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Home , Agranulocyte, Exudate, Phagocytosis

Chapter 14 Defense Mechanisms

Topics • Innate - Non specific – First line of defense - Defense Mechanisms – Second line of defense - Non-specific • Acquired - Specific – Third line of defense

Summary of the major components of the host defenses. First line of defense

• Barriers – Anatomical – Chemical

Anatomical barriers The trachea contain cilia that entrap and propel particles out of the respiratory tract • Skin – Outermost layer Ciliary Escalator – Hair follicles – Skin glands – Dequamation • Mucous – Digestive F – Urinary – Respiratory – Eye

1 Chemical barriers

• Sebaceous secretions • Study of the development of resistance to • Tears and saliva – infectious agents by the body • Acidic pH – Surveillance of the body – Sweat – Recognition of foreign material – Stomach – Destruction of foreign material or agent – Skin • Involve nonspecific ( Second line ) and – Semen specific ( Third line ) immune defense – Vagina - mediated by presence of systems Lactobacillus • White cells (WBC) or leukocytes are involved

Search, recognize, and destroy is the mandate WBC of the • WBC recognize "self" markers on the host – Do not attack or do not respond to host cell • WBC recognize non-self markers on the invading microbe –Attack or respond to microbe

Blood Hemopoiesis

• Stem cells precursors • Production of blood • Hemopoiesis – Starts at the embryonic stage • Components • Yolk sac and liver – Continues during adult stage – Hematopoietic stem cells in marrow

2 Lymphoid The macroscopic composition of whole blood Myeloid

White blood cells • Present in high numbers in blood and • Leukocytes tissue – (large cytoplasmic • Phagocytizes – granules granules) contain digestive • Neutrophils • • First to arrive during an immune • response () – • T cells • B cells •

Eosinophils Basophils • Contain granules with hydrolytic enzymes • Present in low in number in the body • Attach and destroy large eucaryotic • Function is similar to eosinophils. ( worms ) Involved in allergic reactions due to cytoplasmic granules • Associated with inflammation and allergies • Localized basophils are called mast cells

3 Monocytes

• Specific immunity • – T cells  cellular immunity • Differentiate into – B cells  humoral/ immunity (circulation and lymphatics ) and • Third line of defense dendritic cells (tissue associated) • Present throughout the body •

Lymphatic system

• Network of vessels, cells, and tissues that • Fluids extend to most body areas • Vessels • Connected to the blood system • Provides an auxiliary route for the return of • Nodes extracellular fluid to the • Spleen • “Drain off” system for inflammatory response • Thymus • Contains lymphocytes, and • Miscellaneous (GALT

Representation of the lymphatic system. Gut-associated lymphoid tissue (GALT) • Recognized incoming microbes from food • Supply lymphocytes for antibody response • Ex. Appendix, lacteals, Peyer’s patches

4 Non-specific Immunity Inflammation Second Line of Defense • Four major symptoms • Inflammation – Redness • Phagocytosis – Warmth • Interferon – Swelling • Complement – Pain That result in Cellular Damage

Inflammation - 1 Causes

• Trauma • Tissue injury due to physical or chemical agents • Reaction to foreign pathogens or bodies (ie medical implants)

Inflammation - 2 Function

• Mobilize and attract immune components to the site of injury • Localized and remove harmful substances • Destroy microbes and block their invasion • Aid in the repair of tissue damage

5 Chemical mediators during inflammation. 1. Vascular changes

• Blood cells, tissue cells, and release chemical mediators and • Chemical mediators – Vasoactive • Affect endothelial cells, smooth muscles of blood vessels – Chemotactic (chemokines) • Affect WBC

The transmigration of WBCs is followed by . 2.

• Leakage of vascular fluid ( exudate ) into tissue • Exudate - plasma , blood cells (WBC), debris, and • Migration of WBC is called diapedesis or transmigration – Chemotaxis

3. Phagocytosis • Caused by pyrogens – reset the hypothalamic thermostat Neutrophils and (increase temperature) monocytes/ macrophages (and • Pyrogens – Microbes and their products (ex. LPS) dendritic cells) are called – Leukocyte products (ex. lnterleukins) professional phagocytes – IL-1 resets the thermostat • Inhibits microbe and viral multiplication, reduces nutrient availability, increases Eosinophils immune reactions

6 Phagocytosis Macrophages

Neutrophils - First to arrive during an • Monocytes/macrophages  motile immune response (inflammation) • Specialized/Residents: • Neutrophils are primary components – Alveolar  of pus – Langerhan cells  skin Monocytes/Macrophages - – Kupffer cells  liver Differentiate into macrophages • 1) Responsible for phagocytosis (circulation and lymphatics) and • 2) Interact with B and T cells dendritic cells (tissue associated)

Mechanism of Phagocytosis 1. Chemotaxis & binding

• Chemotaxis • Directed by • Ingestion – -associated molecular patterns (PAMPs ) • • Peptidoglycan • Destruction • LPS – Foreign debris

2. Ingestion

• Pseudopods enclose the pathogen or foreign material • Form a or phagocytic

7 3. Phagolysosome

• fuse with the phagosome • Other antimicrobials chemicals are released into the phagolysosome

4. Destruction

• Within the phagolysosome – A) Oxygen-dependent mechanisms – Similar to byproducts of respiration – B) Oxygen-independent mechanisms – due to numerous hydrolytic enzymes • Undigestible debris are released

Interferon

• Produced due to viral , microbe infections, RNA, immune products, and

8 Classes Activity • Ex. Virus - binds to host cell • Interferon alpha • A signal is sent to the nucleus to – Product of lymphocytes and macrophages synthesized (transcription and translation) • Interferon beta interferon – Product of fibroblasts and epithelial cells • Interferon is secreted • • Binds to other host cells – Product of T cells • Host cells produce antiviral proteins – inhibit viral multiplication or translation • Not virus-specific

Interferon is produced, released, and taken-up by a near-by cell, where by original cell is not protected but the recipient cell is protected. Other Roles of Interferon

• Activates and instructs T and development • Inhibits cancer cells • Activates macrophages

Fig. 14.20 The antiviral activity of interferon.

Pathways Complement • Classical • Consist of ~26 blood proteins – Activated by the presence of antibody bound to microbes • Produced by liver hepatocytes, • Lectin lymphocytes, and monocytes – Activated when a host binds a • Pathways sugar (mannan) in the wall of fungi and other • Cascade reaction microbes • Alternative • Stages – Activated when complement proteins bind to or surface components of microbes

9 The three complement pathways, their activators, and the complement proteins involved. Stages

• Initiation • Amplification and cascade • Polymerization • Membrane attack

Table 14.1 Complement pathways

Fig. 14.21a Fig. 14.21b

Fig. 14.21d

10 Complement does 3 things

• Inflammation  C3a, C4a, C5a • Opsonization  • MAC killing  C5-C9

11