Innate and Adaptive Immune System

First layer of innate immunity

Barrier

Prevents entry of pathogens, so immune system does not have to get into action

What are humoral effectors?

Any part of the innate immune system that is soluble, but not cellular

Adaptive innate immune cells

Name 3 things that make skin a good barrier

• Thick + dead

• Impermeable (due to keratin)

• Releases antimicrobial secretions

• Dry surface

What is the mucociliary elevator?

The portion of cilia along the epithelia of the lungs and bronchi that sweep mucus (and debris/pathogens within) up and out.

What stem cells do all immune cells come from?

Bone marrow stem cells —> multipotent progenitor cells

What are sentinel cells and 3 examples of them

They monitor tissues constantly for signs of infection or injury.

Once they detect danger signals (like microbes, damaged cells, or foreign substances), they activate and alert other immune cells.

1. Dendritic cells

2. Macrophages

3. Mast cells

What do dendritic cells do

Captures antigens and migrates to lymph nodes to activate T-cells

What do macrophages do

Engulfs pathogens and releases cytokines

What do mast cells do

Releases inflammatory molecules, such as histamine to increase blood flow, and vascular permeability

Why do immune cells release inflammatory cytokines and chemokines

to recruit and activate other immune cellsW

What is the most common granulocyte

Neutrophil

What pathogens do granulocytes defend against

Bacteria and fungi

Function of monocytes

They circulate in bloodstream, and when an infection is detected, it goes to that location and differentiates, depending on what is needed (macrophages or dendritic cells).

Function of natural killer cells

NK cells detect any cells that have abnormal surface markers, or have downregulated MHC I molecules. And destroy they cells by triggering apoptosis via release of cytotoxic granules

What is MHC I

A molecule on the surface of every body cell. Gets downregulated when infected/cancerous and acts as a marker for NK cells.

Inhibitory molecule that stops NK cells killing cells containing MHC I surface receptors.

What are neutrophils

Most common white blood cell (~60-70%)

They are non-dividing (don’t under mitosis) end stage cells (fully differentiated)

They eat and kill invading microbes using NETs. They follow chemotaxic gradients to reach infection sites.

Usually only in blood, found in tissue only when it is infected.

What are NETs?

Neutrophil extracellular traps - trap and ensnare bacteria using chromatin. Excess NETs can cause blood clotting and organ failure (e.g. in sepsis)

What are complement proteins

Proteins found in high concentration in plasma and tissue fluids, responsible for initiating an enzyme cascade

What is the enzyme cascade

A small number of enzymes triggering a large scale response via amplification

How does the enzyme cascade occur from the perspective of an individual enzyme

Start off as inactive pro-enzymes made of two parts (a and b)

A causes inflammation by attracting innate cells like neutrophils

B sets off the next enzyme in the cascade, or binds to the surface of the microbe

3 causes of complement cascade

What does the complement protein C3b do

C3b coats the surface of a bacterium, tagging it as a target for immune cells. Gives a target for phagocytes to bind to

What does the complement protein C3a do

Degranulate mast cells, promoting inflammation and leukocyte recruitment

How does the membrane attack complex (MAC) form? and what is it

A combination of C5b, C6, C7, C8 and C9 enzymes form a barrel shaped transporter on a microbe surface, causing its destruction

What is a PAMP?

Pathogen associated molecular patterns (molecular patterns usually found of pathogens)

What are PRRs

Pattern Recognition Receptors - molecules expressed by innate immune cells that recognize common molecular structures found on pathogens or damaged cells

What are toll like receptors (TLRs)

key family of pattern recognition receptors. Transmembrane proteins found on the surface or inside immune and other cells.

What is the function or interferon and when is it released

Virus infected cells release interferon, which binds to uninfected cells.

Interferon stimulates production of :

1. RNAase

2. Protein Kinase-R

Which degrade RNA and block protein translation respectively, stopping virus replication.

Two types of T cell

T Helper cells - Enhance immune response of other immune cells

Cytotoxic T cells - Destroy pathogens

What innate immune cell stimulates T-cells?

Dendritic cellsW

What is Ig short for?

Immunoglobulin (aka antibody)

What is clonal selection theory, briefly

The selective breeding of lymphocytes, only allowing the lymphocytes that bind to the pathogenic antigens to proliferate

(billions of random lymphocytes are produced)

3 types of cells that are lymphocytes

T cells, B cells, NK cells

What cells are carriers of the genetic information required to code for previously used unique antigen receptors

Lymphocytes

What are B-cell receptors and what do they do

Receptors on the surface of B-cells that bind to free antigens (e.g. antigens on a pathogenic cell). This means they can bind to pathogens and toxins directly and release BCR(antibody).

What is secreted BCR

A BCR that is secreted from a B-cell is an antibody, which binds to the pathogen

What do T-lymphocytes recognise to bind to

Processed peptides presented on an MHC

Difference between how TCRs and BCRs bind to a pathogen

B-cells bind to a pathogen directly, T-cell are fussy and require a different immune cell (e.g. dendritic cell) to present a pathogen antigen to it.

what are the 4 chains in a B cell receptor

2 x Heavy

2 x Light

What is an epitope?

The part of an antigen that a receptor binds to

Explanation of how antigens are presented to T-cells

1. To reveal epitopes of pathogens, it must be broken into peptides

2. The epitope peptide binds to an MHC molecule on a (e.g. dendrite cell)

3. MHC molecule binds to T-cell receptor

What do MHC molecules do Cytotoxic and T-helper cells bind to respectively

Cytotoxic - MHC I

Helper - MHC II

Where are MHC I molecules expressed

Nearly all body cellsWh

Where are MHC II molecules expressed

Only on Phagocytic immune cells

Dendritic cells

Macrophages

B-cells

What is on a MHC II molecule after the phagocyte has engulfed a protein

Phagocytosed protein of the pathogen (so a T helper cell can bind and boost its power)

What is the purpose of the thymus?

Produce and mature T lymphocytes

What are the 3 types of different genes that are randomly recombined in the thymus to form different antigens for the T-cell (the TCRs)

Variable, Diversity and Joining genes

(also don’t forget about random nucleotides between these genes that give even more diversity)

What is negative selection?

Destruction of self-reacting antigens

Where are B-cells made

Bone marrow

3 Main ways antibodies aid in immune function

What happens in the Germinal Centre

After a B cell is activated by its specific antigen (and receives help from a T helper cell), it migrates to the germinal centre and the following occurs:

1. Clonal expansion

   1. B-cell proliferate, creating many clones of themselves

2. Somatic hypermutation

   1. B-cells change their variable region antibody genes, changing their affinity

3. Affinity maturation

   1. Higher affinity cells survive, lower affinity/self reactive cells apoptose

4. Class switch recombination

   1. B-cells change their isotype (e.g., from IgM to IgG, IgA, or IgE).

5. Differentiation

   1. B cells leave germinal centre and differentiate into memory B-cells or plasma cells

What is the function of the plasma cells

Secrete many antibodies

What is the function of B-memory cells

Long-lived cells that reproliferate when a disease reoccurs