Lecture 5 - Immunity Part 2

Question 1

What makes up the innate immune system?

Answer 1

Non – Specific
Includes barriers e.g. skin & mucosa
Chemical mediators – Leukocytes (but NOT lymphocytes!)
Phagocytic Cells & NK Killer cells
Antigen presenting cells
Physcial mediators – fever

Question 2

What makes up the adaptive immune system?

Answer 2

Specialised Response
B cells
IgG, IgG, IgD, IgE
T Cells
T Helper Cells & Cytotoxic Killer T Cells
Memory Cells

Question 3

What are the cells of the immune system?

Answer 3

Macrophages (and other Phagocytic cells)
2. T- Helper Cells
3. T – Cytotoxic Cells
4. T- Regulatory Cells
5. B Cells

Question 4

What are macrophages?

Answer 4

Macrophages are a large type of phagocytic cell “Big Eater”
is derived from a monocyte
functions in the destruction of foreign antigens (as bacteria and viruses)
serves as an antigen-presenting cell

Question 5

What are T cells?

Answer 5

called T- Cells because they are matured in thethymus.
They recognise foreign particles (antigen) by a surfaceT cell receptor(TCR).

There are two major types of T cells:
thehelper T celland thecytotoxic T cell.
As the names suggest helper T cells ‘help’ other cells of the immune system, whilst cytotoxic T cells kill virally infected cells and tumours.

Question 6

What are cytotoxic t cells?

Answer 6

aka CD8 - Killer T cell

Question 7

What are T helper cells?

Answer 7

CD4 T cell - come to the rescue when any cells come to try to invade

Arguably the most important cell in the adaptive immune response as they help B cells and CD8 Killer cells destroy infected cells.

A mature T Cell is referred to as a CD4+ T cell because is has a CD4 glycoprotein expressed on its surface.

They are called helper cells because one of their main roles is to send signals to other types of immune (WBC) cells
e.g. to B cells and CD8 killer cells, which then destroy the infectious particle.

Made in the bone marrow
Mature in the Thymus
Need to become ACTIVATED
When they become activated they can activate B cells
When B cells become activated, they become PALSMA cells
Plasma cells secrete antibodies

Question 8

What are T cell binding cells?

Answer 8

TCR (T Cell Receptor) cannot bind to the antigen directly.
Instead it needs to have broken-down peptides of the antigen ‘presented’ to it by anantigen presenting cell(APC).
The molecules on the APC that present the antigen are calledmajor histocompatibility complexes(MHC).
There are two types of MHC:
MHC class Ipresents to cytotoxic T cells -
MHC class IIpresents to helper T cells.

Question 9

How are T- Helper Cells Activated?

Answer 9

In two steps:

Interaction with a T Cell Receptor (TCR)

2. Peptide Major Histocompatibility Complex (MHC) class 2 molecules (pMHC 2)

Question 10

What is the Role of the Major Histocompatibility Complex (MCH)?

Answer 10

Sometimes called Human Leukocyte Antigen (HLA)

MCH are group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances

CD4 present on T Helper cells – only binds to MHC II
CD8 present on Cytotoxic cells – only binds to MHC I

Question 11

How are T Cells Activated? - MHC II

Answer 11

CD4 (helper) cells come into contact with an Antigen presenting cell
They bind with the antigen via MHC II molecule
This process activates the CD4 T Helper Cell

This activation causes the release of INTERLEUKIN- 2 CYTOKINES

The released IL -2 cytokines bind to a receptor on their cell surface, which causes a release of CD4 (helper) cells
The binding of ILK-2 causes a cascade of reactions, ending with the replication of T Helper Cells into 2 subtypes:

T Helper 1 CD4+
T Helper 2 CD4+

Question 12

When T Helper cells detect a pathogen or infected cell, they form into one of 2 subtypes what are they?

Answer 12

TH1 Helper Cell

TH2 Helper Cells

Question 13

What are TH1 Helper Cell?

Answer 13

releases molecules that activate macrophages

Question 14

What are TH2 Helper Cells?

Answer 14

activate B Cells
B cells in turn create antibodies
They also release cells which cause coughing, sneezing, diarrhea to help your body get rid of foreign substances.
This group help generate allergy antibodies.

Question 15

What are APC’s?

Answer 15

Antigen presenting cells

Question 16

What are CYTOKINES ?

Answer 16

The equivalent of the bodies wifi/messenger service

Cytokines are small membrane bound proteins which aid cell to cell communication aka. They are cell signalling molecules.

Examples Include:
Chemokines, interferons, interleukins, lymphokines and tumour necrosis factor

They are produced by a broad range of cells, including immune cells like:
Macrophages
B Lyphocytes
T Lymphocytes
Mast Cells
As well as endothelial cells, fibroblasts, and various stromal cells which are involved in triggering inflammation following acute trauma.

Question 17

What is Humoral (T Helper 2) ?

Answer 17

Antibody mediated
Eliminate extracellular pathogens (aka antigens)
B- Cells Major role

B cells bind to the antigen receptors – get help from T Helper cells ( on the cellular mediated side)
T Helper cells come over from cellular immunity, and secrete cytokines
Cytokines transform B-cells into antibody producing cells called PLASMA cells
PC have the capability to produce antibodies for that specific antigen, and so neutralizes the pathogen.

Question 18

What is Cellular (T Helper 1) ?

Answer 18

Cell mediated
Eliminate intracellular pathogens (aka antigens)
T cells Major role

Question 19

Cytokines used to have different names depending either on their origin: for example..

