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
Fig 16.3
Skin & Mucous Membranes
Epidermis
Mucus of mucous membranes
(Muco)-ciliary escalator
Nose hairs
Lacrimal apparatus
Saliva
Fig. 12.3
Ciliary Defense
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
First Line of Defense: Nonspecific Chemical Factors
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
Fig. 12.4
Review
Communicating
Body Compartments
on your own if
necessary • MPS
• Lymphatic system
(Thymus, LNs,
Spleen)
• Blood
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
Compare to Table
12.1
Various Mechanisms of Microbial
Evasion of Phagocytosis!!
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
Inflammation
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
Fig. 12.10
Margination
Diapedesis
Treatment of abscess?
Inflammation review
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:
> 40.7C (> 105F) can be dangerous
(Tachycardia, acidosis, dehydration, seizures)
Death when > 44 - 46C
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
MAC
Complement System Overview
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