PSL301H—Blood and Immune System

Lecture 2: Pathogens and Innate Immunity

Learning outcomes
List the overall function of the immune system
Describe the main types of pathogens
Describe the components of the immune system
List and describe the key elements of the innate immune system
Be able to predict the effect of stimulating/blocking elements of
the innate immune system

Textbook reading: 8th ed. 754-767; (7th ed. 754-765; 6th

ed. 802-814, 5th ed. 783-793)
 Overall function of the immune system

Destroys pathogens

Detects and kills abnormal cells

Remove cell debris from body

ghr.nlm.nih.gov/.../apoptosismacrophage.jpg
Case study: Leon
Leon was doing well in first-year university when he developed a cough
and diarrhea. He felt very tired and achy and went to bed early. The next
morning he had a severe headache and his neck seemed to be stiff. He
went immediately to his doctor. He appeared confused and had a
temperature of 39.2C. He had small areas of reddish-purple discoloration
on his chest, a red throat and enlarged tonsils.

1) What condition might he be suffering from?

2) Given his enlarged tonsils and fever, he likely has an infection, how
does the body fight infection?

3) What is the cause of his fever?

 Types of pathogens

Parasitic worms Fungi Protozoa

Intracellular
and
extracellular

Bacteria Viruses Figures from Interactive Physiology

Viruses
Require cells to replicate

Figure 24.1
Case study: Leon
Leon was doing well in first-year university when he developed a cough
and and diarrhea. He felt very tired and achy and went to bed early. The
next morning he had a severe headache and his neck seemed to be stiff.
He went immediately to his doctor. He appeared confused and had a
temperature of 39.2C. He had small areas of reddish-purple discoloration
on his chest, a red throat and enlarged tonsils.

1) What condition might he be suffering from?

a) Common cold
b) Strep throat
c) Meningitis
d) Influenza
Blood cultures revealed that he had Neisseria
meningitidis (meningococcus),
which causes meningitis

FYI symptoms of meningitis

Interesting case video of student with meningitis:

https://www.youtube.com/watch?v=dYtSWwAndMk
Case study: Leon

2) Given his enlarged tonsils and fever, he likely has an infection, how
does the body fight infection?
 Defence against pathogens

Innate Immunity
• rapid, non-specific

Acquired Immunity
• slower, specific

Figure from Interactive Physiology

Components of the
immune system Tonsils are diffuse
lymphoid tissue

Lymph Encapsulated
Thymus
nodes lymphoid
produces
T lymphocytes Spleen tissues

Gut-associated
lymphoid tissue
(GALT) is a diffuse
Bone marrow lymphoid tissue
produces most
blood cells

Lymphatic
vessels

(a) Figure 24.2

 Lymphatics

Figure from Interactive Physiology

1) Return excess tissue fluid to the blood

2) Transport pathogens/dendritic cells to lymph nodes
3) Transport fat from digestive system to the blood
 Specialized lymphoid organs
Lymph nodes Spleen
- monitor lymph - monitors blood

Figure 24.2 Figure 24.2

Both contain mature immune cells that interact with pathogens and
initiate an immune response
Immune cells found in blood, lymph and tissues
B lymphocytes
T lymphocytes
Natural killer (NK) cells

tissues

tissues

Figure 24.2
 Defence against pathogens

Innate Immunity
• rapid, non-specific

Acquired Immunity
• slower, specific

Figure from Interactive Physiology

 Elements of the innate immune system

1) Physical barriers
2) Phagocytes
-neutrophils – 50-70% WBC
-macrophages
-dendritic cells

3) Natural killer (NK) cells

4) Antimicrobial proteins
5) Inflammation
6) Fever
1) Physical barriers

Figure 24.8
 2) Phagocytes
diapedesis
(extravasation)

chemotaxis
phagocytosis

Figure modified from Molecular Biology of the Cell

chemotaxins = e.g. bacterial toxins, products of

tissue injury, cytokines
 Phagocytosis of pathogens
Toll-like receptors
Pathogen

Phagocyte
Fc receptors
Antibody
molecules
Polysaccharide
capsule

Pathogen

Antibody receptor
Phagocyte Figure 24.9

Antibody is an example of an opsonin

Coating substance with an opsonin = opsonization
 Macrophages and dendritic cells display
antigen fragments
Lysosome
contains
enzyme Phagosome
and oxidants contains ingested
pathogen
Antigen-presenting
macrophage
Nucleus displays antigen
fragments on
surface receptors

Macrophage digests
antigen in lysosome
class II MHC
Figure 24.10 molecule + antigen
 Review question
In rare cases, individuals inherit mutations in a
specific toll-like receptors. What process would be
impaired in these individuals?

