Immunity

Immunity

is having resistance to a particular pathogen (protection from harm).

Leukocytes

Formed in red bone marrow

Include:

Granulocytes: neutrophils, eosinophils,

basophils

Monocytes

Become macrophages when they leave

blood and enter tissues

Lymphocytes

B-lymphocytes, T-lymphocytes, NK

(natural killer) cells

Secondary lymphoid structures

• T- and B-lymphocytes, macrophages, dendritic cells, and NK cells housed in lymph nodes, spleen, tonsils, MALT, lymphoid nodules

Select organs house macrophages

• May be permanent residents of the organ, or migrating macrophages

Epithelial layers of skin and mucosal membranes house dendritic cells

These dendritic cells are usually derived from monocytes; engulf pathogens and migrate into lymph

Connective tissue houses mast cells

• Abundant in dermis and mucosa of respiratory, GI, and urogenital tracts

• Also found in connective tissue of organs (for example, endomysium of muscle)

Innate Defenses

aka “non-specific defenses”

 Present at birth

 This is the immune response that

doesn’t change with the invading

pathogen.

 Barriers, phagocytes, complement,

interferon, inflammation and fever

Adaptive Defenses

 aka “specific immunity”

 This immune response is

specific/unique to the invading

pathogen

 Humoral and Cell-Mediated

Immunity (B and T lymphocytes)

 They “remember” specific

pathogens

Mechanical Barriers

o Cutaneous and mucous membranes

o Tightly packed cells (epithelial tissue)

Chemical Barriers

o Sebum (oil)

o “Acid mantle” in skin

o Mucus

o Enzymes

o Acids

Preventing Entry

Physical barriers of epidermis and

dermis

• Keratinized stratified squamous

epithelium and connective tissue

+ hyaluronic acid in dermis

• Skin releases antimicrobial

substances from sweat glands,

sebaceous glands

• Dermcidin, lysozyme, sebum,

defensins

Microbiome

(commensal microbiota) are microorganisms that reside on body surfaces

(for example, skin, GI tract)

Nonpathogenic AND they interfere with attachment of potentially pathogenic

organisms

Mucous membranes line body openings

Produce mucus and release antimicrobial substances (defensins, lysozyme, IgA)

Cilia in respiratory tract remove trapped microbes; GI tract utilizes saliva, stomach acid to kill ingested microbes; urinary tract flushes microbes away; reproductive tract contains acidic secretions

Second Line of Defense: Nonspecific Internal Defenses

 Should pathogens pass the first line of defense, the second line of defense

(nonspecific internal defenses) is initiated

 Nonspecific internal defenses include

• Selected immune cells

• Antimicrobial proteins

• Inflammation

• Fever

Chemotaxis

The cellular bat signal

Chemicals which are released alert cells to come

to an area of need

Diapedesis

How phagocytes get out of the blood

stream into the tissues.

 These cells stick to the inner walls of the

blood vessels and squeeze through the tiny

gaps between the cells lining the blood

vessel walls. Shape shifters!

Complement system

group of over 30 plasma proteins identified with letter “C”

and number (for example, C2)

Work along with (“complement”) antibodies

Synthesized by liver, continuously released in inactive form

Activation occurs by enzyme cascade

Classical pathway

antibody attaches to foreign substance, then

complement binds to antibody

Alternative pathway

complement binds to polysaccharides of bacterial or

fungal cell wall

Mannose-binding lectin pathway

lectin protein binds to carbohydrate on

some microbes, and complement binds to the lectin

Detection

When harmful invaders like bacteria or viruses enter your body, the complement system detects them.

Activation

This detection triggers a series of reactions, activating complement proteins in your blood, and increasing inflammation.

Tagging

Some of these proteins tag the invaders for opsonization, making them easier for other immune cells to find and destroy

Destruction

Other proteins form the membrane attack complex (MAC), causing them to burst and die (cytolysis)

Cleanup

Finally, the complement system helps clean up the debris, ensuring your body stays healthy

Opsonization

complement protein (opsonin) binds to pathogen, enhances likelihood of phagocytosis of pathogenic cell

Membrane attack complex (MAC)

is a cytolytic effector which forms pores in the plasma membrane of pathogens or targeted cells, leading to cytolysis

Cytolysis

lysis (bursting) of target cell - channel in target cell’s membrane is created -> fluid enters -> causing the cell to lyse

Antimicrobial proteins

function against microbes

Interferons

a class of cytokines that nonspecifically interferes with spread of intracellular pathogens (for example, viruses, intracellular bacteria)

IFN-α and IFN-β produced by leukocytes and virus-infected cells

Bind to neighboring cells and prevent their infection

Trigger synthesis of enzymes that destroy viral nucleic acids, inhibit

synthesis of viral proteins

Stimulate NK cells to destroy virus-infected

cells

IFN-γ (gamma) produced by T-lymphocytes and

NK cells

Stimulates macrophages to destroy virus infected cells

Pattern recognition receptors

(toll-like receptors PRR) on cell surface bind

to patterns on microbe surface

• PRRs recognize and bind to specific molecular patterns found on

pathogens, known as pathogen-associated molecular patterns

(PAMPs). These patterns are unique to microbes and not found in

host cells.

