Mammal Immunity “Module 2”
Lecture 1
Functions of the Immune System
- Immune tolerance: limit damage to self
- Immunological recognition: detecting the presence of a foreign agent
- Generate an immune e3ector function: generate a response tailored to the
type of foreign agent to contain or eliminate it
- Immunological memory: to “remember” and better protect against recurring
agents
Mammalian Immunity Has Three Lines of Defense
- Physical and chemical barriers
o Non specific – no tailor made response to pathogens
- Innate Immunity
o Occurs when physical or chemical barrier is breached – invasion
o Non specific
o Inflammatory response
o Integrates with adaptive immunity – directs the adaptive line of defence
§ Involves multiple immune cells
- Adaptive Immunity
o Specific immunity
o Involves immunity
Foreign Antigens
- Antigenic particles are often associated with a specific characteristic of an
organism
o Detected as foreign when they enter another organism that doesn’t have
that characteristic
- Body sees fragments of parasites, bacteria, viruses, fungi or protozoa
- Body elicits a specific immune response against these foreign molecules
- Pathogen classes:
o Parasites
§ tapeworm
o Protozoa
§ malaria
o Fungi
§ Athletes foot
o Bacteria
§ leprosy
o Viruses
§ AIDS
o Prion
§ CJD
, First Line of Defence
- Physical barriers and Mechanical Defenses
o Skin
§ Tight junctions and gap junctions
§ Shedding
o Nasal hair
o Eyelashes and eyelids
o Mucous membranes
§ Sticky layer that protects beneath cells
§ Epithelial cells that line mucosa can be ciliated
• Propels mucus laden with debris for clearance
o Coughed up, sneezed out, ingested and destroyed
by stomach acid
o Mucociliary clearance
o Urination
- Chemical
o Low pH – prevents colonization
§ Skin = 5.5
§ Gastric acid = 1-3
§ Vagina = 4.4
o Antimicrobial molecules
§ IgA
§ Sebum
• Lubricates and protects skin from invading microbes
• Source of food for resident microbiota
• Digested by lipase enzymes that allow for infection
§ Mucous
§ Lysozyme
§ Beta defensins
§ pepsin
- Biological
o Microbiome
§ Resident microbiota
• Compete against pathogenic microbes for space and
cellular localization
Innate vs Adaptive Immunity
Innate Adaptive
Self/nonself Present, reaction is against foreign Present, reaction is against foreign
discrimination
Lag Phase Absent, response is immediate Present, response can take a
couple days
Specificity Limited, the same response is mounted to a wide Extensive, wide range of antigen
range of agents receptors
Diversity Limited Extensive
Memory Absent Present
,Immune Cells (WBCs) are Derived from Haematopoeisis
- Site: continuous + throughout life in the bone marrow
- Haematopoeietic Stem Cell (HSC):
o Self renewing
o Committed
o Proliferating
- Can lead to myelopoiesis and lymphopoiesis to give myeloid cells and
lymphocytes
o Lymphoid progenitor: adaptive immune cells (B and T cells)
o Myeloid progenitor: innate immune cells
Recognition of Foreign Antigens by Immune Cells
- Recognition of PAMPs via PRRs
- PAMPs = components of pathogens
o Eg. Cell walls, proteins, nucleic acids, flagella
- Complement and antibody receptors on phagocytic cells can identify and bind
to pathogens for clearance
How does Innate Immunity Detect and Clear Foreign Antigens
1. Acute Responses
a. Inflammatory response
i. Dolor, Rubor, Calor, Tumor à pain, redness, warmth, swelling
ii. Bacteria and pathogens enter the wound
iii. Platelets from blood release clotting proteins at wound site
iv. Mast cells secrete factors (proteins from granules) that mediate
vasodilation and vascular contractions (widens blood vessels)
1. Histamine released
v. Neutrophils secrete factors to kill and degrade pathogen
vi. Macrophages + neutrophils remove pathogens by phagocytosis
vii. Macrophages secrete cytokines and chemokines to attract
immune cells to the site (amplification of response)
1. Activate cells involved in tissue repair
viii. Inflammatory response continues until foreign material is
eliminated and wound is repaired
b. Acute phase proteins (CRP, Complement)
2. Anti-microbial factors
a. Complement cascade
i. Synthesized in the liver as inactive precursors and delivered to
blood stream
ii. C1 binds to antibodies that bind to antigens on a foreign microbe
iii. C1 breaks C2 into C2a and C2b and C4 into C4a and C4b
iv. C2a and C4b together form an enzyme (C3 convertase) which
breaks up C3 into C3a and C4b
1. C3a can attract other immune cells to site of infection,
degranulation of mast cells (inflammatory mediator)
, 2. C3b opsonizes pathogens and can break up C5 (leads to
cytolysis)
a. Opsonization (C3b binds to pathogen surface to
form a target for macrophages to phagocytose)
v. C5,C6,C7,C8,C9 = Membrane attack complex
1. MAC makes pathogen membrane porous to cause lysis
b. Antimicrobial peptides
c. cytokines
3. Cellular Responses
a. Macrophages
i. Phagocytosis!!