Answer 19

origin:
lymphokines (produced by lymphocytes),
monokines (monocytes) or
On their activity:
chemokines,
interleukins,
interferon.

Question 20

CYTOKINES CAN ACT AS?

Answer 20

Mediators of the innate immunity (inflammation, chemotaxis, macrophage activation, NK cells) and adaptive immunity (humoral and cellular).
Regulators of lymphocyte activation, proliferation and differentiation.
Stimulators of haematopoietic stem cell growth.

Question 21

What are plasma cells?

Answer 21

Plasma cells can only produce a single kind of antibody in a single class of immunoglobulin.
In other words, every B cell is specific to a single antigen, but each cell can produce several thousand matching antibodies once triggered. This prolific production of antibodies is an integral part of the humoral immune response.

Remember from before-
Activated T Helper cells then activate B cells
When B cells become activated, they become PALSMA cells
Plasma cells secrete antibodies

Question 22

What are T Regulatory Cells (aka Suppressor Cells)?

Answer 22

Specialised sub population of T cells that act to suppress the immune response
Thereby maintain homeostasis & self tolerance
They are able to inhibit T Cell proliferation & cytokine production and therefore play a critical role in preventing autoimmunity

Question 23

What is the complement system?

Answer 23

This is a system which helps or “complement” the ability of antibodies and phagocytic cells to clear pathogens from an organism

Is part of the innate immune system
Made up of a number of small proteins which are found in the blood, but made by the liver.
Some are also made by macrophages and GI mucosa

Normally these small proteins circulate in the blood as inactive precursors.

When stimulated by a trigger (eg. Bacteria), proteases split these small proteins to release active cytokines.

This triggers a cascade (a series) of further cytokine release, which further amplifies the response.

The cytokines disrupt the phospholipid bilayer of the cell membrane (of the invading bacteria)  which kills it.

Complements are soluble proteins and glycoproteins found normally in circulating blood - as inactive forms.
They become activated during an inflammatory reaction.
During the inflammatory response, more complements are brought to the area via interstitial fluid – within dilated blood vessels
(dilated blood vessel are activated by proteolytic cleavage)

The final stage of the complement system is called the MEMBRANE ATTACK COMPLEX (MAC)

Question 24

What is Membrane Attack Complex (MAC)?

Answer 24

In the terminal stage of the complement system (of the innate immune system

Pore like holes are made within the cell membrane of the pathogen
This causes cell swelling
That ultimately leads to cell death

Question 25

What are the Main Functions of the Complement System?

Answer 25

Cell Lysis
Chemotaxis
Opsonisation
Agglutination

Question 26

What is Opsonisation?

Answer 26

Increases phagocytosis by opsonins (C4B & C3B) binding to foreign organisms / pathogens.

Question 27

What is Chemotaxis?

Answer 27

Attracts macrophages and neutrophils via inflammation by inflammatory mediators (C5a – mainly, and to less extent C3a & C4a)

Question 28

What is cell lysis?

Answer 28

Ruptures membranes due to formation of a membrane attack complex (MAC)

Question 29

What is Agglutination?

Answer 29

Causes clustering and binding of pathogens

Question 30

What are the 3 pathways to activate the complement cascade ?

Answer 30

Complement proteins in the circulation are not activated until triggered by an encounter with a:
Bacterium
Virus
an immune complex
damaged tissue
or other substance not usually present in the body.

1.Classical
2.Lectin
3.Alternative

Question 31

What is the Classical Pathway – C1q protein (The compliment system) ?

Answer 31

Initiated by the binding of antigen – antibody complexes to the C1q protein
The globular region of C1q recognized & binds the the Fc region of the antibodies - IgG and IgM
They also bind to bacterial and surface proteins, apoptotic cells and acute- phase proteins.
It still terminated with membrane attack complex (MAC)
This leads to the lysis of of invasive bacteria by insertion into target cell membranes creating functional pores.

Question 32

What is the C3b Protein (The Complement System) ?

Answer 32

Virus fungi, bacteria, parasites, IgA and polysaccharides activate the alternative pathway
The C3b protein triggers this pathway, and the protein directly binds to a microbe.
Foreign material and damaged tissues can also trigger the alternative pathway.
The C3b is free and abundant in plasms, so has the ability to bind to a host cell or pathogen surface.
Regulatory proteins will prevent activation of complement on a host cell

Question 33

What is the Lectin Pathway (The Complement System) ?

Answer 33

A type of cascade reaction in the complement system
Once this pathway is activated, the action of C4 and C2 produces activated complement proteins further down the cascade.
This pathways does not recogonise antibodies which are bound to their targets
Instead, it binds to sugars such as mannose and glucose with –OH groups (via mannose – binding lectin)

Question 34

What are the Similarities between Classical, Alternative & Lectin Pathway?

Answer 34

They are all activated by a cascade of reactions leading to the membrane attack complex
All part of the immune system
Each pathway has unique proteins for initiation
They are activated by certain isotypes of antibodies bound to allergens

Question 35

What are the Differences Between Classical, Alternative & Lectin Pathway?

Answer 35

Classical takes place through binding C1q protein
Alternative takes place through binding of C3b onto foreign surfaces
Lectin Pathway takes place through mannose- binding lectin

Question 36

The final stage of the complement system is called?

Answer 36

The final stage of the complement system is called the MEMBRANE ATTACK COMPLEX (MAC)

Question 37

How many proteins is the complement system made up of?

Answer 37

over 35