basic immunology Flashcards
immunology
the study of how the body defends itself against infection by micro-organisms (including bacteria/viruses/fungi/parasites)
What are the 2 branches of the immune system?
1) innate immunity
2) adaptive immunity
innate immunity
1) natural immune response
2) prevents/limits infection
adaptive immunity
1) acquired responsive
2) eradicates infection
Resistance in innate immunity
unaltered on repeated infection
Resistance in adaptive immunity
improved by repeated infection (memory)
Specificity in innate immunity
generally effective against all organisms
Specificity in adaptive immunity
specific for stimulating organism
Effector cells in innate immunity
1) phagocytes - macrophages + neutrophils
2) NK (natural killer) cells
3) mast cells
4) eosinophils
Effector cells in adaptive immunity
lymphocytes - T-cells + B-cells
Effector molecules in innate immunity
1) lysozyme
2) complement
3) interferons α/β/γ
4) defensins
5) lactoferrin
Effector molecules in adaptive immunity
1) antibodies
2) cytokines
What do surface epithelia do?
line + protect surfaces of the body in contact with the environment + provide a barrier to infection
How do epithelial cells work mechanically?
1) joined by tight junctions
2) flow of air/fluid across the epithelium
3) mucus production + movement by cilia
How do epithelial cells work chemically?
1) fatty acids + salty sweat in the skin
2) lysozyme in saliva/sweat/tears
3) low pH + pepsin in stomach
4) defensins in airway + GIT
4) acidity of urine/vaginal lactic acid
How do epithelial cells work microbiologically?
symbiotic bacteria compete for nutrients
What do phagocytes do?
engulf, digest, + destroy bacteria
macrophages
1) large mononuclear found in tissues
2) circulate in the blood as monocytes
neutrophils
1) multi-lobed nucleus
2) PMN (polymorphonuclear) cells
3) multiple granules in the cytoplasm
4) circulates in the blood
4) most abundant white blood cell
eosinophil
1) bi-lobed nucleus
2) prominent granules released on contact with parasites + ticks
3) mainly found in tissue
4) low level in circulation
5) toxic MBP (major basic protein)
6) ECP (eosinophil cationic protein)
7) EDN (eosinophil-derived protein)
What are the types of granulocytes?
1) neutrophils
2) eosinophils
3) basophils
mast cells
1) found in tissue alongside blood vessels + under epithelial layers
2) protect mucosal surfaces
3) activated mast cells release histamine in allergic reactions
NK (natural killer) cells
1) large granular cytotoxic lymphocyte
2) releases lytic granules to kill virus-infected cells + some tumour cells
3) found in blood
4) activated by IFN (interferons) α, β
What are the cells of the adaptive immune system?
lymphocytes
What are the 2 main types of lymphocytes?
1) B-cells
2) T-cells
What are the stages of immunity in the innate response?
1) adherence of bacteria to epithelium
2) penetration of epithelium (0-4h)
3) local infection of tissues - activation of macrophages
4) macrophages overwhelmed - recruitment of neutrophils (4-96h)
What are the stages of immunity in the adaptive response?
1) bacterial peptides (antigens) spread to lymph nodes (>96)
2) antigens trapped in lymph nodes activate T-cells + B-cells
3) specific antibodies + active T-cells mediate adaptive immunity
PAMPs
1) pathogen associated molecular patterns
2) sequences which are found on pathogens but not on human cells
3) tell the phagocyte that “non-self” is present + provide information on the type of pathogen present
Toll-like receptors
recognise PAMPs
How many Toll-Like receptors are found on human cells?
10
TLR-1
lipopeptide
TLR-2
1) lipopeptide
2) peptidoglycan
TLR-3
dsRNA
TLR-4
LPS
TLR-5
flagellin
TLR-6
1) lipopeptide
2) zymosan
TLR-7
single stranded RNA
TLR-8
single stranded RNA
TLR-9
unmethylated CpG DNA
What TLRs are on the cell surface?
2, 4, 6
What TLRs are intracellular?
3, 7, 8, 9
opsonisation
immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes
What does opsonisation by C3b do?
1) alters the surface of a pathogen
2) facilitates phagocytosis
What is phagocytosis like in unopsonised bacteria?
slow + inefficient
What is phagocytosis like in opsonised bacteria?
fast + efficient
How does C3 form C3b via the alternative pathway?
1) spontaneous hydrolysis of C3 results in low levels of C3b
2) C3b is stabilised by binding to microbial cell surfaces
3) factor B binds to C3b on the cell surface, where it is hydrolysed by factor D
4) C3b,Bb is a C3 convertase, and amplifies the cleavage of C3 to generate high levels of C3b
Does C3b opsonise bacteria?
yes
Does C3b opsonise host cells?
no
What are the results of complement activation?
1) phagocytosis - enhancement of phagocytosis by coating with C3b
2) inflammation - increase of blood vessel permeability + chemotactic attraction of phagocytes
3) cytolysis = bursting of microbe due to inflow of extracellular fluid through channel formed by membrane attack complex C5-C9
What are macrophages important for?
directing the early host response to infection
What do activated macrophages produce?
cytokines
Which cytokines do activated macrophages produce?
