1. Innate immunity provides the first line of defense against pathogens and includes physical, chemical, and cellular barriers that prevent infection and promote destruction of microbes. 2. Physical barriers like skin and mucous membranes block entry of pathogens, while chemical barriers such as stomach acid and antimicrobial peptides help eliminate microbes. 3. Cells of the innate immune system like macrophages, neutrophils, and natural killer cells help detect and destroy pathogens through mechanisms like phagocytosis, cytokine release, and activation of the complement system.

1. INNATE
(NONSPECIFIC)
IMMUNITY
By Aleena Zafar

2. context
■ Introduction
■ Innate immunity
■ Barriers of innate immunity
1. Physical and anatomic barriers
2. Physiological barrier
3. Endocytosis and phagocytosis
4. Inflammation
■ Cell of innate immunity

3. immunity
■ capability of multicellular organisms to resist harmful microorganisms from entering
it.
■ Immunity involves both specific and nonspecific components.The nonspecific
components act as barriers or eliminators of a wide range of pathogens irrespective of
their antigenic make-up.

4. Introduction to immune system
■ The immune system is remarkably adaptive defense system that has evolved in
vertebrates to protect them from invading pathogenic microorganisms and cancer. Its
is able to generate an enormous variety of cells and molecule capable of specifically
recognizing and eliminating an apparently limitless variety of foreign invader.
■ Two types of immunity
■ Innate nonspecific immunity
■ Acquired specific immunity

5. Innate immunity
■ Quick response
■ Generalized
■ Present at birth
■ Block entry of microbes and eliminate succeeded microbes which entered the host
■ No memory
■ Innate immunity include 4 types of defensive barrier
1. physical and Anatomic
2. Physiologic
3. Endocytic and phagocytic barrier
4. inflammatory

6. Physical and Anatomic barriers
■ Prevent entry of pathogens
■ 1st line of defense
■ Skin and surface and mucus membrane are included

7. skin
■ Consist of two layer
1. Outer thin layer the epidermis
2. Inner thick layer dermis
3. Skin PH is 3-5 inhibitory to the growth of most microorganism
4. Few bacteria metabolizes sebum live as commensals responsible for severe form of
acne
5. Isotretinoin prevents sebum formation
6. Break in the skin are obvious route of infection

8. skin
■ The skin also is penetrated by bite of insects like ticks, mite fleas
■ They introduce the pathogen as they feed
■ E.g. plasmodium by mosquitos, bubonic plague is spread by the bite of fleas

9. Mucus
■ Alimentary , respiratory and urogenital tract covered by mucous membrane
■ Mucous membrane consist of two layer
■ Outer epithelial layer
■ Inner connective tissue layer
■ Number of non specific defense mechanisms serve to prevent the entry
■ E.g. saliva tears and mucous secretion

10. Mucus
■ In Lower respiratory and GIT tract the mucous membrane is covered by cilia, which
move In synchronous fashion to propel mucous entrapped Microorganisms from them
■ But some organisms have evolved a way to escape these defense mechanism and
evade the body through mucous membrane.
■ E.g. influenza virus and gonorrhea

11. Physiologic barriers
■ Physiologic barriers include
1. Temperature
Many species are not susceptible to a certain disease simply because their body
temperature inhibits pathogen growth
Chicken displays innate immunity to anthrax because they have high body
temperature

12. Ph (gastric acidity)
■ 2. gastric acidity
■ Provide innate physiological barrier
■ Very few ingested microorganism can survive in low ph. of the stomach
■ one reason newborns are susceptible to one disease that their stomach contents are
less acidic than that of the adults

