immunity Flashcards
What factors determine the outcome of an infection?
- virulence factors
- infectivity of pathogen
- Hosts immune system
What are the key features of the innate immune system?
- fast
- non specialised
- no memory
- always same intensity
- activates adaptive immunit via dendritic cells
What are the 1st and 2nd lines of defence against infections?
1st- physical barriers
physiological barriers
chemical and biological barriers
2nd- phagocytosis
chemicals
inflammationGive 3 physical barriers
- skin
- mucosa (and lymphoid tissue)
- bronchial cilia
Give 4 physiological barriers
- diarrhoea
- vomiting
- coughing
- sneeezing
Give 2 chemical barriers
- low ph
Skin= 5.5, stomach= 1-3, vagina= 4.4 - antimicrobials
IgA in tears, saliva and mucosa prevent microbe binding
lysozymes in tears, sebum, sweat
mucus
beta- defensins on epethilia trap microbes
Give biological defences against infection
Normal flora at points of entry compete with pathogens, produce antimicrobials and synthesise vitamins
eg lactobactillus in vagina
Give some examples of pathogen entry due to failure of the 1st line of defence
Normal flora move
- breach skin (cuts, burns)
- fecal- oral
- faecal- perineal- urethral (UTIs)
- Poor dental hygene (from mouth to blood by gum cuts)
Normal flora overgrows when immunocompromised
- diabetes, AIDS, Malignant disease, chemo
Normal flora depleted by antibiotics
- C.Diff, thrush ect
What, on the pathogen, is recognised by what on the phagocyte?
the PAMP is recognised by the PRR on the phagocyte
Give some examples of PAMPs found on gram- and + bacteria and their corresponding PRR
gram+: peptidoglycans - TLR2 gram- lipopolysaccharide- TLR4 lipoproteins - TLR2
other than PAMPs, how can phagocytes recognise pathogens?
opsonins
Give 3 examples of opsonins
complement protein- C3b and C4b
antibodies- IgG and IgM
Acute phate proteins- CRP, MBL
What bacteria do not have PAMPs and so opsonisation is essential to defend against them?
encapsulated bacteria such as N. meningitis and Strep. pneumonia
Why does splenectomy put you at high risk of septic infections?
- Spleen is where majority of B cells are to filter blood and produce antibodies in repsonse to encountering pathogen
describe oxygen dependent and independent killing of bacteria
Oxygen dependent: - H202, O2•, NO, O• ect produced to kill bacteria by oxidation (more effective) Oxygen independant: - lysozymes - proteolytic and hydrolytic enzymes - lacterferrin, transferrin ect
What effect do Il-1, Il-6 and TNF-a have?
- in liver produce more CRP and MBL (for opsonisation)
- neutrophil mobilisation in bone marrow
- vasodilation, increase vascular permeability and adhesion molecule synthesis for inflammation
- increase body temp (pyrogenic acting on hypothalamus)
What do monocytes look like and what is their role?
- recuited at site of infection and differentiate into macrophages
- look like large cells, mostly made up of necleus that looks either like a fat horseshoe or two overlapping circles
What do neutrophils look like and what is their role?
- recuited to sites of acute inflammation by chemokines
- ingest and destroy pyogenic bacteria such as staph aureus an strep. pyogenes
- most aubundant WBC in blood
- creates the pus as die when phagocytose
- are light pink under H&E stain with 2-5 lobes to their nucleus
What are basophils/ mast cells and their appearance?
- They are early initiators of inflammation, by releasing histamine (vasodilator) and heparine (anticoagulant)
- Basophils circulate in blood in low numbers, mast cells are found in connective tissues
- They both have many dots within them and sort of look like a berry
What does an eosinophil look like, that is its role?
- 2 lobes to its nuclei but stains a darker pink/ red under H&E
- defence against multicellular parasites (worms)
What does an NK cell do?
- kill all abnormal host cells, eg those infected by virus or malignancies
What is the role of dendritic cells?
Present microbial antigens to T cells
What 3 pathways are there to complement activation and how do they work?
classical pathway:
- antibody- antigen recognition (by C1, C2,C4)
Alternative pathway:
- endotoxin/ antigen detection (C3b)
MBL pathway:
- MBL binds to mannose containing residues of proteins on many bacteria (MBL- C2/C4)
What are the 3 effects of complement system activation and which complement proteins coordinate each effect?
- Recuit macrophages by chemoattractants ( C3a and C5a)
- Opsonisation (C3b, C4b)
- Membrane attack complexs’ form and destroy bacteria by creating pores in their membranes (C5,6,7,8,9)
What are the key features of antigen presenting cells?
