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NON SPESIFIK

IMUNNITY

Dr Nur Rahman, STP MP

Email: [email protected]

Prodi D4 Gizi

Politeknik Kesehatan Kemenkes Malang

IMUNOLOGI GIZI


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Summary of Important Aspects of

Innate Defense

Defense Component• First-Line Defenses Physical barriers• Antimicrobial substances

• Normal flora

• Cell Communication Surface receptors

• Cytokines

•

Adhesion molecules• Sensor Systems

• Toll-like receptors (TLRs)

• Complement System

• Phagocytes Macrophages

• Neutrophils

•

Inflammation (a coordinated response• to invasion or damage)

• Interferons

• Fever


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• The complement system consists of about 20

interacting proteins that greatly enhance the

ability of phagocytic cells to identify and

eliminate pathogens.

• The complement proteins are synthesized in

the liver, and they circulate in blood in an

inactive form

The Complement System


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• They can bind directly to the PAMPs on pathogens, andthis tags them in a way that facilitates the identificationand elimination of pathogens by phagocytic leukocytes.

• They trigger the release of histamine from mast cells.

• They facilitate the removal of antigen-antibodycomplexes. Antibodies are generated by the adaptiveimmune system, and, like complement proteins, theytag foreign substances to enhance their removal by

phagocytic cells. However, unlike complement,antibodies are highly specific in their ability to identifypathogens and foreign substances.

Other Functions of the Complement Proteins


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• The elements of the innate (non-specific)

immune system :

• Anatomical barriers,

• Secretory molecules and

• Cellular components


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• Mechanical factors

• Chemical factors

• Biological factors

Anatomical barriers to infections


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Ch i l f


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• The epithelial surfaces.• Thus, the skin acts as our first line of defense against invading

organisms.

• The desquamation of skin epithelium also helps remove bacteriaand other infectious agents that have adhered to the epithelial

surfaces.• Movement due to cilia or peristalsis helps to keep air passages and

the gastrointestinal tract free from microorganisms.

• The flushing action of tears and saliva helps prevent infection of theeyes and mouth.

•

The trapping effect of mucus that lines the respiratory andgastrointestinal tract helps protect the lungs and digestive systemsfrom infection.

Chemical factors PENTING


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Chemical factors


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• Fatty acids in sweat inhibit the growth of bacteria.Lysozyme and phospholipase found in tears, saliva andnasal secretions can breakdown the cell wall of bacteriaand destabilize bacterial membranes.

• The low pH of sweat and gastric secretions prevents growthof bacteria.

• Defensins (low molecular weight proteins) found in the lungand gastrointestinal tract have antimicrobial activity.

• Sweat also contains low molecular weight anti-microbial

peptides that interact with bacterial cell membranes(including MRSA) in which they form a channel that allowsthe passage of water and ions, disrupting thetransmembrane potential, leading to the death of the cell.

Chemical factors PENTING

http://www.mondofacto.com/facts/dictionary?query=Lysozymehttp://www.mondofacto.com/facts/dictionary?query=phospholipasehttp://www.mondofacto.com/facts/dictionary?query=phospholipasehttp://www.mondofacto.com/facts/dictionary?query=Lysozymehttp://www.mondofacto.com/facts/dictionary?query=phospholipasehttp://www.mondofacto.com/facts/dictionary?query=Defensinshttp://www.mondofacto.com/facts/dictionary?query=Defensinshttp://www.mondofacto.com/facts/dictionary?query=phospholipasehttp://www.mondofacto.com/facts/dictionary?query=Lysozyme


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• Surfactants in the lung act as opsonins

(substances that promote phagocytosis of

particles by phagocytic cells).

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Bi l i l f t


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• The normal flora of the skin and in the

gastrointestinal tract can prevent the

colonization of pathogenic bacteria by

secreting toxic substances or by competingwith pathogenic bacteria for nutrients or

attachment to cell surfaces.

Biological factors

f


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• Humoral factors play an important role in

inflammation, which is characterized by

edema and the recruitment of phagocytic

cells. These humoral factors are found inserum or they are formed at the site of

infection.