A) All phagocytosis in the body

B) The ability to defend against extracellular
bacteria
C) The ability of neutrophils to bind to antibodies
D) The ability to defend against bacteria living in
cells
 3) Natural killer (NK) cells cont’d
Kill cells when they are infected with a virus or
cancerous

Normal cell

Virally-infected cell or
cancerous cell
- MHC class I
expression is
reduced. Makes the
cell susceptible to
killing by NK cells
Interferons
Fig. from: Arthritis Res Ther 2004 6:8
 4) Antimicrobial proteins

Interferon: a and b – prevent viral replication in cells

g – activate macrophages and other
immune cells
Complement:
~25 plasma proteins
Destroy target cell membranes
Stimulate inflammation
Attract phagocytes
Enhance phagocytosis
 Complement

C3

Figure modified from

Interactive Physiology
Membrane attack complex
 Complement: Details FYI
CLASSICAL PATHWAY
Antigen-Antibody (IgG or IgM)
Complex

C1 Activated C1 Classical Pathway

C3 convertase
C4 + C2 C4b2a C4b2a3b
Membrane Attack
Complex
Mannose binding
lectins bind mannose C3 C3b C5 C5b C5-9
on pathogen
LECTIN PATHWAY C6 C7 C8 C9

C3 C3b C3bBb C3bBb3b

Alternative Pathway
C3 convertase
Factor B
Microbial Surfaces Factor D
(cleaves Factor B)

ALTERNATIVE PATHWAY
Leon additional information

Leon’s doctor learns that he had meningitis in high school and also that 3
of his 5 siblings have also had meningitis. She suspects that he may
have a defect in his complement system and orders a CH50 complement
test and a genetic test. The tests reveal that Leon and his siblings have a
mutation in C8.

What process is impaired in Leon and affected his siblings?

A) Activation of C1 protein
B) Ability to form a membrane attack complex
C) Ability to stimulate inflammation
D) Ability of his complement proteins to act as an opsonin
 5) Inflammation
Localized tissue response to injury producing

Swelling, redness, heat and pain

Roles
– Slowing the spread of pathogens
– Mobilization of local, regional, and systemic
defenses
– Sets the stage for repair
Figure from Interactive Physiology
 Antibody, complement,
Inflammatory response kinins, clotting factors
move into interstitial
tissue

Figure from Martini (2006) Fundamentals of

Anatomy and Physiology

Kinin cascade leads to formation of bradykinin –

vasodilator and stimulates pain receptors
 6) Fever
What is the cause of Leon’s fever?
Body temperature > 37.2 C
Cause: Pyrogens change the
thermoregulatory set point
in the hypothalamus
Roles:
Speeds up metabolic
activity of host
Inhibits some pathogens
Pyrogens: e.g. bacterial components, interleukin-1
released from activated macrophages
 Review question
What is needed on/in an infected body cell to
cause a natural killer cell to attack it?

a) The activation receptor

b) A reduction in MHC class I molecules
c) A receptor for MHC class I molecules
d) The membrane attack complex
 Friday’s Class
Textbook reading:
8th ed. 768-771, 773 (7th ed. 765-770, 773; 6th ed. 814-818,
822; 5th ed. 794-798, 800)

Case study : Leon’s case study continued

Leon’s doctor suggests he let the head of his student residence know that
he has meningitis so that the head can let other students know that they
should get the vaccine if they have not already been immunized.

1) What is the purpose of the vaccine?

2) Explain how the body responds to a vaccine.