L25-29: immunology

what is immunology

the study of the immune system

what is the medical importance of immunology (5)

• knowledge of the immune system is utilised in vaccination

malfunctions in the immune system leads to:

• immunodeficiencies

• allergies

• autoimmune diseases

• graft rejection

what are immunological techniques used in

research, diagnostics, + therapeutics

what are the two types of immune system

innate + adaptive

which immune system is evolutionarily old

innate

which immune system has a slower response

adaptive

what are the leucocytes of the IIS

phagocytes, natural killer (NK) cells

what are the leucocytes of the AIS

B + T lymphocytes

what are the soluble factors of the IIS

lysozymes, compliments, defensins, interferons, (and many other)

what are the soluble factors of the AIS

antibodies

what are the two lineages developing from haematopoietic stem cells (in bone marrow)

myeloid + lymphoid

how do the IIS + AIS work together

IIS helps to initiate + mediate AIS responses

what are the 5 external barriers to infection

• keratinised skin

• secretions

• mucous

• low pH

• commensals (microbiota)

what are the 3 types of phagocytes

• neutrophils

mononuclear phagocytes

• monocytes

• macrophages

what are 3 features of neutrophils

main phagocyte in blood

short lived + fast moving

lysosomes release enzymes (H₂O₂)

which mononuclear phagocyte is present in the blood

monocyte

which mononuclear phagocyte is present in tissues

macrophage

what are 3 features of mononuclear phagocytes

can be in blood or tissue

long lived (months)

help initiate adaptive responses

what are 3 features of natural killer (NK) cells

kill virally infected cells non specifically

important in self/non-self recognition

may kill cancer cells

how do phagocytes recognise pathogens

have general pathogen recognition receptors (PRRs) that recognise microbe associated molecular patterns (MAMPs) that are shared by many microbes + distinct from ‘self’

how do NK cells recognise pathogens

kill cells unless self proteins (MHC) are recognised

which 3 soluble factors of the IIS are involved in pathogen destruction

complimentary system, defensins, interferons

how many proteins are in the compliment system

~20

what are defensins produced by

neutrophils

what are interferons produced by

virally infected cells

how does the compliment system create an immune response

activated on infection + cause bacterial cell lysis

how do defensins create an immune response

positively charged peptides so disrupt bacterial membranes by inserting into them

how do interferons create an immune response

(bind to receptors + activate a signalling pathway to induce changes in gene expression) → protect uninfected cells + activate macrophages + NK cells

what 2 soluble factors are involved in cell to cell communication

cytokines + inflammatory mediators

what is the function of cytokines

regulate the immune response by binding to cells

what are the 4 visual/experienced features of inflammation

heat

redness

swelling

pain

what are 4 biological features of inflammation

localised response to infection/damage

dilation of blood vessels

increased capillary permeability

phagocytes migrating into tissues

describe the temperature response

on infection, macrophages may release cytokines (e.g. interleukin1/IL-1) →

these act on the hypothalamus →

raises temperature →

stimulate phagocytosis + reduce iron levels in the blood

state 4 types of pathogens

bacteria

viruses

fungi

parasites

how big are bacteria

1-5 μm

how big are viruses

20-400 nm

how big are fungi

2-20 μm

how big are parasites

1 μm - 10 m

what do stem cell precursors in the bone marrow differentiate into

B + T lymphocytes

where do B lymphocytes mature

bone marrow

where do T lymphocytes mature

thymus

what are B lymphocyte receptors

antibodies

what are T lymphocyte receptors

T cell receptors

how do lymphocytes initially differentiate

antigen independent differentiation in primary lymphoid tissue

when do lymphocytes differentiate a second time

in peripheral lymphoid tissue when antigens are detected

what is the B lymphocyte response to an antigen

secretion of antibodies

what is the T lymphocyte response to an antigen

kills infected host + make cytokines

what lymphocyte does humoral immunity involve

B lymphocytes

what lymphocyte does cell-mediated immunity involve

T lymphocytes

what kind of infection is humoral immunity important for

EC bacteria + secondary viral (memory)

what kind of infection is cell-mediated immunity important for

viral + IC bacterial + IC parasitic

what is the clonal selection hypothesis

clonal selection + division of B lymphocytes with a complimentary antibody to the antigen detected.

