The Immune System I

ANPS 020, 2014

McKinley. O’Loughlin & Bidle

Anatomy and Physiology: An integrative approach
References:
Chapter 21 pp. 823 - 839
Chapter 22 pp. 840 - 882
 Objectives
 List the body’s nonspecific defense mechanisms and explain the
function of each
 Define specific resistance, and identify the properties of immunity
 Distinguish between humoral (antibody-mediated) immunity and cell-
mediated immunity
 Describe the mechanisms of B-lymphocyte activation and their
differentiation into plasma cells and memory cells
 Explain the structure and function of antibodies
 Describe the types of T- lymphoctyes and the role of each in the
immune response
 Describe the primary and secondary responses to antigen attack
 Identify the major components of the lymphatic system and explain their
functions
 Describe the structure of lymphatic vessels
 Explain the role of lymphocytes and where they are produced
 Describe the functions of the lymphatic tissues and organs
 Describe several examples of abnormal immune responses and their
role in immune disorders
 Immunity I: Innate (nonspecific) Defenses
Lecture Outline

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)
 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

Any body want
some chips
from
Baltimore?
 Where and how do we defend against
disease pathogens?

These 2 categories of immune mechanisms work together

 Overview of the Immune System (Figure 22.2)

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Immune System

Innate immunity Adaptive immunity

Immediate response to wide Delayed response to
array of substances specific antigen

Skin and mucosal Nonspecific T-lymphocytes B-lymphocytes

Membranes & barriers internal defenses (cell-mediated (humoral immunity)
(prevent entry) immunity)

Cells Chemicals Physiologic responses Plasma cells

(e.g., macrophages, (e.g., interferon, (e.g., inflammation, (synthesize and
NK cells) complement) fever) release antibodies)
 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
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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Major cellular components of the Innate- Nonspecific System

Figure 21.4
All formed elements (except
T-lymphocytes) leave the bone
marrow and directly enter Erythrocyte
and circulate in the blood.
Platelets
WBCs
Neutrophil

Red bone marrow Eosinophil

= site of origin
Basophil

Monocyte Macrophage
Pre-T-lymphocyte

B-lymphocyte Plasma cell

T-lymphocytes
mature in the
Thymus
thymus prior to
circulating in T-lymphocyte T-lymphocyte
the blood. maturation
 Phagocytes: engulf bacteria, release toxic
chemicals, present antigens
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Neutrophil, macrophage, eosinophil: Phagocytic cells

Infectious agent Macrophage Also an APC

engulfed Lysosome
Phagosome
Phagolysosome
destroys infectious
agent

Residue is exocytosed

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
Basophils open up vessels & increase blood flow
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Basophil and mast cell: Proinflammatory chemical-secreting cells

Arteriole
Vasodilation
Basophil

Histamine
Increases capillary
permeability Capillary

Heparin
Anticoagulant
Eicosanoids
Increases inflamation Venule

(b)
 Eosinophils: Parasite-Destroying Cells (Figure 22.3d)

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Eosinophils: Parasite-destroying cells

Cytotoxic chemicals
Parasitic worm

Eosinophil
(d)

Eosinophils also phagocytose antigen-antibody complexes

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)
 Immunological surveillance: NK cells
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NK cell: Apoptosis-initiating cells

Perforin and
granzyme

Perforin forms a
transmembrane pore
Granzymes
enter
NK cell pore, causing
apoptosis of cell
Unhealthy or
unwanted cell

Apoptosis

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
Interferons – signaling molecule (cytokine)
released by viral-infected cells

•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
 Complement Proteins (#C1-C12))
~11 antimicrobial proteins in plasma – ‘complements’ functions of antibodies
They have a number of functions (below) to defend against pathogens
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Opsonization Inflammation Cytolysis Elimination of

immune complexes
Complement
Complement Antigen

C Mast cell Basophil Neutrophil Macrophage MAC Antibody

protein Complement
C
Pathogen Erythrocyte
Pathogen
Inflammation
Macrophage
Complement (C) cross-links
immune (antigen-antibody)
Complement (C) binds to Complement activates and attracts various cells of Complement proteins create complexes to erythrocyte and
pathogen; acts as opsonin innate immunity. MAC to lyse cell. transports to liver and spleen.

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
 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

 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
 Inflammation (Figure 22.6)
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Injured
tissue Formation of
exudate and “washing”
of infected area
Exudate
Bacteria
Lymphatic capillary
Chemotaxis Lymph

Chemical
gradient

1 Release of inflamatory 2 Vascular changes 3 Recruitment of 4 Delivery of Increase in fluid

and chemotactic factors include immune cells plasma uptake by lymphatic
• Vasodilation of • Margination proteins capillaries
arterioles • Diapedesis
Mast cells
• Increase in capillary • Chemotaxis
permeability
Margination Diapedesis
• Display of CAMs
CAMs

Basophil

Neutrophil
 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 E 2

• raises temperature set point of hypothalamus

 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 103 0 in children
• Changes in metabolic pathways and denaturation of proteins
• Possible seizures, irreversible brain damage at greater than 106 0, death above 1090
 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