micro chapter 14 Host defenses

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micro chapter 14 Host defenses

lysozyme

in tears and saliva break apart peptidoglycan cell wall

immunology

the study of all features of the body's second and third lines of defense

Immune defenses: Body compartments

Intracellular - digesting
Extracellular
Lymphatic
Cerebrospinal
Circulatory

Body Compartments that Participate in Immune Function

1. Reticuloendothelial system (RES)
****Provides a passageway within and between tissues and organs
2. Spaces containing extracellular fluid (ECF)
3. Bloodstream
4. Lymphatic system

plasma

1. hundreds of different chemicals
2. Components = water (92%), albumin, globulins, immunochemicals (antibodies), fibrinogen, hormones, nutrients, dissolved gases and waste products

hematopoesis

production of blood cells

pluripotential stem cells

primary precursor of new blood cells

nonspecific chemical defenses

1. Sebaceous secretions and specialized glands- antimicrobial
2. Lysozyme in tears and saliva (break apart peptido)
3. Lactic acid and electrolyte concentrations of sweat
4. Skin's acidic pH and fatty acid content
5. HCl in the stomach
6. Digestive juices and bile in the intestine
7. Semen- antimicrobial chemical
8. Acidic pH in the vagina

immune system is responsible for:

1. Surveillance of the body
2. Recognition of foreign material
3. Destruction of entities deemed to be foreign
4. White blood cells must distinguish self from nonself cells
5. Evaluates cells by examining markers (proteins/sugars) on their surfaces

Origin, Composition, and Functions of the Blood

Circulatory system
- Circulatory system proper
- Lymphatic system

Mast cells

secrete histamine causing vasodilation, and openings occur in capillaries

antigen

anti = antibody
gen = generator

Erythrocytes

1. Develop from stem cells in the bone marrow
2. Lose their nucleus just prior to entering circulation
3. Transport oxygen and carbon dioxide to and from the tissues

Platelets

1. Formed elements in circulating blood
2. Not whole cells
3. Function primarily in hemostasis and in releasing chemicals for blood clotting and inflammation

Neutrophils

Granulocyte
phagocytosis
starts inflammation

Eosinophils

Granulocyte
Attack and destroy large eukaryotic pathogens
Also involved in inflammation and allergic reactions

Basophils

Granulocyte
Parallel eosinophils in many actions

Monocytes

Agranulocyte
1. Discharged by bone marrow into bloodstream, live as phagocytes for a few days, then differentiate into macrophage
2. "Fixed" (lungs, liver, bronchii) and wandering
3. Responsible for
- Many specific and nonspecific phagocytic and killing functions
- Processing foreign molecules and presenting them to lymphocytes
- Secreting biologically active compounds that assist, mediate, attract, and inhibit immune cells and reactions

Dendritic cells (we'll learn more in specific immunity)

Lymphocytes

1. Key cells in the third line of defense and the specific immune response (notice nonself)
2. When stimulated by antigens, transform into activated cells that neutralize and destroy that foreign substance
3. B cells
- Humoral immunity: protective molecules carried in the fluids of the body
- Produce specialized plasma cells which produce antibodies/immunoglobulins
4. T cells
- cell-mediated immunity: T cells modulate immune functions and kill foreign cells (confirm infection & allow start of response

Humoral immunity

protective molecules carried in the fluids of the body
B cells

cell-mediated immunity

T cells modulate immune functions and kill foreign cells (confirm infection & allow start of response

Lymphatic System

1. Compartmentalized network of vessels, cells, and specialized accessory organs
2. Transports lymph through a system of vessels and lymph nodes
3. Major functions
- Provide an auxiliary route for the return of extracellular fluid to the circulatory system proper
- Act as a drain-off system for the inflammatory response
- Render surveillance, recognition, and protection against foreign materials

Lymphatic Fluid

1. Lymph
2. Plasma-like liquid formed when certain blood components move out of blood vessels into the extracellular spaces and diffuse or migrate into the lymphatic capillaries
3. Composition parallels that of plasma, but without red blood cells

Lymphatic Vessels

1. Along the lines of blood vessels
2. Similar to thin-walled veins
3. High numbers in hands, feet, and around the areola of the breast
4. Flow of lymph is in one direction only- from extremities toward the heart
5. Lymph is moved through the contraction of skeletal muscles through which the lymphatic ducts wend their way

Lymphoid Organs and Tissues

1. Lymph nodes
2. Thymus
3. Spleen
4. Gut-associated lymphoid tissue (GALT)
5. Tonsils
6. Loose connective tissue framework that houses aggregations of lymphocytes

