An overview of innate immunity

Microbiology and immunology_1

Introduction to the human body’s defense

Defense against infections caused by pathogens and their products is called immunity

Two types of defense against pathogens

Innate immunity Present at the birth Rapid response Non-specific defense of the body (host)

Adaptive immunity

Acquired Slower response Specific response of the body to a specific pathogen Memory

Innate immunity

Components of the first line of

defense are Skin Mucous membranes

Includes two lines of defense First line of defense

Prevents pathogens from entering the body in the first place

Second line of defense Helps eliminate pathogens that gain access to the body

Skin is composed of an outer layer called epidermis and a deeper layer called dermis

Both epidermis and dermis provide nonspecific defense against infection and colonization by pathogens

The role of skin in innate immunity

Epidermis Physical barrier to the entrance

of pathogens

Continual replacement

A network of phagocytic cells called dendritic cells, phagocytize pathogens nonspecifically

Dermis Contains collagen fibers that provide strength, hair follicles,

glands, blood vessels, and nerve endings

Chemical substances help defend against pathogens Perspiration (sweat glands of the skin)

Salt Lysozyme Antimicrobial peptides (i.e.: defensins)

Sebum (acidity)

Sebaceous glands produce sebum, which lowers the pH of the skin

Blood vessels deliver defensive cells and chemicals

The role of skin in innate immunity

The role of mucous membranes in innate immunity

Line the lumen of the respiratory, digestive, reproductive, urinary tracts: epithelium/deeper connective layer to provide support

Cell of the epithelium are tightly packed to prevent entry of pathogens Shedding of cells carries microbes away Dendritic cells are found below the mucous epithelium

Ciliary escalator of the respiratory tract

Produces and drains tears Blinking spreads tears and washes surface of the eye Lysozyme in tears destroys bacteria

Lacrimal apparatus

It does not destroy toxins of C. botulinum and S. aureus

H. pylori neutralizes stomach acid

Many enteric pathogens are protected by food particles

Lactobacillus acidophilus breaks down glycogen to produce lactic acid, decreasing the pH

Not usually considered part of the first line of defense

The normal microbiota competes with potential pathogens

Use nutrients

Create an unfavorable environment

pH and oxygen availability

Lactobacillus inhibits overgrowth of Candida albicans

Produce bacteriocins

E. coli against Salmonella and Shigella (pathogens)

Promote overall health

Providing vitamins to the host

The role of the normal microbiota in innate immunity

The second line of defense in innate immunity

The second line of defense functions when pathogens penetrate the first line of defense (skin or mucous membranes)

Components of the second line of defense are

Defensive cells

Inflammation, fever (processes)

Antimicrobial substances

Peptides

Complement proteins

Interferons

Components of blood – an overview

Blood is composed of cells and cell fragments within a fluid called plasma

Plasma is mostly water containing many substances including

Ions, nutrients Iron-binding proteins (transferrin) Blood clotting factors Complement proteins Antibodies or immunoglobulins (adaptive immunity)

Serum is the fluid remaining when clotting factors are removed from the plasma

Blood cells

Hematopoiesis is the process by which blood cells are formed from stem cells of the bone marrow

Erythrocytes Carry oxygen and carbon

dioxide in the blood

Platelets (cell fragments) Involved in blood clotting

Leukocytes or white blood cells

Involved in innate and adaptive immunity

Schematic representation of hematopoiesis

Defense Components of Blood

Granulocytes

Defense Components of Blood

Agranulocytes

Defense Components of Blood

Stained blood smears

During microbial infections the number of WBCs can increase (leukocytosis) or decrease (leukopenia)

Detected by a differential white blood cell count Percentage of each type of white cell

in a sample of 100 white blood cells

Defense components of blood and phagocytosis

Neutrophils

Dominate during the initial phase of an infection

Leave the blood vessels by squeezing between

cells lining capillaries (diapedesis)

Macrophages

As the infection progresses, macrophages

dominate

Wandering macrophages leave the blood via

diapedesis

Fixed macrophages are found in specific

tissues/organs of the body

Dendritic cells Mostly skin and mucous membranes

Initiate adaptive immune response

Phagocytosis

Part of the second line of defense that is activated when the first line fails

Cells capable of phagocytosis are called phagocytes

Phagocytosis can be divided into stages

Chemotaxis

Adherence

Ingestion (phagosome)

Maturation (phagolysosome)

Killing (digestion)

Elimination (exocytosis)

Phagocytosis: neutrophil phagocytizes Neisseria

Phagocytosis and examples of pathogens that evade phagocytosis

Ability of a pathogen to cause disease is related to its ability to evade/escape or survive phagocytosis using different strategies Streptococcus pyogenes Streptococcus pneumoniae Haemophilus inflenzae type b Staphylococcus aureus Mycobacterium tuberculosis Plasmodium - malaria Trypanonosoma cruzi

