Intro to immunology Flashcards
Primary function of immune system
Eliminate pathogens
Minimise damage they cause
How are foreign substances recognised by the immune system
Antigens are ANTIbody GENerators
Clonal selection
Maturation into mature and genetically committed cells in bone marrow
Antigen-dependent proliferation and differentiation into plasma and memory cells in peripheral lymphoid tissue
How is the immune response tailored to viruses and intracellular bacteria
Identification and killing of infected cells by cytotoxic T cells
How is the immune response tailored to extracellular fungi, parasites, bacteria
Detection of surface structures by antibodies and destruction by phagocytes
How is the immune response tailored to large parasites
Deposition of toxic substances or killing by mast cells/eosinophils
How is the immune response tailored to immunoprivilged areas
No response as infl would be caused, damaging the tissues
Immunoprivileged areas
CNS
Eyes
Placenta
Reproductive organs
Commensal bacteria
Bacteria that the body has learnt to tolerate - esp in gut
2 kg in whole body
Levels of defence in immune system
External defences
Innate immune system - ‘primitive’
Adaptive immune system - highly spp
Exterior defences of body
Ear Eyes Nasal cavity Skin Urethra Anus Vagina Stomach Trachea and bronchi Mouth cavity
Ear as a defence
Cerumen inhibits bacterial growth
Eyes as a defence
Cleansed by tears which also contain antibacterial chemicals
Nasal cavity as a defence
Hairs and mucus traps organisms
Skin as a defence
Impervious barrier
Urethra as a defence
Urine flow prevents bacterial growth
Anus as a defence
Mucous membrane traps microorganisms
Vagina as a defence
Acidic secretion inhibits growth of pathogens
Stomach as a defence
Acidic juices kill many microorganisms
Trachea and bronchi as a defence
Mucous layer traps microorganisms
Mouth cavity as a defence
Mucous membrane traps microorganisms and the mouth is cleaned by saliva
Innate vs adaptive immune system
Non-spp vs spp
Fast response (mins) vs slow (days)
No memory vs memory
Immune dysregulation
Balance between activation and suppression
Types of immune dysregulation
Hypersensitivity
Autoimmunity
Immunodeficiency
Hypersensitivity
Overaction to benign antigen
Can be presented as anaphylactic shock
Types of hypersensitivity
I - IV
Type I is allergy e.g. hay fever, asthma, hives, eczema
What are allergies mediated by
Particular immunoglobulin, IgE and mast cells
Anaphylactic shock
Severe, life-threatening, allergic response
Tolerance
Immune system distinguishing between ‘self’ and ‘non-self’
What typically happens to self-reactive immune cells
Eliminated by immune system, either in thymus or bone marrow before it reaches the bloodstream
What is autoimmunity caused by
Breakdown of tolerance
Certain genetic and environmental factors can make you predisposed
Examples of autoimmunity
Multiple sclerosis - immune system attack against nerve sheaths on brain/CNS leading to neuromuscular dysfunction
Crohn’s disease - attack on microbiota/ gut epithelium –> poor food absorption
Immunodeficiency
Component of innate/ adaptive immune system absent or defective
Primary immunodeficiency
Inherited
Most common form of primary immunodeficiency
Severe Combined Immunodeficiency (SCID) - no functional adaptive immunity, has low life expectancy
Secondary immunodeficiency
Caused by damage by external agents
Most common form of secondary immunodeficiency
Acquired Immune Deficiency Syndrome (AIDS) - Infection w/ HIV, destruction of Thelper cells –> death by opportunistic infections
Challenges w/ immune system
Transplantation
Cancer
Why does cancer present as a challenge for the immune system
Cancer cells display self-antigen (tolerated) as they are derived from own body and tumour-spp antigens (recognised)
Cancer cells evade immune response by rapid change (mutations) and active inhibition
Immunotherapies against cancer boost body’s natural defences
Primary tissues and organs of the immune system
Development and maturation of adaptive immune cells (lymphocytes) Bone marrow (B cells) and thymus gland (T cells)
Secondary tissues and organs of the immune system
Mature lymphocytes meet pathogens
Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s patches, MALT
MALT
Mucosa Associated lymphoid tissue
How are lymph nodes placed
Strategically around the body as they act as ‘meeting place’ for immune cells
What happens at lymph nodes
Pathogens from infected tissue sites are picked up by dendritic cells and arrive at closest lymph node
Circulating T and B cells enter and congregate at spp regions in lymphoid follicles
If they encounter a ‘matching’ dendritic cells, they’re activated and proliferate
Where do B cells congregate in the lymphoid follicle
Cortex
Where to T cells congregate in the lymphoid follicle
