Immunology related stuff Flashcards
Roles of blood
Transports/distributes stuff
Regulates pH, pressure, osmolaty, temp, electrolytes/ions.
Communicates e.g. via hormones
Defence e.g. via plasma cells, neutrophils, etc.
What does the blood carry/its components
55% plasma - sugars, hormones, water, ions, urea, cholesterol, proteins.
45% WBC, RBC, platelets.
What can be determined from a blood sample/how
Centrifuge to separate plasma from cells. Add EDTA, citrates, etc. - calculate PVC and blood cell count.
Centrifuge again to give haematocrit - RBC: total blood volume, should be 40-50%.
Allow blood to clot and measure clotting time. Centrifuge again to separate clotting factors from serum.
What blood products can be obtained from a blood sample
Blood plasma
Complete blood
Platelet rich plasma
Packed RBC
What can a blood sample tell you about the patient
Kidney function - ions, urea
Respiratory function - O2/CO2
Endocrines - hormones
Pathology - WBCs
Cholesterol
HDL is GOOD
LDL is BAD
Total cholesterol/HDL = risk of heart disease.
Features of inflammation
Red Hot Swelling Pain Loss of function
Acute inflammation vc chronic
Acute = fast, involves neutrophils, prominent and local signs, mild tissue damage.
Chronic = slow, involves plasma cells lymphocytes and phagocytes, few signs but severe and progressive tissue damage. Cycles of repair and destruction.
Acute inflammation - vascular events
Vasoconstriction - to reduce blood loss
Vasodilation - site goes red and warm
Vascular permeability - swelling due to oedema
Vascular stasis - loss of fluid so viscous and slow blood flow.
Acute inflammation - cellular response
Slow blood flow due to vascular events so immune cells move to walls of the vessel.
Cells adhere to epithelial cells (pavementation) and emigrate between them into the tissue.
Cells aggregate around the site of inflammation and carry out their role e.g. phagocytosis.
Outcomes of inflammation
Complete resolution - tissue returns back to normal and doesn’t lose any function.
Healing by fibrosis - Fibroblasts and epithelial cells mature and move to the site of inflammation and produce collagen. Loss of function e.g. muscle can’t contract bc of the non-elastic fibrous tissue.
Chronic inflammation - cycles of healing then destruction e.g. causes of inflammation not resolved.
Causes of chronic inflammation
Continuous low-grade stimuli
Autoimmune problem e.g. body attacks self
Prolonged exposure to toxins
Features of chronic inflammation
Diff cells - plasma cells, lymphocytes, phagocytes
Minimal vascular changes
Scar tissue due to granulation cells in vessels (fibroblasts etc)
Routes of transmission of infection
Horizontal = via the air, water, etc to a large group Verticle = via contact, sperm, genes, etc. to an individual.
Requirements of infection
Reach/enter host
Adhere and colonise
Evade host defences
How can a pathogen adhere to its host
Pili w/ adhesion molecule on the tip can attach to host surface.
Polysaccarides bind to artificial surfaces - important in biofilm production.
Surface proteins on pathogen bind to host’s proteins/glycoproteins.
Colonization of pathogens
Motility is important bc allows pathogen o move through biofilm etc.
Pili can be used for sex.
Biofilms increase resistance to antibiotics and immune cells.
How can a pathogen evade the host’s defenses
Stopping phagocytosis
- Escape from phagosome into the cytoplasm
- Capsule stops phagocyte engulfing it
- Stops lysosomes fusing with the phagosome
- Resists action of lytic enzymes
- Kills phagocyte using toxins
Releases enzymes that breakdown antibodies and other immune cells/proteins.
Release factors that block the complementary site on the antibody, etc.
Mask surface antigens e.g. using a capsule.
Hides in sites that immune cells don’t reach well.
Changes its antigens or covers itself w the body’s antigens.
