Infection and Immunity

What is a primary immune response?

The first time an antigen is encountered. After 7-10 days, there is an antibody response.

What is a secondary immune response?

An encounter with a previously encountered antigen. Memory lymphocytes allow for a faster and stronger response.

What is the structure of an antibody?

They have two light chains and two heavy chains which are held together by inter-chain disulphide bonds. There are two antigen binding sites (Fab) and one effector function controlling region (Fc).

What is the primary response in type one hypersensitivity?

An allergen enters the body and is taken up by a dendritic cell which then expresses a peptide on an MHC molecule. This migrates to the lymph nodes where T cells will activate and proliferate into Th2 cells through the release of IL-4. Th2 cells activate B cells, these leave the lymph nodes to travel toward the allergen entry point. The Th2 cell produces cytokines that instruct the B cell to make IgE.

What is the secondary response in type one hypersensitivity?

Allergen enters the body and is bound to mast cells with IgE, activating the mast cell. These mast cells release pre formed granules (histamine) and newly formed granules (cytokines) which contribute to the tissue specific response.

Immunological tolerance

Ensures that the immune system does not react against the body’s own tissues and cells (self antigens).

Clonal deletion - central tolerance

Prevents the body from generating lymphocytes that recognize self antigen. This occurs in the bone marrow (B cells) and the thymus (T cells).

Anergy - peripheral tolerance

Some self reactive lymphocytes will escape from central tolerance into the periphery. Dendritic cells presenting self peptide will bind to autoreactive T cells and inactivate them.

Suppression - peripheral tolerance

Some cells that do not die in central tolerance will develop into Treg cells. These can inhibit activation of autoreactive lymphocytes.

Ignorance - tolerance

Antigens contained in privileged regions (eyes) are released and activate autoreactive lymphocytes.

Positive selection of T cells during central tolerance

T cell receptors are judged on their affinity for self MHC molecules. If there is no affinity, they undergo death.

Negative selection of T cells in central tolerance

Tests the affinity of the T cell receptor for self antigen. If they react too strongly they undergo apoptosis.

How are B cells educated in central tolerance

Newly rearranged B cell receptors are tested against self antigen, if they react too strongly they undergo apoptosis.

What are the four requirements for autoimmune disease

1. Escape of autoreactive clones from central tolerance

2. Autoreactive clones encounter self antigens

3. Peripheral tolerance failure

4. Autoreactive tissue damage

What type of autoimmune disease results from type II and III HS

Type II HS results in organ specific autoimmune diseases.

Type III HS results in systemic autoimmune diseases.

Gram stain technique

Bacterium is stained with crystal violet, iodine is added. A decolouriser is added which washes out the stain or doesnt. A counterstain is added, if this is taken up it goes red and is gram negative, if the crystal violet/iodine remains, it is purple and gram positive.

Gram positive bacteria features

• Polysaccharide capsule

• Peptidoglycan cell wall (thick)

• Cell membrane that is an osmotic barrier and also houses electron transport chain

• 70s prokaryotic ribosome

• DNA with no nucleus and mitochondria

Gram negative bacteria features

• Polysaccharide capsule

• 70s prokaryotic ribosome

• DNA with no nucleus or mitochondria

• Peptidoglycan cell wall (thin)

• Inner cell membrane houses electron transport chain and is an osmotic barrier

• Outer cell membrane

Acid fast bacteria

This is an exception to gram positive bacteria features.

There is a mycolic acid outer layer which repels gram stain.

What are the three ways that bacteria can move without flagella?

Twitching - attaching to something on the surface and dragging itself

Gliding - forming adhesion complexes with the surface

Sliding - spreading through growth

Obligate aerobes

Requires oxygen to make ATP, does this through aerobic respiration.

Micro-aerophile

Requires a low oxygen content

Facultative anaerobe

Survives in the presence of oxygen and without it. Switches between aerobic respiration and fermentation for ATP production.

Aerotolerant anaerobe

Cant produce ATP by aerobic respiration but is tolerant to oxygen.

Obligate anaerobe

Cant tolerate oxygen and produces ATP by fermentation.

Biofilms

A sticky matrix that bacteria secrete to stick to surfaces and build a community and protect from harmful environements.

Closed pangenome

A large core genome and small accessory genome. Most genes in the species are shared, little are variable.

Open pangenome

A small core genome and large accessory genome. Most genes in the species are variable, little are shared.

