mucus linings trap dirt and microbes
- S@cky layer that protects beneath cells
- Epithelial cells that line mucosa can be ciliated
§ Propels mucus laden with debris for clearance
• Coughed up, sneezed out, ingested and destroyed by stomach
acid
- Endothelia à @ght junc@ons, single layer lining blood vessels
§ Creates BBB (blood brain barrier)
§ Protects CNS
1.2 Mechanical defenses
- Gag reflex
- Coughing to expel
- Peristalsis
- Flushing ac@on of urine + tears
- Urine kept sterile through kidney, bladder and ureters ac@on
- Eyelashes + eyelids
- Blinking bathes eye in tears to remove debris
- Scratching
1.3 Microbiome
- Resident microbiota
- Compete against pathogenic microbes for space and cellular localiza@on
- An@bio@cs can change microbiota and lead to disease and asthma
2. Chemical defenses
2.1 Chemicals + enzymes in the body
, - Salivary an@bacterial enzymes
- Tears – an@bacterial enzymes
- Stomach acid – low pH kills harmful microbes
- Bodily fluids
- Sebaceous glands à sebum produc@on
§ Lubricates and protects skin from invading microbes
§ Source of food for resident microbiota
§ Digested by lipase enzymes that allow for infec@on
2.2 An@microbial pep@des
- Non specific cell derived mediators
- Can be specific or broadly effec@ve
- Produced at steady state but mainly during invasion by pathogens
- Killing mechanisms vary
§ Destruc@on of RNA and DNA
§ Interference with cell wall synthesis
§ Damage pathogenic plasma membranes
§ Resident microbiota produce oleic acid to kill pathogens
AMP Secreted by Body site Pathogens Mode of ac@on
inhibited
Defensins Epithelial cells, Throughout Fungi, bacteria Disrup@on of
macrophages, body + many viruses membrane
neutrophils
Dermicidin Sweat glands Skin Bacteria and Disrupts
fungi membranes +
ion channels
Hista@ns Salivary glands Oral cavity Fungi Disrup@on of
intracellular
func@oning
Bacteriocins Resident GI tract Bacteria Disrup@on of
microbiota membrane
Cathelicidin Epithelial cells, Skin Bacteria + fungi Disrupts
macrophages membrane
and other cell
types
2.3 Plasma protein mediators
- Plasma = fluid por@on of blood similar to serum
- Contains electrolytes sugars, lipids and proteins
- Blood coagulants nonspecific immune substances
- Acute phase proteins
§ Produced in the liver and secreted into blood in response to
inflammatory molecules of the immune system
, APP Func@on
C-reac@ve protein Coats bacteria (opsoniza@on) to prepare for
Serum amyloid A phagocy@c inges@on
Ferri@n Bind and sequester ion to inhibit growth of
Transferrin pathogens
Fibrinogen Involved in blood clot forma@on that trap
pathogens
Mannose binding lec@n Ac@vates complement cascade
- Cytokines
§ Soluble + act as communica@on signals between cells
§ S@mulate produc@on of chemical mediators or other cell func@ons
• Cell prolifera@on
• Cell differen@a@on/inhibi@on
• Apoptosis
• Chemotaxis
§ Ac@ons =
• Autocrine
• Paracrine
• Endocrine
§ Classes =
• Chemokines
o Chemotac@c recruit leukocytes to site of infec@on
• Interleukins
o Ac@vate immune and non immune cells
• Interferons
o Inhbit viral replica@on
- Complement proteins
2.4 Cytokines
2.5 Inflamma@on elici@ng mediators
3. Cellular defenses
3.1 Granulocytes
3.2 Agranulocytes
Second line = nonspecific
4. Phagocytosis
5. Protec@ve protein cytokines
6. NK cells
7. Inflamma@on
Third line = specific/acquired immunity
8. Cell mediated
9. Humoral
, Lecture 2
Second Line of Defense
Importance of the immune system à