Bacteria that are part of biofilms are more resistant to

phagocytosis such as Pseudomonas aeruginosa

Nonphagocytic Killing

Killing by eosinophils Attack parasitic helminths Secrete toxins that weaken or kill the helminth High numbers of eosinophils indicative of a helminth infestation

Larval stage of a liver fluke

Killing by natural killer (NK) lymphocytes Kill infected cells and tumor cells causing cytolysis or inducing

apoptosis Normal body cells are recognized by their membrane proteins

similar to those of the NK cells Killing by neutrophils

Produce chemicals (such as hypochlorite) that kill nearby pathogens

A strategy that leads to suicide of neutrophils Generate extracellular fibers called neutrophil extracellular

traps (NETs) that “trap” Gram positive and Gram negative bacteria, killed by antimicrobial peptides

Nonphagocytic Killing

Inflammation

Nonspecific defensive response to tissue damage from various causes, including microbial infection

Characterized by redness, heat, swelling, and pain

Two types

Acute inflammation

Develops quickly and is short lived

Beneficial (destroys, removes or walls off pathogens)

Chronic inflammation

Long-lasting and can lead to disease

Inflammation: second line of defense in innate immunity

Inflammation involves

Vasodilation

Increased permeability of blood vessels

Migration of phagocytes to the infected area

Blood clotting and repair of damaged tissue

Inflammation: second line of defense in innate immunity

Inflammatory mediators are released by damaged cells or other cell types (macrophages, basophils/”platelets”, mast cells), and include

Prostaglandins and histamine

The dilating effect of inflammatory mediators on small blood vessels

Increased vasodilation helps deliver clotting factors/defensive cells

Leads to redness and localized heat associated with inflammation

Increased vascular permeability during inflammation

Increased permeability allows phagocytes to leave the blood stream and reach the site of infection (margination/diapedesis)

Leakage of fluids causes the swelling (edema) and pain associated with inflammation (pressure on nerve endings)

Bacteria

A cut penetrates the epidermis

barrier, and bacteria invade.

Damaged cells release

prostaglandins, leukotrienes,

and histamine (shown in

green here).

Prostaglandins and

leukotrienes make vessels

more permeable. Histamine

causes vasodilation, increasing

blood flow to the site.

Macrophages and neutrophils

squeeze through walls of

blood vessels (diapedesis).

Increased permeability allows

antimicrobial chemicals and

clotting proteins to seep into

damaged tissue but also

results in swelling, pressure on

nerve endings, and pain.

Swelling Heat

Nerve ending

Blood clot forms.

More phagocytes migrate to

the site and devour bacteria.

Accumulation of damaged

tissue and leukocytes forms

pus.

Undifferentiated stem cells

repair the damaged tissue.

Blood clot is absorbed or falls

off as a scab.

Fever

A body temperature over 37°C

The most frequent cause of fever is an infection caused by bacteria or viruses

Results when pyrogens trigger the hypothalamus to increase the body’s temperature

Various types of pyrogens

Bacterial toxins

Antibody-antigen complexes

Phagocytes that have phagocytized pathogens

Constricted vessels carry less blood to the skin, causing it to feel cold to the touch (chill associated with fever)

The crisis of a fever occurs when the thermostat is reset to 37C and the body begins to cool by Perspiring Lowering metabolic

rate Dilating blood vessels

in the skin

Fever

Antimicrobial substances of innate immunity

The complement system is a defensive system of proteins produced by the liver

Found circulating in the blood and within tissues

Activation leads to

Opsonization

Inflammation

Cytolysis

Activation of the complement system

The complement system can be activated in three ways

Classical pathway

Antibody-antigen complex

Alternative pathway

Contact with a pathogen

Lectin pathway

Mannose-binding lectin, MBL

Antimicrobial substances of innate immunity

Classical pathway

Details of the figure will not be part of your next exam!!!

Alternative pathway

Details of the figure will not be part of your next exam!!!

Lectin pathway

Details of the figure will not be part of your next exam!!!

Membrane attack complex (MAC)

Interferons (IFN) are proteins released in response to viral infections

Interferon alpha and beta

Trigger production of antiviral proteins in neighboring uninfected cells, inducing an anti-viral state

Interferon gamma

Stimulates activity of macrophages (phagocytosis)

Interferons activate NK cells, which kill virus-infected cells

Antiviral response of the innate immunity

Interferons and antiviral proteins

Details of the figure will not be part of your next exam!!!

Hepatitis C viruses Infects ~ 200 million people

worldwide

Prevents production of interferon

Viral protease seems to be involved

Used to treat certain other viral infections such as hepatitis A/B