Chapter 16: Nonspecific Responses

• The immune system functions to recognize and destroy that which is foreign (non self) - including invading microbes and their secretions, toxins, and enzymes and non normal cells

• The immune system consists of 2 components:– Nonspecific or innate (inherent) immunity– Specific or adapted (acquired after birth) immunity

Innate or nonspecific immunity

• Acts to prevent microbes from getting into the body and the elimination of those that have already penetrated

• Defenses are present at birth

• Acts against all microbes in the same way – Is not specific

• Always ready to respond to damage or invasion

1st line of defense – physical barriers

• Skin – the dermis and epidermis provide mechanical protection however this barrier can be broken by cuts and abrasions, insect bites, and injections. – The top layer of dead epidermal cells contain

a protein called keratin which is a poor source of carbon for microbes. These dead cells are continually being sloughed off along with the microbes that are on the them.

1st line of defense – physical barriers

• Skin cont. – It is home to normal microbiota which are

antagonistic to pathogens– Flushing effects of sweat glands helps to

remove microbes– A cut in the skin allows Staphylococci to enter

the blood– An arthropod bite acts like a hypodermic

needle – allow microbes that cause disease like malaria or plague to enter

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1st line of defense – physical barriers

• Mucous membranes line the internal body cavity and act as a mechanical barrier to microbes.– Cilia in airways propel microbes and mucus

into the pharynx (throat) where they are swallowed into the stomach

• Stomach acid destroys the microbes

1st line of defense – physical barriers

• Lacrimal apparatus manufactures and drains away tears – flushing action, blinking of eyes

• Saliva carries microbes to the harsh environment of the stomach

• Hairs and cilia– Nasal hairs trap large particles, may initiate a sneeze

to expel – Ciliated epithelium (respiratory tract) called the ciliary

escalator moves microbes trapped in mucus out of the respiratory tract

1st line of defense – physical barriers

• Epiglottis – covers the larynx when swallowing and keeps microbes from entering the lower respiratory tract

• Flow of urine removes microbes from the urogenital tract

• Vaginal secretions remove microbes from the female body

• Defecation and vomiting expel pathogens and toxins

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1st line of defense chemical factors

• Sebaceous glands of the skin produce an oily substance called sebum which forms a protective film over the skin and lowers the pH of the skin to pH 3-5– Which inhibits the growth of pathogenic fungi

and bacteria

• Sweat, tears and saliva contain the enzyme lysozyme which hydrolyzes the peptidoglycan in the cell walls of bacteria

1st line of defense chemical factors

• Gastric juice (pH 1.2 – 3) and enzymes destroy microbes and toxins– Except toxins of Clostridium and Staphylococcus– Helicobacter pylori – neutralizes acid and causes

ulcers

• Vaginal tract has a low pH due to the normal microbiota Lactobacillus producing various acids– Ab therapy kills off bacteria allowing Candida to

overgrow causing a yeast infection

1st line of defense genetic components

• Species immunity – some hosts are immune to diseases of other hosts– Ex. Cats don’t get mumps and humans don’t

get distemper– Not true for zoonotic pathogens that attack a

broad spectrum of animals

• Differences in susceptibility in the same species ex. Gene for sickle cell anemia – resistant to malaria

2nd line of defense – formed elements in the blood

• Phagocytes are WBCs that originate in the bone marrow, circulate in the bloodstream for awhile, then leave the circulation, and develop in the tissues– Macrophages are found in the spleen, bone marrow,

lymph nodes, brain• They develop from monocytes and monocytes are not

phagocytic• Wandering macrophages – roam tissues and go to sites of

infection or inflammation• Fixed macrophages enter tissues and organs and remain

there

2nd line of defense – formed elements in the blood

• Phagocytes continued– Neutrophils (PMNs) –phagocytic and motile,

active in the initial stages of an infection– Eosinophils – produce toxic substances

against some parasites, some phagocytosis

Leukocytes = White Blood Cells

The Phagocytic Process

• Chemotaxis = phagocytes are attracted to the area of invading microbes

• Adherence = phagocyte’s plasma membrane attaches to a microbe or particle surface

• Ingestion = pseudopods surround the bacterium and bring it into the phagocyte’s cytoplasm where fusion with lysosomes take place – now called phagolysosome

The Phagocytic Process

• Digestion =lysosomal enzymes digest the bacterium in newly formed phagolysosomes

• The process ends with the elimination of bacterial debris during egestion

Phagocytosis“It is the toll-like receptors

on macrophages that enable them to sense that the material is microbial in origin, and must therefore

be eliminated quickly.”

Chemotaxis = movement

toward infections.

