adaptive immune system

innate immunity specificity

• not very specific

• can identify a bacterium but doesn’t identify what bacterium it is

• for structures shared by classes of microbes (‘molecular patterns’)

adaptive immunity specificity

• much more specific

• because of use of T cells and antibodies

• they’re more sophisticated

• for structural detail of microbial molecules (antigens)

innate immunity receptor

• toll-like receptor

• N-formyl methionyl receptor

• mannose receptor

• encoded in gremlin; limited diversity

adaptive immunity specificity

• TCR

• encoded by genes produced by somatic recombination of gene segments; greater diversity

• can create almost an unlimited number of T cell and B cell receptors

innate immunity distribution of receptors

• nonclonal

• identical receptors on all cells of the same lineage

adaptive immunity distribution of receptors

• clonal

• clones of lymphocytes with distinct specificities express different receptors 

innate immunity discrimination of self and non self 

• yes 

• host cells are not recognised or they may express molecules that prevent innate immune reactions

adaptive immunity discrimination of self and non self 

• yes 

• based on selection against self-reactive lymphocytes 

• may imperfect (giving rise to autoimmunity)

• very specifically tells you if something belongs or doesn’t 

what are the steps that T cells and B cells do

• new protein synthesis 

• proliferation (clonal expansion)

• differentiation

• homeostasis 

what happens to a naive B lymphocyte

• naive B lymphocyte is activated 

• they come across an antigen and second signals 

• new protein synthesis of a large lymphocyte (lymphoblast)

• clonal expansion- make more B cells 

• differentiation into an effector B lymphocyte; antibody-secreting cell, a memory B cell, or go through apoptosis 

what are the 3 things that B cell lymphoblasts can differentiate into 

• effector B lymphocyte: antibody-secreting cell

• memory B cell

• go through apoptosis 

what happens to a naive T cell

• naive T lymphocyte is activated 

• they come across an antigen and second signals 

• new protein synthesis of a large lymphocyte (lymphoblast)

• clonal expansion- make more T cells 

• differentiation into an effector T lymphocyte; cytokine-producing cell or CTL, a memory T cell, or go through apoptosis 

what are the 3 things a T lymphoblastic can differentiate into

• effector T lymphocyte: cytokine- producing cell or CTL

• memory T cell

• go through apoptosis

what is humoral immunity driven by

• B cells

what is cell-mediated immunity driven by

• T cells

what are the 2 different types of T cells that drive cell-mediated immunity

1. helper T cells

2. cytolytic T lymphocytes (cytotoxic T cells)

what is the function of humoral immunity

blocks infections and eliminate extracellular microbes

what is the function of the helper T cell cell mediated immunity

activate macrophages to kill phagocytose microbes

what is the function of the CTL cell mediated immunity

kill infected cells and eliminate reservoirs of infection

what is the microbe in humoral immunity

extracellular microbes

what is the microbe in T helper cell cell mediated immunity 

phagocytosed microbes in macrophage

what is the microbe in CTL cell mediated immunity

intracellular microbes (e.g. viruses) replicating within infected cell 

what is the responding lymphocyte in humoral immunity

B lymphocyte

what is the responding lymphocytes in cell mediated immunity

• helper T lymphocytea

• cytolytic T lymphocytes

what are the 2 classes of MHC 

• MCH class I 

• MHC class II

what is MHC class I a marker of and where do we find it 

• marker for our cells, will actually tell other cells the this particular cell belongs to our body

• found in every single nucleated cells in our body

where do we find MHC class II

• on antigen presenting cells 

• i.e. dendritic cells, macrophages, and B cells 

which MHC interacts with T cells 

both interact with T cells 

which one of the MHC classes is CD8+ involved with

• MHC class I

• cytotoxic T cells 

which one of the MHC classes is CD4+ involved with 

• MHC class II

• T helper cells 

what is MHC class I really important in

activating T cells because it interacts with TCR and also shows the TCR an antigen

what is TCR

T cell receptor

where is MHC inherited from

inherited from parents

how many MHC I and MHC II do we have on our cells

more than one

what is the importance of having more than 1 MHC class I and MHC class II on our cells