- If the innate arm is deficient:
- Can succumb to infec@on easier/shorter dura@on
§ Neutropenia, CGD and MPO deficiency
- Normal + effec@ve immune system can eliminate pathogens
- If adap@ve immune system is defec@ve:
- Chronic infec@ons
§ Low CD4 count in HIV and TB granuloma
1. Barrier surfaces
2. Hematopoiesis
a. Blood cells originate from one mul@potent stem cell
b. 3 major categories of blood cells
i. Red (erythrocytes)
1. O2 transport
ii. Platelets (thrombocytes)
1. Blood clot forma@on
2. Tissue repair
iii. White blood cells (leukocytes)
1. Nonspecific mechanisms of innate + adap@ve immunity
c. Body is separated into primary and secondary hematopoiesis sites
i. Primary lymphoid organs
1. Where cells originate (stem cell produc@on sites)
a. Bone marrow
b. Thymus
ii. Secondary lymphoid organs
1. Where cells from primary organs seed
2. Spread throughout body
iii. Cells migrate through bloodstream + lympha@c system to 2ndary
lymphoid organs
3. Innate acute inflammatory response
a. Any form of infec@on/injury results in acute inflammatory response
b. Innate cells migrate to site of injury
i. Neutrophils = first to arrive
1. Can be aLracted via stress signals
c. Pus build up
d. Can resolve, heal or remain chronic
e. Edema = blockade of further entry
f. Recruitment of leukocytes (PMNs = polymorphonuclear leukocytes)
g. Release of mediators
i. His@dine
ii. Prostaglandins
iii. Short lived lipids
h. Cytokine + chemokine release
Lecture 1
First Lines of Defense
First line of defense = non-specific
1. Physical defenses
1.1 Physical barrier defenses – non specific responses
- Skin – barrier to entry
- Tight junc@ons + gap junc@ons between epidermis layers and epithelial layers
§ Forma@on of close cell to cell contact to prevent microbial entry
- 3 layers
§ Epidermis
• Kera@n
• Frequent shedding
§ Dermis
• Hair follicles, sweat glands, nerves, blood vessels
§ Hypodermis
• FaLy @ssue
• Blood and lymph vessels
- 3kg weight and 25m2 area
- Mucus linings trap dirt and microbes
- S@cky layer that protects beneath cells
- Epithelial cells that line mucosa can be ciliated
§ Propels mucus laden with debris for clearance
• Coughed up, sneezed out, ingested and destroyed by stomach
acid
- Endothelia à @ght junc@ons, single layer lining blood vessels
§ Creates BBB (blood brain barrier)
§ Protects CNS
1.2 Mechanical defenses
- Gag reflex
- Coughing to expel
- Peristalsis
- Flushing ac@on of urine + tears
- Urine kept sterile through kidney, bladder and ureters ac@on
- Eyelashes + eyelids
- Blinking bathes eye in tears to remove debris
- Scratching
1.3 Microbiome
- Resident microbiota
- Compete against pathogenic microbes for space and cellular localiza@on
- An@bio@cs can change microbiota and lead to disease and asthma
2. Chemical defenses
2.1 Chemicals + enzymes in the body
, - Salivary an@bacterial enzymes
- Tears – an@bacterial enzymes
- Stomach acid – low pH kills harmful microbes
- Bodily fluids
- Sebaceous glands à sebum produc@on
§ Lubricates and protects skin from invading microbes
§ Source of food for resident microbiota
§ Digested by lipase enzymes that allow for infec@on
2.2 An@microbial pep@des
- Non specific cell derived mediators
- Can be specific or broadly effec@ve
- Produced at steady state but mainly during invasion by pathogens
- Killing mechanisms vary
§ Destruc@on of RNA and DNA
§ Interference with cell wall synthesis
§ Damage pathogenic plasma membranes
