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

¤ Mononuclear Phagocyte System (MPS) – provides a passageway for phagocytes to move between tissues and organs

¤ Includes lymph nodes, spleen, tonsils, gut-associated lymphoid tissue (GALT), and mucosa-associated lymphoid tissue (MALT)



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 in MPS        

¤ Dendritic cells - act as antigen-presenting cells in MPS

¤ 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: Phagocytosis

¤ Process by which phagocytes engulf and digest material

¤ Phagocytes cells include neutrophils, monocytes, and macrophages

¤ Pattern Recognition Receptors (PRRs) – recognize and bind pathogen-associated molecular patterns (PAMPs)

¤ PAMPs include peptidoglycan and LPS

¤ 6 steps:

¤ Chemotaxis

¤ Adherance

¤ Engulfment (forms phagosome)

¤ Phagolysosome formation

¤ Destruction & digestion (enzymes)

¤ Exocytosis




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: 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 hostŐs 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