• each of them is better at presenting one particular antigen than another one

• helps us present a vaster range of antigens and helps activate lots of different T cells

what is co-dominant expression

both parental alleles of each MHC gene are expressed

what is the significance of co-dominant expression

increases number of different MHC molecules that can present peptides to T cells 

what are polymorphic genes

when many different alleles are present in the population

what is the significance of polymorphic genes

ensures that different individuals are able to present and respond to different microbial peptides

what is the significance of MHC-expressing cell types

• CD4+ helper T lymphocytes interact with dendritic cells, macrophages, and B lymphocytes

• CD8+ CTLs can kill any virus-infected cell

what are the 2 ways antigens are captured and presented to T cells

• lymph node captures antigen from epithelium and connective tissue

• blood-borne antigens are captured by antigen-presenting cells in the spleen

what happens if a microbe gets through the skin

we have cells in the tissue that can eat them up

how will antigen end up in the lymphatic vessel 

if a dendritic cell eats up the pathogen (dendritic cell-associated antigen), and then makes its way into the lymph nodes

what are the 2 types of dendritic cells 

• immature cells 

• mature cells

where are immature dendritic cells found

• in the epidermis

• they sit underneath our skin

where do the mature dendritic cells reside

in T-cell rich areas of lymph nodes and the spleen

give the general overview of how an antigen is captured and presented

1. antigen capture by dendritic cells

2. loss of dendritic cell adhesiveness

3. migration of dendritic cells

4. maturation and migration of dendritic cells 

5. mature dendritic cells present the antigen to a naive T cell

what is a naive T cell 

a T cell that hasn’t come across an antigen yet and hasn’t been activated yet 

what are immature dendritic cells very good at

• eating up antigens

• ‘hoovering’ them up 

• markopinocytosis

• phagocytosis

what are mature dendritic cells very good at

• MHC-expression

• B7

• adhesion molecules

• best APC for T cells 

what is the general pathway of intracellular processing of protein antigens

1. antigen uptake

2. antigen processing

3. MHC biosynthesis

4. peptide-MHC association

what happens in the Class II MHC pathway for intracellular processing of protein antigens

1. endocytosis of extracellular microbe

2. microbe travels in a vesicle that goes inside cell

3. antigen in vesicle broken down into different peptides

4. vesicle containing MHC class II and vesicle containing peptides fuse together

5. peptide binds to MHC complex

6. complex transported to cell surface

7. ready to engage with CD4+

what happens in the Class I MHC pathway for intracellular processing go protein antigens 

1. cytosolic microbe (inside cell but not inside a vesicle)

2. microbial protein made inside cell, producing peptides in cytoplasm 

3. binding of free peptides to MHC class I 

4. MHC complex transported to cell surface 

5. presents itself for CD8+ binding 

where are the T cells produced 

bone marrow 

where do the T cells mature

Thymus

what happens in the thymus

• TCR-recombination

• positive selection 

• negative selection 

where do the mature T cells go 

secondary lymphatic organs 

what are the secondary lymphatic organs

• blood 

• lymph nodes

• spleen 

when T cells enter the thymus what do they not have in them 

they dont have CD4+ or CD8+ T cells 

what is the 1st chain of TCR made of

TCR-beta

what is the first step of T cell development

make TCR

what is the second chain of TCR made of

TCR-alpha

what happens when both the TCR chains are made

CD4+ and CD8+ are produced 

what does a T cell undergo once it has both chains and CD4+ and CD8+ 

positive and negative selection 

what happens when the T cell doesn’t recognise the MHC complex with an antigen 

• no binding 

• no selection

• they cant become activated and T cells cant be selected

• therefore apoptosis

what happens when there is weak binding between the T cell and MHC complex

• enough binding to have the cell activated

• positive selection

• therefore survival 

what happens when there is strong binding between the T cell and MHC complex 

• strong binding could potentially cause activation in the absence of an antigen by MHC alone 

