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
