Chapter 14

 

Host Defenses I

 

 

Defense Mechanisms of the Host

§ First Line of Defense – nonspecific barriers that block invasion at the portal of entry

§ inborn and nonspecific

§ Second Line of Defense – protective cells and fluids involved in inflammation and phagocytosis

§ Third Line of Defense - highly specific and acquired throughout life by exposure to foreign material

§ provides long term immunity

§ Antigen - any substance that is recognized as foreign and initiates an immune response

                       

 

First Line: Barriers at the Portal of Entry

§ Skin

§ Dermis - contains tightly woven fibrous connective tissues

§ Epidermis - contains a water-repelling protein called keratin

§ The outermost layers continually slough off, taking microbes with them

§ Mucus membranes

§ Line the digestive, respiratory, and urogenital tracts

§ Bathed in mucus and other secretions that trap & wash away microbes

§ Peristalsis helps move microbes toward body openings where they are more easily eliminated (intestinal tract)

§ Cilia propels microbes toward body openings as well (respiratory tract)

§ Normal Resident Flora (Microbiota)

§ Can block access of pathogens to epithelial surfaces and compete for nutrients

§ Nonspecific Chemical Defenses

§ Lysozymes - enzymes that degrade peptidoglycan

§ found in body secretions including tears, saliva, and mucus

§ effective against Gram (+) bacteria

§ High acidity

§ urine, sweat, gastric juices, and vaginal secretions

 

 

Overview of the Second and Third Lines

§ There are three major responsibilities of the immune system:

§ surveillance of the body

§ recognition of foreign material

§ self versus non-self

§ destruction of foreign material

 

 

The Lymphatic System

§ Collection of tissues and organs that help bring immune cells into contact with antigens

§ Lymphatic vessels carry immune cells

§ Secondary lymphoid organs - sites where lymphocytes gather

§ lymph nodes, spleen, tonsils, adenoids, appendix, Peyer’s patches

§ Primary lymphoid organs - where lymphocytes originate and mature

§ bone marrow and thymus

 

 

Cells of the Immune System

§ Hematopoiesis – the production of blood cells

§ occurs in the bone marrow                                         

§ immature stem cells differentiate into highly specialized, mature cells

§ red blood cells (erythrocytes)

§ platelets (thrombocytes)

§ white blood cells (leukocytes)

 

 

Types of Leukocytes: Granulocytes

§ Contain cytoplasmic granules and a lobed nucleus

§ Neutrophils – phagocytes that ingest and destroy bacteria and damaged cells

§ most abundant

§ also called polymorphonuclear neutrophils (PMNs)

§ granules contain digestive enzymes

§ Basophils – involved in allergic reactions and inflammation

§ least numerous

§ granules contain histamine and heparin

§ increase capillary permeability during inflammation

§ Eosinophils - attack eukaryotic pathogens, especially worms and fungi

§ granules contain digestive enzymes and toxic chemicals                  

§ also involved in allergic reactions

 

 

Types of Leukocytes: Agranulocytes

§ Monocytes – phagocytes in the blood that can differentiate into 2 types of cells in tissues:

§ Macrophages - act as phagocytes and antigen-presenting cells       

§ Dendritic cells - act as antigen-presenting cells

§ Both important in third line of defense               

§ Lymphocytes – involved in third line of defense

§ B-cells - involved in antibody-mediated immunity

§ T-cells - involved in cell-mediated immunity      

§ Natural Killer (NK) cells - involved in antibody-dependent cellular cytotoxicity (ADCC)

§ induce death in virus-infected cells or cancer cells

§ release perforin to punch holes in the  membrane      

§ secrete granzymes that induce cell death

 

 

The Second Line of Defense: Inflammation

§ A coordinated response to invasion or tissue damage

§ Identified by 4 classic symptoms:  redness, warmth, swelling, and pain

§ Can be acute (last minutes or hours) or chronic (last days, weeks, or years)

§ 5 Stages of Inflammation:

§ Chemotactic factors - attract leukocytes to the site of injury

§ chemical mediators and cytokines are released

§ Vasoactive factors - cause dilation of small blood vessels and leakage of fluid

§ can cause swelling (edema)

§ Clotting factors - contain the site of damage and block further invasion

§ Phagocytes destroy microbes and dead tissues

§ contributes to pus formation

§ monocytes, lymphocytes, and macrophages clear damaged tissue, produce antimicrobial proteins, or kill infected cells

§ Tissue is repaired or replaced with connective tissue

 

 

The Second Line of Defense: Phagocytosis

§ Process by which phagocytes engulf and digest material

§ Phagocytic cells include neutrophils, monocytes, and macrophages

§ Most pathogens have acquired the ability to evade one or more steps of phagocytosis

§ 6 steps:

§ Chemotaxis

§ Adherance

§ Engulfment (forms phagosome)

§ Phagolysosome formation

§ Destruction & digestion (enzymes)

§ Exocytosis

 

 

The Second Line of Defense: Fever

§ One of the strongest indicators of infectious disease

§ Caused by pyrogens that act on the hypothalamus to increase body temperature

§ Thought to inhibit the growth of temperature-sensitive organisms and increase the host’s metabolism and defense responses

§ Endogenous pyrogens - produced by leukocytes

§ ex. Cytokines

§ Exogenous pyrogens – produced by infectious agents

§ ex. bacterial endotoxin (LPS)

 

 

The Second Line of Defense: Interferon

§ Produced by leukocytes in response to viruses, RNA, immune products, and various antigens

§ Inhibits virus replication, inhibits tumor progression, and regulates immune responses

§ Include interferons alpha, beta, and gamma

 

 

 

The Second Line of Defense: Complement System

§ Series of normally inactive, circulating proteins that become active in the presence of certain stimuli  (microbes or antibodies)

§ Work to destroy bacteria and certain viruses

§ There are 9 main complements (C1-C9)

§ Complement activation leads to 3 protective outcomes:

§ Inflammation – C3a and C5a increase permeability and act as phagocyte chemoattractants

§ foreign cell lysis - C5b, C6, C7, C8, and C9 aggregate to form membrane attack complex, creating holes in target membrane

§ Opsonization - coating of C3b to the foreign particle making it easier for phagocytes to adhere to its surface