13. Soluble factors
■ A variety of soluble factors also contribute to non specific immunity
1. Lysozyme a hydrolytic enzyme found in mucus secretion is able to cleave the
peptidoglycan layer of bacterial cell wall
2. Interferons a group of proteins are produced by virus infected cells and induced a
generalized antiviral state
3. Complement is a group of serum proteins that circulate an inactive proenzyme state
these proteins can be activated by verity of specific and non specific immunologic
mechanisms that convert inactive proenzyme into enzyme as a result controlled
enzymatic cascade damaging the organism membrane and facilitate their clearance

14. Endocytic and phagocytic barriers
■ Ingestion of extracellular molecule
■ Endocytosis
■ Extracellular tissue fluids are internalized by cells
■ Small region of plasma membrane invaginates
■ Forming about 0.1um endocytic vesicle
■ Endocytosis occur through one of the two process
■ Pinocytosis
■ Molecule are internalized through non specific membrane invagination

15. ■ Because pinocytosis is non
specific the internalization of
macromolecules occur in
proportion to their
concentration

16. Receptor mediated endocytosis
■ Macromolecules are internalized by binding to a specific receptors
■ Following internalization by either process the endocytic vessel fuse with each other
and delivered to endosomes
■ Endosome acidic compartment serve as a sorting function
■ Acid environments facilitates dissociation of the receptors ligands
■ Remaining endosome fuse with primary lysosomes to form a structure secondary
lysosomes
■ Primary lysosome contained digestive enzyme like protease, nuclease and lipases and
other hydrolytic enzyme

17. ■ With in secondary lysosome
ingested macromolecules are
then digested into small
break down products e.g.
peptides nucleotides and
sugar
■ Eliminated from the cell

18. phagocytosis
■ Involve the ingestion of particulate material including whole pathogenic
microorganisms
■ Plasma membrane expends around the particle materials to form large vesicle called
phagosomes
■ Expansion of membrane require participation of microfilaments
■ One particulate material is ingested it form phagosome
■ Fuse with lysosome
■ Then digested by endocytic process

20. Difference between endocytosis and
phagocytosis
endocytosis phagocytosis
Small vesicle Large vesicles
No microfilament involve Participation of microfilament
Virtually all cell are capable of endocytosis Specialized cell are capable of phagocytosis
Blood monocytes, neutrophils and tissue
macrophages

21. Barrier
created by
inflammatory
responses
■ Inflammation
■ a localized physical condition in which part of
the body becomes reddened, swollen, hot, and
often painful, especially as a reaction to injury or
infection.
■ Celsus described four signs of inflammation
1. Rubor redness
2. Calor heat
3. Dollor pain
4. Tumor swelling
In second centuryA.D another physician Galen
added a fifth sign
Functio laesa loss of function

22. steps
■ Three major events during
inflammation
1. Vasodilation
2. Increase capillary
permeability
3. Influx of phagocytic cells

23. vasodilation
■ An increase of diameter of blood vessels
■ Any injury cause engorgement of capillary network
■ Engorged capillary are responsible for redness also called erythema
■ And increase in tissue temperature (Heat)

24. Increase in capillary permeability and
influx of phagocytic cell
■ Increase in capillary permeability facilitates an influx of fluid and cell from the
engorged capillaries into the tissue
■ The fluid that accumulate has much higher content of protein
■ Accumulation of exudate contribute to tissue swelling (edema)
■ Increase capillary permeability also accumulate influx white blood cell to injured tissue
a process called diapedesis

26. Cells of innate immunity
■ The white blood cells involve in innate immunity are
■ Monocytes (which develop into macrophages)
■ Neutrophils
■ Eosinophils
■ Basophils
■ Natural killer cells
■ Other participants in innate immunity are
■ Mast cells
■ The complement system
■ Cytokines

27. Monocytes and macrophages
■ Macrophages develop from a type of white blood cell called monocytes. Monocytes
become macrophages when they move from the bloodstream to the tissues.
■ over a period of about 8 hours, monocytes enlarge greatly and produce granules
within themselves, becoming macrophages.
■ The granules are filled with enzymes and other substances that help kill and digest
bacteria and other foreign cells. Macrophages stay in the tissues.They ingest bacteria,
foreign cells, and damaged and dead cells.
■ Macrophages secrete substances that attract other white blood cells to the site of the
infection.They also helpT cells recognize invaders and thus also participate in
acquired immunity.

