Immune system intro and basic Flashcards
What is the immune system? What is its overall function?
Complex cellular network all over the body, involved in clearing pathogens, recognising danger signals, distinguishing self from non self, allowing beneficial commensal bacteria to survive
How does the innate immune system recognise AG? How are the receptors coded?
Uses Patter Recognition Receptors (PRRs), with 2 categories. PAMP recognise molecular patterns present only on pathogenic AG, and react accordingly
DAMPs recognise signals from lysed cells or self AG in an unusual place, and being activated
Hundreds of different receptor, all with 1 gene-germ line encoded-limited diversity but fast expression of a similar receptor
How does the adaptive immune system recognise AG? how are the receptors coded?
AG specific receptors on B and T cells. BCR recognise intact AG, T cell needs processing and presentation. Highly specific to an epitope-only activate when a specific AG is shown.
Millions of possibility for each AG, not all coded but used VDJ recombination
What are the main differences between Innate and Adaptive?
Innate: independent of previous exposure, depends on pre-existing components => fast, but limited PRR diversity
Adaptive: Memory and adapts to exposure. Depends of receptor diversity and clonal expension once AG seen=> slow but highly specific for foreign AG
What are primary lymphoid organs? Describe anatomy and general organisation of each
Primary organs are sites of lymphocyte production (lymphopoeisis). Bcells-Bone marrow, Tcells-thymus
Thymus-between both lungs between heart and sternum. 2 lobes-exterior cortex, interior medulla (with hassals corpuscule inside)-connected by lobule to other lobe. site of T cell differentiation and maturation-output reduces with age (so new TCR reduces with age)
Bonne marrow-within bone, site of all heamatopoeisis by Stem cells (t cells migrate to thymus, B cells stay in BM), In foetus, all bones have sone-very cellular BM (red marrow). Adults-mostly large flat bones (illiac, ribs)-mostly fat (yellow marrow)
What are secondary lymphatic organs? What is the lymphatic system? Describe the general anatomy of each
Organs where lymphocytes can interact with circulating AG and other lymphocytes. 3 main parts: lymph nodes, spleen and musocal associated tissue
Lymph nodes: All over the body, connected to lymph drainage-2/3L recycled/day to superior vena cava. Nodes are bean shaped, with central medullary sinus (connected to veins) and several afferent and efferent lymphatic vessels. Split into slices with lymphoid follicules on outsided (b cells) and germinal centers (t cells)-directed by chemotaxis. Arteries end in a high endothelial venule, where cells pass into tissue
Spleen-Under diaphragm,, right lateral of liver-red and white pulp for RBC and WBC. Arteries go to hilum. White pulp made of maginal zone and periarterial zone, and b cells in primary follicule and T cells in periaterial lymphatic sheath (white pulp too)
MALT-muscosa associated tissue (like skin)-form a physical barrier but have large surface areas with many cells-heavily defended. Eg gut epithelia has lymphatic acess but also peyers patches (and M cells to capture gut AG). Peyers have 2 B cells area and a T cell area, and are connected to lymphatic. Overall mostly B cells and has germinal centers during infections.
Skin-cutaneous immune system, has a lot of DC in epidermis and T/B cells sitting in dermis. Connected ny lymph too
Explain the importance and mechanism for lymphocyte circulation and recirculation.
There are millions of lymphocytes with different receptors, and they have to be able to meet their one specific AG-circulate around to increase chance of seeing its AG. Usually, DC takes AG to 2ndary tissue, and then lymphocytes circulate to and fro. Lymphocytes go from blood to lymph and continue, until death or activation
Entry into tissue is similar to other-rolling. Chemotaxis attracts, selectin binds loosely allowing rooling, and then intergin stops the lymphocyte, allowing it to pass through the HEV.
