Download Host Defenses I: Nonspecific Defenses

Ch 12
Host
Defenses I:
Nonspecific
Defenses
SLOs
Differentiate between innate and adaptive immunity.
Define and explain PRRs and PAMPs
Differentiate physical from chemical factors, and list examples of
each.
Describe the role of normal microbiota in innate resistance.
Classify phagocytic cells, and describe the roles of granulocytes
and monocytes.
Define and explain phagocyte and phagocytosis.
Explain the different stages of inflammation.
Describe the cause and effects of fever.
Describe the activativation of complement and describe the 3
outcomes.
Explain the antiviral action of interferons
Describe the role of transferrins and antimicrobial peptides in
innate immunity.
12.1 Defense Mechanisms of the Host
 Immunity: Ability to ______________________.
 Susceptibility: Lack of ________________to a disease.
 Innate immunity: ________________Specific or not?
 Acquired immunity: __________________________
Fig. 12.1
First Line of Defense:
Physical Factors
Skin & Mucous Membranes
 Epidermis
 Mucus of mucous membranes
 (Muco)-ciliary escalator
 Nose hairs
 Lacrimal apparatus
 Saliva
Fig 16.3
Ciliary Defense
Fig. 12.3
First Line of Defense:
Nonspecific Chemical Factors
 Fungistatic fatty acids in sebum
 Skin pH and osmolarity
 Lysozyme in ______________________
 pH of gastric juice
 Transferrins in blood
Also important: Antagonism and
competitive exclusion of normal microbiota
Concept Check
For each of the barriers below, state
whether it is a physical, chemical, or
genetic barrier.
A. Hydrochloric acid of the stomach
B. Sloughing of skin
C. Lysozyme in saliva and tears
D. Mutation in the gene for complement
proteins
E. Ciliary escalator
12.2 SECOND AND THIRD LINES OF DEFENSE:
AN OVERVIEW
Kick in if 1st level of defense breached
System of protective cells and fluids
Includes inflammation and phagocytosis
Rapid action at local and systemic levels
Immune system responsible for:
• Body surveillance
• Recognition of foreign and abnormal
material
• Destruction of these entities
The Body’s Defensive Cells
Can you name them?
 Host has PRRs (Pattern Recognition Receptors), e.g.:
Toll-like receptors (TLRs). These attach to
 Pathogen-associated molecular patterns (PAMPs)
 Binding to PRRs induces release of cytokines that
regulate the intensity and duration of immune
responses
PRRs
=?
PAMP recognition
Formed Elements of Blood
Formed Elements in Blood
Phagocytosis
Phagocytosis
Natural killer cells
Destroy target cells
Cell-mediated
immunity
Produce antibodies
Blood clotting
Fig. 12.7
Review
Communicating
Body Compartments
on your own if
necessary
• MPS
• Lymphatic system
(Thymus, LNs,
Spleen)
• Blood
Fig. 12.4
12.3 The Second Line of Defense
Generalized and nonspecific defenses that
support and interact with specific immune
responses:
- Phagocytosis
- Inflammation
- Fever
- Antimicrobial proteins
Phagocytosis: Cornerstone of
Inflammation and Specific
Immunity
Neutrophils (part of PMNs):
 General purpose phagocytes
 Early inflammatory response to bacteria
and other foreign materials and to
damaged tissue
 Primary component of pus
Monocytes and Macrophages
Stationary Macrophages, e.g.:
Fig. 12.8
Process/Phases of Phagocytosis
Phagocytes engulf and kill microorganisms
1. Chemotaxis
2. Adherence: Recognition and attachment
3. Ingestion: Engulfment and creation of
phagosome
4. Digestion:
a.
Fusion of phagosome with lysosome
b.
Destruction and digestion
c.
Residual body  Exocytosis
Phagocytosis
Various Mechanisms of Microbial
Evasion of Phagocytosis!!
Compare to Table
12.1
Inflammation
Tissue damage leads to inflammatory response
Purpose:
 Destroy pathogen
 limit spread of infection
 pave way for tissue repair
 Powerful defense mechanism but has potential
to CAUSE disease. CVD due to chronic
inflammation? Aging?
 Easily identifiable by 4 (5) cardinal signs:
Rubor, Calor, Tumor, Dolor, and loss of function
The 3 Stages of Inflammation
1. Vascular Reaction: Vasodilation and increased
vessel permeability due to histamine,
chemokines, prostaglandins, and other cytokines
2. Pus Formation: Phagocyte migration and
phagocytosis
 Margination and diapedesis (emigration)
 Chemotaxis(due to various cytokines and
components of complement system)
3. Resulution: Tissue repair and scar formation.
Depends on type of tissue
Diapedesis
Margination
Fig. 12.10
Inflammation review
Treatment of abscess?
Fever: An Adjunct to Inflammation
Abnormally High Body Temperature.
______________acts as body’s thermostat.
Normally set at?
Exogenous vs. Endogenous pyrogens
Endotoxin causes phagocytes to release
interleukin–1 (IL–1). IL-1 acts on hypothalamus
Fever cont.
Thermostat set to higher temp. Body reacts
how?
What happens when no more IL–1?
Beneficial effects of moderate fever:
Inhibited pathogen growth
Increased cellular metabolism  e.g.:
 Increased transferrin production
 Increased T cell production
 Faster repair mechanisms
Problematic effects of high fever:
> 40.7C (> 105F) can be dangerous
(Tachycardia, acidosis, dehydration, seizures)
Death when > 44 - 46C
Antimicrobial Proteins
1. Interferons
2. Complement system
3. Antimicrobial peptides
4. Iron-binding proteins: _____________
Interferons (IFNs)
 Family of small glycoproteins
 Not virus-specific
 -IFN and -IFN: Produced by virus infected
cells. Mode of action is to induce uninfected cells to
produce antiviral proteins (AVPs) that inhibit viral
replication.
 -IFN: Produced by T- lymphocytes. Causes
neutrophils and macrophages to phagocytize bacteria.
Also involved in tumor immunology.
 Recombinant interferons have been produced. However
short-acting and many side-effects. No effect on already
infected cells.
Interferons (IFNs)
Compare to Fig 12.11
Complement System Summary
Series of >30 plasma (serum) proteins,
activated in a cascade
3 outcomes of complement system:
1. Enhances inflammatory response, e.g.:
attracts phagocytes
2. Increases phagocytosis through
opsonization or immune adherence
3. Creates Membrane Attack Complexes
(MACs)  Cytolysis
The Complement System
Compare to
Fig 12.12
Complement System Overview
MAC
Opsonins (complement proteins or
antibodies) coat bacteria and promote
attachment of micro-organism to phagocyte 
Process is called ______________
Some bacteria evade
complement system!!
Antimicrobial Peptides
• Produced by MM and phagocytes
• 15 – 20 amino acids
• Cause bacterial cell lysis by inserting
themselves into
prokaryotic
membranes
• Research looks for
ways to turn them into
therapeutic drugs
Fig 12.13