Paracortex
What changes occur to the lymph node after activation of lymphocytes
Architecture
Size of the node
What other tissues/organs contain organised lymphoid tissues
Spleen and MALT
Haemotopoiesis
‘Making of blood’
How immune cells are generated
Takes place in the bone marrow after birth
What determines what multipotent stem cells in the blood differentiate into
The growth factors received by the myeloid or lymphoid progenitors
Where do monocytes differentiate into macrophages
Circulate in blood before migrating to tissues
Why do the names of macrophages change
Depending on where they’re found
Alveolar macrophages
Found in lung
Histocytes
Macrophages found in connective tissues
Mesangial cells
Macrophages found in the kidneys
MIcroglial cells
Macrophages found in the brain
Kupffer cells
Macrophages found in the liver
Function of macrophages
Phagocytosis
Antigen presentation
Process of phagocytosis
Bacterium becomes attached to pseudopodia
Bacterium is ingested, forming phagosome
Phagosome fuses w/ lysosome
Lysosomal enzymes digest captured material
Digestion products are released from the cell
Pseudopodia
Membrane invaginations
Endogenous pathway of antigen presenting
Ag presentation to cytotoxic T cells via MHC class I CD8
Exogenous pathways of antigen presenting
Ag presentation to helper T cells via MHC class II CD4
Why do dendritic cells have lower degradation potential
Better APC’s than macrophages
Leads to antigen preservation
Immature dendritic cells
Antigen uptake in peripheral tissues
Mature dendritic cells
Migration to lymph nodes and Ag presentation
What do dendritic cells activate
Adaptive immune response after finding matching T or B cell
Granulocytes
Contain granules and have multi-lobed nucleus
Neutrophils, basophils, eosinophils
Stained eosinophils colour
Appear pink
Stained basophils colour
Appear blue
Stained neutrophils colour
Appear purple
PMN
Polymorphonuclear neutrophils
What % of circulating granulocytes is made up by neutrophils
95%
How are macrophages similar to neutrophils
Both phagocytose bacteria but much shorter lived (few days - die after phagocytosis)
Chemotaxis of neutrophils
Attracted by IL-8
Follows to site of infection
How do neutrophils kill and digest bacteria
Netosis
Release nuclear elastase from granules (antimicrobial)
NE goes to nucleus, chromatin expands and is relegated from the cell to capture bacteria
What do eosinophils, basophils and mast cells kill
Larger parasites e.g worms
These are coated by IgE and this allows target recognition - corresponding receptor
Attach to parasite and starts degranulation and release of toxic contents (histamines, proteases)
Eosinophils, basophils and mast cells association w/ allergies
IgE
Overreaction to harmless antigens e.g dust mites’ compounds
Release cytotoxic compounds, histamine –> infl
Abundance of NK cells in the blood lymphocytes
5-10%
How do certain viruses and cancer stop Ag presentation
Down regulation of MHC class I Infected cell has lack of MHC class I molecules NK cell receives only +ve signals --> becomes activated
Generative lymphoid organs
Bone marrow
Brain
Peripheral lymphoid organs
Lymph nodes
Spleen
Mucosal and cutaneous lymphoid tissues
Types of T helper cells
Th1 cells help macrophages digest pathogens
Th2 cells help B cells to produce antibodies
CD4 involved in Class II MHC pathway
Class I MHC pathways
CD8 (cytotoxic T cells) kill virus-infected cells
Innate barriers to infections
Mucosal surfaces
Features of mucosal surfaces
Tight junctions in epithelial layers
Goblet cells, Paneth cells secrete antimicrobial peptides and enzymes and mucus
Cells involved in innate immune system
Dendritic cells Macrophages Mast cels NK cells Granulocytes
Cells involved in adaptive immune system
B cells
T cells
CD4+ T cell and CD8+ T cell
Steps in innate immunity
Recognition
Disposal
Communication
Recognition in innate immunity
PAMPs and DAMPs
PAMPs
Pathogen Associated Molecular Pathways
Signal production of cytokines to stimulate immune cells
What are PAMPs recognised by
Toll-like receptors on macrophages, neutrophils, epithelial cells of gut and lung
Where are PAMPs found
Plasma membrane
In endosomes/ phagosomes
How do we recognise microbes despite their rapid evolution
Using highly conserved and essential features that are different to us e.g cell walls (peptidoglycan), nucleic acids (CpG DNA), sugars (lipopolysaccharides, mannam), flagella
DAMP
Damage Associated Molecular Pattern
Disposal in innate immune system
Microbes killed by phagocytic cells
Broken up into common units presented to immune system
Recognition by complements
Uses 30 diff proteins
3 main pathways: lectin, classical and alternative
Leads to infl, phagocytosis and MAC (membrane attack complex)
Activation of lectin pathways
Microbial sugars (yeasts and bacteria)
