Principles of Innate Immunity Flashcards
Components of Innate Immune system
1) Physical Barrier
2) Innate immune cells
3) circulating effector proteins (-complement system + antimicrobial peptides)
4) cytokines
I: Physical Barrier
where: - skin, GI, resp, Genitourinary tract
function:
- > provides physical barrier to infection
- > produces locally produced antibodies (DEFENSINS + cathelicidians)
II: Innate Immune cells
a) types of phagocytes
- Neutrophils
- Monocytes (mature in tissue to form macrophages)
- peritoneum,pleura
- lungs
- bone marrow, spleen
- liver (kupffer cells)
- Brain (microglia)
- Bone (osteoclasts)
II: Innate Immune cells
b) recognition of microbes (PAMPS)
Microbes have - PAMPs
1) virus -> dsRNA, special DNA (unmythlenated CpG DNA)
2) Bacteria -» LPS
3) fungi -> B-GLucan
II: Innate Immune cells
b) recognition of microbes (PRR)
PRR recognise PAMPS.
Types:
1) Intracellular NOD -like receptor:
- looks for unknown molecules (free DNA, viral RNA, peptidoglycan degradation residues)
2) Membrane bound PRR
- Toll Like Receptor
- C-type Lectins
- > mannose receptor: usually found on neutrophils.
- > Dectins: - binds to B-Glucan
-Scanvenger receptor
II: Innate Immune cells
b) recognition of microbes (TLR)
- TLR have extracellular and intracellular domain.
- can be extracellular (recog bacteria) or intracellular (virus)
- Ligand binds to TLR
- Recruitment of Adapter
- Activation of Protein kinases
- activation of TFS
- Transcription of genes
END EFFECT:
- cytokine production
- Adhesion molecules upregulated
II: Innate Immune cells
c) elimination of Microbes
PHAGOCYTOSIS - ways it mediated
Phagocytes can bind to microbe in two ways:
-Direct binding
-Opsoninzation (Fc receptor on phagocyte binds to antibody which binds to microbe.
Or c3b receptor binds to c3b.
II: Innate Immune cells
c) elimination of Microbes
PHAGOCYTOSIS - mechanism
- Phagocyte binds to microbe.
- Phagocyte membrane zips around the molecule.
- Microbe is ingested (phagosome)
- Fusion of phagosome with lysosome .
- Killing of phagocyte by –> lysosomal enzymes/ production of NO /ROS
II: Innate Immune cells
c) elimination of Microbes
Oxidative Bursts
if lysosomal enzymes do not kill the microbe, oxidizing agents will be generated to kill the microbe.
- USEFUL FOR MICROBES WITH PROTECTIVE COATS.
- enzymes found on -> phagosome/perioxosome.
02 –(NADH oxidase) –> O2- –superoxide dismu->H2O@—> OCl- + OH-
Chronic Granulomatous Diseas (CGD)
- Mutation in gene coding for NADH oxidase subunite.
- DECREASE in ROS production.
- LEads to: Recurring bacterial + fungal infections.
Leukocyte Adhesion Deficiency Type-1
- Deficit/abscence of B2- integrins
- causes defective leukocyte ahdesion/migration.
Eosinophils granulocytes
Contain: - MBP, ROS production.
Activated function: -> killing of antibody-coated parasites.
Basophil granulocytes/mast cells
Contain: - Histamine, Heparin
Function: -> Degranulation
- > synthesis of lipid mediators
- > cytokine synthesis
Natural killer cells
- constitute 5-20% of mononuclear cells in the blood + spleen.
- closely related to lymphocyte
- recgonise infected/stressed cell.
effector function: –> -direct killing (perforins, granzymes)
–> - secretion of inflammatory cytokine
ACTIVATION REGULATED BY BALANCE BETWEEN ACT AND INACT SIGNALS.
types of circulation effector proteins?
1) complement system
2) Antimicrobial peptides
What activates the complement system
Classical pathway -> Antigen:Antibody complex
Lectin pathway -> lectin binds to pathogen surface
Alternative pathway -> pathogen surface
What does complement activation lead to?
1) Recruitment of inflammatory + immunocompetent cells [C3A, C5A]
2) Opsonisation of Pathogen (C3B)
3) killing of pathogen (membrane attack complex)
Membrane attack complex
1) C5b + C6 + C7
2) forms complex, c7 binds to membrane.
3) C9 binds to complex, polymerises -> forms pore.
PORE LEADS TO H2O and IONS entering to cause lysis and swelling.
Name circulating antimicrobial peptides
1) Mannose- Binding Lectins:
- opsonization of microbes.
- activation of complement system (lectin pathway)
2) C-Reactive Protein (CRP)
- opsonization
- activate complement system
- important marker of inflammation
Name non-circulating antimicrobial peptides
1) Defensins:
- cationic peptides
- produced by epithelial cells + leukocytes
2) cathelicidins:
- produced by epithelial cells + granulocytes.
3) Lactoferrin:
- neutrophil secondary graniules
- released into the lysosome
TNalpha
Major source: - activated mononuclear phagocytes
TNFa- mediated responses?
- > recruitment & activation of neutrophils + monocytes
- > hypothalamus: fever
- > liver: synthesis of Acute phase proteins
- > muscle/fat: catabolism
- > many cell types: apoptosis
