16Innate

Immunity: Nonspecific Defenses of the Host

Student Learning Outcomes

Differentiate between innate and adaptive immunity.Define toll-like receptors.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 two of the three pathways of activating complement and

describe the 3 outcomes. Compare and contrast the actions of -IFN and -IFN with -IFN.Describe the role of transferrins and antimicrobial peptides in innate

immunity.

The Concept of Immunity

Immunity: Ability to ______________________.

Susceptibility: Lack of ________________to a disease.

Innate immunity: ________________Specific or not?

Adaptive immunity: __________________________

Fig 16.1

The Body’s Defensive Cells

Can you name them?

Host Toll-like receptors (TLRs) attach to

Pathogen-associated molecular patterns (PAMPs)

Binding to TLRs induces release of cytokines that regulate the intensity and duration of immune responses

TLRs = ?

PAMPs recognition

Horseshoe structure of TLR3, showing attached sugars (spheres) and internal structures

Fig. 16.7

First Line of Defense: Skin & Mucous Membranes

Fig 16.3

Physical Factors Epidermis

Mucus of mucous membranes (Muco)-ciliary escalator Nose hairs Lacrimal apparatus Saliva

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

1st Line Defense in

Human

Mastering: Host Defenses – The Big Picture

Red Blood Cells Transport O2 and CO2

White Blood Cells:Phagocytosis

Histamine

Kill parasites. Involved in allergies

Formed Elements in Blood

Compare to Table 16.1

Formed Elements in BloodWhite Blood Cells cont:

Phagocytosis

Phagocytosis

Natural killer cellsDestroy target cells

Cell-mediated immunity

Produce antibodies

Blood clotting

Second Line of Defense: Formed Elements in Blood

20-25%

3-8%

0.5-1%%

2-4%60-70%

Process of Phagocytosis

Phagocytes engulf and kill microorganisms

Steps of phagocytosis:

1. Chemotaxis

2. Adherence: Recognition and attachment

3. Ingestion: Engulfment and creation of phagosome

4. Digestion:

1. Fusion of phagosome with lysosome

2. Destruction and digestion

3. Residual body ExocytosisFig 16.7

Phases of Phagocytosis

Foundation Fig 16.7

Inhibit adherence: capsules, M protein S. pyogenes, S. pneumoniae

Kill phagocytes: Leukocidins S. aureus

Lyse phagocytes: Membrane attack complex

L. monocytogenes

Escape phagosome Shigella

Prevent phagosome-lysosome fusion HIV

Survive in phagolysosome Coxiella burnetti

Microbial Evasion of Phagocytosis

Phagocytosis and Evasion of Phagocytosis

Phagocytosis: Microbes That Evade It

Virulence Factors: Inactivating Host Defenses

Virulence Factors: Hiding From Host Defenses

Review the Following MasteringAnimations

Phagocytosis: Mechanism

Phagocytosis: Overview

InflammationTissue damage leads to

inflammatory responsePurpose:

Destroy pathogen limit spread of infection pave way for tissue repair

Acute-phase proteins activated (such as TNF-, kinins, and other cytokines) quickly leads to 1st stage of inflammation (?)

4 (5) cardinal signs:?

The 3 Stages of Inflammation

1. Vasodilation and increased vessel permeability due to histamine, kinins, prostaglandins, and other cytokines

2. Phagocyte migration and phagocytosis Margination and diapedesis (emigration) Chemotaxis(due to various cytokines and

components of complement system) Pus formation

3. Tissue repair and regeneration depends on type of tissue

Inflammatory Process

DiapedesisMargination

Fig 16.8

Treatment of abscess?

Inflammation review

Fever: Abnormally High Body Temperature

Hypothalamus releases prostaglandins that reset the thermostat

Body reacts to raise the temperature. How?

When no more IL–1, body temperature falls (crisis).

Hypothalamus acts as body’s thermostat. Normally set at?

Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1= endogenous pyrogen

Beneficial effects of moderate fever:

Inhibited pathogen growth

Increased cellular metabolism e.g.: Increased transferrin production Increased IL–1 activity T cell production Faster repair mechanisms

Problematic effects of high fever:

> 40.7C (105F) can be dangerous (Tachycardia, acidosis, dehydration)

Death at temp. > 44 - 46C

Antimicrobial Substances

1. Complement system

2. Interferons

3. Transferrins: _________________

4. Antimicrobial peptides: cause bacterial cell lysis. Produced by mucous membrane cells and phagocytes.

Complement System Summary

Series of 30 plasma (serum) proteins, activated in a cascade

3 effects 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 FoundationFig 16.9

MAC

Complement System Overview

Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte Process is called ______________

Fig 16.12

Classical Pathway

Alternative Pathway

Fig 16.13

Does not require a specific antibody to get started

Some Bacteria Evade Complement

Capsules prevent Complement activation

Surface lipid-carbohydrates of some Gram-negatives prevent MAC formation

Enzymatic digestion of C5a by Gram-positives

Mastering Animations: Complement System1. Overview2. Activation3. Results

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 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)

Fig 16.15

Review Questions: 1 – 4 and 9 Multiple Choice Questions: 1 – 3, 5, 6, and 8

– 9 Critical Thinking Questions: 1 and 2Clinical Application Questions: 2 and 3