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