Innate Immunity - Las Positas Collegelpc1.clpccd.cc.ca.us/lpc/zingg/Micro/lecture...

16Innate

Immunity:

Nonspecific

Defenses

of the Host

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

SLOs

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.

TLRs on Ms, dendritic cells, epithelial cells

Cytokines!

PAMPs recognition

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

Fig. 16.7

http://upload.wikimedia.org/wikipedia/commons/0/06/TLR3_structure.png


The Concept of Immunity

Susceptibility: Lack of resistance to a disease.

Immunity: Ability to ward off disease.

Innate immunity: Defenses against any pathogen.

Adaptive immunity: Immunity, resistance to a specific pathogen.

Fig 16.1


Physical Factors

Epidermis: consists of tightly packed cells with keratin, a protective protein

Two other protective physical factors of skin?

Mucus of mucous membranes

Lacrimal apparatus

Saliva

Nose hairs

(Muco)-ciliary escalator

First Line of Defense: Skin and Mucous Membranes

Fig 16.3


Chemical Factors

Fungistatic fatty acids in sebum

Low pH (3-5) of skin

Lysozyme in _______________________

Low pH (?) of gastric juice

Transferrins in blood

Also important: Antagonism and

competitive exclusion of normal microbiota

1st Line Defense in

Human

ANIMATION Host

Defenses: The Big Picture

host_defenses_big_pic.html


Second Line of Defense: Formed Elements in Blood Compare to Table 16.1

20-25%

3-8%

0.5-1%%

2-4%

60-70%


Process of Phagocytosis

Phagocytes engulf and kill microorganisms

Steps of phagocytosis:

• Chemotaxis

• Recognition and attachment

• Engulfment and creation of phagosome

• Fusion of phagosome with lysosome

• Destruction and digestion

• Residual body Exocytosis

Fig 16.7

Phagocytosis

Foundation Fig

16.7

Inhibit adherence: M

protein, capsules

Streptococcus pyogenes, S.

pneumoniae

Kill phagocytes:

LeukocidinsStaphylococcus aureus

Lyse phagocytes:

Membrane attack

complex

Listeriamonocytogenes

Escape phagosome Shigella

Prevent phagosome-

lysosome fusionHIV

Survive in

phagolysosomeCoxiella burnetti

Microbial Evasion of Phagocytosis


Phagocytosis and Evasion of Phagocytosis

ANIMATION Phagocytosis: Microbes That Evade It

ANIMATION Virulence Factors: Inactivating Host Defenses

ANIMATION Virulence Factors: Hiding From Host Defenses

ANIMATION Phagocytosis: Mechanism

ANIMATION Phagocytosis: Overview

phagocytosis_microbes.html

virulence_inactivating.html

virulence_hiding.html

phagocytosis_mechanism.html

phagocytosis.html


Inflammation

Tissue damage leads to inflammatory response

Purpose: Destroy pathogen limit spread of infection pave way for tissue repair

4 cardinal signs:?

Acute-phase proteins (Chemical mediators) activated: Complement proteins Cytokines Specialized proteins such as fibrinogen and

bradykinin


The Three Stages of Inflammation

1. Vasodilation and increased vessel permeabilitydue to histamine (and other cytokine) release edema

2. Phagocyte migration and phagocytosis

Margination and diapedesis (emigration)

Chemotaxis(due to various cytokines and components of complement system)

Pus formation

Factors challenging effectiveness of phagocytosis

3. Tissue repair and regeneration depends on type of tissue

Inflammatory Process

Diapedesis

Margination

Compare to Fig 16.8

Treatment of abscess?


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

Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1 is an 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. The complement system

2. Interferons

3. Transferrins: bind serum iron

4. Antimicrobial peptides: cause bacterial

cell lysis. Produced by mucous

membrane cells and phagocytes.

TheComplement System

Compare to Foundation

Fig 16.9


Complement System Summary

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

Three 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

Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte Opsonization

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.

ANIMATION Complement System: Activation

ANIMATION Complement System: Overview

ANIMATION Complement System: Results

complement_activation.html

complement.html

complement_results.html


Interferons (IFNs)

Family of glycoproteins

Host-cell-specific but 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

Unnumbered Figure 16.1a

Applications of

Microbiology:

Serum Collection

Unnumbered Figure 16.1b

Innate Immunity - Las Positas Collegelpc1.clpccd.cc.ca.us/lpc/zingg/Micro/lecture...

Documents

Transcript of Innate Immunity - Las Positas Collegelpc1.clpccd.cc.ca.us/lpc/zingg/Micro/lecture...