They reside in strategic locations: - Skin (SALT) - Mucous membranes (GALT, NALT, BALT, GUALT) - lymphoid organs (spleen, nodes) - blood circulation They capture pathogens - for phagocytosis of whole micobe or macropinocytosis (soluable particles like toxins) They show diversity in pathogen sensors - Many differnt PRRs - on and inside the cells
Where are dendritic cells found? What do they present to?
lymph, mucosa, blood
present to naive T cells
Where are langerhans cells found? What do they present to?
Skin
present to naive t cells
What type of cells to macrophages and B cells present to
effector T cells (B cells also present to naive T cells)
How are antigens presented?
By major histocompatability complexs (MHCs)
What are the key features of MHCs?
- co- dominant expression (both parents are expressed so you have more differnt ones)
- highly polymorphic (many alleles so many differnt antigens presented) peptide binding cleft
- broad specificty (many peptides presented by same MHC)
What is the difference in function between class 1 MHC and class 2 MHC?
Class one are present in all nucleated cells and present antigens from intracellular microbes
Class two are present only in dendritic cells, macrophages and B cells, they can present antigens from extra cellular microbes also
What receptors do class 1 and class 2 MHCs activate?
Class 1- CD8
Class 2- CD4
What subtypes of MHC1 and MHC2 are there?
MHC1- A, B and C
MHC2- DR, DQ, DP
Why do some people with HIV progress to AIDS much more slowly than others?
Some people have MHCs that present peptides that are key to the survivial of the HIV virus, some people have MHCs that are less essential to survivial so they can mutate them in order for infected cells not to be recognoised
Having MHCs that correspond to host peptides can cause many autoimmune conditions, what is the name of the MHC that causes type 1 diabetes in 50-75% of pts?
HLADQ2
Describe the endogenous (intracellular) pathway for antigen presentation, for example after a viral infection
- Viral peptides degraded by proteasome
- Antigenic peptides transported into RER by TAP1/2
- Antigenic peptides bind with corresponding MHC in RER
- Both MHC1 and 2 can bind to the antigenic peptides
- They go to cell membrane where they are presented to CD4+ and CD8+ t cells
Describe the process for antigen presentation of an exogenous (extracellular) pathogen
- Phagocytosis of extracellular pathogen
- Endosome forms and extracellular pathogens peptides degraded
- MHC class 2 travel from RER to endosome
- They bind to endosome surface with corresponding peptides attaches
- Endosome fuses with cell membrane to present antigen to CD4+ receptors
why do graft vs host reactions occur?
- When recipient has different MHCs to donor
- Peptides from donor material are presented to host and illicit immune response because the host hasn’t seen this peptide before
- In donor these were presented from foetus so recognised as self or they were never presented at all
What occurs after an extracellular microbes peptides are presented by MHC class 2 receptors? (humoral response)
- CD4+ naive T cells with complementry TCR (t cell receptor) to the antigen peptide bind to MHC2
- Co stimulatory signals such as cytokines and CD80/86- CD28 receptors also bind
- Naive T cell becomes activated to CD4+ T helper cell (Either TH2 or TH17)
- TH17 produced Il-17 which recruits neutrophils and monocytes
- TH2 produces Il-4 and Il5 which cause b cells to produce antibodies (including IgE) which causes mast cells to release histamine ect and eosinophils to be activated
What occurs after and intracellular peptides are presented to naive T cells (cell mediated response)
- MHC1 bind to CD8+ naive cells and MHC2 binds to CD4+ naive T cells with correct TCR receptor (costimulatory signals also present)
- The activated naive CD4+ cell becomes a CD4+ T- helper cell 1 (THC1)
- CD4+ cells activate CD8+ cells
- CD8+ cells become cytotoxic T cells
- cytotoxic T cells bind with cells presenting MHC1 with same antigen and release perforins to kill the infected cell
- The THC1 also released interferon gamme (IFNg) which activates B cells to secrete antibodies and attracts/ activates macrophages to kill the opsonised microbes
What type of antibodies are presented in the primary and secondary immune responses?
primary= 1st infection= IgM secondary= sebsequent infections= IgG
What are the functions of IgM?
complement activation
What are the functions of IgG?
An opsinisor- activates Fc- dependant phagocytosis
Complement activation
neonatal immunity
toxin/ virus neuralisation (high affinity and opsonises so can be given to give passive immunity)
What does IgE do?
Immunity against helmithins (released from eosinophils)
Mast cell degranulation
What does IgA do?
Mucosal immunity- in saliva, mucus ect
weak opsonisor and complement activator
What causes a fever in an immune response?
- release of Il-6 (pyrogen)
- bacterial peptides
What is the structural difference between MHC1 and MHC2?
MHC1 only has one intramembrane domaine
MHC2 crosses the membrane twice