Humoral barriers to infection

http://www.mondofacto.com/facts/dictionary?query=edemahttp://www.mondofacto.com/facts/dictionary?query=phagocyteshttp://www.mondofacto.com/facts/dictionary?query=phagocyteshttp://www.mondofacto.com/facts/dictionary?query=phagocyteshttp://www.mondofacto.com/facts/dictionary?query=phagocyteshttp://www.mondofacto.com/facts/dictionary?query=edema


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• Complement system

Coagulation system

Lactoferrin and transferrin

Interferons

Lysozyme

Interleukin-1


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• Complement systemThe complement system is the major humoral non-specific defense mechanism

• Coagulation system For example, beta-lysin, a protein produced by platelets during coagulation can lyse many Grampositive bacteria by acting as a cationic detergent.

Lactoferrin and transferrin

By binding iron, an essential nutrient for bacteria, these proteins limit bacterial growth.

Interferons Interferons are proteins that can limit virus replication in cells.

Lysozyme Lysozyme breaks down the cell wall of bacteria.

Interleukin-1

Il-1 induces fever and the production of acute phase proteins, some of which are antimicrobialbecause they can opsonize bacteria.


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• There are several simple physical and chemical

barriers that constitute and important first

line of defense.

Physico-chemical barriers to infections


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System/Organ Activecomponent

Effector Mechanism

Physico chemical barriers to infections

Skin Squamous cells; Sweat Desquamation; flushing, organic acids

GI tract Columnar cells Peristalsis, low pH, bile acid, flushing, thiocyanate

Lung Tracheal cilia Mucocialiary elevator, surfactant

Nasopharynx and eye Mucus, saliva, tears Flushing, lysozyme

Circulation and lymphoid organs Phagocytic cells

NK cells and K-cell

LAK

Phagocytosis and intracellular killing Direct and antibody

dependent cytolysis

IL2-activated cytolysis

Serum Lactoferrin and Transferrin Iron binding

Interferons Antiviral proteins

TNF-alpha antiviral, phagocyte activation

Lysozyme Peptidoglycan hydrolysis

Fibronectin Opsonization and phagocytosis

Complement Opsonization, enhanced phagocytosis, inflammation

Cellular barriers to infection


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• Neutrophils

Macrophages

Natural killer (NK) and lymphokine activated

killer (LAK) cells

Eosinophils


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• Neutrophils Polymorphonuclear cells (PMNs, figure 4) are recruited to the site of infectionwhere they phagocytose invading organisms and kill them intracellularly.

Macrophages Tissue macrophages (figure 5, 6, 7) and newly recruited monocytes (figure 4 and8), which differentiate into macrophages, also function in phagocytosis and

intracellular killing of microorganisms. In addition, macrophages are capable ofextracellular killing of infected or altered self target cells. Furthermore,macrophages contribute to tissue repair and act as antigen-presenting cells, whichare required for the induction of specific immune responses.

Natural killer (NK) and lymphokine activated killer (LAK) cells NK and LAK cells can nonspecifically kill virus infected and tumor cells. These cells

are not part of the inflammatory response but they are important in nonspecificimmunity to viral infections and tumor surveillance.

Eosinophils Eosinophils (figure 6a and b) have proteins in granules that are effective in killingcertain parasites.


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• Sel neutrofil polimorfonuklear (PMN, angka 4) direkrut ke tempat infeksi dimana mereka menfagositosis menyerang organisme dan membunuhmereka intraseluler.

• makrofag makrofag Tissue (gambar 5, 6, 7) dan monosit yang baru direkrut(gambar 4 dan 8), yang berdiferensiasi menjadi makrofag, juga berfungsidalam fagositosis dan pembunuhan intraseluler mikroorganisme. Selain

itu, makrofag mampu membunuh ekstraseluler dari sel target diriterinfeksi atau diubah. Selanjutnya, makrofag berkontribusi perbaikan jaringan dan bertindak sebagai sel antigen-presenting, yang diperlukanuntuk induksi respon imun spesifik.

