Immunology Flashcards
Types of immune response
Innate
Adaptive
Features of innate immune system
Immediate
Non-specific
Lacks memory
Features of the adaptive immune system
Takes few days to start, peaks at 1-2 weeks
Highly specific
Has memory
Components of the innate immune system
Barriers
Cytokines
Cells (from common myeloid progenitor)
Compliment
Common myeloid progenitor cells
Generates: Megakaryocyte (then makes platelets) Erythrocyte (RBCs) Mast cells Myeloblast
Myeloblast
Resides in bone marrow. Activated by cytokines.
Generates:
Basophil
Neutrophil
Eosinophil
Monocytes (creates macrophage and dendritic cells)
Common lymphoid progenitor
Generates:
Natural killer cells
Small lymphocytes (then matures to T lymphocytes and B lymphocytes)
Neutrophils
Innate immune system. First cells to arrive at site of infection.
Granular leukocyte. Multi-lobed nucleus.
Most abundant WBC (40-70% of plasma)
Main action against bacteria/fungal.
Phagocytose mircoorganisms.
Monocytes
Involved in response to bacteria infection.
Kidney bean shaped nucleus.
5-10% of plasma WBCs
Remain in blood before migrating into tissues and differentiating into macrophage.
Macrophage
Main population of phagocytic cells within tissues. Longer lifespans (months-years).
Large, single-lobbed, round nucleus.
Phagocytose microorganisms
Organ/tissue specific macrophages
CNS - microglial cells
Liver - Kupffer cells
Lungs - Alveolar macrophages
Skin/mucosa - Langerhans cells
Dendritic cells
Antigen presenting cells.
Linking innate and adaptive immune systems.
Activate naive T cells by presenting antigens on MHC II.
Eosinophils
1-3% of circulating WBCs
Bi-lobed, sausage shaped nucleus.
Granules contain (Major basic protein, cationic protein, peroxidase), molecules toxic to parasites.
Main action is against parasitic infections.
Phagocytose antigen-antibody complexes.
Also increased in allergy/autoimmune disease
Basophils
Bi-lobed S shaped nucleus
Contain histamine granules.
Cause local inflammatory response through interaction with IgE.
Mediate type 1 hypersensitivity reactions
Lymphocytes
Agranular WBCs.
Respond to viral infection
Round densely-staining nuclei.
Differentiate to: NK cells, T cells, B cells
Natural killer cells
Non-specific immunity against cells displaying foreign proteins (cancer/virally infected cells).
Detect and kill pathogens as part of innate.
Detect abnormal cells and release perforins and cytolytic proteins causing lysis.
T cells
Form in bone marrow, mature in thymus.
Adaptive immune system.
Types: cytotoxic (CD8), T-helper (CD4), Memory T.
Cytotoxic T cells
CD8
Activated by MHCI (on infected normal cell)
Stimulated by IL-12/IL-18.
Kill virus infected cells
T-helper cell
CD4
Activated by by MHCII (antigens presenting cell)
Many different types
B cells
Form and mature in bone marrow
Adaptive immune system
Humeral immunity by secreting antibodies
Mature into plasma cells (antibody secreting cells) and B memory cells
Cytokines - functions
Pro-inflammatory
Homeostatic
Cytokines: pro-inflammatory functions
Chemokine: recruit immune cells to site of infection/injury
Cytokines: homeostatic functions
Attracting cells acquired for angiogenesis
Immune surveillance and allowing T-cell/dendritic cells to migrate
Development of lymph organs
Types of cytokines
Interferons
Interleukins
Tumour necrosis factor
Interferons
Released by host cells in response to pathogen and tumour cells
Type-I (interferon-alpha/beta)
Type-II (interferon-gamma)
Type-III
Type-I interferons (interferon alpha/beta)
Interfere with viral replication
Autocrine/paracrine signalling
Up regulate NK cells and MHCI on surface (meaning NK and cytotoxic T can more easily recognise infected cell)
Type-II interferons (interferon-gamma)
NK, cytotoxic T and Th1 all produce interferon gamma in response to IL12/IL18
Activates macrophages and increases ability to kills pathogens by enhancing pinocytosis and lysosome function
Upregulates MHCII expression
Interleukins
Produced by T cells, monocytes and macrophages
Promotes production and differentiation of B and T lymphocytes
Activates neutrophils and NK
Produces fever (IL-6), raises acute phase proteins (CRP)
Promotes vascular permeability, increasing recruitment of cells to area of infection/injury
Tumour necrosis factor
Produced by macrophages when encountering endotoxin
Can be produced by mass cells/B cells/T cells
TNF alpha/beta:
Local induction of apoptosis
Increasing vascular permeability
Neutrophil chemotaxis
Suppression of appetite
Complement
Part of innate immunity
Complement components mostly made in liver.
Complement system: activation
Classical pathway
Mannose-Binding Lectin pathway
Alternative pathway
All 3 pathways produce C3 convertase
Complement system: effects
C3 convertase - activates C5, which activates C6, C7, C8, C9 in a cascade.
