Immune system

Immune system provides

Resistance to disease causing microorganism (bacteria,fungi,viruses)

Body has three lines of defense that together provide

Resistance to disease, or immunity

Three lines of defense in order

Surface barriers, innate internal defenses, The adaptive defense system

surface barriers

Provide first line of defense

Consists of intact skin and mucosae (structural barriers designed to keep invaders out)

innate internal defenses

Provide second line of defense

Called into action whenever first line penetrated - General response

Relies on inflammation and internal defenses (antimicrobial proteins and phagocyte) to inhibit spread of invaders

The adaptive (specific) defense system

provides the body's third line of defense

Elite fighting force to attack identified enemies.-Specific response

Response takes much longer to mount than innate response

Innate and adaptive defenses are

Integrated always working together

Innate and adaptive systems

Release and recognize(bind to) many of the same defense molecules

Innate response

Have specific pathways to target certain foreign substances (not as nonspecific as once's thought)

Proteins released during innate response

Alert cells of adaptive system to presence of specific foreign molecules in body

When immune system operating effectively

It protects body from most infectious microbes and cancer cells

Surface berries and innate internal defense are

In place at birth ready to resist invading pathogens(harmful or disease microbes

adaptive immune system called into action

To reinforce and enhance innate defense when they alone cannot protect us

Innate defense reduce Workload of adaptive systems-

By preventing entry and spread of microbes

surface barriers are

skin and mucous membranes, along with their secretions

Surface barriers skin

Heavily keratinized epidermis highly effective for most microbes

Mucosae provide

similar mechanical barriers within the body (lining the tracts)

These Barriers produce protective chemicals that inhibit or destroy microbes

Acid , enzymes, mucin, defensins, and other chemicals

Acid

Acidity of skin,vaginal, and stomach secretions inhibits bacteria growth called mantle

Enzymes

Lysozyme of saliva, respiratory mucus, and lacrimal fluid kills many microbes; proteins-digesting enzymes in stomach kill many microbes

mucin

sticky mucus (protein mucin dissolved in water) that lines digestive and respiratory tract traps microorganisms

Defensins

broad-spectrum antimicrobial peptides secreted in response to barrier breach and inflammation; inhibit microbial growth

other chemicals

some lipids in sebum and dermcidin in eccrine sweat are toxic to back

respirtatory tract also has structural modifications to stop pathogens

Mucus coated hairs in nose trap inhaled particles

Cilia of upper tract sweep dust and bacteria-laden mucus toward mouth

surface barriers breached by nicks or cuts trigger

the internal second line of defense that protects deeper tissues

intact skin epidermis

forms mechanical barrier that prevents entry of pathogens and other harmful substances into body

acid mantle of skin

Skin secretions (sweat and sebum) make epidermal surface acidic, which inhibits bacterial growth; also contain various bactericidal chemicals

Keratin

provides resistance against acids, alkalis, and bacterial enzymes

intact mucous membranes

form mechanical barrier that prevents entry of pathogens

Mucus

traps microorganisms in respiratory and digestive tracts

nasal hairs

filter and trap microorganisms in nasal passages

Cilia

Propel debris laden mics away from nasal cavity and lower respiratory passages

gastic juice

contains concentrated hydrochloric acid and protein-digesting enzymes that destroy pathogens in stomach

acid mantle of vagina

inhibits growth of bacteria and fungi in female reproductive tract

Lacrimal secretion (tears); saliva

Continuously lubricate and cleanse eyes (tears) and oral cavity (saliva); contain lysozyme, an enzyme that destroys microorganisms

urine

Normally acid pH inhibits bacterial growth; cleanses the lower urinary tract as it flushes from the body

Second line of defense includes

Nonspecific cellular and chemical means to protect body;

phagocytes, natural killer cells ,inflammation, fever, antimicrobial substances

Pattern Recognition Receptors (PRRs)

Indentifies potential pathogens recognizing (binding to) specific-shaped molecules (e.g., carbohydrates) found on them, but not normal human cells

Toll-like receptors (TLRs)

play central role in triggering immune responses

-Humans have 11 different TLRs,

each recognizes a particular class of attacking microbe

Many cells (including macrophages and epithelial cells lining respiratory and G I tracts)

ave T L R s, allowing them to recognize invaders and initiate inflammation.

Phagocytes:

white blood cells (WBC)) that ingest and digest (eat) foreign invaders and cellular debris

Neutrophils

most abundant phagocytes; phagocytize infectious material in tissues

Macrophages

most active phagocytes

Free macrophages wander through tissue spaces; e.g., alveolar macrophages

wander through tissue spaces; alveolar macrophages

free macrophages

deprived from WBC called monocytes

Fixed macrophages

are permanent residents of particular organs; Kupffer macrophages of liver

fixed macrophages

formed in embryo (not derived from monocytes)

Phagocytosis Starts when

Phagocyte receptors bind particle, which is then pulled inside and enclosed within a membrane-lined vesicle

The particle is enclosed within a membrane-lined vesicle, forming a

Phagosome.

