Immunology Flashcards
Immunity
state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease
What is the first line of defence?
physical and chemical barriers that are always ready and prepared to defend the body from infection
Skin
barrier function
has its own microbiome
Tears, mucus and saliva
openings are potential entry points so are protected by secretions
may contain anti-microbial peptides or enzymes
pathogens
Cilia
very fine hairs lining our windpipe that move mucus and trapped particles away from the lungs
can be bacteria or material like smoke/dust
Stomach acid
HCl secreted by parietal cells lowers the pH
activates proteases such as pepsin in the stomach and kills pathogens
Urine flow
regularly pushes out pathogens from the bladder adn urethra
Friendly bacteria
naturally occuring and form microbiome in gut, skin, mouth and vagina
acts as competition to reduce pathogens ability to colonise/grow
can be disrupted by antibiotics/antibacterials
Pathogen associated molecular patterns
how the body distinguishes between pathogen and self cells
the things that are different between them
Damage associated molecular patterns
similar to PAMPs
used to identify damaged self cells
Toll like receptors
largest family of receptors that detect PAMPs
highly expressed in macrophages, dendritic cells and neutrophils
How do TLRs exert their effect?
molecular signalling cascade through downstream effectors like Jun/Fos TFs and NFkB
changes gene expression
Myeloid white blood cells
provide innate immune protection
macrophages, neutrophils and dendritic cells
Lymphoid white blood cells
generate adaptive immunity
What does activation of the innate immune system lead to?
blood vessels become dilates and permeable to facilitate wbc access
pro-inflammatory cytokines released
fever inhibits pathogen proliferation and catalyses chemical reactions of immune system
How can a local immune response be dangerous systemically?
loss of plasma volume
crash of blood pressure
cytokine storm
Neutrophils
short lived phagocytic abundant in blood but not tissues, respond and migrate to sites of infection (make up most of puss)
Macrophages
long lived professional phasgocytes abundant in areas likely to be exposed to pathogens like airways and the gut
Eosinophils
specialists in attacking objects too large to engulf
Adaptive immunity
can generate highly specific responses to specific pathogens
can indentify, target and destroy vast range of pathogens and toxins
When can adaptive immunity become lethal?
if directed towards host molecules/proteins
if directed towards harmless foreign molecules
What are the 2 primary lymphoid organs?
thymus- T cells
bone marrow- B cells
Lymphatic system
lymphocytes develop in primary organs and then migrate to secondary oragns where they are exposed to foreign antigens
lymph drains into bloodstream and cells circulate
Natural killer cells
take part in early defence against foreign cells and autologous cells undergoing stress
are lymphoid cells by considered part of innate immune response
Antibody responses
secreted soluble immunoglobins of various types tht bind to antigens, produced by B-lymphocytes and ultimately secreted by the plasma cells
What are the 3 subtypes of T cells ?
cytotoxic T cells
helper t cells
regulatory t cells
Cytotoxic t cells
directly kill infected host cells
Helper t cells
activate macrophages, dendritic cells, B-cells and cytotoxic T-cells by secreting a variety of cytokines and displaying a variety of co-stimulatory proteins on their surface
Regulatory t cells
use similar strategies to inhibit function of helper T cells, cytotoxic T cells and dendritic cells
How is the adaptive immune system activated?
binding of an antigen to activated cells leads to their proliferation and clonal expansion
triggers differentiation into effector cells
Dendritic cells
specialist phagocytic cells derived from monocytes
express a large variety of recognition receptors
phagocytose pathogens, cleave them into peptides to bind to MHC
migrate to lymphoid tissues to stimulate T cells
What are the 5 classes of antibodies?