Lymph Nodes

1. Small, encapsulated, bean-shaped organs
2. Usually found in clusters along lymphatic channels and large blood vessels of the thoracic and abdominal cavities
3. Major aggregations: axillary nodes, inguinal nodes, cervical nodes

Spleen

1. Similar to a lymph node except it filters blood instead of lymph
2. Filters pathogens from the blood

Thymus

1. Site of T-cell Maturation
2. Thymus originates in the embryo
3. High rates of activity and growth until puberty
4. Shrinks gradually through adulthood
5. Thymic hormones help thymocytes develop specificity to be released as mature T cells

Miscellaneous Lymphoid Tissue

1. Bundles of lymphocytes lie at many sites on or just beneath the mucosa of the gastrointestinal and respiratory tracts
2. Tonsils
3. Breasts of pregnant and lactating women
4. GALT in the intestinal tract
- Appendix
- Peyer's patches
5. Mucosal-associated lymphoid tissue (MALT)
6. Skin-associated lymphoid tissue (SALT)
7. Bronchial-associated lymphoid tissue (BALT)

GALT

in the intestinal tract
- Appendix
- Peyer's patches

MALT

Mucosal-associated lymphoid tissue

SALT

Skin-associated lymphoid tissue

BALT

Bronchial-associated lymphoid tissue

Second Line of Defense

1. generally nonspecific but supports & interacts w/specific immune response
Inflammation
Phagocytosis
Interferon
Complement

The Inflammatory Response

1. Cascade of events
2. injured tissues release chemicals (chemotactic)
3. selectins appera on endothelial capillaries (stickey surface)
4. integrins on neutrophils help them attach to endothelial integrins receptors. this is called margination.
5. mast cells release histamine
6. histamine causes vasodilation, and openings occur in capillaries
7. neutrophils change shape and squeeze thru capillaries. this is call extravastion/diapedesis
8. neutrophils & others are attracted to site by chemotactic
9. ingest & destroy invading bacteria

chemotactic

injured tissues release chemicals

margination

integrins on neutrophils help them attach to endothelial integrins receptors

extravastion/diapedesis

WBC/neutrophils change shape and squeeze thru capillaries

The Inflammatory Response: A Complex Concert of Reactions to Injury

1. Reaction to any traumatic event in the tissues
2. Classic signs and symptoms
Rubor (redness)
Calor (warmth)
Tumor (swelling)
Dolor (pain)
3. Fifth symptom has been added: loss of function

Rubor

redness

Calor

warmth

Tumor

swelling

Dolor

pain

Chief Functions of Inflammation

1. mobilize & attract immune components to site of injury
2. set in motion mechanisms to repair tissue damage & localize & clear away harmful substances
3. detroy microbes & block further invasion

Vascular Changes: Early Inflammatory Events

1. Controlled by nervous stimulation, chemical mediators, and cytokines (released when damage to tissue) released by blood cells, tissue cells, and platelets in the injured area
2. Vasoactive mediators affect the endothelial cells and smooth muscle cells of blood vessels.
3. Chemotactic factors (chemokines) affect white blood cells
4. Cause fever, stimulate lymphocytes, prevent virus spread, and cause allergic symptoms
5. Arterioles constricted at first but quickly vasodilation takes place

Vasoactive mediators

affect the endothelial cells and smooth muscle cells of blood vessels.

Chemotactic factors

chemical mediators that stimulate the movement of WBC(chemokines) affect white blood cells

Chemicals Released by Damaged Cells:
Histamine

Produced by mast cells
Vasodilation, increased permeability of blood vessels (allows cells to escape ex. monocytes)

Chemicals Released by Damaged Cells:
kinins

are the chemicals
Vasodilation, increased permeability of blood vessels
Play a role in chemotaxis by attracting phagocytic neutrophils

Chemicals Released by Damaged Cells:
prostaglandins

Intensify histamine and kinin effect
Powerful stimulants of inflammation of pain

Chemicals Released by Damaged Cells:
leukotrienes

Increased permeability of blood vessels, phagocytic attachment
Stimulate contraction of smooth muscle

Edema

1. Exudates: the fluid that escapes through gaps in the walls of postcapillary venules
2. Contains plasma proteins, blood cells, and cellular debris
3. May be clear (serous) or may contain red blood cells or pus (accumulated phagocytes, cellular debris, and pyogenic bacteria)
4. Diapedesis: how WBCs leave the blood vessels and into tissue spaces
5. chemotaxis: the tendency of WBCs to migrate in response to a specific chemical stimulus

Exudates

the fluid that escapes through gaps in the walls of postcapillary venules

Diapedesis

how WBCs leave the blood vessels and into tissue spaces
aka extravasation

chemotaxis

the tendency of WBCs to migrate in response to a specific chemical stimulus (gradient)