• negative selection 

• therefore apoptosis 

• as this can lead to tissue damage and auto-immune diseases

what happens when APCs activated both naive CD4+ and CD8+ T cells 

• APC recognises an antigen 

• naive CD4+/CD8+ T cells become activated

• once activated they release a cytokine (IL-2)

• binding leads to the proliferation of the T cell 

• differentiation

• leads to the production of either effector CD4+ T cells and memory CD4+ T cells or effector CD8+ T cells and memory CD8+ T cells 

what is the function of effector CD4+ T cells

activation of macrophages, B cells, and other cells 

what is the function of effector CD8+ T cells

killing of infected ‘target cells’'; macrophage activation

what is required for the activation of naive CD4+ and CD8+ T cells 

co-stimulation of T cells 

what are the 2 signals required in co-stimulation of T cells 

1. TCR-MHC

2. CD28-CD80/CD86

what is CD80/CD86 also known as

B7-1 and B7-2

how many T helper cells need to become activated at the same time for a cell to be activated

at least 3 T helper cells

what does the CD4 receptor help with

• adhesion

• helps the complex stay stable top allow signal transduction 

what is the TCR receptor responsible for

antigen recognition

what are the CD3, CD28, and B7-1/B7-2 receptors responsible for 

signal transduction

what is the LFA-1 and ICAM-1 receptor responsible for

• adhesion

• helps stabilise the whole interaction between the 2 cells to ensure transduction can occur 

what are the 2 types of T cells that CD4 T-cells differentiate into 

• Th1

• Th2

how do Th0 cells differentiate into Th1

• requires activated dendritic cells and infected macrophages to release the cytokine IL-12

• this triggers differentiation

what cytokine is released for the process of differentiation for Th1

IL-12

what cytokines are produced from the process of differentiation for Th1

• IFN-gamma

• TNF

• IL-2

how do Th0 cells differentiate into Th2

• mast cells need to be activated 

• releasing the cytokine IL-4 

• this drives differentiation into a Th2 cell 

• when we need B cell activation

what cytokine is released for the process of differentiation into Th2

IL-4

what are the cytokines produced from the differentiation process into Th2

• IL-4

• IL-5

• IL-10

why does the release of IL-4 drive differentiation of other Th0 cells

• positive feedback loop

• IL-4 is required for the differentiation for Th0 to Th2

what is Th1-cytokine really good at

fighting intracellular pathogens i.e. viruses, bacteria, and parasites inside cells

interferon-gamma as a Th1 cytokine 

• Th1 marker cytokine

• macrophages; activation, MHC-up-regulation

• elimination of intracellular bacteria 

• anti-viral function

TNF as a Th1 cytokine

• macrophages; activation, NO-production

• elimination of intra-cellular bacteria

• dendritic cells; maturation, migration

INF-gamma effect on macrophage

activation; increased MHC

TNF effect on macrophage

NO production

lymphotoxin effect on macrophage

lysis of infected cells

IL-3/GM-CSF effect on macrophage

production/differentiation 

IL-4 as a Th2 cytokine

• ‘Th2 marker’ cytokine

• activation, growth of B cells 

• essential for IgE, Th2 development

IL-5 as a Th2 cytokine

• B cell differentiation, IgA synthesis 

• growth/differentiation of eosinophils 

IL-10 as a Th2 cytokine

• regulatory cytokine

• inhibitor of macrophage function

what is Th2 important for

important for antibody-answer (‘soluble’ pathogens) and allergic reactions

what are the 2 mechanisms for T-cell mediated cytotoxicity 

1. non-secretory mechanism 

2. secretory mechanism

what is the non-secretory mechanism

• ligand induced, via a receptor 

• binding of the death receptor Fas (on the target cell) and FasL (ligand on CTL)

• signals for cell to undergo apoptosis 

what is the secretory mechanism

• through perforin-and granzym 

• makes holes in the target cell and kill the target cell