IgG
IgM
IgD
IgE
IgA
IgG
msot common antibody found in the body
made up of 2 copies of 2 proteins linked by covalent disulphide bonds
What are the 2 parts of antibodies?
constant domains- interact with other parts of the immune system and is always the same
variable domains- make up antigen binding sites and differ
Junctional diversification
gain or loss of nucleotides during recombination
Allelic exclusion
choice of one allele during recombination
Somatic hypermutation
process in which point mutations accumulate in the antibody V-regions of both the heavy and light chains, at rates that are about 10 6-fold higher than the background mutation rates observed in other genes
BCL-6
transcriptional repressor expressed in germinal centres
binds to sites in the p53 promoter
switches off expression leaving them without watch keeper oversight
P53 pathway
pathway that acts as a watch keeper for cells experiencing double stranded breaks and high levels of DNA damage
will cause them to undergo apoptosis
What are the 2 ways antigen presenting dendritic cells can respond to T cells?
activate or tolerise
What are t cells activated by?
partially degraded antigens displayed on the surface of antigen presenting cells
MHC proteins on these cells bind to peptide fragments and carry them to cell surface
What proteins do activating dendritic cells present?
MHC with foreign antigens
stimulating ligands
cell-cell adhesion molecules
What do tolerising antigens present?
self antigens on their MHCs but without the co-stimulatory activator protein
T cell receptors
how t cells bind to MHCs
like immunoglobins, contain variable domains and hyper variable loops
Candida albicans
yeast that usually lives on/in our bodies without issues but can become pathogenic if it is transformed into its pseudohyphal filamentous form
What can induce candida to turn into its hyphal form?
phagocytosis by macrophages
Staphylococcus aureus
gram positive spherical bacterium frequently found in the upper respiratory tract and on the skin
produces protein A
Protein A
a cell wall protein that binds to the constant domain of IgGs which means they are covered with self proteins so no longer recognised by innate immune system
HIV
RNA lentivirus that specifically infects t helper cells, dendritic cells and macrophages expressing NK, CD4 + CD8
infected cells no longer function and t cells target the adaptive immune system
immune deficiency leads to infections and cancers
What cancer is only usually seen in HIV patients?
kaposi’s sarcoma
Type I diabetes
immune system develops t killer cells that attack insulin producing beta cells within islets or langerhans
Multiple scerosis
immune system responds to proteins within the myelin sheath of neurons within the CNS
can be ultimately fatal
Autoimmune inflammatory diseases
rheumatoid arthritis
psoriasis
crohns disease
IBD
ulcerative colitis
What cancers are HIV/ immunocompromised patients more susceptible to?
kaposi’s sarcoma
basal cell carcinoma
hepatocellular carcinoma
Immunosenescence
immune competence decreasing with age
suggests decreased immunosurveillance against cancer contributes to increased disease in the elderly
What proves the existance of tumour-specific antigens that can be recognised as non-self
tumours rejected when transplanted into syngeric hosts
transplantation of normal tissues is accepted
What are the 3 phases of cancer immunoediting?
elimination phase- tumour cells killed
equilibrium between immune and tumour cells
tumour cells escape as immune system is unable to destroy them, becomes clinically detectable
What kills tumour cells in the elimination phase?
NK
CD4+
CD8+
Why are there limits on the immune systems ability to fight cancer on its own?
does not see cancer as foreign
recognises cancer cells but response isn’t strong enough
cancer cells release chemicals that stop the immunse system finding them
What mechanisms lead to the extreme diversity of anitbodies?
somatic hypermutation
allelic exclusion
junctional diversification
What processes lead to somatic hypermutation?
activation of b lymphocytes by t cells causes them to proliferate in lymphatic follicles which creates germinal centres
in germinal centres expression of AID and repression of P53 drives mutations
Affinity maturation
mutations may cause antibodies to improve which will be the ones that survive and are cloned, antibodies with mutations that reduce their efficacy are got rid of
means that after initial immunisation there is a progressive increase in affinity
AID
activation induced deaminase
enzyme that drives mutations in germinal centres
What types of cancer immunotherapies are there?
immunomodulators
checkpoint inhibitors
cytokines
cancer vaccines
monoclonal antibodies
oncolytic viruses
CART cell therapy
(CAR) T cell therapy
chimeric antigen receptor T cell therapy
patients T cells and infected with a recombinant virus that causes the expression of a TCR
TCR has an antigen binding domain to a specific tumour antigen
generates t cells which can attack tumour cells, transfused back into patient
Oncolytic viruses
viruses that have been modified in a lab to infect and kill certain tumour cells
Cancer vaccines
vaccines that direct an immune response designed to prevent a specific cancer epitope or cancer causing pathogen (eg. HPV)
