Immunology - lesson 1
16 nov 2020
Defense against bacteria and against viruses are separate main pathways, overlap a bit.
8 subjects we learned about, make PPT slides about what we remembered.
Upload powerpoints in teams files everything in there need to know from last year that’s
important.
Which cells produce IgA?
o Plasma cells producing especially IgA, one with a high affinity. Antibodies only
produced by plasma cells. Plasma cells differentiate from B-cells.
1. Chemical and physical barriers
Block 90% of bacteria
Physical barriers
Prevents pathogen from entering the body.
Every surface connected to the outside, includes:
Skin: multilayered epithelium (tight junctions), there is layer of dead skin cells, corneum (hornlayer)
Oral mucosa: has mucus, ciliary action, flow (throw up)
Respiratory epithelium: ciliary action to move pathogens and other antigens that are in our lungs, for
example, back to the mouth so we can swallow it and destroy it in the stomach or spit it out.
Intestine is organ, prevents pathogen from entering; flow (diarrhea), mucus
Chemical barriers
Molecular mechanism that attack pathogens directly.
Includes antimicrobial proteins like lysozyme, defensin, C3 (that activates) complement system.
Skin: fatty acids, salty, dry, commensal bacteria
Oral mucosa: low pH (stomach), mucus, commensal bacteria
Respiratory tract: some chemicals
Physical and chemical barriers are first line of defense, where most viruses and bacteria are blocked.
SARS-CoV-2 don’t get it inside always, skin is blocking it, wash hands to wash it off.
Don’t say skin itself is physical barrier, the skin is organ. Block bacteria and viruses/pathogens
because of multilayered epithelium of the skin or corneum and the tight junctions, they are parts of
the skin. Virus or bacteria get in skin, parts of skin will block the pathogens.
Commensal bacteria are always part of it.
2. Phagocytes and their killing
Innate immune system (second line of defense)
Different phagocytes. They are all white blood cells
Macrophages
Dendritic cells
Monocytes
Granulocytes
o Neutrophils can phagocytose, not that good in it. Kill via:
NETosis
Respiratory Burst
, Lysozyme
o Eosinophils can’t phagocytose
o Basophils can’t phagocytose
Cells can phagocyte
Different types of phagocytosis:
Receptor induced phagocytosis, when there is virus present.
Pattern recognition receptors recognize DAMPs (Danger Associated Molecular Patterns) or
PAMPs (Pathogen Associated Molecular Patterns)
Antibody dependent phagocytosis opsonization
Phagolysosome (phagosome + lysosome come together) specific antigen is degraded
Phagocytosis
It is the taking up of MO into the cell.
Types:
Macrophages
o Longliving, in tissues, first responders in tissues
Neutrophil
o Shortliving, in blood
Monocyte
o Longliving, in blood
Immature dendritic cells (DCs)
Sequence of phagocytosis:
Chemotaxis calling phagocytes to the scene of infection
Recognize the MO, based on their PAMP or DAMPs (patterns), with PRR
Phagocytose
o Taking up the MO in a phagosome/endosome
Killing the MO
Produce cytokines/chemokines
Killing of the MO:
Three different ways:
Fusing endolysosome with taken up MO it’s degraded by acids (degranulation of
lysosomes)
Respiratory burst (oxygen dependent)
NETsonly possible with neutrophils. Release cell contents to trap and kill bacteria.
Pattern recognition receptors (PRR):
Different receptors on phagocyte, which can detect different target cells. They all recognize particular
types of patterns (DAMPs, PAMPs, proteins (LPS), glycoproteins, sugars).
Pattern recognition is very important for phagocytosis.