28. Neutrophils
■ Neutrophils, the most common type of white blood cell in the bloodstream, are
among the first immune cells to defend against infection.They are phagocytes, which
ingest bacteria and other foreign cells. Neutrophils contain granules that release
enzymes to help kill and digest these cells.
■ Neutrophils circulate in the bloodstream and must be signaled to leave the
bloodstream and enter tissues.The signal often comes from the bacteria themselves,
from complement proteins, or from damaged tissue, all of which produce substances
that attract neutrophils to a trouble spot. (The process of using substances to attract
cells to a particular site is called chemotaxis.)
■ Neutrophils also release substances that produce fibers in the surrounding tissue.
These fibers may trap bacteria, thus keeping them from spreading and making them
easier to destroy.

29. Eosinophils
■ Eosinophils can ingest bacteria, but they also target foreign cells that are too large to
ingest. Eosinophils contain granules that release enzymes and other toxic substances
when foreign cells are encountered.These substances make holes in the target cell’s
membranes.
■ Eosinophils circulate in the bloodstream. However, they are less active against
bacteria than are neutrophils and macrophages.One of their main functions is to
attach to and thus help immobilize and kill parasites.
■ Eosinophils may help destroy cancer cells.They also produce substances involved in
inflammation and allergic reactions. People with allergies, parasitic infections, or
asthma often have more eosinophils in the bloodstream than people without these
disorders.

30. Basophils
■ Basophils do not ingest foreign cells.They contain granules filled with histamine, a
substance involved in allergic reactions.When basophils encounter allergens (antigens
that cause allergic reactions), they release histamine. Histamine increases blood flow
to damaged tissues, resulting in swelling and inflammation.
■ Basophils also produce substances that attract neutrophils and eosinophils to a
trouble spot.

31. Natural Killer Cells
■ Natural killer cells are called “natural” killers because they are ready to kill as soon as
they are formed. Natural killer cells recognize and attach to infected cells or cancer
cells, then release enzymes and other substances that damage the outer membranes
of these cells. Natural killer cells are important in the initial defense against viral
infections.
■ Also, natural killer cells produce cytokines that regulate some of the functions ofT
cells, B cells, and macrophages.

32. Mast Cells
■ Mast cells are present in the tissues.Their function resembles that of basophils in the
blood.When they encounter an allergen, they release histamine and other substances
involved in inflammatory and allergic reactions.

33. Complement System
■ The complement system consists of more than 30 proteins that act in a sequence: One protein activates another, which
activates another, and so on to defend against infection.This sequence is called the complement cascade.
■ Complement proteins have many functions in acquired immunity as well as innate:
■ Killing bacteria directly
■ Helping destroy bacteria by attaching to them and thus making the bacteria easier for neutrophils and macrophages to
identify and ingest
■ Attracting macrophages and neutrophils to a trouble spot
■ Neutralizing viruses
■ Helping immune cells remember specific invaders
■ Promoting antibody formation
■ Enhancing the effectiveness of antibodies
■ Helping the body eliminate dead cells and immune complexes (which consist of an antibody attached to an antigen)

34. Cytokines
■ Cytokines are the messengers of the immune system.White blood cells and certain
other cells of the immune system produce cytokines when an antigen is detected.
■ There are many different cytokines, which affect different parts of the immune
system:
■ Some cytokines stimulate activity.They stimulate certain white blood cells to become
more effective killers and to attract other white blood cells to a trouble spot.
■ Other cytokines inhibit activity, helping end an immune response.
■ Some cytokines, called interferons, interfere with the reproduction (replication) of
viruses.
■ Cytokines also participate in acquired immunity.