Opsonisation (C3b binds to antigens on pathogen stimulating neutrophils/macrophases to phagocytose)
Lysis of pathogens (membrane attack complexes, formed from C5b + several factors. MAC ruptures bacterial cell membrane)
Chemotaxis (attracts neutrophils/macrophages to site of infection)
Inflammation (C3a/C4a/C5a bind to mast cells/basophils and cause degranulation. Histamine and serotonin release increases vascular permeability)
Barriers to infection
Physical
Physiological
Chemical
Biological
Barrier to infection: physical
Skin: multiple layers of dead, keratinised epithelium
Mucous membranes: resp/GI/urinary. Epithelial layer has tight junctions.
Bronchial cilia.
Secretion: tears, urine, saliva, bila, mucus
Barriers to infection: physiological
Diarrhoea
Vomiting
Coughing
Sneezing
Barriers to infection: chemical
pH: skin (5.5), gastric (1-3), vagina (4.4)
Molecules:
IgA (tears/saliva/mucous membranes)
Lysozyme (sebum, sweat, panted cells in small bowel)
Mucus
Defensins
Enzymes
Barriers to infection: Biological barriers
Normal flora are non-invasive commensal microorganisms.
Outcompete pathogens for attachments and resources
Components of the adaptive immune system
Antibodies
Cells (NK, cytotoxic T, Th, B)
Antibodies: structure
2 heavy chains
2 light chains
Antibodies: classification/types
IgG IgA IgM IgD IgE
IgG
Most abundant
Present on surface of mature B cells
Only antibody able to cross placenta
IgA
Move prevalent antibody in secretions, forms a barrier layer at mucosal surfaces
High levels in breast milk
Neutralises pathogens and hinders attachment to epithelial receptors
IgM
Expressed on surface of B-cells an monomers
Secreted as pentameters
First to be produced during foetal development
First to be produced by B-cells against new infection.
IgD
Present of surface of B cells.
Has role in B cell and antibody production
IgE
Mainly found on mast cells
Associated with allergy, and type 1 hypersensitivity reactions
Triggers histamine release from mast cells and basophils
Part of response to parasitic infections
Functions of antibodies
Opsonisation Neutralisation Complement activation Immune complexes Antibody mediated cell mediated cytotoxicity
Antigen presentation
Major histocompatibility complexes (MHC)
MHC I: all nucleated cells
MHC II: antigen presenting cells
Antigen presenting cells
MHC II
Dendritic cells
B cells
Macrophages
T cells and antigen presentation
T cells recognise MHCs using T-cell receptor (TCR)
Coreceptors:
CD4 (Th): MHC II
CD8 (Cytotoxic): MHC I
Hypersensitivity reactions
Type I
Type II
Type III
Type IV
Type I hypersensitivity
Allergic/anaphylactic
IgE mediated
Type I hypersensitivity: pathophysiology
First exposure: APCs present antigen to naive T-cells, turning them into Th2. IL4/IL5/IL10 release. IL4 causes B cells to produce specific IgE. IL5: eosinophils. IgE binds to mast cell surface.
Second exposure: mast cells with specific IgE degranulate (histamine, proteases)
Early phase (minutes): H1 receptor (bronchial smooth muscle contraction, blood vessel dilation/inc permeability
Late phase (8-12hs): eosinophils/basophils/Th2 mediated by IL4/IL5/IL10
Type 1 hypersensitivity: examples
Atopic disease
Asthma
Anaphylaxis
Churg-Strauss Syndrome
Type 2 hypersensitivity
“Cytotoxic” or Antibody dependent
IgM/IgG/complement/MAC mediated
Type 2 hypersensitivity: pathophysiology
Self-reactive B cells are not destroyed and form a IgM or IgG (assisted by CD4 cells)
These antibodies bind to antigens on the surface of host cells: Intrinsic antigens (normally made by host cells) or Extrinsic antigens (attaches to the host cell)
5 mechanisms:
1: complement activation (C3a/C4a/C5a) & neutrophil degranulation
2: MAC
3: Opsonisation and phagocytosis
4: antibody dependent cell mediated cytotoxicity (ADCC): NK degranulation
5: antibody mediated cell dysfunction (non-cytotoxic, e.g. myasthenia graves/graves)
Type 2 hypersensitivity: examples
Autoimmune haemolytic anaemia Rheumatic heart disease Goodpasture's syndrome Grave's disease Myasthenia gravis
Type 3 hypersensitivity
Immune complex mediated
IgG, complement and neutrophil
Type 3 hypersensitivity: pathophysiology
IgG binds to soluble antigen forming immune complex
Deposits in basement membrane of vessels and causes compliment activation
Neutrophils attempt to phagocytose but cannot and degranulate into vessels, causing vasculitis
Disease where immune complexes are deposited (kidneys/joints)
Type 3 hypersensitivity: examples
Systemic lupus erythematosus
Serum sickness
Rheumatoid arthritis
Post-strep glomerulonephritis
Type 4 hypersensitivity
Cell-mediated immune response
T cell
Type 4 hypersensitivity: pathophysiology
APC presents antigen using MHCII to Th
Th matures to Th1 (effector cell)
Th1 produces IL12, IFN-gamma (activates macrophages). Activated macrophages release pro-inflammatory cytokines and lysosomal enzymes/complement/ROS (causing tissue damage)
Type 4 hypersensitivity: examples
Contact dermatitis Graft versus Host disease Multiple sclerosis Coeliac disease Hashimoto's thyroiditis