Toll-like receptors
NOD-like receptors
RIG-I-like receptors
Scavenger receptors
C-type lectin receptors
3. NK cells and complement system
NK cells= Natural killer cells
Innate immune system, they are lymphoid cells
Interferons secrete gamma. They can kill virus infected cells, also cancer cells
Mainly act against intracellular infections
Extrinsic and intrinsic pathway
Intrinsic: perforins and granzymes activation caspases apoptosis
, Extrinsic: TRAIL recognized DR4/5 (Death Receptor)
Natural killing cells
Part of innate immune system
Lymphoid cells
Kills virus infected cells and cancer cells recognizing MHC
Excrete IFNγ
Signals required:
ADCC
o Killing
o Antibody-dependent cell-mediated cytotoxicity
o Fc receptor (FcγRIII = CD16) on NK cell binds to antibody (IgG1) on target cell
NKG2D
o Recognize MIC-A and MIC-B
o Stress induced ligands: heat shock, oxidative stress
KIR
o Killer immunoglobulin receptor
o Inhibiting receptor
o Recognize MHC-I
o Killing of target cell starts when MCH-I is missing
Positive signal recognition Negative signal recognition
NK cell NKG2D KIR
FcγRIII
Target cell MIC-A/B MHC-I
IgG1
Two receptors/signals on NK cell bind to receptor/signal MIC-A/B positive signal
KIR binds to MHC-I on target cell. No or not enough MHC-I positive signal
How do they kill?
Intrinsic
o Formation of pores in the membrane (perforine)
Granzymes go in the cell and activate caspases/DNAse, leading to apoptosis
Extrinsic
o Receptor recognition (DR4/DR5 receptor)
TRAIL on NK cell gets activated, when there is a positive signal, and binds to
DR4 and DR5 on target cell (receptor recognition)
If the activation signals are enough caspases activated
apoptosis
Kills viral infected cells, and cancer cells.
Important is MHC recognition. If MHC recognition is lacking, the target cells are more quickly and
easily killed.
Completement system
Three ways to activate complement system
Classical pathway starts with IgM binding on surface, cascade in which C3 convertase
cleaves one, etc. leads to terminal route, where you can form MAC pore cell is
disrupted
Alternative pathway spontaneous hydrolysis, C3 binding to B different C3 convertase
(C3bBb) compared to classical and MBL pathway. Factors B and D
MBL/lectin pathway MBL binds to mannose on pathogen surface. MBL has same C3
convertase and steps as classical pathway.
Three functions
, Terminal route Lysis C5 to C9 forms membrane attack complex (MAC) pore cell is
disrupted
Chemotaxis C3a and C5a, send out molecules that attract cells of immune system, maybe
triggers inflammation.
Opsonization C3b binds to bacteria and this bacterium is opsonized and is easier killed by
phagocyte like a macrophage.
4 different routes:
Route Classic Lectin Alternative Termination
Beginning IgM binds to C1q Mannose binds Sometimes C5 into C5a and
C1r, C1s to MBL, MASP spontaneous C5b
splicing of C3.
Most of the time
it starts through
classic or lectin
routeC3b binds
to B factor
Others that are C2a, C2b, C4a, C2a, C2b, C4a, Bb factor, D C5, C6, C7, C8, C9
needed C4b C4b factor makes a pore
in the cell
C3 convertase C3 convertase by C3 convertase by
C4bC2a C4bC2a C3bBb
C3 convertase is needed to start the other routes.
Different beginnings of the different routes. Classical and lectin route leading to C3 convertase,
essential part of complement pathway.
All these pathways lead to C3 convertase and this leads to the following functions:
Chemotaxis: Concentration gradient. Recruit phagocytic cells to the site of infection and
promote inflammation
Opsonization: Phagocytosis. Destroy the pathogen.
Lysis: Membrane attack complex. MAC-complex formation disrupt cell membrane and
causes cell lysis.
Only the terminal pathway leads to cell lysis.
4. Antigen presentation
Innate immune system
Dendritic cells
Bridge between innate and adaptive immune system
MHC II antigen presentation
Toll like receptors are kind of PRRs
Macrophages
Present antigens on MHC II does this by phagocytosis
Recognized pathogens (PAMPs) with PRR (pattern recognition receptor)
o Toll like receptors are kind of PRRs
Adaptive immune (verworven) system (B or T cells)
B-cell
MHC II antigen presentation
MHC II CD4
Phagocytosis, recognizes antigens (DAMPs and PAMPs) with PRR