• Once PRRs detect PAMPs, they trigger signaling pathways that

activate various immune responses. This includes the production of

cytokines and chemokines, which help recruit and activate other

immune cells.

Neutrophils and macrophages destroy

engulfed particles

Intake vesicle fuses with lysosome

forming phagolysosome

Digestive enzymes break down the unwanted substances

Respiratory burst

produces reactive oxygen-containing molecules that help destroy the microbes

Dendritic cells destroy

destroy particles and then present fragments

Antigens are presented on dendritic cell surface to T-lymphocytes

 Necessary for initiating adaptive immunity

 Macrophages can also perform antigen presentation

NK (natural killer) cells

destroy unhealthy/unwanted cells

Form in bone marrow, circulate in blood, and accumulate in secondary lymphoid structures

Perform immune surveillance

patrol body, detect unhealthy cells

They destroy virus

-infected cells, bacteria-infected cells, tumor cells, cells of transplanted tissue

They kill by releasing cytotoxic chemicals

Perforin creates a transmembrane pore in unwanted cell

Granzymes enter pore and cause apoptosis of cell

Apoptosis

is cell death that causes shriveling rather than lysis

Eosinophils

attack multicellular parasitic worms

Degranulate, release enzymes and other toxic substances

Release proteins that form transmembrane pores in parasite

Participate in immune responses of allergy and asthma

Engage in phagocytosis of antigen-antibody complexes

Basophils circulate in the

blood

Mast cells in

connective tissue, mucosa, internal organs

Chemicals increase movement of

fluid from blood to injured tissue

chemotactic chemicals attract

immune cells

Histamine

increases vasodilation and capillary permeability

Heparin

acts as an anticoagulant

Eicosanoids

released from their plasma membrane also increase inflammation

Inflammation (inflammatory response)

: an immediate, local, nonspecific response of

vascularized tissue to injury, infection

Major response of innate immunity (inflammation is the first step in tissue healing!

Events of inflammation

Injured tissue -> basophils, mast cells, and infectious organisms release chemicals that initiate response

Inflammatory mediators cause vascular changes:

: increase blood flow and capillary

permeability

Increasing number of immune cells present, as well as antibodies and nutrients.

Increased endothelial expression of molecules for leukocyte adhesion: cell-adhesion

molecules (CAMs)

Inflammatory mediators

Histamine

Kinin

Eicosanoids: PG-E (prostaglandin)

and LT (leukotriene)

ILs (interleukins)

Effects of inflammation

Fluid (exudate) moves from blood to injured, infected area

• Exudate allows protein, immune cells to eliminate pathogens and promote

healing

• Increase in fluid movement because of loss of plasma proteins (due to

increased capillary permeability) - decreases capillary osmotic pressure, thus

decreasing fluid reabsorption into blood

• Extra fluid is taken up by lymphatic capillaries in the area (“washing”) - carries

away debris and allows lymph node monitoring of its contents

• Within 72 hours, inflammatory response slows

• Macrophages eat bacteria, damaged host cells, dying neutrophils; Tissue

repair begins as fibroblasts form new connective tissue

Cardinal signs of inflammation

• Redness from increased blood flow

• Heat from increased blood flow and increased metabolic activity within the area

• Swelling from increase in fluid loss from capillaries

• Pain from stimulation of pain receptors

• Due to compression (extra fluid) and chemical irritants (kinins, prostaglandins,

microbial secretions)

• Loss of function from pain and swelling in severe cases

Chronic Inflammation

has detrimental effects (tissue damage and loss of function)

Events of fever

 Pyrogens circulate through blood and target hypothalamus

 In response, hypothalamus releases prostaglandin E2

 Hypothalamus raises temperature set point leading to fever

 Fever stages: onset, stadium, and defervescence

A fever becomes dangerous when it reaches 104°F (40°C) or higher

At this point, you should seek medical attention, may experience symptoms

like seizures, confusion, trouble breathing, or severe pain

Body proteins can denature

Certain metabolic pathways can’t function

Death likely if temperature greater than 108F

Onset

temperature begins to rise

Hypothalamus stimulates constriction of dermal BV (less heat loss)

Shivering of muscle generates more heat

Stadium

elevated temperature is maintained

Metabolic rate increases to promote elimination of harmful substance

Liver and spleen bind zinc and iron, slowing microbial reproduction

Defervescence

time when temperature returns to normal

Hypothalamus no longer stimulated by pyrogens, prostaglandin release decreases

Hypothalamus stimulates mechanisms to release heat (for example, vasodilation of

skin blood vessels, sweating)

Benefits of fever

Inhibits reproduction of bacteria and viruses

Promotes interferon activity

Increases activity of adaptive immunity

Accelerates tissue repair

Increases CAMs on endothelium of capillaries in lymph nodes—additional

immune cells migrating out of blood

Recommended to leave a low fever untreated