Activation of classical pathways
Antibodies
Acute phase proteins
Produced in liver in response to infl
Liver is stimulated by IL1, IL6 and TNF
Adjuvant
Parts of a pathogen used to activate innate cells in immune systems (macrophages, dendritic cells)
Role of IgG
Antibodies bind Fc receptors to activate immune defence
IgG is secreted into blood and removed pathogens from blood and tissues
IgG binds pathogen w/ variable region, leaving Fc domains exposed. Fc domains cluster to generate a recruitment signal
What do Fc domains recruit
Complement –> lysis of pathogens (MAC)
What does Fc binding to Fc receptors lead to
Binding to Fc receptors on macrophages leads to phagocytosis and killing in lysosomes
Can be helped by complement
Opsoninisation and Fc
Phagocytic cells carry Fc receptors and also receptors for complement
Fc domains exposed by antibody on pathogen allows recognition by phagocytic cells
Fc receptors interactions trigger phagocytosis by releasing proteosomes or ROS
ROS
Reactive oxygen species
What is IgA made and secreted by
B cells in response to infection of mucosal surfaces but doesn’t stay in blood
Role of IgA
IgA binds an IgA receptor and is secreted across epithelial cells (protects mucosal surfaces)
Tail of IgA binds to an IgA receptor and this complex is then able to bind to pathogens that haven’t entered body
IgE receptors
Found on mast cells, eosinophils and basophils
What does IgE define
The Ag spp of mast cells, eosinophils and basophils, allowing them to recognise Ag
Joining chain
Protein linking two IgA molecules
Why do mast cells release histamine
To open up the sites of parasite infections to the rest of the immune system
What do eosinophils release
Peroxidase Ribonucleases Deoxyribonuclease Lipase Plasminogen
What is the same for each subtype of antibody
‘Variable’ region
Why do the Fc domains differ
Differences in coding sequences but lies in same Ig gene
Which molecules have variable and constant regions
Antibodies
T-cell receptors
What does the constant region bind
Fc receptors
T cell receptors
Stay attached to the surface of the T cells
Granules in cytotoxic T cells
Contain enzymes e.g perforins are released into the space between the T-cell and infected cells
Repeated sequences in Ig genes
Variable region
Diversity region
Joining region
What does gene rearrangement allow
One of the duplicated sequences in each region to be used to make the protein
1st gene rearrangements
Select diversity and joining regions Constant region (Fc) is constant
2nd gene rearrangements
Selects the variable region and the constant regions (Fc) is constant
VDJ recombination
Brings one of the remaining variable sequences next to the DJ combi, genes within the loop are removed by RAG proteins
What does VDJ recombination provide
Antibody and T-cell diversity
Rearrangement of T-cell receptors
Creates diversity
Only rearranges once and only on one chromosome
Rearrangement of T and B cells
Rearrange genes at random and each cell can only rearrange genes once
What happens to the T-cells that have rearranged the right genes segments
Bind Ag —> triggers cell division (clonal expansion)
What happens to the T-cells that don’t rearrange the right gene segments
Can’t bind antigen so they die
How do B-cells get T-cells help
By becoming APC’s
What happens when T-cells and B-cells agree on the antigen
The T-cell is activated by the T-cell receptor
The T-cells then express ligands that can bind to B-cells
Co-stimulation
What does co-stimulation induce
Cytokine secretion from the T-cell
Plasma cells and memory cells
Plasma B cells proliferate to make antibodies secreted into bloodstream – remove the membrane anchor and secrete immunoglobulin
Memory B cells retain the membrane bound receptor and can keep communicating w/ T-cells
Diff cytokines released by T helper cells drives diff types of B-cells
What does IL4 drive
Memory B cells
What does IL10 drive
Plasma cells
When does antibody class switching occur
Once VDJ recombination is complete
Features of IgM
Seen in primary immune response
Low affinity, broad specificity
How is IgM produced
Signals for the B-cell receptor and cytokine trigger the removal of the membrane anchor
The mu region is added
2nd antibody class switch
Replaces membrane anchor w/ gamma sequence to make IgG
Features of IgG
Seen in secondary immune repose
High affinity, narrow specificity
Antibody classes
Mu - IgM
Gamma - IgG
Alpha - IgA
Epsilon - IgE
Followed by membrane anchor
How are isotopes generated
Switching of constant domains during recombination
Uses same variable regions
What is isotype switching controlled by
Cytokine secretion from Thelper cells
Which interleukins control isotype switching for IgG
IL4
IL6
Which cytokines control isotype switching for IgA
IL5
TGF beta
Which interleukin controls isotype switching for IgE
IL4
