Immune systems Flashcards
What is the immune system?
A highly regulated and complex network of tissues, cells and molecules that protects an organism from pathogens
What are the 2 main arms of the immune system in vertebrates?
Innate and adaptive
Describe the innate immunity arm
Intracellular leads to NK cells and extracellular leads to phagocytes and both lead to pathogen destruction
Describe the adaptive immunity arm
Intracellular leads to Tc cells which leads to pathogen destruction
Both intracellular and extracellular lead to the production of Th hells which leads to either the production of B cells and antibodies or phagocytes and both of those lead to pathogen destruction
What are the 4 types of infection?
Virus
Bacteria
Protozoa
Helminth
What type of stem cells are cells of the immune system developed from?
Pluripotent stem cells
What arm of the immune system are lymphoid cells involved in?
Adaptive
What arm of the immune system are myeloid cells involved in?
Innate
Where are t cells produced?
In the thymus
Where do T cells migrate to?
The lymph nodes
What are the 2 types of T cell?
CD4+ and CD8+
What are and what do CD4+ T cells do?
They are Th cells and secrete cytokines and interact with B cells
What are and what do CD8+ T cells do?
They are Tc cells and directly kill infected self cells and interact with macrophages
What type of T cells are targeted by HIV?
CD4+
Where are B cells formed?
In the bone marrow
Where do B cells mature?
In germinal centres (secondary lymphoid tissues)
What do B cells do?
Produce and secrete antibodies which recognise foreign antigens
What are the 3 types of phagocytes?
Neutrophils
Monocytes
Macrophages
What do phagocytes do?
Patrol the body looking for invaders to perform phagocytosis on
What arm of the immune system are phagocytes part of?
Innate arm
What are macrophages involved in?
Phagocytosis
Bactericidal mechanisms
Antigen presentation
What are macrophages derived from?
The monocyte
Where do macrophages reside?
In tissues
What are macrophages called in the liver?
Kupffer cells
What are macrophages called in the brain?
Microglia
What are macrophages called in the kidneys?
Mesangial cells
What are macrophages called in bones?
Osteoclasts
Why are eosinophils called so?
They stain with eosin
What do eosinophils do?
Kill antibody-coated parasites that cannot be digested by binding to them and degranulating and dissolving their cell surface
What do eosinophil granules contain?
Peroxide and histaminase (anti-inflammatory)
What are natural killer (NK) cells?
Large granular lymphocytes
What arm of the immune system are NK cells part of?
Innate
What do NK cells do?
Release lytic granules that kill some virus infected cells
How do NK cells detect virus infected cells?
Changes in the cell surface molecules
How do NK cells kill?
Induce lysis and apoptosis
What does the bone marrow consist of?
Fat cells Bony tissue (trabeculae) Fibroblasts Collagen Dendritic cells
Where do lymphocytes start their lives?
In the bone marrow
What organs does the bone marrow take over from after the body has progressed past the late fetus?
The liver and the spleen
Where does the initial phases of B cell selection take place?
In the bone marrow
Where are mature B cells (plasma cells) returned to and for what reason?
Return to the bone marrow to secrete antibody to repeated antigen exposure
Where are partly mature B cells exported from?
The bone marrow
What is the thymus?
A primary lymphoid organ
What does the thymus produce?
Mature T cells
Where is the thymus located?
Above the heart
When is the thymus the most active?
During foetal development
When does the thymus atrophy?
Throughout adulthood
What are the 2 secondary lymphoid organs?
The spleen and the lymph nodes
Where is the spleen located?
Below the diaphram
What is the spleen composed of?
Red pulp (red blood cells) White pulp (lymphoid tissues)
What does the spleen do?
A maturation organ for B cells
A blood filter to remove dead blood cells and bacteria in the red pulp
Main site for response against blood-borne antigens in the white pulp
Source of B cells that respond to bacterial cell wall antigens in the absence of T cells
What percentage of lymphocytes are lodged in the spleen?
25%
Where are lymph nodes located?
Scattered along the lymphatic vessels
What do lymph nodes contain?
T cells
B cells
Accessory cells
What are the 3 main parts of the lymph nodes?
Cortex
Medulla
Capsule
When does adaptive immunity occur?
After the initial innate response which can be days or weeks later
What is the purpose of adaptive immunity?
It is the basis of an organism becoming immune to a pathogen
What is the major component of adaptive immunity?
The production of antibodies by B-cells
What do T-cells do during adaptive immunity?
Either help B-cells mature or they can become killer cells
What are pathogens made up of?
Proteins and carbohydrates
What are the proteins on a pathogen called when the evoke an immune response?
Antigens
Describe how antigens are displayed on the surface of antigen presenting cells
Macrophages and other antigen presenting cells break up bacteria and viruses and present their antigens on the surface
These antigen proteins are then combined with a self protein called major histocompatibility complex (MHC) and this allows T-cells and B-cells to recognise them through their own cell surface receptors (TCR) and (BCR)
What are the 2 main functions of a T-cell?