What forms after the phagosome fuses with a lysosome?

Phagolysosome

What happens inside the phagolysosome in macrophages and neutrophils?

The phagolysosome is acidified, and lysosomal enzymes digest the contents.

What happens if pathogens are resistant to lysosomal enzymes?

Some pathogens can resist lysosomal enzymes, making them harder to destroy.

How do helper T cells respond to pathogens that aren't killed by macrophages ( tuberculosis bacillus)?

Helper T cells stimulate the macrophage to produce a respiratory burst to help kill the resistant pathogens.

These T cells that stimulate the macrophage to produce respiratory bust kill pathogens by

-Releasing highly destructive free radicals

-Producing oxidizing chemicals (hydrogen peroxide and "bleach")

Increasing pH and osmolarity of phagolysosome, which activates other protein-digesting enzymes

Defensins (secreted by neutrophils) also help by

Piercing membrane of pathogen

How do some microbes evade phagocytosis, and how does the immune system counter this?

Some microbes have external capsules that hide their carbohydrate signatures. The immune system counters this by coating pathogens with opsonins (complement proteins or antibodies), which act as "handles" for phagocytes, accelerating phagocytosis. This process is called opsonization.

What do phagocytes do when they can't ingest their targets?

Phagocytes release toxic chemicals into the extracellular fluid. Neutrophils can undergo netosis, releasing a sticky net of their own DNA and proteins to trap and kill pathogens.

Unlike macrophages, neutrophils

Rapidly destroy themselves in the process.

Natrual Killer Cells (NK Cells)

Are large granular lymphocytes (nonphagocytic) that police blood and lymph

How do NK cells detect and kill abnormal cells?

NK cells look for general abnormalities, such as the lack of "self" MHC proteins, and can kill cancer and virus-infected cells before the adaptive immune system is activated.

By inducing

Apoptosis (like cytotoxic T cells) and secrete chemicals that enhance the inflammatory response.

inflammation

is a nonspecific response to any tissue injury

inflammation causes

trauma, intense heat, irritating chemicals, or infection

What does the suffix "-itis" signify in medical terms?

The suffix "-itis" signifies inflammation (tonsillitis, appendicitis, and tendonitis)

Benefits of inflammation

-Prevents spread of pathogens

-Disposes of cell debris and pathogens

-Alerts adaptive immune system

-Sets stage for repair

Four cardinal signs of acute inflammation are

redness, heat, swelling, pain

How does inflammation begin?

Inflammation begins with a flood of inflammatory chemicals released into the extracellular fluid (ECF) by injured or stressed tissue cells, and immune cells.

What is the role of histamine in inflammation?

Histamine, released by mast cells, is a potent inflammatory chemical. Other chemicals include kinins, prostaglandins, and cytokines

What happens if inflammation is prompted by pathogens?

A group of plasma proteins called complement is activated to form potent inflammatory chemicals.

What effects do inflammatory chemicals have on blood vessels?

Inflammatory chemicals dilate local arterioles and make capillaries leakier.

How do inflammatory chemicals affect immune cells?

Many inflammatory chemicals attract phagocytes to the area and mobilize lymphocytes and other elements of adaptive immunity.

Histamine

Histamine is a potent inflammatory chemical released by mast cells. It causes blood vessel dilation and increases capillary permeability, contributing to inflammation.

Kinins (bradykinin and others)

What is the effect of local vasodilation during inflammation?

Local vasodilation causes hyperemia (increased blood flow), bringing more immune cells and chemicals to the affected area, leading to redness and heat.

What is the role of increased capillary permeability in inflammation?

Increased permeability allows exudate, containing clotting factors and antibodies, to seep into tissue, helping flush foreign material into lymphatics for processing.

What important proteins are delivered to the interstitial fluid during inflammation?

Increased permeability delivers proteins like complement and clotting factors to the interstitial fluid (ISF).

What is the role of fibrin mesh during inflammation?

Fibrin mesh (clot) acts as a scaffold for tissue repair and isolates the injured area to prevent the spread of pathogens.

What causes swelling and pain during inflammation?

Local swelling (edema) results from exudate build-up, while pressure on nerve endings and bacterial toxins, along with the effects of prostaglandins and kinins, contribute to pain.

What is phagocyte mobilization?

The process where neutrophils, followed by monocytes, flood damaged tissue to fight infection. It involves four steps.

Four steps of phagocyte mobilization.

1. Leukocytosis

2. Margination

3. Diapedesis

4. Chemotaxis

Leukocytosis

increase in the number of white blood cells; characteristic of inflammation

Margination

Phagocytic cells cling to the inner walls of the capillaries and postcapillary venules

Diapedesis

soon the neutrophils flatten and squeeze between endothelial cells—a process called diapedesis

chemotaxis

inflammatory chemicals act as chemotactic agents that promote positive chemotaxis of WBCs toward injured area