Introduction to Immunology Flashcards
Innate vs Adaptive Immunity
Innate:
Primary line of defence
immediate response
recognises certain threats
no antigen presentation
no clonal selection
no immunological memory
Adaptive:
Secondary line of defence
Delayed response
Recognises all threats
Antigen presentation
Clonal selection
Immunulogical memory
State four functions of innate immunity
Form physical barriers - skin, mucus, cilia, commensals
Form biochemically unfavourable environments - sweat, lysozyme, gastric acidity
Phagocytosis of invading organisms - macrophages, monocytes
Destruction of extracellular parasites - eosinophils
Name 5 sites of lymphoid tissue
MALT: adenoids, tonsils
Thymus: Tcell maturation
BALT: macrophages
lymph nodes: peripheral lymphoid tissue
Kupffer cells: macrophages in liver
Spleen: secondary lymphoid organ,
GALT: Peyers patches in ileum, appendix
BM: haematopoeisis, B-cell maturation
SALT: dendritic cells, macrophages
What are the humoural components of the immune system?
Acute phase proteins
Lectin
Complement
Antibodies
Cytokines
Describe the interactions between T-cells and their target cells
TH cells help generate the immune response by binding to MHC Class II on antigen presenting cells. TH1 cells help stimulate the immune response by activating macrophages which release inflammatory cytokines. TH2 cells actiate B cells which differentiate into plasma cells and release antibodies.
TC cells generate a cytotoxic response by binding to MHC Class I on infected cells and inducing apoptosis
Treg cells interact with Tc cells to modulate the immune system. Also involved in immune tolerance to self-antigens and are thought to be involved in autoimmune disesase
Which 3 leukocytes are granulocytes?
Neutrophils
Eosinophils
Basophils
Name 5 different types of lymphocytes
NK cells
Treg
T-helper
T-cytotoxic
B-cell
What are the four main types of humoural factor in the immune system?
Acute phase proteins
Complement
Antibodies
Cytokines
Give four examples of iatrogenic causes of compromised barrier immunity
Injection
Catheter
Mechanical ventilator
Antibiotics
Cannula
Describe the process of phagocytosis
Chemotaxix and adherence of microbe to phagocyte
Ingestion of microbe by phagocyte
Formation of a phagosome
Fusion of the phagosome with a lysozome
ROS and enzymes digest ingested microbe
Formation of residual body containing indigestible material
Discharge of waste materials
Describe the function of NK cells
NK cells are lymphocytes that function in the innate immune response. Capable of direct and antibody-dependent cellular cytotoxicity.
NK cells are activated through a lack of stimulation of inhibitor receptors.
Normally all human cells express MHC Class I on their surface, however this is downregulated in virus-infected and malignant cells. Lack of MHC Class I on the cell surface activates the NK cell which releases perforin onto the target cell membrane and releases cytotoxic chemicals
What are PAMPs? Give 3 examples
Pathogen associated molecular patterns.
LPS, Flagellin, bacterial DNA
Describe the complement cascade
The complement cascade is activated through three distinct pathways: classical, alternative and MBL.
The classical pathway is triggered by Ag-Ab complex binding to C1, or by direct binding of C1 to the pathogen surface.
The MB-lectin pathway, is triggered by mannan-binding lectin, a normal serum constituent that binds some encapsulated bacteria
The alternative pathway, which is triggered when C3 binds directly to pathogen surfaces
All three pathways result in the cleavage of C3 and C5 which result in inflammation, opsonisation of pathogens and the formation of the MAC which causes cell lysis.
Describe the function of MHC
MHC proteins present antigens on the cell surface which are recognised by T-cells.
MHC Class I are present on all cell types and present endogenous (intracellular) antigens e.g. viral peptides, neoplastic antigens to CTLs
MHC Class II are only found on APCs and present exogenous antigen (e.g. engulfed material) to Th cells
Describe antigen presentation in MHC I and MHC II molecules
Presentation of endogenous antigen:
Cytosolic proteins are digested by proteosomes into small amino acids. These are taken up into the ER via the TAP transporter where they are cleaved and loaded onto an MHC Class I molecule. The mature MHC I molecule is transported to the cell surface
Presentation of exogenous antigen:
External material are internalised by APCs via phagocytosis and digested in phagolysosomes. MHC Class II molecules which are made in the ER are transported to the cytosol where they are loaded with antigenic peptides and transported to the cell surface.