Methods of sterilisation
Heat
- dry/hot air oven = 160 degrees, 60 mins
- wet/autoclave = 121, 15mins, 15 or 134, 30mins, 3.
Radiation
Chemicals e.g. formaldehyde.
Methods of disinfection
Need to clean first so that chemicals/agent etc can reach everywhere.
Heat - boil for 15 mins
Chemicals
Innate immunity
Non-specific Present from birth/instinct Doesn't rely on immune recognition Not long-lasting 1st line of defense Includes barriers, serum proteins and phagocytic cell
Active immunity
Specific Quicker response Longer lasting Response and memory rely on antigen recognition Needs immune cells e.g. lymphocytes etc.
What is an Ab (immune)
Antibody = specific/ binds to the epitope of an Ag (foreign protein that ilicists an immune response)
Humoral
Cell and soluble proteins
Where do immune cells develop from
Pluripotent stem cells differentiate into mulitipotent cells and then into unipotent stem cells in the bone marrow.
These differentaite into blood cells and some end up in tissues.
Immune system cells size
10-14 µm, apart from monocytes (14-24 µm)
Types of immune system cells
Neutrophils Monocytes Macrophages Basophils Eosinophils Mast cells B-lymphocytes T-lymphocytes Natural killer cells
Neutrophils
Polymorphonuclear leukocytes
Innate immunity
Phagocytosis:
- Primary granules contain acid hydrolases and proteins to degrade the macrophage.
- Secondary granules contain lysozyme.
- Have Fc and complement receptors
- Secrete superoxides and toxins to kill.
Monocytes
Mononuclear leukocytes Innate and active immunity. Phagocytosis to remove foreign and dead material using lysosomes. Have Fc, complement receptors, etc. GRT macrophages
Macrophages
Mononuclear leukocytes
Innate and active immunity.
Phagocytosis and Ag-presenting.
Basophils
Polymorphonuclear leukocytes
Deal with parasites and allergic reactions.
Very similar to mast cells.
Lead to the release of histamine and IgE.
Eosinophils
Polymorphonuclear leukocytes
Parasites and allergic reactions.
= Histamine released, neutrophils and causes bronchospasms.
Mast cells
Very similar to basophils.
For allergic reactions and parasites.
Causes release of histamine and IgE.
B-lymphocytes
Mononuclear leukocytes
Active immunity
Recognise Ag on APC and produce antibodies by differentiating into plasma cells and differentiate into memory cells (Bm)
T-lymphocytes
Mononuclear leukocytes Active immunity - Help to produce antibodies (Th2) - Release toxins to kill cells (Tc) - Kill intercellular pathogens (Th1) - Regulate immune response (T reg)
Natural killer cells
Induce apoptosis e.g. in virally infected cells and tumor cells.
What are the main immune cells in the blood (by quantity)
Neutrophils (65%)
B/T-Lymphocytes and NK cells (25%)
Types of soluble immune factors
Immunoglobin Antibodies
Complements, C’
Cytokines
Chemokines
What are Ig and different types
Soluble serum proteisn bound to B-cells as part of their antigen receptor. IgG IgA IgM IgD IgE
IgG
The normal one (one heavy chain, hinge region and 2 light chains)
IgA
Secretory e.g. in saliva, milk, etc.
Has a secretory component and a J chain.
Can be dimer or monomer
IgM
Basically 6 IgG’s bound by a J chain.
Too large to cross endothelium so stays in blood.
Usually makes primary contact w Ag.
IgD
Bound to mature B-cells
IgE
V strong IgE receptor on mast cells and basophils so they’re always very concentrated w IgE.
When IgE binds to Ag, histamine is released.
For allergic reactions and parasites.
What are C’ and how can they be activated.
A protein that kills but need to be activated to be functional.
3 pathways
1. Classical = Ab binds to Ag on the microbe.
2. Alternative = C’ binds to the microbe.
3. Lectin = Mannose binds to lectin on the microbe.
Cytokines and different types
Protein secreted by immune and non-immune cells. Directs the immune response. INF IL1, 2 CSF TNF
INF
Interferon cytokine.
