Overview of the Immune System: Innate vs. Adaptive Defenses Innate-Nonspecific Defenses First Line of defense: Physical barriers Second Line of defense: - Major cellular components Phagocytes Basophils Eosinophils NK cells - Chemical signals Interferons Complement Proteins Inflammation Fever (pyrogens)

1. The Immune System
Amjad KhanAfridi
Chapter # 13
Abasyn University, Peshawar

2. The Immune System

3. 1. Overview of the Immune System: Innate vs. Adaptive Defenses
2. Innate-Nonspecific Defenses
A. First Line of defense: Physical barriers
B. Second Line of defense:
- Major cellular components
• Phagocytes
• Basophils
• Eosinophils
• NK cells
- Chemical signals
• Interferons
• Complement Proteins
• Inflammation
• Fever (pyrogens)
Immunity I: Innate (nonspecific) Defenses

4. Why do we need an Immune System?
Introduction:
Pathogens are microscopic organisms that cause disease
(Each attacks in a specific way)
Viruses, Bacteria, Fungi, Parasites, and Protozoans
Other environmental substances challenge the lymphatic system
Environmental pathogens (poison ivy, etc)
Toxins (not metals – joint transplants)
Abnormal body cells such as cancers
The Immune system is coupled with the Lymphatic system

5. Where and how do we defend against disease pathogens?
 Immunity is
 The ability to resist infection and disease
 Many body cells and tissues are involved in the implementation of immunity
(Not just lymphocytes and other immune cells)
 Innate (Nonspecific) Defenses (we are born with this capability)
 Can involve the epithelium on the body surface (integument) or occur in
connective tissue, in the GI system and/or may involve a cellular response
 Respond immediately to many different harmful agents
 Do not require a previous exposure to a foreign substance
 Adaptive (Specific) Defenses (these components develop with time)
 Lymphocytes (B, T, NK): Are major players in the immune response but
other cells and participants in the innate system work cooperatively
 Identifies, attacks, and reinforces immunity to a specific pathogen
These 2 categories of immune mechanisms work together

6. Overview of the Immune System
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Immune System
Adaptive immunity
Delayed response to
specific antigen
B-lymphocytes
(humoral immunity)
T-lymphocytes
(cell-mediated
immunity)
Plasma cells
(synthesize and
release antibodies)
Physiologic responses
(e.g., inflammation,
fever)
Chemicals
(e.g., interferon,
complement)
Cells
(e.g., macrophages,
NK cells)
Skin and mucosal
Membranes & barriers
(prevent entry)
Immediate response to wide
array of substances
Innate immunity
Nonspecific
internal defenses

7. Innate - Nonspecific Defenses: 7 categories
 1st line of defense
 Physical barriers: Skin and mucosal barriers - keep hazardous materials outside the
body
 2nd line of defense
 Phagocytes: neutrophils and macrophages: engulf pathogens and cell debris
 Immunological Surveillance: natural killer cells (NK cells) destroy abnormal cells.
 Interferons: Chemical messengers that coordinate the defenses against viral
infections. Antiviral proteins do not kill viruses but block replication in cell
 Complement: Complement action of antibodies to destroy pathogens
 Inflammation: Triggers a complex inflammatory response limiting the spread of
infection
 Fever: A high body temperature which increases body metabolism, accelerates
defenses and accelerates body defenses

8. Physical Barriers – 1st line of defense
• Outer layer of skin; Hair; Epithelial layers of
internal passageways; dermis
• Secretions that flush away materials: Sweat
glands, lacrimal glands, mucus, and urine
• Secretions that kill or inhibit
microorganisms: Enzymes, antibodies (IgA
in tears), and stomach acid.
• Direction of secretion (one way direction -
urination) can prevent or retard the
movement of pathogens into the body

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Erythrocyte
Platelets
Neutrophil
Eosinophil
Basophil
Monocyte
B-lymphocyte
T-lymphocyte
Pre-T-lymphocyte
T-lymphocytes
mature in the
thymus prior to
circulating in
the blood.
Red bone marrow
= site of origin
All formed elements (except
T-lymphocytes) leave the bone
marrow and directly enter
and circulate in the blood.
Macrophage
T-lymphocyte
maturation
Thymus
Major cellular components of the Innate- Nonspecific System
Plasma cell
WBCs

10. Phagocytes: engulf bacteria, release toxic chemicals,
present antigens
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Residue is exocytosed
Phagolysosome
destroys infectious
agent
Phagosome
Lysosome
Macrophage
Infectious agent
engulfed
Neutrophil, macrophage, eosinophil: Phagocytic cells
• Originally WBCs – they migrate into connective tissue
• The “clean-up crew”: phagocytose debris and digest via lysosomes
• Neutrophils enter first then macrophages (derived from monocytes)
• Eosinophils involved with parasitic infections and antigen-antibody complexes
Also an APC

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(b)
Venule
Eicosanoids
Histamine
Basophil
Arteriole
Basophil and mast cell: Proinflammatory chemical-secreting cells
Heparin
Vasodilation
Increases capillary
permeability Capillary
Anticoagulant
Increases inflamation
Basophils open up vessels & increase blood flow

12. Eosinophils: Parasite-Destroying Cells
Eosinophil
Parasitic worm
Cytotoxic chemicals
Eosinophils: Parasite-destroying cells
(d)
Eosinophils also phagocytose antigen-antibody complexes

