Microbes-L14-Adaptive Immunity 2: Anti TB Immunity

what are some downsides of immune system?

1. if uncontrolled can attack our own tissues

   - usually have a tolerance for antigens

what are the innate and adaptive cells?

innate- neutrophils, NK cells, macrophages(have PRR’s) and secrete cytokines, dendritic cells

adaptive- T cells(T cell receptors), and B cells(have antibodies)

what do the cells in the innate do? what do the cells in the adaptive do?

presentation- macrophages and dendritic cells

phagocytosis- neutrophils and macrophages- also make cytokines

• T cells have T cell receptors- make cytokines- CD4 and CD8

• B cells- make antibodies

receptors of the innate system? what do these innate cells do specifically?

• macrophages have pathogen recognition receptors- not very specific for any one single antigens

• they take up bacteria and present them to T cells- their PRR’s bind to the pathogen associated molecular pattern PAMP- ie LPS

• dendritic cells activate naive T cells

discuss macrophages- receptors types, roles

innate immunity

• macrophages in the bone marrow- go to various tissues- liver(kupffer cells)

• have non specific receptors- PRRs, Fc and complement receptors

• have Fc and complement receptors- macrophages recognise and engulf pathogens when they’re “tagged”- with Fc receptors and compliment receptors- which helps target the antibody

• phagocytose and kill microbes

• and present the antigen to T cells

explain dendritic cells- what do they activate, how they go from immature to mature

• only cell that can activate naive T cells in lymph nodes

• once activated by a dendritic cell- T cell can become an effector T cell(fight infection) and memory T cell

• dendritic cells- (immature)reside in lung, gut etc- encounters pathogen by PRRs and detect PAMPs- takes it up and activates dendritic cell and migrate to lymphatic tissue(mature)- activate naive T cells

discuss neutrophils- how long do they live, when are they mobilised?

they are short lived- last 2/3 days at most

• first cells mobilised to phagoctyose

• important against pyogenic pus forming bacteria- kill bacteria and then die

• non dividing cell

• polymorphic leucocyte- has distinct shape

3 defining features of the adaptive immunity

antigen recognition- discriminates self from non self T cell receptor and antibodies

1. specificity- each lymphocyte recognises 1 antigen

2. diversity- large no. of lymphocyte specificty- infinite capacity to responds

3. memory- can recall interaction with an antigen. when antigen is recognised by T cell- some become memory cells

produces highly regulated cytokines: cause inflammation- has regulatory cells, cytokines and immune checkpoints to turn this response off

what are adaptive immune responses?

B cells

• bone marrow- make A- antibody producing plasma cells

• receptor- Ig

• antibody recognises unmodified naive antigen

• mediate humoral imunity- promote phagocytosis, activate compliment system, neutralise pathogen

T cells

• bone marrow/thymus

• has CD4(helper) and Cd8 T cells(cytotoxic)

• T cell receptor- unique to particular antigen

• recognise processed antigen on APC(Antigen presenting cell) in association with MHC molecules- MHC I-CD8, MHCII-CD4

• mediate cellular immunity-interacting with infected or abnormal cells or regulating others

difference between humoral immunity and cellular immunity

Humoral immunity involves B cells producing antibodies that recognize and neutralize pathogens, while cellular immunity involves T cells directly attacking infected or abnormal cells and regulating immune responses.

3 signals for T cell activation

1. T cell receptor recognises and binds to peptide presented on MHC molecule on the surface of an antigen presenting cell(dendritic etc)

   • MHC I presents to CD8 cytotoxic cells

   • MHC II presenting to CD4 helper cells

2. costimulatory signals are needed- CD80/CD86(dendritic) interaction with CD28(naive T cell)- 2nd signal

3. polarising cytokines that come from dendritic cells and other innate ones

difference between CD8 and CD4 T cells?

CD8- presented by MHC I- cytotoxic cells

CD4- presented by MHC II- helper cells

explain antibody molecules and explain T cell receptors.

1. have a contant region- same for all antibodies of a specific clas

2. has a variable region- specific to each antibody and binds to a specific antibody

TCR- T cell receptors

• have a singular arm structure- still has constant and variable region

• variable region- diversity- recognise a specific epitope displayed by MHC on the surface of antigen presenting cells

what are epitopes? how do they bind? 4 steps

Epitopes are specific regions on antigens that are recognized and bound by antibodies or T cell receptors. They are crucial for the specificity of immune responses.

1. antibodies bind to epitopes

2. epitopes recognised by T cells are buried- must be broken into fragments

3. epitope binds to a self MHC molecule(APC)

4. T cell then binds to the MHC complex(on antigen presenting cell)

explain the MHC structure- where are they found? what do they bind to? how do they bind?

MHC found on antigen presenting cells such as dendritic cells and bind to the epitope

• MHC- 2 alpha helices with a cleft and beta sheets

• peptide epitope is held by IONIC interactactions- peptide is pos and MHC neg- held in place

• T cell binds on top

difference between CD8 and CD4

• class 1 MHC-CD8- usually virus infected- becomes effector cytotoxic T cell-kills infected cell

  • virus needs host cell to replicate/bacteria need nurtients

  • viral DNA translated to proteins through ER and golgi- get processed as MHC I peptides as a viral class I MHC peptide

CLASS 1:PRESENT PEPTIDES FROM INTRACELLULAR ANTIGENS!!! IE VIRAL PROTEINS TO CD8!!

• class 2 MHC-CD4- becomes activated T helper cells- which help B cells become secreting plasma cells by mediating cell responses

  • process the cell by ENDOCYTIC route

  • antigen taken up by antigen presenting cell

  • goes into the endosome and fuses with the lysosome- proteases inside with low pH which denatures the protein

    CLASS 2: PRESENT PEPTIDES FROM EXTRACELLULAR THE CELL! TO CD4!!

CD4 MHC II- what do they secrete?

Th1- IFN- gamma- autoimmunity- intracellular- macrophages

th2- IL-4- extracellular pathogens- allergies- antibodies

Treg cell- IL-10- immune regulation- stops maturation of dendritic cells etc

Th17 cell-IL-17- immunity to infection/inflammation- autoimmunity-recruits neutrophils

immune response to a pathogen- 6 steps

1. recognition- detect pathogen using PRRs and PAMPS, APC present this to MHC molecules T cells recognise this

2. clonal expression- T and B cell activated- rapid division

3. differentiation of responder cells- ie T cells- CD8 cytotoxic or CD4 helper, memory cells, plasma cells

4. recruitment and activation of effectors- macrophages, neutrophils, NK cells, more T and B

5. effector function- eliminate using antibodies, cytotoxic T cells, macrophages, compliment

6. down regulation- regulatory T cells like Treg stop

how do antibodies work?

• CD4 activate B cells to make plasma cells- for making antibodies- specific to antigen

1. neuralisation- bind directly to pathogen and block ability to bind to host cell receptors

2. opsonisation- coating of antigen with antibodies- make it easier to recognise and engulf it- Fc constant to Fc receptor- promotes phagocytosis

3. complement activation- in the blood can be activated by antibodies- enhances opsonisation and lyses some bacteria