PENGENALAN SISTEM IMUN

dr. Rahmawati Minhajat. PhD.,SpPD

Fakultas Kedokteran Universitas Hasanuddin

Imunitas (Immunity) kekebalan atau resistensi terhadap penyakit, khususnya penyakit infeksi.

Sistem Imune kumpulan sel-sel, jaringan & molekul yang berperan pada kondisi resistensi terhadap infeksi.

Respon imun reaksi sel & molekul terhadap infeksi mikroba.

Immunology ilmu yang mempelajari sistem kekebalan tubuh dan responnya terhadap patogen.

Fungsi fisiologi sistem imun

mencegah dan mengeradikasi infeksi

Immunitas dapat diinduksi pada seseorang melalui:

- Infeksi atau vaksinasi (active immunity)

- Transfer antibodi atau limfosit dari seseorang yang sudah mendapat/mempunyai kekebalan (passive immunity)

Dua tipe respon imun:

Innate immunity

Adaptive immunity

=natural =native =nonspecific =nonadaptive

Immunity/immune response

=spicific =acquared Immunity/immune response

This type of host defence is always present in healthy individuals, prepared to block the entry of microbes & to rapidly eliminate microbes that succeed in entering host tissue

The type of host defence that is stimulated by microbes that invade tissues, that is, it adapts to the presence of microbial invaders

Imunitas nonspesifik

Positif:

- Selalu siap

- Respon cepat

- Tidak perlu ada pajanan ebelumnya

Negatif:

- Dapat berlebihan

- Kekurangan memori

Imunitas spesifik

Negatif:

- Tidak siap sampai

terpajan

- Respon lambat

Positif:

- respon intens

- Perlindungan lebih baik pada pajanan berikutnya

Presentasi antigen

Sitokin

Peranan sistem

imun

nonspesifik

Pertahanan

fisik/mekani

k

(kulit, epitel)

Pertahanan

humoral

(komplemen,

protein fase

akut, sitokin,

dll)

Pertahanan

biokimia

(enzim, asam

lambung, dll)

Pertahanan

selular (fagosit,

sel NK, eosinofil,

dll)

Organ Lymfoid 1. Organ Limfoid Primer a. Bone marrow - Tempat limfosit B dan T diproduksi - Tempat pematangan sel B b. Thymus - Tempat pematangan sel T 2. Organ Limfoid Sekunder a. Limphonodes b. Spleen c. Malt (Mucosa Associated Lymphoid Tissue). - Gastrointestinal tract - Respiratory tract - Genitourinaria tract

The lymphatic system

The major lymphatic vessels and collections of lymph nodes

Hematopoesis di Bone marrow

Thymus

-A bilobed organ - anterior mediastinum

Cortex dense collection of T lymphocytes (thymocytes= T lymphocytes at various stage of maturation)

Efferent lympatic vessels drain into mediastinal lymph nodes

Medulla contains mostly mature T lymphocytes

Only mature T cells exit the thymus and enter the blood circulation and peripheral lymphoid tissues

Secondary limphoid organs

Lymph nodes

Spleen

Cutaneous immune system

Mucosal immune system

Where lymphocytes responses to foreign antigens

Connective tissue & virtually all organs except the CNS Poorly defined

(Bone marrow)

(thymus))

Spleen

The lymphatic system

The major lymphatic vessels and collections of lymph nodes

-Naive T cell chemokine receptor CCR7 that binds the CCL9 & CCL21 chemokines produced in the T zone. -Nive B cell chemokine receptor CXCR5 which recoqnized a chemokine CXCL13 produced only in follicles (B cell zone)

Lymph nodes

Spleen

Major site of immune responses to blood-borne antigens

Cutaneous immune system

Langerhans cell encounter microbes

Activated by engagement of Toll-like receptors

The cells lose their adhesiveness for epidermis

Enter to lymphatic vessels, begin to Express the CCR7 chemokine receptor

Migrate to T cell zones lymph nodes in respons to chemokines produced in thar location.

Epidermis

Dermis Intraepidermal lymphocytes only + 20% of skin associated lymphocytes >> CD8+ Cotains T lymphocytes (CD4+ and CD8+ cells)

Phenotypic markres Activated or memory cells

-Intraepithelial layer >> T cell (>>CD8+/10% TCR) and TCR have limited diversity of antigen receptors - Lamina propria mixed population of T cells (>>CD4+) and B cells (plasma cells), macrophages, dendritic cells, eosinophils, mast cells. -Peyers patches follicles : >> B cells Interfollicular region:

M cells: transport macromolecules From intestinal lumen into subepithelial tissue. Transepithelial transport mechanism =transitosis. Deliver antigens to peyers patch

Defense in innate immunity

Epithelial barrier natural antibiotics present in epithelia To block the entry of microbes

Phagocytes, NK cells, plasma protein (complement system)

All these mechanisms of innate immunity specifically recognize and react against microbes but do not react against noninfectious foreign substances

If microbes do breach epithelia & enter the tissues or circulation

Different mechanisms of innate immunity may be specific for molecules produced by different classes of microbes

To providing early defense against infections, innate immune responses enhance adaptive immune responses against the infectious agents.

Innate immune recognize structures shared by classes of microbes.

adaptive immune express receptors that specifically recognize different substances (antigens) produced by microbes as well as noninfectious molecules.

adaptive immune are only triggered if microbes or their antigens pass through epithelial barriers & delivered to lymphoid organs where they can be recognized by lymphocytes

adaptive immune - produce antibodies - to eliminate microbes in extracellular fluids - to activate T limphocytes and eliminate microbes living inside cells - use the cells and molecules of the innate immune system to eliminate microbes

Types of adaptive immunity

Antibodies are produced by B lymphocytes secreted into circulation and mucosal fluids. They neutralize & eliminate microbes and microbial toxins that are present in blood and in the lumens of mucosal organ.