Overall circuit ressembles : naive in blood goes to lymph node-circulates in lymph until recyled by vena cava. Once it enters a node with its AG, activates and migrates to site of infection thought blood
What are CD markers? Why are they important? where are they found? Give an overview of T and B cell response, and mention APC
Lymphocytes (B and T cells) look the same-large agranular cytoplasm and large nucelus. Therefore need to find another way to differentiate them-use surface proteins. Used AB to see what sticks to what-from that create a classification-cluster of differentiation
T cells all express CD3-subsets have CD4 or CD8. Express many others too -about 3.75x10^11 T cells-2/3s are CD4, 1/3 CD8-and both need presenting by MHC on TCR to be active
B cells-no subsets, uses BCR to directly reocgnise AG. CD19 and 20 on all of them-but no CD3,4,8. Express MHC II for presenting AG to Tcells. Once it recognised an AG, it undergoes clonal selection and activation, to produce AB specific to the epitope
APC-cells capable of uptaking and processing AG to show to T cells. 3 main ones- DC, B cells and activated macrophages
Describe the barriers that contribute to the innate immune system
Several barriers-
anatomical-skin (mechanical barrier, acidic environement)
Muscous membrane- (mucous trap pathogens outside)
Physiological-body temp, low pH (stomach acid), chemicals (in tears)
Phagocytic (cells ingest materials)
Inflammatory (immune response)
List the 7 main cells of the innate immune system, their indentifying characteristic and their function
Neutrophils-main phagocytic cell (40-70% of leukos)- to activate, need to inflitrate tissue, bind pathogen, intake it and kill it
Move following chemotaxis and again-selectin then integrins.
can bind opsonins (any molecule that coat organism to make phagocytose easier (AB, complements)
Killing mechanisms mostly - O2 idenependent (enzymes, proteins) or 02 dependent (ROS, RNS, Superoxide, bleach)
Can also used Neutrophil extracellular traps (NETs) where cells release their chromatin to create a trap
Eosinophils-phagocytose, granules of histamin, help B cells produce IgA
Basophils-granule release and act as APC
Macrophages-monocyte in blood-enlarge in tissue
Activate in tissue with PRRs, leading to cytokine production and phagocytosis. CAn also act as APCs
Mast cells-Sit in tissue (possibly acient precursors)-sit in mucus, connective tissue-recognise and phagocytose bacteria-vasodilation and permeability. VERY readily bind IgE
Dendritic cells-APC
NK cells-Large granulated-cytotoxic and lyse target (10% of blood lymhpo). No AG receptor, bind AB coated celsl
activate and regulate response-best vs tumours and viruses
Describe what cytokines are, giving exemples
Cytokines are small secreted proteins that communicate cell to cell-usually acts locally. Low conc is enough, and regulated by having a short lifetime
exemples include:
Interleukines (Leukocyte-IL-x)
Interferons (antiviral prots-INF-x)
Chemokines (make gradient for chemotaxis)
Growthfactors (Proliferation and differentatiaion)
cytotoc tumor necrosis factiors (TNF)
Can act in a autocrine, paracrine or endocrine fashion (distant cells)
Main ones - IL1 and TNFa are alarms cytos
IL6 is an acute phase signal, IL8-chemotactic for neutrols IL10 is a stop signals
What is the complement system? How is it activated? what does it do?
Complement system is a cascade of enzymes-about 30 prtoeins, at high conc. Once triggered, the first enzyme activates the 2nd one (more than 1), and the 2nd the 3rd, etc. usually cleave target and the cleaved part also plays part in signal-amplifies FAST
Activation has 3 ways: Alternative pathway is when immune cells bind bacterial surfaces directly, recognise it and activate complement). Lectin pathway is when Mannan binding lectin C reactive prot is present (only in infections), and classical is ABs binding receptors activating it
All these ways converge to C3B (on the way making pro inflammatory cytokines)-C3B is the main opsonin of the pathway. The enzyme, C3A, goes on to make the membrane attack complex (MAC) which makes holes into bacteria-killing them
generally: Lyse, opsionise, activate inflamation, clear immune complexes
Controlled because of the need for activation, dillution in body and specific proteins that stop it if not the right signals
What is a systemic actue phase response? what are the markers?
Local inflamation might be accompanied with systemic response (fever, increase WBC prod, prod of acute phase prots)-usually induced by cytokines Acute phase prots are usually markers CRP-activator of lectin pathway Mannan binding lectin (MBL)-also Complement Fibrinogen (clotting)
