Immunology Flashcards
The immune system must…
Discriminate self from non-self.
Innate immunity
Instinctive, non-specific, does not depend on lymphocytes, present form birth.
Adaptive immunity
Specific, acquired/learned, requires lymphocytes, ABs.
Both innate and adaptive immunity are made up of…
Cells and soluble factors (humoral).
Centrifuged blood sample
Upper fluid - plasma (water and electrolytes)
Middle layer - white fluffy layer (leukocytes)
Lower layer 45% - eythrocytes/platelets.
Define serum
Plasma without fibrinogen and other clotting factors.
Haematocrit
RBC volume
Polymorphonuclear leukocytes
Neutrophils
Eosinophil
Basophil
Mononuclear leukocytes
Monocytes -> macrophages
T-cells -> T-regs, T-helper (1,2), T-cytotoxic, Th17
B-cells -> plasma cells
Other cell types in the immune system
Mast cell, NK cells, Dendritic cells (Kupffer in the liver, Langerhans in the skin)
Soluble factors of the immune system
Complement proteins
Antibodies ABs
Cytokines and chemokines
Complement proteins
~20 serum proteins secreted by the liver - precursors. Only activated during the immune response.
MOA of the complement system.
Direct lysis.
Attract more leukocytes to the site
Coat invading organism (opsonisation).
Antibodies
Bind to AGs
Immunoglobulins Ig’s
Soluble or cell surface (BCR)
MADGE (5 classes)
Immunoglobulins
Light chains (lamda and kappa)
Heavy chains
Fab portion
Fc portion
Hinge region
Serum = 75%
IgM is a
Pentamer
Antibodies link microbe to…
Phagocytes (Fc region of Ab on microbe binds to Fc receptor on phagocyte).
Cytokines
Proteins secreted by immune and non-immune cells
Interferons IFN
Antiviral resistance in uninfected cells
INF-alpha and beta
Produced by virus infected cells
INF-gamma
released by activated T-cells
Interleukins (IL)
Can be pro- (IL-1) or anti-inflammatory (IL-10).
Can cause cells to divide, differentiate and to secrete factors.
Colony Stimulating Factors (CSFs)
Division and differentiation of bone marrow stem cells -> precursors for leukocytes.
Tumour Necrosis Factors
TNF-alpha and beta
Mediate inflammation and cytotoxic reactions.
Chemokines
Attracts leukocytes to the site.
Innate immunity
Non-specific
1st line defence
Provides barrier to AG
Instinctive
Present from birth
Slow response
No memory
Adaptive immunity
Specific AG response
Learnt behaviour
Memory to specific AG
Quicker response
Innate immunity is composed of
Physical and chemical barriers
Phagocytic cells (mostly neutrophils and macrophages)
Blood proteins (complement and acute phase)
Inflammatory response
Tissue damage (trauma) or infection.
- Coagulation
- Acute inflammation (leukocyte - recruitment)
- Kill pathogens, neutralise toxins, limit pathogen spread.
- Clear pathogens and dead cells
- Proliferation of cells to repair damage
- Remove blood clot - remodel ECM
- Re-establish normal structure and function.
Definition of inflammation
A series of reactions that brings cells and molecules of the immune system to the sites of infection or damage.
Hallmarks of inflammations
Increased blood supply
Increased vascular permeability
Increased leukocyte transendothelial migration - extravasation
Acute inflammation
Complete elimination of a pathogen followed by resolution of damage, disappearance of leukocytes and full regeneration of tissue.
Chronic inflammation
Persistent, un-resolved inflammation.
How are microbes sensed in the blood and in tissues?
In blood - monocytes and neutrophils
In tissues - macrophages and dendritic cells.
PRR
On cells
PAMP
On microbes
Complement proteins can…
Lyse microbes directly by the membrane attack complex.
Chemotaxis - C3a and C5a
Opsonisation - C3b
Extravasation
AKA diapedesis
Endothelial cells normally express GAGs.
Infections (TNF-alpha) -> E-selection on endothelial cells and neutrophils have CD15 which binds to E-selection= slows down neutrophils.
This allows the chemokine receptors to bind to chemokines.
Eventually Integrin binds to ICAM-1 -> PCAM-1 paracellularly and neutrophils go through.
Neutrophils
Rolling - adhesion - extravasation
Phagocytosis
Binding - engulfment - phagosome formation - fuse with lysosome= phagolysosome -> lysis and antigen presentation on MHCII
Why do we need the adaptive immune system?
Microbes evade innate immunity.
Intracellular viruses and bacteria (Mycobacterium tuberculosis) hide from innate immunity.
Need memory to specific AG.
Cell-mediated immune response (T-cell)
Against intracellular microbes
Humoral (AB) mediated immune response (B-cells)
Extracellular microbes
Cell-mediated immunity requires.
APC + T-cells requires intimate cell to cell contact.
Control AB responses via contact with B cells.
Directly recognise and kill virally infected cells.
Also need: MHC
Intrinsic/Endogenous AGs
Extrinsic/Exogenous AGs
Recognise self or non-self.
T lymphocytes
Respond to presented AGs.
T cell selection
T cells that recognise self are killed in the foetal thymus as they mature.
TCR
Recognise foreign AGs in association with MHC
Intracellular virus
Class I (All cells have it) Tcytotoxic (CD8) kill infected cells.
Extracellular (phagocytosed)
Class II (APC only) Thelper (CD4) help B cells make ABs to extracellular pathogen, can help directly kill.
T cell and AG recognition = activation
Co-stimulatory molecules
CD28 on T cell bind to CD80/CCD86 on APC = this is required for full T-cell activation.
Activation - IL-2 is secreted and binds to IL-2R on T cell (autocrine) -> division, differentiation, effector function, memory.
T helper 1
Produces IL-2 and IFN-gamma (kills intracellular pathogen).
T helper 2
AB production
Tcytotoxic
CD8 + MHCI = T cytotoxic
Forms proteolytic granules and releases perforins and granulysin - also induced apoptosis.
T helper 1 activation
APC presents AG with MHC II to naive CD4 T cell.
High levels of IL-12 activate naive cells to CD4 Th1 cells.
Th1 cells travel to secondary lymphoid tissue (spleen, lymph nodes)
Activated CD4 Th1 proliferate (clonal expansion and memory T cells)
Th1 cell recognises AG on infected cells via TCR.
Th1 secretes IFN-gamma: stops virus spread and activated macrophages.
B cell activation
B cells express membrane bound Igs (IgM, IgD)
Each B cell make only one AB that only binds to one epitope on one AG.
B cells that recognise self…
Killed in the bone marrow.
B cells present AG to T cells
Via MHC II.
mIgM or mIGD binds to AG -> phagocytosis
Peptide displayed on surface with MHCII
TCR on naive Thelper binds to MHCII
Lots of other co-stimulatory molecules are required.
T cells help B cells
APC eats AG and presents to T helper via MHC II.
Primed Th2 cells.
Th2 cells bind to B cells that are presenting AG (via MHCII).
Th2 secreted CKs: IL-4, 5, 10, 13)
These cause B cells to divide (clonal expansion) and differentiate:
Plasma cells (AB forming cells) and Memory B cells.
Antibodies may
Neutralise toxins by binding to them
Increase opsonisation
Activate complement system.
