Immunology Lectures 1-7 Flashcards
(45 cards)
1
Q
Components of innate immunity
A
structural - e.g. epithelia
Soluble - e.g. complement
Cellular - phagocytes
2
Q
Haematopoiesis
A
the generation of leukocytes and erythrocytes.
- HSCs sustain blood cell throughout life
- capable of self renewal
- multipotent
3
Q
Myeloid cells
A
phagocytes all able to recognise microbes though specific receptors
4
Q
Neutrophil
A
- short lived normually found in blood
- migrates during inflammation
- highly phagocytic granulocyte
- produces vast repertoire of antimicrobial factors
5
Q
Dendritic cells
A
- found throughout the body, sentinels of the immune system
- phagocytic
- crucial link between innate and adaptive immune response, via secretion of soluble factors that affect cell function (cytokines) and antigen presentation (to T cells)
6
Q
Macrophage
A
- Found in most, if not all tissues
- highly phagocytic and antimicrobial
- directs both innate and adaptive through secretion of cytokines and antigen presentation
7
Q
Eosinophil
A
- found in blood, gut lungs and urogenital tract
- important in helminth infection
- involved in allergy and asthma
contains toxic granules and inflammatory mediators
8
Q
Mast cell
A
- found in tissues
- involved in allergy and histamine release (increase vessel permeability)
9
Q
Lymphoid
A
- targeted secretory cells
- found in blood and tissues
- cells are crucial for recognising changes in tumour cells and virally infected cells. target and kill these cells
10
Q
The steady state - immediate response
A
structural barriers e.g. skin, barriers, mucosal pH
11
Q
Soluble molecules in immediate response
A
Defensins = antimicrobial peptides, secreted by epithelial cells
Lysozyme = secreted by macrophages
The complement system
12
Q
Cells in immediate response
A
- the tissues phagocytes: macrophages, dendritic cells
- natural killer cells, mast cells
13
Q
Pathogen Associated Molecular Patterns PAMPs
A
- Bacteria PAMPs - cell wall components
- Microbe Associated Molecular patterns bacterial DNA
- certain bacterial proteins
14
Q
Viral PAMPS
A
- ssRNA, dsRNA, sugars, MAMPs
15
Q
Yeast
A
- sugars (β-glucans)
16
Q
Helminths
A
- sugars (chitin)
17
Q
How are PAMPs/MAMPs recognised?
A
- PAMPs are recognised specifically by pattern recognition receptors (PRRs)
- found in all multicellular organisms
- germline genes encoded - evolved to recognise PAMPs
- ‘know’ the difference between harmful and non-harmful entities
- found mainly on phagocytes (macrophages, neutrophils, dendritic cells)
- survey all physiologically environments
- soluble, plasma membrane (cell surface), cytoplasm in vacuoles
18
Q
strategy for discovering immune genes
A
- loss of function
- gain of function
19
Q
Surface pattern recognition receptors
A
- recognise various PAMPs
- major classes - toll receptors, carbohydrate binding lectins
- able to signal to produce appropriate responses and production of various cytokines and immune regulators
20
Q
PRRs survey all cellular environments
A
- soluble
- intracellular
- vascular sensors
21
Q
Damaged associate molecular patterns DAMPs
A
- molecules from dying/ damaged cells enhance the immune response
- potential molecules released from damaged tissues and dying cells
- HSPs, ATP, nuclear proteins (HMGB-1), extracellular matrix components (hyaluronic acid)
- not normally released when cells undergo suicide ion a cont5rolled fashion (apoptosis)
- these help distinguish between ‘naturally’ dying cells and damaged/killed cells
22
Q
Steps of Phagocytosis
A
Step 1: recognition - direct binding vis phagocytic receptors, indirect pathogen binding via Fc receptor, complement receptor - opsonised
Step 2: uptake, signalling and actin driven cytoskeletal remodelling
Step 3: appropriate processing - microbe killing or non-inflammatory removal of dead/apoptotic cells
- production of inflammatory signals to alert cytokines and recruit chemoattractants and other cells, macrophages.