2nd line of Defense - Inflammation

• Inflammation – is a reaction to injury or infection, it is a local response– Ex. Cat scratch, blistering of a burn, infection, allergy

sxs• Acute inflammation – short lived, responsible for

a single episode or injury• Chronic inflammation – lasts for weeks or years,

response to continuous or multiple episodes of injury

• Inflammation is a process that limits the extent of injury

The Process of Inflammation

• Tissue damage ex. Nail in skin w/ bacteria– Mast cells are tissue cells that trigger an inflammatory

rx. By releasing histamine which is a chemical mediator that dilates blood vessels and increases vascular permeability to plasma proteins

– Dilation of blood vessels increase the flow of blood at the site of irritation

– Dilation BVs increases delivery of leukocytes -WBCs

The Process of Inflammation

• Margination – neutrophils and monocytes stick to endothelium of blood vessels close to the injury

• Emigration – the WBCs start getting between the endothelial cells and squeeze there way out of the vessels to reach the injured area

• Phagocytosis – neutrophils augment phagocytosis while monocytes differentiate into macrophages .

Inflammation

Inflammation

4 Cardinal signs of inflammation

• 1. redness (rubor) – due to increased blood flow to the area of injury – vasodilation

• 2. swelling (tumor) – edema – blood leaks from vessels and you get an accumulation of fluid– Fluid dilutes toxic substances– Fluid may contain pus which is a mixture of

plasma, dead tissue cells, WBCs, dead bacteria

4 Cardinal signs of inflammation

• 3. heat (calor)- due to increased blood flow and the action of pyrogen ( a fever producing substance in the blood)

• 4. pain (dolor) – caused by injury to the local nerves

• 5. the final stage if inflammation is tissue repair

Fever is a systemic response that accompanies inflammation

• Body temperature is set and maintained by the hypothalamus (brain)

• Fever is initiated when a circulating substance called pyrogen sets the hypothalamus to a higher setting

• Pyrogens are exogenous (coming from outside of the body) or endogenous (originating internally)– Exogenous pyrogens are products of infectious

agents– Endogenous pyrogens are liberated by monocytes,

neutrophils, macrophages during phagocytosis

Fever is a systemic response that accompanies inflammation

• Benefits of fever:– Inhibits multiplication of temperature sensitive

microbes– Increases metabolism and stimulates the

immune response

• Complications of fever are tachycardia, dehydration, electrolyte imbalance, seizures, delirium, coma

2nd line of defense: The Complement System

• Consists of 30 different proteins circulating in the bloodstream that act in an ordered sequence or cascade – 1 protein activates another, etc.– There are 9 major components C1-C9 that are

sequentially activated to participate in inflammation, phagocytosis, and cytolysis

3 different complement pathways

• 1. Classical pathway – rapid, efficient – Antibody-microbe complex binds to and

activates C1 which triggers the complement cascade

– C3 initiates cytolysis and opsonization (coating of microbes) to promote attachment of phagocyte to microbe

3 different complement pathways

• 2. Alternative pathway – slower, less efficient– Does not involve antibodies like the classical

pathway– Pathogen surface binds to C3 – Once the complement proteins combine and

interact – C3 participates in inflammation, cytolysis, and opsonization

3 different complement pathways

• 3. Lectin pathway– Macrophages stimulate the liver to release

lectins which enhance microbial opsonization by binding to cell CH2Os

– Lectin coated pathogens bind to C4, C2

Results of complement activation

• Cytolysis – 5 complement proteins bind to form a complex called

the Membrane attack complex (MAC) which embeds itself in the plasma membrane of the microbe

– Channels are created in the membrane and water and salt leak into the microbe causing the cell to lyse.

• Inflammation can develop from complement proteins which combine with mast cells and trigger the release of histamine. Histamine increases blood vessel permeability.

Results of complement activation

• Opsonization – promotes attachment of a phagocyte to a microbe.– Complement C3 coats the microbe and then

reacts with receptors on the phagocytes for attachment

• Complement can be inactivated by regulatory proteins in the blood that cause the break down of activated complement

Com

plem

ent 1. Inactive

complement proteins are in constant circulation.

2. Complement proteins are

activated by various mechanisms.

3. These are the consequences...

2nd line of defense: Interferons

• Interferon is a group of proteins that act to interfere with viral replication.

• They are small proteins that are in 3 different types:– Alpha and Beta INFs are produced by virus infected

host cells and diffuse to neighboring uneffected cells• They induce uninfected cells to manufacture mRNA for

synthesis of antiviral proteins that interfere w/ viral multiplication

• They have no effect on viral multiplication of cells already infected

2nd line of defense: Interferons

• Interferons of a species are active against a number of different viruses – they are not virus specific

• Gamma INF is produced by lymphocytes and induce nuetrophils and macrophages to kill bacteria by phagocytosis