Transcript ANPS 020 Cornbrooks 02-07

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 cellmediated 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?

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
Overview of the Immune System (Figure 22.2)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Immune System
Innate immunity
Adaptive immunity
Immediate response to wide
array of substances
Skin and mucosal
Membranes & barriers
(prevent entry)
Nonspecific
internal defenses
Cells
(e.g., macrophages,
NK cells)
Chemicals
(e.g., interferon,
complement)
Delayed response to
specific antigen
T-lymphocytes
(cell-mediated
immunity)
Physiologic responses
(e.g., inflammation,
fever)
B-lymphocytes
(humoral immunity)
Plasma cells
(synthesize and
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Major cellular components of the Innate- Nonspecific System
Figure 21.4
All formed elements (except
T-lymphocytes) leave the bone
marrow and directly enter
and circulate in the blood.
Erythrocyte
Platelets
WBCs
Neutrophil
Red bone marrow
= site of origin
Eosinophil
Basophil
Monocyte
Macrophage
Pre-T-lymphocyte
T-lymphocytes
mature in the
thymus prior to
circulating in
the blood.
B-lymphocyte
Thymus
T-lymphocyte
maturation
T-lymphocyte
Plasma cell
Phagocytes: engulf bacteria, release toxic
chemicals, present antigens
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Neutrophil, macrophage, eosinophil: Phagocytic cells
Infectious agent
engulfed
Macrophage
Lysosome
Phagosome
Also an APC
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Basophil and mast cell: Proinflammatory chemical-secreting cells
Arteriole
Vasodilation
Basophil
Histamine
Increases capillary
permeability
Capillary
Heparin
Anticoagulant
Eicosanoids
Increases inflamation
(b)
Venule
Eosinophils: Parasite-Destroying Cells (Figure 22.3d)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
NK cell: Apoptosis-initiating cells
Perforin and
granzyme
Perforin forms a
transmembrane pore
Granzymes
enter
pore, causing
apoptosis of cell
NK 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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Opsonization
Inflammation
Complement
Complement
C
Elimination of
immune complexes
Cytolysis
Mast cell
Basophil
Neutrophil
Macrophage
Pathogen
MAC
protein
Antigen
Antibody
C
Complement
Erythrocyte
Pathogen
Inflammation
Macrophage
Complement (C) binds to
pathogen; acts as opsonin
Complement activates and attracts various cells of
innate immunity.
Complement proteins create
MAC to lyse cell.
Complement (C) cross-links
immune (antigen-antibody)
complexes to erythrocyte and
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)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Injured
tissue
Formation of
exudate and “washing”
of infected area
Exudate
Bacteria
Lymphatic capillary
Chemotaxis
Lymph
Chemical
gradient
1 Release of inflamatory
and chemotactic factors
Mast cells
2 Vascular changes
3 Recruitment of
immune cells
include
• Vasodilation of
• Margination
arterioles
• Diapedesis
• Increase in capillary
• Chemotaxis
permeability
Margination
Diapedesis
• Display of CAMs
CAMs
Basophil
Neutrophil
4 Delivery of
plasma
proteins
Increase in fluid
uptake by lymphatic
capillaries
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
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
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