23
Q
Uptake and degradation in macrophages and dendritic cells
A
- activates degrading enzymes
- low pH aids killing of microbes
- increasing acidity
- proteinases, lipases, hydrolytic enzymes - lysozyme
24
Q
killing mechanisms of macrophages and dendritic cells
A
- proteolytic and hydrolytic enzymes
- Reactive oxygen species/reactive nitrogen species
- antimicrobial peptides
- nutrient deprivation
25
outcome of phagocytosis by macrophages and dendritic cells
- killing
- presentation (activation of T cells)
- removal of apoptotic cells
- production of cytokines and inflammatory molecules critical for inflammation
26
Inflammation
the general term for the accumulation of fluid, plasma proteins and leukocytes that is initiated by physical trauma, infection or local immune response
27
Three stages of inflammation
- initiation
- recruitment of effector cells (mainly neutrophils)
resolution (switching off and removal of cells)
28
Importance of neutrophils
- severe congenital neutropenia (born with low numbers of neutrophils) usually die in infancy of severe infections
- chemotherapy induced neutropenia - can lead to infection/death
- Acute Myeloid Leukaemia - immunocompromised due to immature myeloid cells
29
initiation of inflammation
- damaged cells, bacterial uptake by macrophages and mast cells degranulation all lead to increase in vessel permeability
- increased permeability leads to increase in soluble components from blood, antibodies and complement
- chemokines and bacterial products facilitate chemotaxis ( movement up a chemical gradient)
- inflammatory cytokines up regulate adhesion molecules on the endothelium and neutrophils allowing the recruitment of cells form the blood
30
stages of leukocyte recruitment
- rolling
- activation (by chemokines)
- firm adhesion
- extravasation (diapedesis)
31
Leukocyte migration and recruitment (postcode model)
- leukocyte adhesion and migration mediated via cell surface adhesion receptors and chemokines receptors found on leukocytes and endothelia cells
- the temporal-spatial expression as well as there activation state of adhesion and chemokine receptors and there ligands acts as a 'postcode' for leukocyte migration.
- not just important in neutrophil migration but also lymphocyte recirculation NK cell and dendritic cell migration mhe10
32
neutrophil killing
once at the site of inflammation the normally tightly regulated neutrophils are activated by PAMPs and proinflammatory cytokines
33
Neutrophils deliver multiple anti-microbial molecules
neutrophils first activated - by PAMPs and TNF-a
Oxidative burst NADPH - oxygen free radicals, hydrogen peroxides
Nitric oxide synthetase - reactive nitrogen species
Myeloperoxidase - formation of bleach
34
Neutrophils deliver multiple antimicrobial molecules
- primary granules
- secondary granules
- tertiary granules
- cytoplasm
- host tissue damage
35
Natural Killer NK cells
- specialised granular lymphocytes
- crucial for defence against tumour and virally infected cells
- do not tend to recognise pathogens directly, detect affects of the pathogen on the host cell
- either detect the lack of host proteins of the induction of stress proteins
36
how do NK cells kill?
- granules contain perforin and granzyme B
- perforin forms pores to allow entry on granzyme B and other granzymes
- granzymes B trigger apoptosis of target cells
37
4 phases of Adaptive immune response
1. establishment of infection
2. induction of adaptive response
3. adaptive immune response
4. immunological memory
38
Function of B-lymphocytes
- produce antibodies
- 10-15% of lymphocytes
- triggered by antigen to differentiate into plasma cells and B memory cells
- combat bacterial and some viral infections
39
Function of T-lymphocytes
- cell mediated immunity
- 75-80% of lymphocytes
- combat viruses, fungi, intracellular bacteria and cancerous cells
40
How does immunological memory confer long lasting protection?
- more responder cells available
- more efficient antigen recognition/activation - may not require costimulatory signals for activation.
- rapid and effective migration to tissues and lymph nodes - express different homing/ chemokine receptors that naïve T cells
- produce more cytokines or antibodies
- long lasting, memory cells can persist for years
41
Primary lymphoid organs
- bone marrow
- thymus
- initial sites for production of lymphocytes
- lymphocytes 1st express antigen receptors
42
Secondary Lymphoid organs
- lymph nodes
- spleen
- mucosal associated lymphoid tissue
- sites where lymphocytes first encounter antigens
43
where does antigen independent differentiation occur?
- In the primary lymphoid organs
- Bone marrow B cells
- Thymus T cells
44
Where does antigen dependent differentiation occur?
- In the secondary lymphoid organs
45
Lymph Nodes
- provides site for resting B cells and T cells
- filter lymph cells and foreign material
- where B cells and T cells first recognise and respond to antigen
- antigen recognition can drive antigen dependent differentiation
- where products of adaptive immune response are generated