Describe the components of adaptive cell mediated immunity
Adaptive cell-mediated immune responses involve the destruction of infected cells by cytotoxic T cells, or the destruction of intracellular pathogens by macrophages activated by TH1 cells. Mainly directed at intracellular pathogens.
Cytotoxic activity of CTLs requires recognition of antigen on MHC Class I of the infected cell and a simultaneous co-stimulatory signal from and APC (e.g. dendritic cell)
Activation causes clonal expansion and differentiation of the CTL cells. This effector T-cell progeny can act on any target cell that displays antigen on its surface.
Memory Tcells maintain immunological memory of the antigen
Describe the process of adaptive humoural immunity
The humoral immune response is mediated by antibody molecules that are secreted by plasma cells.
Antigen on APCs binds to the BCR which signals B cells and is then internalized and processed into peptides that activate Th cells.
Signals from the bound antigen and Th cell induce the B cell proliferation and differentiation into a plasma cell secreting specific antibody.
These antibodies cause opsonisation, neutralisation and complement activation.
B memory cells maintain immunological memory
Describe the process of inflammation in response to infection
Macrophages are activated by the presence of bacteria in the tissue or via IFNg release from active NK cells.
Activated macrophages are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues and produce chemokines that direct the migration of neutrophils to the site of infection.
Endothelial cells of the blood vessels express adhesion molecules which allow neutrophils and monocytes to migrate through the blood vessel walls.
The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation.
Describe the process of clonal selection
Each lymphocyte bears a single type of receptor with a unique specificity. Lymphocytes bearing receptors for ubiquitous self molecules are deleted an an early stage in lymphoid cell development
Interaction between a foreign molecule and a lymphocyte receptor with high affinity leads to lymphocyte activation
The differentiated effector cells derived from an activated lymphocyte has receptors identical to those of the original cell.
Decribe the role of cytokines in the immune response
Cytokines are small polypeptides released by a cell in response to an activating stimulus that change the behaviour of the cell.
Interleukins: They can be pro-inflammatory ot anti-inflammatory.
Chemokines: chemoattractant molecules that guide cells involved in the innate and adaptive immune response from the blood into the tissues
Immune memory
Immune memory is sustained by long-lived antigen-specific lymphocytes that were induced by the original exposure and that persist until a second encounter with the pathogen.
Presence of memory cells meand that the immune response produced on the second encounter is more rapid and specific to the pathogen.
Immune tolerance
Immune tolerance results from clonal deletion of lymphocytes that recognise ubiquitous self antigen and clonal inactivation by tissue-specific antigens presented in the absence of co-stimulatory signals.
This prevents auto-immune responses
Give three histological features of chronic inflammation
Infiltration with mononuclear cells (macrophages, lymphocytes)
Tissue damage/destruction
Repair with angiogenesis and fibrosis
Features of acute vs. chronic inflammation
Acute:
Immediate response to tissue injury
Rapid
Innate IR
Neutrophil
Hours/weeks
Prominent vascular response
Chronic:
Persistent reaction to inflammation or injury
slow response
adaptive IR
Lymphocytes and macrophages
Weeks, months, years
Eosinophils
Target multicellular parasites (e.g. helminths) by releasing toxic granules (leukotrienes and peroxidases).
Specific granules target parasites while primary granules alter the airway and vasculature. This plays a role in allergic diseae e.g. asthma
Mast cells and Basophils
Release histamine and pro-inflammatory mediators. Involved in the allergic response.
What is barrier immunity?
Non-immunological host defence mechanisms that prevent infectious agents from entering the body.
Physical barriers: Skin, mucus, cilia, commensal organisms
Biochemical barriers: lysozyme, spermine, gastric acidity
Name three phagocytic cells
Neutrophils
Monocytes
Macrophages
What is the function of acute phase proteins?
Acute phase proteins rapidly increase in concentration during inflammation.
Mediate rapid, non-specific cytotoxicity and have pro-coagulant effect.
Useful biomarkers of inflammation
Include: CRP, Alk Phos, Ferritin
Interferons
Proteins produced by virus infected cells (IFNa, IFNb) and Th cells and NK cells (IFNg) which inhibit viral replication and cause cell cytotoxicity.