1) TNFa
2) IL-1
3) IL-8
4) IL-6
5) IL-12
Which cytokines do activated macrophages produce?
1) TNFa
2) IL-1
3) IL-8
4) IL-6
5) IL-12
What do IL-1 and TNFa do?
1) activate endothelial cells lining the blood vessels
2) increase the expression of adhesion molecules + neutrophil chemoattractants such as IL-8
What does IL-8 do?
1) recruits neutrophils from the blood into tissues
2) enhances the binding of neutrophils to adhesion molecules
What does IL-6 and IL-12 do?
1) activates lymphocytes
2) induces maturation of T-cells + increases antibody production by B-cells
When does production of IL-1, TNFa + IL-8 occur?
early response (4-96h)
When does production of IL-6 and IL-12 occur?
adaptive response
What are the symptoms of inflammation?
1) rubor
2) calor
3) tumor
4) dolor
rubor
redness
calor
heat
tumor
swelling
dolor
pain
rolling adhesion (step 1)
migration of neutrophils across the endothelium
tight adhesion (step 2)
1) IL-8 receptor on PMN binds to IL-8 endothelium
2) adhesion molecule LFA-1 on PMN binds to ICAM-1 on endothelium
diapedesis (step 3)
high levels of IL-8 in tissue attracts PMN
migration (step 4)
PMN migrate to site of infection
What are the steps of neutrophil recruitments through tissue?
1) leukocytes integrate multiple directional signals
2) leukocytes prioritise distant/novel chemoattractant source
3) end target-derived attractants are dominant over regulatory cell-derived agonists
Where do B- and T- lymphocytes originate?
stem cell (bone marrow)
What are the receptors on the surface of B-cells called?
immunoglobulins
T-Cell receptor (TCR)
protein complexes found on the surface of T-cells
Where do B-cells mature
bone marrow
Where do T-cells mature?
thymus
naïve T-cell
T cell that has matured and been released by the thymus but has not yet encountered its corresponding antigen
naïve B-cell
B-cell that has matured and entered the bloodstream but has not yet been exposed to the APC specific to its B-cell receptor (BCR)
What did Edward Jenner (1796) do?
1) first immunisation experiment
2) innoculation of a healthy individual with a mild form of disease (cowpox) protected against the lethal form of the disease (smallpox)
What did Louis Pasteur (1880) do?
the demonstration that immunisation of cows with heat attenuated anthrax protected against the lethal effects of live anthrax
What did Emil Adolf von Behring (1890) do?
demonstration of the transfer of immunity to diphtheria via specific antibodies in guinea pig serum
clonal selection hypothesis
hypothesis which states that an individual lymphocyte (specifically, a B cell) expresses receptors specific to the distinct antigen, determined before the antibody ever encounters the antigen
postulates of the clonal selection hypothesis
1) each lymphocyte bears a single type of receptor with a unique antigen specificity
2) interaction between a foreign antigen + a lymphocyte receptor capable of binding that antigen leads to lymphocyte activation
3) the differentiated cells derived from an activated lymphocyte bear receptors of identical specificity to those of the parent cell
4) lymphocytes bearing receptors specific for self antigens are deleted at an early stage of development and are therefore absent from the repertoire of mature lymphocytes
How is the diversity of lymphocyte antigen receptors generated?
by rearrangement of gene segments coding for T-cell receptors on T-cells and surface immunoglobulins on B-cells
What are the 3 important consequences of gene rearrangement?
1) enables a limited number of gene segments to generate a very diverse set of proteins
2) as each cell assembles a different set of gene segments to code for its antigen receptor, each cell expresses a unique receptor
3) as gene rearrangement involves an irreversible change in a cell’s DNA, all the daughters of that cell will inherit genes coding for the same receptor (a clone)
What are the professional antigen presenting cells (APC)?
1) macrophage
2) dendritic cell
3) B-lymphocyte
macrophage
specialised to internalise + present particulate antigens to T-cells
dendritic cells
specialised to trap antigens in tissue (lung + skin) + migrate to the lymph nodes to present antigens to T-cells, sole function
B-lymphocyte
cell-surface immunoglobulins allow B-cells to internalise large amounts of specific antigen + present it to T-cells
MHC
major histocompatibility complex cells
Where are MHC class I molecules found?
all nucleated body cells (except red blood cells)
What do MHC class I bind?
virus-derived peptides
What do MHC class II bind?
bacteria-derived peptides
Where are MHC class II molecules found?
professional APC
What does T-cell activation depend on?
recognition of antigen presented on an MHC molecule to TCRs
What is co-stimulation important for
signalling for antigen presentation + T-cell activation
What are the 3 most important functions of macrophages?
1) phagocytosis of opsonised bacteria at site of infection
2) regulation of neutrophil recruitment to sites of infection by cytokine synthesis
3) presentation of foreign antigens to naive T-cells in the lymph nodes
What are the 3 most important functions of activated T-cells?
1) activation of macrophages by CD4+ helper T-cells (Th1 cells)
2) activation of B-cells by CD4+ helper T-cells (Th2 cells) to generate an antibody response
3) killing of virus infected cells by CD8+ cytotoxic T-cells
