IMM DASAR-1

8/2/2019 IMM DASAR-1

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Against Micro-organisme, Parasitesand Fungi.

Hypersensitivity reaction

(include Allergy). Autoimmun diseases.

Transplantation (organ, bone

marrow).

Terhadap Micro-biota, Parasit dan Jamur.

reaksi hipersensitivitas

(termasuk alergi).

Basic concepts in Immunology


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We live surrounded by

microorganism (viruses, fungi,

bacteria and parasites) We become ill only relatively

rarely

Immune response againstpathogens (2 system)

Kita hidup dikelilingi oleh



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Innate Immunity / inborn

Non-spesific defense against infection

Macrophages, Neutrophils

Its action does not depend on prior

exposure to a particular pathogensPhagocytosis

Imunitas bawaan / bawaan

Non-spesifik pertahanan terhadap infeksi

Makrofag, Neutrofil



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Innate Immunity in pathogen elimination


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Innate Immunity

Activate Complement system and theywill destroy the pathogen

Acute phase proteins produced by the

liver, stimulate the macrophage functionagainst infection

Those protein binds to bacterial surface

and activates complement system toeliminate bacteria directly and enhance

their elimination by macrophages.

bawaan Imunitas


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Innate Immunity

Secreted IL6 by the macrophage will

stimulate the liver to produce

acute phase proteins i.e : C-reactive protein

Serum amyloid protein

Mannose binding protein

Fibrinogen

bawaan Imunitas


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C-reactive protein

C-reactive protein binds to

Phosphorylcholine on bacterial surfaces

Mannose binding protein binds Mannosa

residu on bacterial surfaces

C-reactive protein and Mannose binding

protein respons like antibody

Opsonisation and activates the

complement cascade

Protein C-reaktif mengikat

hos hor lcholine ada ermukaan


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Inflammatory response

Infection bacteria triggermacrophages to release inflammatorymediators.

Vasodilatation and increased vascularpermeability cause redness and heat (calordan rubor)

Leakage of cells and fluids cause swellingand pain (dolordan tumor)

Blood vessel walls become sticky allowingblood cells to migrate into tissue.

T-cells activated by macrophagesmay


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Acquired / Adaptive Immunity

Specific immunity

Acquired during the lifetime of anindividual

Response to a spesific pathogen

Lymphocytes (its receptors)Antibodies

Acquired / adaptif Imunitas

spesifik kekebalan



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Lymphatics System

Organs in Immune System

Central (Bone Marrow and Thymus)

Peripher(Adenoid, Tonsil, Peyers

Patches, Appendix, Spleen, Lymph

Nodes)

Thoracic duct

Right Subclavian Vein and Left

Subclavian vein

Sistem limfatik

Immune System


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Growth factors in the Hematopoietic system

Act on proliferation and maturation of the

cells.

Secreted proteins termed Cytokines aremessenger molecules that can

communicate signals from one cell type to

another. They can instruct the receiving cells to

proliferate, differentiate, secrete additional

cytokines, migrate or die.


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Hematopoietic stem cells

The Bone marrow contains at least twotypes of stem cells. Mesenchymal stem cell which constitute

the bone marrow stroma and under

appropriate signals can differentiate intoadipocytes, osteocytes, chondrocytes andmyocytes

Hematopoietic stem cell which gives rise tothe formed elements of the blood andproduce growth factors including IL-3, -4,-6and-7, G-CSF, GM-CSF, SCF, flt-3, EPO,

TPO, etc.


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Cytokine families They are able to support proliferation of

hematopoietic precursors (colonystimulating factors)

Particular cytokine responses influence the

differentiation stage of the cell, its positionwithin the cell cycle (whether quiescent or

proliferating)

Cytokine action is transient and usuallyshort range

Mereka mampu mendukung proliferasi

prekursor hematopoietik (koloni


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Clonal Selection of Lymphocytes

(Bone Marrow and Thymic gland) single typereceptor on Lymphocytes

can recognize all possible antigens.

However, we normally do not makeimmune responses against our owntissues.

