biomedis imunsistem (1)

Immune System

necessity of recognition of and discrimination between SELF and FOREIGN

Evolution of effector functions for maintaining SELF and destruction of FOREIGN

Principles of the Immune System

failure of recognition of and discrimination between

SELF and FOREIGN:

1) Loss of identity (absorbtion, death) 2) Horror autotoxicus (autoimmunity) 3) Collateral damage

Principles of the Immune System

Immunology

Latin: Immunis, immunitas = free of duties/taxes

Protection/surveillance of HOST against: 1) Infectiones (Pathogenes) 2) Toxines (biological + chemical) 3) altered SELF: tumours 4) removal of death SELF cells (e.g. after apoptosis) 5) Transplantes 6) fetus (=transplant, parasite)

Parts of the Immune System

Innate Adaptive

- NO memory -prompt/fast

- unspecific

- memory - needs to be generated after 1st contact - specific

humoral cellular

Complement Antibodies

Phagocytes Lymphocytes (T und B)

Parts of the Immune System

Blood smear

O,14%

4,7%

95 %

Phagocytes

Polymorphonuclear Granulocytes

Named after staining of Granula

Neutrophils Eosinophils Basophils

Monocytes

Differentiate into M or DC

>90% 2-5% 0,1-1% Parasites Allergies Bakterien/Fungi

Degranulation Phagozytosis

Bakterien/fungi Phagozytosis

Antigenpresentation

60-70% 10%

Phagocytosis

Lymphocytes

T cells B cells NK cells

60% 2-5% 10%

innate adaptive Bone marrow

plasma cells

CD16, CD56 CD3 CD19

Antibody secretion Cell killing Cell killing

CD4 T helper=TH

CD8 T cytotoxic=Tc

Immune regulation

Antibody maturation

Percentage of PBMCs

First line defences of the immune system

pathogen

What does protet us

Before

the pathogen can enter the 2ssue?

First line defences of the immune system

pathogen

physical/ chemical barrier of skin and mucosa

Acid enviroment skin/stomach (pH 5,5): antifungal mucosa; cilia competition (commensal versus pathogen) Bacteriocidal Substances (enzymes, defensins) in secreted fluids (saliva, sudor,lachrymal) sIgA

Main principles

pathogen

Avoidance of adhesion

bacteriocidal

Acid enviroment skin/stomach (pH 5,5): antifungal mucosa; cilia competition (commensal versus pathogen) Bacteriocidal Substances (enzymes, defensins) in secreted fluids (saliva, sudor,lachrymal) sIgA

Bacteriocidal substances in secreted fluids Enzymes: lysozyme

murein degradation peroxidase killing by radicals lactoferrin Fe competition

Bacteriocidal peptides: -defensines

-defensines Cathelicidin (LL-37) Histatins membrane penetration influence of bacterial functions

Structural classes of defensines

Defensin

12 50 aa, bermuatan posi=f, memiliki domain hidrofobik dan amphipha=k.

Broad spectrum an=microbial ac=vi=es Bakteri gram + dan Fungi (inc. yeast) Parasit (protozoa, nematoda) Enveloped virus (HIV)

Defensin

Protein paling banyak di Neutrophils Kill phagocytosed pathogens

How ? Unsure Merusak integritas membran. Selek=tas : membrane yang =dak mengandung kolesterol.

Berguna sebagai agent terapeu=k.

Defensines: induction and immunmodulation

Clinical case A 16 year old boy has an small accident with a scratch at the right foot. Few Hours later: around the wound 3 cm Erythema with swelling/edema. Wound and surrounding appears to be warmer and painful.

Rubor redness

Tumor swelling

Calor warming

Dolor pain

Functio laesa loss of function

1.Phase: reaction of local inflammation

Plasma enzymes

Complement

Bradykinin

Activation of

pathogen Physical/ chemical barrier of the skin and mucosa

1) wound repair (clotting, Thrombocytes, angiogenesis) 2) Activation of Plasma enzymes

Bradykinin dolor=pain complement

Kill/Lyse pathogen

Mediators Anaphylatoxine

Chemotaxis Mark target (opsonization)

Kallikrein-Kinin-System

Coagulation

Faktor XII (Hagemann)

Pre-kallikrein

Kallikrein

Kininogen Kinine (Bradykinin,

Kallidin)

Plasmin Trypsin Bacterielle Enzymes Snake poisson

Complement System

complement

MBLectin pathway

C3

C3b C4 C2

C3 convertase C4b2b

MBL

C5

Pathogene surface

Membrane attacking complex

MAC

(C9)n

C3 convertase C3b,Bb

Alternative pathway

Incorporation into Pathogenic membrane

(pores, lysis)

C3 C3a

C5b

C5 Convertase: C3b,Bb plus C3b C4b2b plus C3b

C3 C5a

Ana

laph

ylat

oxin

e

Plasmaproteases Antibody

Classical pathway

Plasma enzymes

Mast cells

Activation of


Mast cell activation

Degranulation (few minutes)

C3a C5a

Mast cells (Basophile Eosinophile)

activated Complement

Histamin

Vasodilatation

itching

Nerve cells

Anaphylatoxines

Dolor pain

Endothelial cells

Pre-formed Bradykinin

Rubor redness

Tumor swelling

anaphylactic shock

Degranulation

C3a C5a

Mast cells (Basophiles

Eosinophiles)

Komplement activation

Histamin

Vasodilatation

Blood pressure

Shock IgE crosslinking

FcR

Bradykinin Endothelial gap junctions

Plasma enzymes

Mast cells

macrophages

Activation of


Pathogenes

Bacterias Viruses fungis Parasites

Who is recognized as Aliens?

Protoazoas helminth Milben

Gram + Gram Extracellular (z.B. Staphylococcus) Intracellular (e.g. Mycobacterias) Gut flora?

dsRNA ssRNA dsDNA ssDNA

Candida aspergillus

What is recognised as alien?

What is distinguishing us from pathogens??

Pathogenes


Pathogen associated molecular patterns (PAMPS)

What is distinguishing us from pathogens??

Pathogenes



Pathogene Human

Cell wall cell membrane DNA not methylated DNA methylated Mannose-rich cell surface rather Galactose outside Poly-Aniones insight Formyl-Residue Start-Methionin naked or

cut off

Bacteria:

Viruses: dsRNA ssRNA dsDNA ssDNA

Protozoa: surface glycans lipids HSPs

Metazoa Glycans


Toll-like receptor (TLR)

The most important and best-understood receptors in the innate system.

10 TLRs iden=ed in human toll-like : receptor Toll in Drosophila

TLR Large domain: Leucine-rich repeats (LRRs) Human LRR: 18-27 repeats Single transmembrane helix Signaling domain (common to TLR and other receptors)

Lipopolysaccharide (LPS)

LPS recognize by TLR-4 Protein agelin : TLR-5 ddRNA : TLR-3

The target of TLR is a key component of the pathogen. Muta=on cannot easily block recogni=on by TLR TLR for heterodimers : enhance or inhibit PAMP

recogni=on.

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biomedis imunsistem (1)