13. How do phagocytes invade the area of
infection or injury?
- Inflammatory factors –
released by mast cells, etc.
- Vasodilation – capillaries
become permeable
- Margination – WBCs slow
down & align on the vessel wall
-Diapedesis – blood cells leave
vessels & enter the CT
-Chemotaxis – blood cells
follow a chemical gradient
(move toward the source ie.,
bacteria)

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Recognizes unhealthy cell (usually expressing abnormal proteins or viral
proteins – uses perforins (make a hole in the membrane) and granzymes
(initiate apoptosis – programmed cell death via gene expression
Apoptosis
Unhealthy or
unwanted cell
NK cell
Granzymes
enter
pore, causing
apoptosis of cell
Perforin forms a
transmembrane pore
Perforin and
granzyme
NK cell: Apoptosis-initiating cells
Immunological surveillance: NK cells

15. •Binds receptors of neighboring cells:
• promotes macrophage function and apoptosis of infected cell
• triggers synthesis of enzymes destroying viral RNA or DNA
• triggers synthesis of enzymes that inhibit synthesis of viral proteins
Interferons – signaling molecule (cytokine) released by
viral-infected cells

16. Complement Proteins)
C
C
Elimination of
immune complexes
Antigen
Antibody
Complement
Erythrocyte
Complement (C) cross-links
immune (antigen-antibody)
complexes to erythrocyte and
transports to liver and spleen.
Complement proteins create
MAC to lyse cell.
Complement activates and attracts various cells of
innate immunity.
Complement (C) binds to
pathogen; acts as opsonin
Macrophage
Pathogen
Complement
Inflammation
Opsonization Cytolysis
Complement
MAC
protein
Pathogen
Inflammation
Macrophage
Neutrophil
Basophil
Mast cell
~11 antimicrobial proteins in plasma – ‘complements’ functions of
antibodies They have a number of functions (below) to defend against
pathogens
Opsonin – coats pathogen to make appear different and thus recognizable by
macrophages
Inflammation - Activates mast cells, basophils, neutrophils, and macrophages
to increase inflammatory response -
Cytolysis – causes cell lysis (Big MAC attack)
Eliminates Antigen-Antibody complexes on RBCs killed in spleen

17. Innate Immunity: Inflammation
 Redness - increased blood flow
 Heat - increased blood flow and increased metabolic activity
 Swelling - increase in fluid loss – capillaries to interstitial space,
capillaries become more permeable due to histamine and other chemicals
 Pain - stimulation of pain receptors from compression from interstitial
fluid; chemical irritation by kinins, prostaglandins, microbe substances
 Loss of function - (may occur in severe cases)
 Acute inflammatory response
 a local, nonspecific response -- typically lasts 8-10 days
 sometimes persists in process of chronic inflammation

18. Innate Immunity: Inflammation
• Immediate, local, nonspecific response
• Major effector of innate immunity that helps eliminate infectious agents
• 1st step: chemicals like histamine, leukotirenes, prostaglandins and
chemotactic factors released
• 2nd step: response in blood vessels = vasodilation and increased capillary
permeability
• 3rd step: leukocytes (WBCs) recruited via margination and diapedesis. Also
cells undertake chemotaxis and migrate toward (up the gradient) of
chemical agents (bacterial secretions)
• Neutrophils, eosinophils, macrophages clean up the area

19. Inflammation
1 4
3
2
Formation of
exudate and “washing”
of infected area
Exudate
Increase in fluid
uptake by lymphatic
capillaries
Delivery of
plasma
proteins
Diapedesis
Chemotaxis
Chemical
gradient
Injured
tissue
Bacteria
Release of inflamatory
and chemotactic factors
Mast cells
Neutrophil
CAMs
Lymphatic capillary
Lymph
Basophil
Recruitment of
immune cells
• Margination
• Diapedesis
• Chemotaxis
Vascular changes
include
• Vasodilation of
arterioles
• Increase in capillary
permeability
• Display of CAMs
Margination

20. Innate Immunity: Fever
• Fever
• Abnormal elevation of body temperature -- at least 1°C from normal (37°C)
• May accompany inflammatory response
• Due to excess fluid loss so requires increased fluid intake to prevent dehydration
• Events of fever
• Results from
• release of pyrogens such as interleukin 1, interferons
• toxins from infectious agents, drug reactions toxins, brain tumors
• Pyrogens released and circulate through the body
• target hypothalamus and cause release of prostaglandin E2
• raises temperature set point of hypothalamus

21. Innate Immunity: Fever
• Benefits of fever
• Inhibits reproduction of bacteria and viruses
• Promotes interferon activity
• Increases activity of adaptive immunity
• Accelerates tissue repair
• Increases CAMs on endothelium of capillaries in lymph nodes
• additional immune cells migrating out of blood
• Recommended to leave a low fever untreated
• Risks of a high fever significant above 100 degrees F
• High fevers potentially dangerous above 1030 in children
• Changes in metabolic pathways and denaturation of proteins
• Possible seizures, irreversible brain damage at greater than 1060, death above 1090

22. Summary of Innate - Nonspecific Processes
o Barriers – epithelium, secretions , fluid flow
o Cells: phagocytes (neutrophils, macrophages, eosinophils), NK
cells
o Chemical signals – inteferons, complement proteins,
inflammatory mediators, pyrogens for fever
Nonspecific (Innate) because each process works
no matter what the problem is. On an evolutionary basis the
innate mechanisms were present prior to the development of
lymphocytes and the Adaptive Processes