these B lymphocytes differentiate into plasma cells that secrete soluble antibodies + differentiate into memory cells

also states lymphocytes that recognise self are deleted early in development

how do T lymphocytes recognise antigens

can only recognise antigens bound to host cells

what occurs in primary lymphoid tissue

lymphocytes reach maturity + acquire their specific receptors

what occurs in secondary lymphoid tissue

mature lymphocytes are stimulated by antigens

describe the basic antibody structure

Fab arms that are variable in sequence to bind different antigens specifically

Fc body is constant in sequence + binds to complimentary Fc receptors on phagocytes + NK cells

hinge is flexible to allow mobility of the Fab arms

what kind of molecule is an antibody

class of soluble glycoproteins: immunoglobulin

how are the polypeptide chains in an antibody structures

2 light chains (25kD) and 2 heavy chains (50kD) for a complete molecular weight of 150kD

state the 5 immunoglobulin classes + what differs between them

IgG

IgM

IgA

IgD

IgE

differ in aa sequence of the heavy chain

where are IgG immunoglobulins found and what is their purpose

main class in serum + tissues

important for secondary/memory responses + only class that can cross the placenta

where are IgM immunoglobulins found and what is their purpose

important in primary responces

where are IgA immunoglobulins found and what is their purpose

in serum + secretion

protect mucosal surfaces (unknown role when present in blood)

where are IgD immunoglobulins found and what is their purpose

found in low concentrations in serum

unknown function

where are IgE immunoglobulins found and what is their purpose

present in very low levels in serum

protects against EC parasites + involved in allergy

what are the 2 types of light chains

kappa + lambda

(not class restricted)

how IgA structured in serum

monomer

how is IgA structured in secretions

dimer

how is IgM structured

pentamer

what type of immunoglobulins does the primary response involve

IgM innitially with IgG present later

what type of immunoglobulins does the secondary response involve

IgG + IgA or IgE depending on type of pathogen/site of infection

IgM also present

how are the variable + constant regions of an antibody encoded

seperate exons

how can variable region exons change

can recombine + mutate during B cell differentiation to give different antibody specificities

what regions does an antibody contain

variable + constant

how do variable regions change between antibodies

differ between antibodies with different specificities

how do constant regions differ between antibodies

same for antibodies of a given H chain class / L chain type

how do antibody Fab arms protect against infection + state which immunoglobulins utilise each method

neutralise - IgG + IgA

immobilise motile microbes - IgM

prevent binding to + infection of host cells

form complexes

how do antibody Fc regions protect against infection + state which immunoglobulins utilise each method

activate complement - IgG + IgM

bind Fc receptors

which immunoglobulins bind to phagocyte Fc receptors

IgG + IgA

which immunoglobulins bind to NK cell Fc receptors

IgG

which immunoglobulins bind to mast cell Fc receptors

IgE

what is the role of compliment

defence against bacteria + some role in defence against viruses

what is the compliment classical pathway

activation specifically by antigen/antibody complexes

name the 3 pathways of compliment activation

classical, MB-lectin, + alternative

how is the classical compliment pathway activated

two antibodies bind to one antigen → C1 interacts with 2 Fc regions to be activated → activation of C1, C4, + C2 leads to generation of a C3 convertase → C3 cleaved into C3a + C3b → C3b joins C3 convertase to make C5 convertase

what are the 3 major biological activities of compliment

activation of WBCs - C5a + C3a (less potently)

opsonization (inc. binding + phagocytosis) - C3b

cell lysis - membrane attack complex (C5-9)

how does C9 attack the membrane of a bacteria

hollow cylinder shape that forms pores in membrane

which types of bacteria are not susceptible to the membrane attack complex

gram +ve

what is an opsonin

EC proteins that induce phagocytosis when bound to a cell

which classes of antibodies can act as opsonins

IgG + IgA

how do antibodies induce phagocytosis

antibodies coat bacterium + Fc receptors of phagocyte bind to antibodies → pseudopods extend + fuse to form a phagosome → lysosomes fuse with the phagosome to form a phagolysosome

how is bacteria killed in a phagolysosome

enzymes (lysozymes)

competitors (lactoferrin)

reactive oxygen species (H₂O₂)

what occurs when antibodies bind to Fc receptors on NK cells

IgG mediates antibody dependent cell-mediated cytotoxicity (ADCC)

secretions (e.g. perforin) cause target cell to undergo apoptosis

what occurs when antibodies bind to Fc receptors on mast cells

IgE mediates allergy or defence against large parasites

IgE binds to specific Fc receptors on sensitised mast cells → allergen bound to IgE activates mast cell + causes degranulation → releases inflammatory mediators (e.g. histamines) causing local inflammation

what is antisera

serum with antibodies

what is the polyclonal b cell response

the activation of multiple different b cell clones specific to different epitopes on the same antigen

define epitope

‘shape’ an antibody binds to

what are the issues with the polyclonal b cell response

may lack fine specificity + difficult to standardise

also differences between animals or even different bleeds from the same animal

what are monoclonal antibodies

identical b cells derived from a single B lymphocyte

how are monoclonal antibodies produced

B cells taken from an animal immunised with a specific antigen + fused with a tumour cell line → results in hybrid cells that make a specific antibody + divides indefinitely

state the 4 functions of antibodies in research, diagnostics, + therapy

1. ID + label molecules in complex mixtures

2. ID pathogens

3. characterise cell surface proteins + ID cell types

4. humanised antibodies used in therapy