§ Resident microbiota produce oleic acid to kill pathogens
AMP Secreted by Body site Pathogens Mode of ac@on
inhibited
Defensins Epithelial cells, Throughout Fungi, bacteria Disrup@on of
macrophages, body + many viruses membrane
neutrophils
Dermicidin Sweat glands Skin Bacteria and Disrupts
fungi membranes +
ion channels
Hista@ns Salivary glands Oral cavity Fungi Disrup@on of
intracellular
func@oning
Bacteriocins Resident GI tract Bacteria Disrup@on of
microbiota membrane
Cathelicidin Epithelial cells, Skin Bacteria + fungi Disrupts
macrophages membrane
and other cell
types
2.3 Plasma protein mediators
- Plasma = fluid por@on of blood similar to serum
- Contains electrolytes sugars, lipids and proteins
- Blood coagulants nonspecific immune substances
- Acute phase proteins
§ Produced in the liver and secreted into blood in response to
inflammatory molecules of the immune system
, APP Func@on
C-reac@ve protein Coats bacteria (opsoniza@on) to prepare for
Serum amyloid A phagocy@c inges@on
Ferri@n Bind and sequester ion to inhibit growth of
Transferrin pathogens
Fibrinogen Involved in blood clot forma@on that trap
pathogens
Mannose binding lec@n Ac@vates complement cascade
- Cytokines
§ Soluble + act as communica@on signals between cells
§ S@mulate produc@on of chemical mediators or other cell func@ons
• Cell prolifera@on
• Cell differen@a@on/inhibi@on
• Apoptosis
• Chemotaxis
§ Ac@ons =
• Autocrine
• Paracrine
• Endocrine
§ Classes =
• Chemokines
o Chemotac@c recruit leukocytes to site of infec@on
• Interleukins
o Ac@vate immune and non immune cells
• Interferons
o Inhbit viral replica@on
- Complement proteins
2.4 Cytokines
2.5 Inflamma@on elici@ng mediators
3. Cellular defenses
3.1 Granulocytes
3.2 Agranulocytes
Second line = nonspecific
4. Phagocytosis
5. Protec@ve protein cytokines
6. NK cells
7. Inflamma@on
Third line = specific/acquired immunity
8. Cell mediated
9. Humoral
, Lecture 2
Second Line of Defense
Importance of the immune system à
- If the innate arm is deficient:
- Can succumb to infec@on easier/shorter dura@on
§ Neutropenia, CGD and MPO deficiency
- Normal + effec@ve immune system can eliminate pathogens
- If adap@ve immune system is defec@ve:
- Chronic infec@ons
§ Low CD4 count in HIV and TB granuloma
1. Barrier surfaces
2. Hematopoiesis
a. Blood cells originate from one mul@potent stem cell
b. 3 major categories of blood cells
i. Red (erythrocytes)
1. O2 transport
ii. Platelets (thrombocytes)
1. Blood clot forma@on
2. Tissue repair
iii. White blood cells (leukocytes)
1. Nonspecific mechanisms of innate + adap@ve immunity
c. Body is separated into primary and secondary hematopoiesis sites
i. Primary lymphoid organs
1. Where cells originate (stem cell produc@on sites)
a. Bone marrow
b. Thymus
ii. Secondary lymphoid organs
1. Where cells from primary organs seed
2. Spread throughout body
iii. Cells migrate through bloodstream + lympha@c system to 2ndary
lymphoid organs
3. Innate acute inflammatory response
a. Any form of infec@on/injury results in acute inflammatory response
b. Innate cells migrate to site of injury
i. Neutrophils = first to arrive
1. Can be aLracted via stress signals
c. Pus build up
d. Can resolve, heal or remain chronic
e. Edema = blockade of further entry
f. Recruitment of leukocytes (PMNs = polymorphonuclear leukocytes)
g. Release of mediators
i. His@dine
ii. Prostaglandins
iii. Short lived lipids
h. Cytokine + chemokine release
