HSCI 365- Adaptive Immune System

Adaptive immune system description

• Slow acting

• Highly specific

• Unique immune cells activated to respond to single pathogen

• Memory

• 2nd infection has faster response than 1st

What are the two adaptive responses?

Customized defense against a particular pathogen

Antibody mediated

• Plasma cells (B cell derivative) produce antibodies

Cell Mediated

• T cells are activated and directly attack unwanted cells

Describe origins of B and T cells

• B cells differentiate and mature in Bone marrow

• T cells differentiate and mature in Thymus

• After early childhood, new B and T cells are derived from established colonies in peripheral lymphoid tissues

What are lymphocyte receptors?

• B and T cell receptors bind antigens

• A given lymphocyte can only bind one unique antigen

Describe the 5 antibodies

Extracellular activity

• IgM = serves as BCR (B Cell Receptor) for antigen attachment and produced early

• IgG = is the main immunoglobulin in blood, produced during reinfection

• IgE = protects against parasitic worms; allergic reactions

• IgA = is in digestive, respiratory, urogenital secretions; breastmilk

• IgD = is on B cells; function unclear

What is each function on antibodies (arms and tail)?

arms= specificity

tail= functionality

How do antibodies work (physical hindrance and amplification of innate responses)?

Physical hindrance:

• Neutralize bacterial toxins to prevent them from interacting with other cells

• Agglutinate to form clumps

Amplification of innate responses:

• Activate complement system

• Enhance phagocytosis

• Stimulate NK cells

Describe B cells

• Produce antibodies by binding antigens directly (T-independent)

• Most will internalize the antigen and present it for T helper cells which bind the presented antigen and stimulates B cells (T-dependent)

Describe clonal selection

• Plasma cells make antibodies

• Dormant memory cells expand clone

Describe active immunity

Primary immune response:

• takes time to form plasma cells

Secondary immune response:

• much faster response

Describe T cells

• Clonal and antigen specific, form a memory pool, have primary and secondary responses

• Must directly contact their targets

• Activated by a foreign antigen only when the cell also has a self-antigen (major histocompatibility complex)

• Die once the antigen is gone

Describe cytotoxic T cells

• Mostly target virus-infected host cells

• Host cell presents viral particles on newly synthesized MHC —> Cytotoxic T cell recognizes and binds the viral antigen —> Cytotoxic T cell releases chemicals that destroy the cell before the virus can replicate in the nucleus

How do killer cells kill?

Both cytotoxic and T cells do this

Cytotoxic T cells can also release enzymes into the cells

• In cytotoxic cells have granules that contain molecules called perforin → immune cell bind to target cell → there is a space where the granules release the perforin → holes are inside the host cell → perforin molecules are released → there is some calcium in the space that will activate the perforin → once perforin is activated, it will form channels → water can enter and cells will burst → direct killing of host cells 

• Granzymes very similar to digestive enzymes = indirect killing 

Describe helper T cells

• 60-80% of circulating T cells

• Orchestrate much of immune response

• Secrete cytokines that augment antibody production, T cell activity; attracts neutrophils, macrophages; activates eosinophils 

• HIV selectively destroys helper T cells, macrophages

• Drugs slow progression and allows body to repopulate these cell types

Describe regulatory T cells

• 5-10% of circulating helper T cells

• Suppress immune responses

• Maintain tolerance to self-antigens

• Specialized to inhibit both the innate and adaptive immune response

Describe antigen presenting cells

• T cells need help from antigen presenting cells (macrophages, dendritic cells)

• APCs engulf and process antigen and complex them with MHC to present on their surface

• Helper T cell can now bind

• Dendritic cell engulfs bacterium → large molecules of engulfed bacterium are broken down by lysosomes to produce antigenic peptides → New MHC molecules has been synthesized by endoplasmic reticulum- Golgi complex → antigenic peptides bind to newly formed MHC molecules → antigen is displaced on cell surface bound to MHC molecules– the cell is now an an APC 

What are MHC molecules?

• Tells immune cells that these are the host cells 

What are Class I MHC cells?

• On the surface of all nucleated body cells

• Cytotoxic T cells bind to Class I 

• Co-receptor links cells together 

What are Class II MHC cells?

• Found on select subset of immune cells which are going to be the APCs and B cells 

• Helper T cells bind to Class II 

• Co-receptor links cells together 

Describe APC activation of T Helper Cells

• Bacterium is taken up by phagocytosis and degraded in a lysosome → Bacterial antigenic peptides are displayed on APC cell surface bound to class II MHC molecules and presented to helper T cells with TCRs that recognize the antigen → APC secretes cytokines that activate T cell → activated T cell secretes cytokines that stimulate T cell to proliferate to expand clone of selected cells → Cloned helper T cells are ready to activate B cells and enhance other immune activities 

Describe T- Dependent Antigens to activate B cells

BCR binds to antigen. Antigen is internalized by receptor- mediated endocytosis and its macromolecules degraded. Antigenic peptides produced are displayed on cell surface bound to class II MHC molecules → TCR of a helper T cell recognizes specific antigen on B cell, and CD4 preceptor links the two cells together → Helper T cell secretes cytokines that stimulate B cell proliferation to produce clones of selected cells → Some cloned B cells differentiate into plasma cells, which secrete antibodies specific for the antigen, while a few differentiate into memory B cells → Antibodies bind with antigen, targeting antigenic invader for destruction by the innate immune system

What are autoimmune diseases?

• Self-antigens modified by drugs, chemicals, viruses, mutations so they’re no longer tolerated • In pregnancy, fetal cells (with foreign paternal antigens) gain access to maternal blood

• Females with persistent fetal cells may trigger a gradual immune attack against their related antigens

More common in females since estrogen enhances immune activity, Pregnancy requires complex immune adjustments to tolerate the fetus

How to prevent fetal rejection?

• Placental trophoblasts do not express the classical MHCs

• Express factors that inhibit maternal blood and tissue NK cells

• Specialized uterine NK cells promote placenta growth instead

• Maternal regulatory T cells increases

• Placenta prevents maternal immune cells from entering fetal tissues, breaks down maternal cytokines, secretes immunosuppressive molecules

• Paternal antigens are shed, maternal immune system forms blocking antibodies that coat antigens

Describe immune surveillance

Cytotoxic T cells (prior exposure to cancer cells), NK cells, and macrophages secrete interferons and interferons enhance cytotoxic t cells which inhibits multiplication of cancer cells