Benefits of Edema and Chemotaxis

Dilutes toxic substances
Fibrin clot can trap microbes and prevent further spreading
Phagocytosis occurs immediately (not dependent on antigen signal)

pyogenic bacteria

ability to make pus

Late Reactions of Inflammation

1. Long-lived inflammation attracts a collection of monocytes, lymphocytes, and macrophages to the reaction site
2. Macrophages clear pus, cellular debris, dead neutrophils, and damaged tissue
3. B lymphocytes produce antibodies/immunoglobulins
4. T lymphocytes kill intruders directly
5. Late in the process the tissue is repaired or replaced by connective tissue (scar)

Fever

1. An abnormally elevated body temperature
2. FUO: cause of fever is unknown
3. Initiation of fever
- pyrogen sets the hypothalamic "thermostat" to a higher setting
a. Muscles increase heat production
b. Peripheral arterioles decrease heat loss through vasoconstriction
- Pyrogens can be exogenous or endogenous
- Macrophages release two potent pyrogens :
1. interleukin 1 - communication btw wbc (endogenous)
2. tumor necrosis factor (TNF)

pyrogen

a substance that causes a rise in body temperature

endogenous

originating or produced within an organism or one of its parts (GN bacteria lipopolysaccharide layer is the causative agent)

exogenous

originating outside the body

exotoxin

a toxin that is secreted and acts upon a specific cellular target
are released by bacteria

endotoxin

a bacterial toxin that is not ordinarily released. endotoxin is composed of a lipopolysaccharide complex of GN bacteria
- are exogenous pyrogens
ex. E. coli

benefits of fever

1. inhibits multiplication of temp.sensitive MO
2. impedes the nutrition of bacteria by reducing the availibility of iron
3. increases your metabolism & stimulates immune reactions & naturally protective physiological processes

Phagocytosis: Cornerstone of Inflammation and Specific Immunity

1. General activities of phagocytes
- Survey the tissue compartments and discover microbes, particulate matter, and injured or dead cells
- Ingest and eliminate these materials
- Extract immunogenic information (antigens) from foreign matter

Three main types of phagocytes

1. neutrophils
2. monocytes
3. macrophages

Histiocytes:

specialized macrophages that migrate to a certain tissue and remain there during their life span

phagocytosis

1. something on surface that triggers attachment
2. phagosome
3. lysosome - organelle containing lysozyme
4. lysozyme - breaks apart peptidoglycan
5. protease - break apart proteins

Interferon

Antiviral Cytokines and Immune Stimulants
1. Interferon (IFN): involved against viruses, other microbes, in immune regulation and intercommunication
2. Three major types: alpha, beta & gamma
3. All three classes produced in response to viruses, RNA, immune products, and various antigens
4. Bind to cell surfaces and induce changes in genetic expression (can tell cell what to transcribe & translate)
5. Can inhibit the expression of cancer genes and have tumor suppressor effects

Complement

1. Over 30 blood proteins that work in concert to destroy bacteria and certain viruses
**Cascade reaction AKA as domino effect

2. Three different pathways that all yield similar end results
Classical pathway
Lectin pathway
Alternative pathway

classical pathway

activated by antibody.
C3 cleaved,
results in
1. opsonization =ability to phagosize (like putting handles on a capsule)
2. inflammation = (mast cell releases histamine)
3. cytolysis = ring of proteins inserted one at a time, causing a hole and lysis occurs

Lectin pathway

activated by mannose on surface
results in
1. opsonization =ability to phagosize (like putting handles on a capsule)
2. inflammation = (mast cell releases histamine)
3. cytolysis = ring of proteins inserted one at a time, causing a hole and lysis occurs

Alternative pathway

activated by factors BDP (recognize a complex on microbes
results in
1. opsonization =ability to phagosize (like putting handles on a capsule)
2. inflammation = (mast cell releases histamine)
3. cytolysis = ring of proteins inserted one at a time, causing a hole and lysis occurs

Complement Cascade

1. Initiation - this is the variation
2. Amplification and cascade
3. Polymerization
4. Opsonization, Inflammation and formation of Membrane attack complex (MAC) (many different proteins. ring, hollow center, makes a hole, things leak out and cell lyses). Purpose for each of these? (36)

Membrane attack complex (MAC)

cytolysis
many different proteins. ring, hollow center, makes a hole, things leak out and cell lyses

chemokine

chemical mediators (cytokines) that stimulate the movement of SBC

cytokine

chemical substance produced by WBCs and tissue cells that regulate development, inflammation & immunity

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