What are the three methods for horizontal gene transfer in bacteria?

Transformation - Bacteria picks up DNA from the outside

Transduction - Bacteria is infected with a virus and takes its DNA

Conjugation - Bacteria makes a bridge between each other

Three types of bacteria

Free living

Facultative intracellular - can live in or out of cell

Obligate intracellular - requires cell to live

Reservoir

Source of the microbe

Transmission

How the agent gets from the reservoir to the site of infection

What are the four steps in causing an infection?

1. Establishing a foothold - prevent being washed away

2. Evading host defenses

3. Proliferation - getting nutrients to survive

4. Causing damage via chronic inflammation and carcinogenesis

What are the two ways that bacteria can stick to a surface?

Non-specific adhesion molecules

• often reversible

Specific adhesins

• gram negative - pili and fimbriae

• gram positive - cell wall proteins and MSCRAMM

MSCRAMM

microbial surface components recognising adhesive matrix molecules

What are the ways that bacteria hide from the immune system?

1. Using a capsule to protect surface proteins from being recognised

2. Invading host cells

3. Mimicking the host by having Ig bind the opposite way

4. Binding to host proteins

5. Binding to factor H

6. killing phagocytes

7. Changing antigen

Symptoms and causes of peptic ulcer disease.

This is a breakage in the gut lining. It is caused by helicobacter pylori and causes upper abdominal pain, vomiting, weight loss, and bleeding.

H. pylori - establishing a foothold

Resisting stomach acid by secreting urease, this produces a cloud of ammonia to neutralise acid.

Swims into the mucus layer to avoid stomach acid via flagella and helix shape.

Bacteria attaches to epithelia via babA adhesin binding to Lewis b carbohydrate receptor.

H. pylori - evading host defenses

LPS is poorly recognised by TLR4 and flagella subunits poorly recognised by TLR5, these result in low cytokine production.

VacA inhibits phagocyte maturation, T/B cell proliferation.

Coated with plasminogen and cholesterol to mimic the host.

H. pylori - Inflammation of antrum

D cells lose function, increasing stomach acid and gastrin production. Acid leaks into the duodenum, duodenal ulcer results.

H. pylori - inflammation of corpus

P cells lose function, loss of acid production and gastric ulcer results.

H. pylori - carcinogenesis

CagA within the CAG pathogenicity island causes a phosphorylation cascade that causes neutrophil death, barrier disruption, inflammation, and cell proliferation of the host.

This causes release of ROS from the mitochondria.

How is stomach acid produced?

Food makes G cells produce gastrin, ECL cells produce histamine, P cells produce stomach acid.

Acid is sensed in D cells which produce somatostatin which stops G cells from producing gastrin.

Cells in the fundus

Mucus secreting cells, parietal cells, ECL cells.

Cells in the antrum

G cells, ECL cells, D cells.

Exotoxins disease vs intoxication

Disease - caused by a pathogen establishing a niche on the host body and causing disease aided by toxins

Intoxication - pathogen produces a toxin which is ingested

Cholera toxin

B subunit binds to GM1 receptor and is taken into the endoplasmic reticulum. The A subunit then causes disease. cAMP is increased, causing increased CFTR, and increased secretion of water.

Enterohemorrhagic E. coli (EHEC)

B subunits bind Gb3 and are transferred to the ER, ribosome is inactivated, causing cell death.

B subunits bind Gb3, inactivating ADAMTS 13, causing clotting

Binding to factor H increases complement, increasing inflammation.

Staphylococcal food poisoning

S. aureus produces toxins that resist stomach conditions.

Cytolysins

Proteins that bind to a receptor on a cell and form a pore on the cell membrane resulting in cell death.

Exoenzymes

Proteins secreted by microorganisms. Lipases, proteases, DNAses.

What is the bacteria responsible for meningococcal disease

Neisseria memingitidis. This is a gram negative bacteria that is spread through saliva and respiratory secretions.

What is a blood infection of neisseria meningitidis?

Meningococcemia. This results in bluish blotchy skin, fast breathing / breathlessness, and limb, joint, and muscle pain.

What is a spinal cord and brain infection of neisseria meningitidis?

Meningitis. This results in sensitivity to bright light, seizures, high fever, vomiting.

How do superantigens trigger toxic shock?

They allow antigen presenting cells to bind non specific T cells, resulting in massive production of pro inflammatory cytokines.