Antibodies do not have access to microbes that live and divide inside infected cells

Antibodies produced by B lymphocytes are designed to specifically recognize extracellular microbial antigen. Able to recognize many different types of microbial molecules, including proteins, carbohydrates & lipids

Whereas, T lymphocytes recognize antigens produced by intracellular microbes. T lymphocytes recognize only microbial protein antigen

Phase of adaptive immune responses

Antigen recognition

Decline

Elimination of antigen

Activation of lymphocytes

Memory

Lymphocytes require at least two types of signals: - antigen binding to the antigen receptors of lymphocytes (signal 1) is required to initiate all immune responses - signal 2 are provided by microbes & by innate immune responses to microbes are needed for activation of lymphocytes in primary immune responses

Innate Immunity

dr. Rahmawati Minhajat, PhD

Innate Immunity = natural/native immunity

-Always present - ready to recognize & eliminate microbes

- They recognize & respond to microbes but do not react againts nonmicrobial substances. -May also be triggered by host cells that are demaged by microbes

Innate Immunity - specifically targets microbes - a powerful early mechanism before adaptive immunity becomes active -Not only provides the early defense against infections but also instructs the adaptive immune system. Conversely adaptive immune responses often uses mechanism of innate immunity to eradicate infections

There is a constant bidirectional cross-talk between Innate Immunity and adaptive immunity

Imunitas nonspesifik

Positif:

- Selalu siap

- Respon cepat

- Tidak perlu ada pajanan ebelumnya

Negatif:

- Dapat berlebihan

- Kekurangan memori

Imunitas spesifik

Negatif:

- Tidak siap sampai

terpajan alergen

- Respon lambat

Positif:

- respon intens

- Perlindungan lebih baik pada pajanan berikutnya

Presentasi antigen

Sitokin

Recognition of microbes by the Innate Immunity

Component of innate Immunity recognize structures that are shared by various classes of microbes and are not present on host cells

Each component of innate Immunity may recognize many bacteria or viruses or fungi

For instance: Phagocytes express receptors for bacterial lipopolysaccharide (LPS/endotoxin), which is present in many bacterial species but not produced by mammalian cells. Other receptors of phagocytes recognize terminal mannosa residues on glycoproteins (many bacteril glycoprotein Have terminal mannosa). Phagocytes recognize & respond to double-stranded RNA, which is found in many viruses but not in mammalian cells

The receptors of the innate immunity system are encoded in the germline and are not produced by somatic recombination of genes

It is estimated that total population of lymphocytes can recognize billion different antigens, but innate immunity Probably recognize less than a thousand microbial patterns.

Innate imunity system responds in the same way to repeat encounters with a microbe, whereas the adaptive immune system responds more efficiently to each successive encounter with microbes

Components of innate immunity

- Epithelia - Phagocytes ( neutrophils and monocytes/ macrophages) - Natural killer (NK ) cells - Complement system - Cytokines

Phagocytes ( neutrophils and monocytes/macrophages)

Neutrophils = polymorphonuclear leucocytes (PMN) The most abundant leukocytes in the blood (4000-10.000 per mm3)

Infections production of neutrophils from bone marrow increases rapidly ( 20.000 per mm3 ) Production of neutrophils is stimulated by cytokines, known as colony-stimulating factors, that are produced by many cell types In response to infections and act on bone marrow stem cells to stimulate Proliferation and maturation of neutrophils precurssors. Neutrophils are the first cells type to respond to most infections, particularly bacterial and fungal infections. Neutrophils ingest microbes in the circulation & they rapidly enter extravascular tissues at site of infection, where they also ingest the microbes and die after a few hours

Monocytes are less abundant than neutrophils (500-1000 per mm3) Ingest microbes in circulation and tissue. Unlike neutrophils, monocytes that enter extravascular tissue survive in these site for long periods; in the tissues, these monocytes differentiate into cells called macrophages

Neutrophils and monocytes migrate to extravascular sites of infection by binding to endothelial adhesion molecules and in response to chemoactractants (chemokines)

There are several different types of receptors, specific for different structures or patterns are frequently found on microbial molecules : -Toll-like receptors (TLRs) -Receptors that recognize N-formylmethionine-containing peptides (produced by microbes but not host cells -Mannosa receptors -Integrins (Mac-1) - Scavenger receptors Machrophages also express receptors for cytokines, such as interferon (INF-)

Natural killer cells (NK cells)

NK cells are a class of lymphocytes that respond to intracellular microbes

By killing infected cells and by producing the macrophage activating cytokine

(INF-)

NK cells recognize host cells that have been altered by microbial infection

The complement system

Collection of circulating and membrane-associated proteins that are important in defense againts microbes (>> proteolitic enzymes

Complement activation involves the sequential activation of these enzyme (enzymatic cascade)

Complement cascade may be activated by one of three pathway

Alternative pathway

Classical pathway

Lectin pathway

It is triggered when some complement proteins are activated on microbial surfaces and cannot be controlled because complement regulatory protein are not present on microbes (but are present on host cells) this pathway is component of innate immunity

It is triggered after antibody bind to microbes or other antigens and It thus component of humoral arm of adaptive immunity

It iss activated when a plasma protein, mannosa-bindi ng lectin, binds to terminal mannosa sidues on the surface glicoproteins of microbes. This lactin activates proteins of classic pathway, but because it is initiated in the absence of antibody it is a component of innate immunity

Central component of complement is a plasma protein called C3

Selamat Belajar

Innate immune recognize structures shared by classes of microbes.

adaptive immune express receptors that specifically recognize different substances (antigens) produced by microbes as well as noninfectious molecules.