Help B-cells and secrete cytokines
Kill virally infected cells
What class of MHC does CD4+ cells recognise?
MHC class II
What class of MHC does CD8+ cells recognise?
MHC class I
How are T-cells selected in the thymus?
T-cell precursors enter the thymus and TCR gene rearrangement is initiated
The thymocytes at this stage are double positive as they have both CD4+ and CD8+
T-cells expressing a TCR that binds strongly to MHC are negatively selected and die and vice versa
Where does T-cell selection take place?
In the thymic medulla
Why are some T-cells eliminated?
The have high avidity as they bind too closely across multiple binding sites
How are T-cells eliminated?
They undergo apoptosis
Describe how T-cells are mobilised?
They encounter a cell such as a dendritic cell that has digested an antigen and is displaying the antigen fragments bound to its MHC molecules
Cytokines then help the T-cell mature
The MHC-antigen complex activates the T-cell receptor and the T-cell secretes cytokines
What do the cytokines that T-cells secrete do?
Some spur the growth and proliferation of more T-cells
What are the 2 things that T-cells do when they have been mobilised?
Some become cytotoxic and track down virally infected cells
Some become helper cells and secrete some cytokines that attract fresh macrophages, neutrophils, other lymphocytes and other cytokines to direct recruits once they arrive on the scene
What is the main function of B-cells?
To secrete antibodies after capturing the antigen on their cell bound receptor molecules and interaction with T-cells
Describe how B-cells are matured
The B-cell precursor rearranges its immunoglobulin genes
Negative selection occurs in the bone marrow
The B-cells migrate to peripheral lymphoid organs and secrete antibodies and memory cells in the bone marrow and lymphoid tissue
Why must B-cells and CD4+ T-cells interact?
B-cells must get ‘second signals’ from a T-cell or it will lead to anergy
What is anergy?
B-cells turn off
Describe how T-cells and B-cells interact in order to trigger the B-cell into producing antibodies
The B-cell is triggered when it encounters its matching antigen
The B-cell engulfs and digests and displays the antigen fragments bound to its MHC molecules
This attracts a matching T-cell
Cytokines secreted by the T-cell help the B-cell to multiply and mature into antibody producing plasma cells
Antibodies are then released into the blood and lock onto matching antigens
Antibody-antigen complexes are then cleared by the complement cascade or by the liver and spleen
What are the 2 chain types in an antibody?
Light and heavy chains
What are the 2 regions in an antibody?
Variable and constant regions
What 4 components is the heavy chain composed of?
3 constant domains CH1,CH2,CH3
1 variable domain VH
What 2 components is the light chain composed of?
1 constant domain CL1
1 variable domain VL
What part of the antibody do the variable domains make up?
The antigen binding site
What is each variable and constant domain made up of?
An immunoglobulin fold
Why is antibody diversity so important?
To ensure that all organisms can mount a specific immune response to specific pathogens
What are the 3 types of antibodies?
Isotypes
Allotypes
Idiotypes
Describe isotypes
They are present in all healthy individuals
Describe allotypes
They are genetically restricted and have variation within the CH region
Describe idiotypes
The individual antigenic characteristics of a given antibody molecule based on its variable region
How many antibodies are present in humans?
10^11
What are the 5 classes of antibodies?
IgG IgD IgE IgA IgM
Describe IgM antibodies
The first antibody produced in an infection
Resides on the B-cell as an antigen receptor
Secreted as a pentamer held together by a J chain
Has 10 binding sites thus is effective at agglutinating bacteria and activating complement
Describe IgG antibodies
Four subclasses (IgG1, IgG2, IgG3, IgG4) which have slightly different properties
Most prevalent antibodies in serum
Only antibodies that can cross the placenta
Describe IgA antibodies
A dimer held together by a J chain
Contain a secretory component
Protects the mucosa
Secreted locally by plasma cells in saliva, milk and tears
Describe IgD antibodies
Low levels in serum (0.3 mg/L)
Main function is as a B-cell antigen receptor
Describe IgE antibodies
Major antibody class involved in inflammation and protection from parasitic worms
Serum levels are very low
Binds to IgE receptors on a mast cell via its Fc region
Re-exposure to antigen results in mast cell triggering
Associated with antibody-mediated allergy
How can antibodies neutralise virus or bacteria?
Antibody binding to a virus or a bacteria can neutralise it directly by interfering with a cell surface receptor
How can antibodies induce lysis or phagocytosis?
IgG/IgM can activate the classical arm of complement resulting in lysis of an antigen bearing cell of phagocytosis
How can Tc cells be activated by antibodies?
Binding of the antibody-antigen complex to antigen receptors on certain cell types results in the effector cell being activated
How is immunological memory created?
Stimulated B-cells proliferate and mature
Some become memory plasma cells
Re-exposure of antigens to these primed B-cells causes them to respond rapidly
