IMUNITAS ALAMI DAN IMUNITAS ADAPTIF

Ratna Kusumawati

sistemimun

benda asing= antigen

Respons imun

nonspesifik

spesifik

selular homural

Organisasi Sistem Imun Tubuh• antigen dan imunogen• imunitas bawaan dan didapat• imunitas humoral dan seluler

Elemen dan Komponen Sistem imun• komponen seluler• komponen humoral

The Phases of Immunity

IMUNITAS

INNATE IMMUNITY

KOMPONEN SELULER

Fagosit: MakrofagNeutrofil

Sel NK

ADAPTIVE IMMUNITY Lymphocyte T Lymphocyte B

INNATE IMMUNITY

KOMPONEN HUMORAL

KomplemenFagosit:

dllADAPTIVE IMMUNITY

Antibodi

KOMPONEN INNATE IMUNITY

Innate Immunity• Innate immunity predates development of

adaptive immunity

• Does not produce protective immunity– No memory response– Prerequisite for developing adaptive immunity

• Non-antigen-specific immunity– Found in plants, invertebrates and vertebrates

Innate Immunity

• 1. Provides a barrier to prevent the spread of infection– Mechanical (tight junctions, movement)– Chemical (fatty acids, enzymes, pH,

antimicrobial peptides)– Microbiological (normal flora)– Mucosal surfaces

• Nasopharyngeal, Oral, Respiratory, Intestinal tract Urogenital tract

– Skin (epithelial cells)• Wounds, burns, insect bites

Innate Immunity

• 2. Identifies and eliminates pathogens – Non-adaptive recognition systems– Activates molecules that target the microbe and

aid in it’s identification.• These factors may be expressed at the surface or within

cells, released from immune cells or are secreted and present within circulatory system

Innate Immunity• 3. Initiates an inflammatory response

– Reaction to injury or infection• Trauma to tissues or cells• Presence of foreign matter (self vs. non-self)• Infectious agents (viruses, bacteria, fungi)

– Delivers effector molecules & immune cells to the site of infection

– Components• Leukocytes & secreted factors• Blood vessels• Plasma proteins

Innate Immunity• 4. Provides signals to activate and regulate the

type of adaptive immune response generated– Stimulation of co-stimulatory molecules

• B7 family (CD80/86, PD-L, ICOSL)• TNFR family (OX40L)

– Induction of a cytokine/chemokine response• Cytokines: IL-12, IL-23, IL-4• Chemokines: CXCR1, CXCR2, CCL20

» a variety and depends on stimulus

Identification of Microbes• Recognition

– Receptors – Pattern Recognition Receptors (PRRs)

• Fixed in the genome, ie gene rearrangement is not needed

– Distribution• Non-clonal, ie all cells of a class are identical

• Differentiation– Pathogen vs. Commensal

Identification of Microbes• PRR

– Recognize conserved molecular patterns on microbes called microbe associated molecular patterns (MAMPs) which are not present on the host

• Not limited to pathogens– Identify a class of microbes

• LPS, LTA, peptidoglycan, lipoarabinomannan, dsRNA, mannans, b-glycans

– MAMPs are often essential for microbe survival• Action Time

– Immediate activation of effectors– Delays need for adaptive immunity

Pattern Recognition Receptors (PRRs)

• Three broad classes of PRRs based on expression profile, localization, function– 1) PRRs that signal an infection

• Include the Toll Receptor Family (TLR)• Expressed external or internally • Activation of “pro-inflammatory” signaling pathways

– NFkB and MAP kinase signaling pathways» Antimicrobial peptides (Defensins) / lysozyme,» Inflammatory cytokines (TNFa, IL-8, IL-1)

• Regulate activation of adaptive immune response» co-stimulatory molecules

– 2) Phagocytic (endocytic) PRRs• Expressed on the surface of phagocytic cells

– (MQs, PMNs, DCs)

• Mediate uptake of microbe into phagocytes

– 3) Secreted PRRs• Secreted by MQs, epithelial cells, liver• Activate C’, opsonize microbial cells, function as

accessory proteins for MAMP recognition

Pattern Recognition Receptors (PRRs)

Secreted PRRs activate the Complement (C’) System

• Complement system is activated by innate immunity• Recognition by Complement receptors (CR)

• CR1, CR2, CR3, CR4, C5a, C3a

• Comprised of plasma proteins that when activated forms a triggered enzyme cascade– Zymogens – activated by the cleavage of other proteases

• Precursor enzymes

• Function– Facilitates the uptake & destruction of pathogens by phagocytes– Induces an inflammatory responses

Inflammatory Response

Inflammatory Response

Leukocyte Adhesion

Phagocytosis• Phagocytosis

– Definition: uptake of large particles (>0.5 mm)– Actin-dependent, clathrin-independent– High rate & efficiency of internalization

• Professional phagocytic cells– Macrophages– Neutrophils

• These cells have phagocytic receptors• External receptors

– FcR, CR3, Mannose receptor• Internal receptors

– TLRs

Sistem Komplemen• komponen komplemen• regulasi aktivitas komplemen• defisiensi komplemen

IMUNITAS

Types of Adaptive immunity• Cell-mediated immunity: Immunity mediated by T

cells via:– Direct lysis of target (infected) cells– Production of cytokines that activate infected cells to kill

pathogens• Humoral immunity: mediated by antibodies

produced by B cells– Antibodies bind to whole or fractions of antigens outside

cells

Division of Labor, yet cooperative!!

• T cells mediate cellular immunity:– Control of intracellular pathogens– Control of tumors

B cells mediate Humoral immunity: Control of extracellular pathogens Mediates allergy and hypersensitivity

T and B cells cooperate for effective immunity T cell help may be needed for B cell activation and B

cells may present Ag to T cells

Imunoglobulin• struktur• biosintesis dan metabolisme• sifat biologik• perkembangan • dasar genetik

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infeksiprimer

infeksisekunder

IgG

IgM

IgG

IgM