• Sel-sel pembunuh alami (NK) dan limfokin pembunuh diaktifkan (LAK) selNK dan LAK nonspesifik dapat membunuh virus terinfeksi dan tumor sel.Sel-sel ini bukan merupakan bagian dari respon inflamasi tetapi merekapenting dalam imunitas nonspesifik terhadap infeksi virus danpengawasan tumor.

• Eosinofil eosinofil (gambar 6a dan b) memiliki protein dalam butiran yangefektif dalam membunuh parasit tertentu.

PHAGOCYTOSIS AND INTRACELLULAR KILLING


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• Phagocytic cellsNeutrophiles/Polymorphonuclear cells

Monocytes/Macrophages

• Response of phagocytes to infection

• Initiation of Phagocytosis

Fc receptors

Complement receptors

Scavenger receptors

Toll-like receptors

• Phagocytosis

PHAGOCYTOSIS AND INTRACELLULAR KILLING PENTING

Respiratory burst and intracellular


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Respiratory burst and intracellular

killing

• Ada peningkatan konsumsi glukosa dan

oksigen.

• Jumlah oksigen yg mengandung kemampuan

membunuh bakteri menjadi fagositosis.

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• Oxygen-dependent myeloperoxidase-

independent intracellular killing

• Oxygen-dependent myeloperoxidase-

dependent intracellular killing

• Detoxification reactions


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Reaction Enzyme

H2O2 + Cl- --> OCl- + H2O

Myeloperoxidase

OCl- + H2O -->1O2 +Cl

- + H2O

2O2 + 2H+ --> O2

- + H2O2 Superoxide dismutatse

H2O2 --> H2O + O2 Catalase


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NITRIC OXIDE-DEPENDENT KILLING


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NON-SPECIFIC KILLER CELLS

• NK and LAK cells

Natural killer (NK) disebut juga large granular

lymphocytes (LGL)• NK cells can be identified by the presence of

CD56 and CD16 and a lack of CD3 cell surfacemarkers.

• NK cells are capable of killing virus-infectedand malignant target cells tapi tdk efisien.


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• pembunuh alami ( NK ) disebut also limfosit

granular besar ( LGL ) sel NK dapat

diidentifikasi dengan adanya CD56 dan CD16

dan kurangnya CD3 penanda permukaan sel .Sel NK mampu membunuh virus yang

terinfeksi dan sasaran ganas sel TAPI tdk

pengerjaannya efisien


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• How do NK and LAK cells distinguish a normal cell from a virus-infected or malignant cell? NK and LAK cells have two kinds ofreceptors on their surface – a killer activating receptor (KAR) and akiller inhibiting receptor (KIR). When the KAR encounters its ligand,a killer activating ligand (KAL) on the target cell the NK or LAK cellsare capable of killing the target. However, if the KIR also binds to its

ligand then killing is inhibited even if KAR binds to KAL. The ligandsfor KIR are MHC-class I molecules. Thus, if a target cell expressesclass I MHC molecules it will not be killed by NK or LAK cells even ifthe target also has a KAL which could bind to KAR. Normal cellsconstitutively express MHC class I molecules on their surface,however, virus infected and malignant cells down regulate

expression of class I MHC. Thus, NK and LAK cells selectively killvirus-infected and malignant cells while sparing normal cells.


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• Bagaimana sel NK dan LAK membedakan sel normal dari sel yangterinfeksi virus atau ganas ? sel NK dan LAK memiliki dua jenisreseptor pada permukaannya - pembunuh mengaktifkan reseptor (KAR ) dan pembunuh menghambat reseptor ( KIR ) . Ketika KARpertemuan ligan , pembunuh mengaktifkan ligan ( KAL ) pada seltarget sel NK atau LAK mampu membunuh target . Namun, jika KIR

juga mengikat ligan maka pembunuhan terhambat bahkan jika KARmengikat KAL . Ligan untuk KIR adalah molekul MHC kelas I .Dengan demikian , jika sel target mengekspresikan kelas I MHCmolekul tidak akan dibunuh oleh sel NK atau LAK bahkan jika target juga memiliki KAL yang bisa mengikat KAR .