This is called Self Tolerance Lymphocytes with receptors for self

antigens are eliminated (Clonal deletion)Cell death occurs by Apoptosis enis rese tor tun al " ada Limfosit da at


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T-CELLS The Thymus provides the environment for

T-cell differentiation Thymic epithelial cells produce a series of

peptide hormones which mostly seemcapable of promoting the appearance of T-cell differentiation markers.

Several have been well characterizedincluding Thymulin, Thymosin 1,Thymic humoral factor andThymopoietin (hormon tsb)


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Clonal Selection of Lymphocytes

(Bone Marrow and Thymic gland) The remaining mature Lymphocytes

(naive lymphocytes) migrate to the

periphery.Continuous recirculation of naive

lymphocytes through the peripheral

lymphoid organs, to which antigen iscarried from any site of infection

Lymph from most sites in the body is

returned to the Thoracic duct


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T-CELLS

Activated T-cells proliferate in response tocytokines

T-blasts expressed surface receptors forIL-2 and proliferate in response to IL-2

IL-2 is single peptide (15.5kDa)

IL-2 receptors are not present on restingcells but are synthesized within a fewhours after activation.


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B-CELLS B-lymphocyte precursors, pro-B-cells are

present among the islands of hematopoietic cells

in fetal liver by 8-9 weeks of gestation.

Production of B-cells by the liver wanes and ismostly taken over by the bone marrow for the

remainder of life.

B-cells have different stages in their

development and a series ofdifferentiation

markers associated with B-cell maturation


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B-CELLS

Proliferation and maturation of B-cell

responses are mediated by cytokines

The activation of B-cells by Th cells leadsto upregulation of the surface receptor for

IL-4

IL-2 and IL-13 contributes to Clonalproliferation and expansion of the

activated B-cell population


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Activation of B- and T-Lymphocytes

Lymph nodes are sites of activation of

lymphocytes by antigen.

Naive lymphocytes enter lymph nodescontinuously from the blood

When a lymphocyte with an appropriate

receptorbinds to the trapped antigen itceases to recirculate and becomes

activated


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Activation of B- and T-Lymphocytes

Activated cells are called lymphoblasts,

they become proliferate and differentiate

into an effector- and memory- cells. Clonal expansion & Clonal differentiation

Those lymphocytes (T- dan B-cells) have

the same receptor as their original ones. B-receptor : 2 antigen recognized site

T-receptor : 1 antigen recognized site


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Activation of B- and T-LymphocytesActivation of B- and T-Lymphocytes

Effector cells :

B-cells Plasma cells

T-cells T-cytotoxic

T-Helper

T-inflammatory

T-cell receptorrecognize only peptide

which is presented by MHC/HLA

molecules on the cell surface.


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MajorMajorHistocompatibilityHistocompatibility ComplexComplex

MHCMHC/ HLAHLA (Human Leucocyte Antigen)

is a protein which is synthesized in the

cell, present an antigen on the cell

surface which will be recognize by T-

cell Receptor..

We can find MHC class I on the cell

surface of all cells except those

Erythrocytes and Thrombocytes

This protein can activate CD8+ T-cells


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Major Histocompatibility ComplexMajor Histocompatibility Complex

MHC class II molecules are cell-surface

glycoproteins, that deliver peptides and

activate CD4+ T-cells MHC class III : part of the Complement

system : C4, C2, Factor B and Isozyme

21-hydroxylase MHC class IV : similar with those MHC

class I but has restricted distribution.


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Major Histocompatibility ComplexMajor Histocompatibility Complex

MHC class I and II have similar threedimentional structure, although they have

distinct sub-unit structure.

MHC cIass I consist of 3 loci (A,B,C) andHLA class II consist of several region (DR,

DQ, DP, DO, DN etc.)

MHC molecules binds peptide and presentit on the cell surface, where they will be

recognize by T-cell receptors.


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Relative Risk of HLAupon particular disease

(Certain disease associate with HLA antigen).


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MHC class I molecules do not leave the

Endoplasmic Reticulum unless they bind peptides


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Degradation and transport of antigens that bind

MHC class I molecules

Th MHC l II i t d i i t h i


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The MHC class II associated invariant chain

delays peptide binding and targets MHC class II

molecules to the endosome (acidified intracellular

vesicles)


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