The immune system and its diseases

Gunnar Houen

Professor, Dr. scient.

Statens Serum Institut

Why do we have an

immune system ?

Lymph nodes

Tonsils

Thymus

Spleen

Intestine

Bone marros

Blood

Thymus

Lymph nodes and spleen

Intestinal immune system

Pathogens = non self

Immune system

Tissues (self)

Pathogens (non-self)

Immune system

GH

Defence against pathogens

§  Physical barriers §  Shedding (flow) §  Immune system §  Hygiene §  Isolation §  Antibiotics §  Surgery

Infection

Self Non self Immune system

Infection

GH

Immune system function

Self Non-self Innate Adaptive

Innate Immunity Adaptive Immunity

No memory

No time lag

(Not antigen specific)

A lag period

Antigen specific

Memory

Immuneresponse - timecourse

Immune responses

§  Pathogen killing (innate)

§  Infected cell killing (innate, adaptive)

§  Antigen removal (innate, adaptive)

Innate/adaptive immune system

Extracellular immune system

§  Innate: C’, N, M, NK, D, Ma, Ba, E, NKT, IgM, IgD,

§  Adaptive: IgG, IgA, IgE, T, B,

Intracellular immune system

§  Innate: Inflammasomes, RNAse, proteases (autophagy), ……

§  Adaptive: miRNAs ?

Early innate: Complement

Later innate: (PM)N

Polymorphonuclear cells

Neutrophilic granulocyte

Most Abundant White Blood Cell

Very Short Lifetime (1 – 3 days)

Late innate: NK cells

Immune system

Pathogens

Immune evolution/evasion

Immune evasion strategies

Immune system

Pathogens

Antistoffer – det humorale immunforsvar

Antistoffer – det humorale immunforsvar

Antistoffer

Immunologiske feed-back loops

T4

Ag

Ab

D/M

B

Ab

MHC II Cytokiner

MHC II Cytokiner

GH

Infection

Self Non self Immune system

Infection

GH

Pathogen strategies

Extracellular Intracellular

§  Viruses - +

§  Bacteria + +

§  Fungi + +

§  Parasites + +

Pathogen occurrence

Extracellular Intracellular

§  Viruses + +

§  Bacteria + +

§  Fungi + +

§  Parasites + +

Immune responses

§  Pathogen killing (innate)

§  Infected cell killing (innate, adaptive)

§  Antigen removal (innate, adaptive)

Antigens

§  Proteins §  Carbohydrates §  Lipids §  Nucleic acids §  Haptens

§  Cellular immune system

N, E, Ma, Ba, NK, D, M, T, B, NKT, …..

§  Humoral immune system

C’, PAMPARs, Abs

Cellular immune system

Antigen-presenting cells

Dendritic cells

Receptor-mediated Ag uptake (pM - nM conc.)

When Ag is captured ability to capture Ag declines

http://www.rcsed.ac.uk/Journal/vol46_1/4610003.htm#INTRODUCTION

Dendritic cells in skin

Dendritic cells in lymph nodes

Innate immune responses

§  Antigen detection: PAMPs

§  Pathogen killing: C’, N,

§  Infected cell killing: NK

§  Antigen removal (Ag-driven)

Adaptive immune responses

§  Antigen removal

§  Infected cell killing §  Antigen nature and location determines

the immune response

Roy, 2003 (www)

Endogenous and Exogenous Antigen Presenting Pathways

Immunological feed back loops

Extracellular antigens

T4

Ag

Ab

D/M

B

Ab

MHC II Cytokines

MHC II Cytokines

GH

Immunological feed back loops

Intracellular antigens

T8

Ag D/M

C

MHC I Cytokines

MHC I Cytokines

GH

Antigen nature and location/uptake determines the antigen processing pathway used

Cytosolic compartment Endogenous processing

(Viral antigens)

Vesicular Compartment Contiguous with extracellular fluid

Exogenous processing (Streptococcal, Mycobacterial antigens)

INTRACELLULAR REPLICATION

EXTRACELLULAR OR INTRAVESICULAR (ENDOSOMAL) REPLICATION

Figure 5-2

Adaptive Immunity = T, B lymphocytes