• Sel-sel normal konstitutif mengekspresikan molekul MHC kelas Ipada permukaannya , namun, terinfeksi virus dan sel ganas turunmengatur ekspresi dari kelas I MHC . Dengan demikian , sel NK danLAK selektif membunuh sel yang terinfeksi virus dan ganassementara hemat sel normal

Natural Killer Cells (NK Cells)


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• Vertebrates have "histocompatibility molecules,"referred to as "major histocompatibility complex"molecules (MHC).

• Theses are large glycoprotein molecules that are found

in the cell membranes of most vertebrate cells. Inhumans, the MHC molecules (also referred to as MHCantigens) are called Human Leukocyte Antigens (HLA).

• The MHC molecules play an important role in helping

our immune cells to distinguish between our own cells(self) and foreign cells or substances (non-self).


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• K cells (Figure 14)

Killer (K) cells are not a morphologically distinct type ofcell. Rather a K cell is any cell that mediates antibody-dependent cellular cytotoxicity (ADCC). In ADCC

antibody acts as a link to bring the K cell and the targetcell together to allow killing to occur. K cells have ontheir surface an Fc receptor for antibody and thus theycan recognize, bind and kill target cells coated withantibody. Killer cells which have Fc receptors includeNK, LAK, and macrophages which have an Fc receptorfor IgG antibodies and eosinophils which have an Fcreceptor for IgE antibodies.


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• Killer ( K ) sel bukan tipe morfologis yang berbeda darisel . Sebaliknya sel K adalah setiap sel yang menengahisitotoksisitas sel antibodi - dependent ( ADCC ) . DalamADCC antibodi bertindak sebagai penghubung untukmembawa sel K dan sel target bersama-sama untuk

memungkinkan membunuh terjadi . sel K memilikipada permukaannya reseptor Fc untuk antibodi dandengan demikian mereka dapat mengenali , mengikatdan membunuh menargetkan sel-sel dilapisi denganantibodi . sel-sel pembunuh yang memiliki reseptor Fctermasuk NK , LAK , dan makrofag yang memilikireseptor Fc untuk antibodi IgG dan eosinofil yangmemiliki reseptor Fc antibodi IgE .

Given the effectiveness of intact skin


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Given the effectiveness of intact skin,

our major vulnerabilities are:

• The respiratory tract: we take air from theexternal environment into our respiratory tractand lungs continually - every minute, every hour,every day, as long as we live.

• The gastrointestinal tract: we eat and drink everyday, and this provides another potential portal forentry of pathogens.

• The genito-urinary tract: the urethra and vagina

are potential portals for entry of microbes,especially during sexual encounters

• Even the eyes provide a portal of entry

These are our major vulnerabilities but we have


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These are our major vulnerabilities, but we have

evolved non-specific defenses for these.

•The mucous membranes of the eyes are bathed in tears, which contain an enzyme called lysozymethat attacks bacteria and helps protect the eyes from infection.

• The hairs and mucus in our nose trap inhaled particles, and the walls of our respiratory tract arelined with cells that secrete mucus to trap particles and pathogens.

• The cells lining the respiratory tract have cilia, hair-like projections that beat in a coordinated wayto sweep mucus and entrapped particles up to the pharynx, where it can be swallowed orexpectorated.

• Coughing and sneezing can be thought of as mechanical means of expelling pathogens and noxious

chemicals• Our digestive tract also provides barriers. Acid in the stomach and enzymes in the intestine destroy

pathogens. The gastrointestinal tract also has cells that secrete mucus, which acts as a barrier.

• The gastrointestinal tract is also surrounded my smooth muscle cells that propel thegastrointestinal contents in a wavelike fashion referred to as peristalsis. Noxious gastrointestinalcontents can be expelled by diarrhea, which involves both increased flushing from secretion of fluidinto the GI tract and increases peristalsis. Vomiting is a complicated reflex that provides anothermeans of expelling noxious materials

•The urethra is periodically flushed by urine.

• The acidic pH of the vagina makes it inhospitable for many pathogens.

• Biological barriers: The normal bacteria on our skin and in our respiratory, digestive, and uro-genitaltracts protect us by competing with pathogens for attachment and essential nutrients.


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Innate Immunity

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