Post on 29-Jul-2020
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