Viruses resistance to non-infected cells to reduce spread.
Secreted by infected cells and by activated Th1.
IL1 and 2
Pro-inflammatory and anti-inflmmatory.
Increase or dampen the immune response.
Tell cells what to do e.g. secrete, differentiate, divide.
CSF
Colony stimulating factor.
Affects dividing and differentiation of bone marrow stem cells.
TNF
Tumour necrosis factor
mediate inflammation and cytotoxic reactions.
Chemokines
Proteins that direct cell movements e.g. attract specific cells to the site of inflammation or infection.
Barriers in innate immunity
Physical e.g. skin, skin secretions (low pH)
Physiological e.g. pH, temp.
Mucosal membrane e.g. saliva, mucous, cilia beating, tears.
What does a breach in barrier result in
Damage to cells/infection = inflammation, immune cells brought to the site.
Hallmarks = increased blood supply, vascular permeability and extravasation.
Acute response to barrier breach.
- Coaggulation
- Inflammation
- Immune cells etc do their job e.g. bacteria killed, waste removed, toxins neutralised, etc.
- Repair
- Back to normal.
How does the body sense microbes
Complement e.g: -
- increase opsonisation so more phagocytosis.
- Chemotaxis so phagcytes move more to site of infection.
- Cell lysis by directly attacking membrane.
TLR and PRR recognise PAMP (Toll-like receptors, pattern recognition receptors, pathogen associated molecule patterns)
Events in extravasation
Charge on endothelium stops the WBCs slowing down and sticking until they are told to.
GAGs on the surface of the endothelial cells make them sticky and slow down the WBCs
Chemokines in the endothelial cells attract the WBCs so permanent adhesion (between adhesion molecules on endothelial cells and integrins on WBCs)
WBC migrate through the endothelium by following the dradient made by the chemokines (more chemokines by the site of inflammtion)
Mechanisms of killing
O2 independent = lysosomes, proteins, acids, TNF
O2 dependent = Reactive oxygen intermediates, free radicals, nitric oxide
How does nitric oxide affect the body (immune system related)
vasodilator, anti-microbia, increases extravasation
Inflammatory accessory molecules
C reactive protein and mannose binding lectin cause opsonisation and activate C’
Surfactant protein reduces virus’ ability to infect cell walls.
Cell-mediated adaptive immunity requirements
Intimate contact so can recognise and kill cells directly.
MHC, intracellular and extracellular antigens to recognise self and non-self.
T-cells only work on bound antigens e.g. not soluble.
T-cells, B-cells and MHC all play roles.
What happens to the T/B cells that recognise self?
Killed while in the thymus or bone marrow = selection
How does MHC work and what are the different class’s
Self and non-self proteins displayed on membrane = invasion alert.
Class 1 = Intrinsic e.g. viruses. Acts on all cells. Responds by differentiating into a Tc and directly killing.
Class 2 = Extrinsic. Acts on APCs. Responds by becoming a Th and aiding B-cells.
What is needed for T-cell activation/Ag recognition
TCR needs to recognise Ag and CD4 or 8 and the can bind to MHC and be activated.
T-cell also secrest IL2 which binds to the IL2 receptor on the t-cell (endocrine) and makes cell differentiate, divide, etc.
What are the different fates of a naive T-cell
Naive cell + CD8 = Tc and directly kills cells (apoptosis and releases proteolytic granules)
Naive cell + CD4:
- w/ lots of IL12 = Th1 (acts directly on cells e.g. apoptosis and recognises Ag on infected cell using MHC and TCR)
- w/ little IL12 (cytokine) = Th2 (helps B-cells make Ab)
What is clonal expansion
Proliferation of cells
Ab effector functions
Binds to toxins and neutralises it.
Increases optonisation.
Activate complements
Links innate and adaptive immunity