1. Occurs at cell membrane whereby invagination of the
membrane leads to formation of a phagosome
2. Fuses with lysosome to form phagolysosome
ii. Eiiciency is enhanced by opsonization (C3b functioning)
iii. Can present antigens like DCs
1. DCs = most eiicient
iv. Neutrophils and DCs can also phagocytose
b. Natural killer cells
Innate and adaptive immunity are integrated
- Innate immunity triggered first à adaptive immunity
- Gradual shift from innate to adaptive as the threshold of infection increases
- Establishment of infection
o Innate response kicks in within 4 hours of physical and chemical barrier
being breached
- Inductive phase
Lecture 1
Functions of the Immune System
- Immune tolerance: limit damage to self
- Immunological recognition: detecting the presence of a foreign agent
- Generate an immune e3ector function: generate a response tailored to the
type of foreign agent to contain or eliminate it
- Immunological memory: to “remember” and better protect against recurring
agents
Mammalian Immunity Has Three Lines of Defense
- Physical and chemical barriers
o Non specific – no tailor made response to pathogens
- Innate Immunity
o Occurs when physical or chemical barrier is breached – invasion
o Non specific
o Inflammatory response
o Integrates with adaptive immunity – directs the adaptive line of defence
§ Involves multiple immune cells
- Adaptive Immunity
o Specific immunity
o Involves immunity
Foreign Antigens
- Antigenic particles are often associated with a specific characteristic of an
organism
o Detected as foreign when they enter another organism that doesn’t have
that characteristic
- Body sees fragments of parasites, bacteria, viruses, fungi or protozoa
- Body elicits a specific immune response against these foreign molecules
- Pathogen classes:
o Parasites
§ tapeworm
o Protozoa
§ malaria
o Fungi
§ Athletes foot
o Bacteria
§ leprosy
o Viruses
§ AIDS
o Prion
§ CJD
, First Line of Defence
- Physical barriers and Mechanical Defenses
o Skin
§ Tight junctions and gap junctions
§ Shedding
o Nasal hair
o Eyelashes and eyelids
o Mucous membranes
§ Sticky layer that protects beneath cells
§ Epithelial cells that line mucosa can be ciliated
• Propels mucus laden with debris for clearance
o Coughed up, sneezed out, ingested and destroyed
by stomach acid
o Mucociliary clearance
o Urination
- Chemical
o Low pH – prevents colonization
§ Skin = 5.5
§ Gastric acid = 1-3
§ Vagina = 4.4
o Antimicrobial molecules
§ IgA
§ Sebum
• Lubricates and protects skin from invading microbes
• Source of food for resident microbiota
• Digested by lipase enzymes that allow for infection
§ Mucous
§ Lysozyme
§ Beta defensins
§ pepsin
- Biological
o Microbiome
§ Resident microbiota
• Compete against pathogenic microbes for space and
cellular localization
Innate vs Adaptive Immunity
Innate Adaptive
Self/nonself Present, reaction is against foreign Present, reaction is against foreign
discrimination
Lag Phase Absent, response is immediate Present, response can take a
couple days
Specificity Limited, the same response is mounted to a wide Extensive, wide range of antigen
range of agents receptors
Diversity Limited Extensive
Memory Absent Present
,Immune Cells (WBCs) are Derived from Haematopoeisis
- Site: continuous + throughout life in the bone marrow
- Haematopoeietic Stem Cell (HSC):
o Self renewing
o Committed
o Proliferating
- Can lead to myelopoiesis and lymphopoiesis to give myeloid cells and
lymphocytes
o Lymphoid progenitor: adaptive immune cells (B and T cells)
o Myeloid progenitor: innate immune cells
Recognition of Foreign Antigens by Immune Cells
- Recognition of PAMPs via PRRs
- PAMPs = components of pathogens
o Eg. Cell walls, proteins, nucleic acids, flagella
- Complement and antibody receptors on phagocytic cells can identify and bind
to pathogens for clearance
How does Innate Immunity Detect and Clear Foreign Antigens
1. Acute Responses
a. Inflammatory response
i. Dolor, Rubor, Calor, Tumor à pain, redness, warmth, swelling
ii. Bacteria and pathogens enter the wound
iii. Platelets from blood release clotting proteins at wound site
iv. Mast cells secrete factors (proteins from granules) that mediate
vasodilation and vascular contractions (widens blood vessels)
1. Histamine released
v. Neutrophils secrete factors to kill and degrade pathogen
vi. Macrophages + neutrophils remove pathogens by phagocytosis
vii. Macrophages secrete cytokines and chemokines to attract
immune cells to the site (amplification of response)
1. Activate cells involved in tissue repair
viii. Inflammatory response continues until foreign material is
eliminated and wound is repaired
b. Acute phase proteins (CRP, Complement)
2. Anti-microbial factors
a. Complement cascade
i. Synthesized in the liver as inactive precursors and delivered to
blood stream
ii. C1 binds to antibodies that bind to antigens on a foreign microbe
iii. C1 breaks C2 into C2a and C2b and C4 into C4a and C4b
iv. C2a and C4b together form an enzyme (C3 convertase) which
breaks up C3 into C3a and C4b
1. C3a can attract other immune cells to site of infection,
degranulation of mast cells (inflammatory mediator)
, 2. C3b opsonizes pathogens and can break up C5 (leads to
cytolysis)
a. Opsonization (C3b binds to pathogen surface to
form a target for macrophages to phagocytose)
v. C5,C6,C7,C8,C9 = Membrane attack complex
1. MAC makes pathogen membrane porous to cause lysis
b. Antimicrobial peptides
c. cytokines
3. Cellular Responses
a. Macrophages
i. Phagocytosis!!
1. Occurs at cell membrane whereby invagination of the
membrane leads to formation of a phagosome
2. Fuses with lysosome to form phagolysosome
ii. Eiiciency is enhanced by opsonization (C3b functioning)
iii. Can present antigens like DCs
1. DCs = most eiicient
iv. Neutrophils and DCs can also phagocytose
b. Natural killer cells
Innate and adaptive immunity are integrated
- Innate immunity triggered first à adaptive immunity
- Gradual shift from innate to adaptive as the threshold of infection increases
- Establishment of infection
o Innate response kicks in within 4 hours of physical and chemical barrier
being breached
- Inductive phase
