Infection and the immune reponse 🦠

When is an inborn error of immunity established & what is it caused by

At birth caused by inheritance or mutations.

Define a virus

obligate intracellular parasite that requires a host to replicate and facilitate the spread

What can IEI lead to

Minor increased risk of infections all the way to an inability to control any infection

What are the two types of mutation

Monogenic and polygenic

Monogenic - a mutation in one gene

Polygenic - a mutation in more than one gene

When is an acquired immunodeficiency established

They are not present at birth and can occur at any time after birth

What can be the causes of AIDS

Malnutrition, infection, age, certain drugs such as immunosuppressant.

List the types of IEI

SCID

ADA

Hyper-IgM syndrome

Chronic granulomatous disease

List the types of AIDS

HIV

Malnutrition driven immunodeficiency

Age - associated immunodeficiency

Autoimmune associated immunodeficiency associated with Covid-19

What is the causes of SCID, its effects and how is it treated

Defect in the IL2RG gene found in both T and B cells.

The IL2RG encodes the receptor that many cytokines use, some of these cytokines are required for T and B cell development such as IL-7

Bone marrow transplant

What is the causes of ADA, its effects and how is it treated

Mutation in this enzyme leads to a build up of intracellular S-AHC which can be toxic to lymphocytes

Bone marrow transplant and a corrected version of the ADA is inserted into the patients own bone marrow and is then reinserted into the patient

What is the causes of Hyper-IgM syndrome, its effects and how is it treated

Defect in a T cell molecule which leads to a poor antibody response in adaptive immune system.

Often due to a mutation in the CD40L gene

Can be treated with bone marrow transplant

How does CD4 T cell communicate to B cell

Using CD40L and CD40

What is the causes of HIV, its effects and how is it treated

HIV can lead to acquired immunodeficiency syndrome

Treated with ART which can limit or prevent development of AIDS

They bind to CD4 receptors, and can cause apoptosis of other cells, cause the T cell to destroy itself and can cause the inappropriate or excessive immunoglobulin production.

What is the causes of malnutrition driven immunodeficiency, its effects and how is it treated

Can affect cells in the innate and adaptive immune system

It can cause more infections due to poor immunity or mortality

Age associated immunity deficiency and what it causes

Individuals of older age are likely to have more memory cells, although the production of naive lymphocytes is fewer, thymic output decreases, inflam-aging. This causes poorer response to infections, vaccines and tumours

Define allergy

Allergy refers to the hypersensitivity of non-self cells and usually forms a harmless trigger caused buy IgE antibodies.

Define auto-immunity

A misdirected immune response that occurs when the immune system is attacked by itself caused by IgG

What antibodies are involved in the immune response

IgG, IgE, IgM, cytokines

What cascade is caused by IgE

IgE > mast cells > cytokines, leukotrienes > histamine

Cytokines in allergies

cause inflammation > airways narrow causing wheezing and secretion of snot

Leukotrienes in allergies

Bronchioconstriction > secretion of snot and airways narrowing causing wheezing

Histamine in allergies

Histamine > vasodilation and bronchioconstriction > shock, swelling, airways narrowing causing wheezing

What does specific auto-immunity cause

If it is organ specific then it damages the structure and functions of organs and tissues.

What does non-specific auto-immunity do

If it is non specific then it has an impact on wide-spread molecules in the systematic or common cellular structures such as blood vessels, cell nuclei or connective tissue

How is rabies transmitted

Transmitted through broken skin and mucus membranes, it invades the nerve cell, can travel up the axon of the nerve and into the brain causing encephalitis

How is rabies prevented

Can be treated using a highly effective drug such is made using inactive rabies virus and vaccine adjuvant

How is rabies treated

The individual is given the vaccine alongside purified rabies immunoglobulin

List the 2 acute viral infections

Influenza and Herpes

List the chronic viral infections

HIV

Hep B

Hep C

What is influenza

A resp tract infection

What is herpes

Ubiquitous viral infection which often appears as a listening rash on mouth or genitalia, it can rarely lead to encephalitis

What are the preventions of acute viral infections

Oseltamivir and Aciclovir

How does oseltamivir prevent acute viral infections

It stops the virus being shed by the host cell, it then cannot spread to other cells

It can also target gene expression/replication

How does aciclovir prevent acute viral injections

In low doses this is minimally toxic but in high doses it can lead you to encephalitis. It needs a protein to activate it

What are preventions of the chronic viral infections

HAART, combination therapy and HIV injections

What is the mechanism of HARRT

they are protease, RNA transcriptase and integrase inhibitors, this can be successful in stopping the transmission and symptoms of HIV as they are complete inhibitors.

What is the structure of a virus

They have a genome centre made up of either DNA or RNA. This is coated with a capsid. The virus can either be naked or enveloped so some will have a lipid bilayer. Both are coated within glycoproteins which can bind to receptors, these give viruses their specificity.

What is tropism

The specificity of a virus to the host

Name the types of tropism

Cellular tropism

Tissue tropism

Host tropism

What are capsids composed of

capsomeres, these are several polypeptides grouped together, they can be helical or iscohedral.

What is the structure of the lipid membrane

Layer of lipid membrane - containing lipids, plasma membrane, nuclear membrane, golgi apparatus and ER

Proteins

Glycoproteins

What is the role of glycoproteins

To facilitate host cell entry, bind to receptors meaning different viruses have different glycoproteins and this allows he to have their specificity.

Simply outline the process of virus replication in DNA

The glycoprotein of the virus binds to the receptor on the cell, the virus attaches and can be absorbed into the cell, they are uncoated meaning they loose their capsid and are now just the genome. The capsid undergoes transcription by host ribosomes into mRNA using RNA polymerase and can then be translated to form proteins. Using this genetic material the assembly of new viruses is caused and they can now leave the cell causing apoptosis, moving out or moving to neighbouring cells.

How is RNA sectioned into groups for translation

negative and positive double stranded RNA

negative single stranded RNA

Simply outline the process of transcription of RNA in viruses

-ve & +ve double stranded, -ve single stranded are converted to +ve sense RNA and can then be directly used for translation

+ve single stranded can be used directly tilt as mRNA and can then be translated

Retrovirus must use reverse transcriptase to covert RNA into negative DNA which can then be integrated in the host cell DNA and then transcription is carried out to form mRNA

State the 3 types of genetic variation

Viral mutations

Gene recombination

Gene reassortment

Outline mutations and how they effect DNA

Substitution, Deletion, Insertion. These cause slight changes to genetic material and RNA polymerase cannot detect these mutations hence how they go undetected. This is known as antigenic drift as it is a subtle effect

Outline gene recombination and reassortment and how they effect DNA

Recombination: exchange of entire genes between two strains.

Reassortment: exchange of segments of genomes between strains

Both result in antigen is shift as it is drastic effects.

What structure does HIV have

enveloped, singl stranded +ve sense RNA retrovirus, it has 120 glycoproteins composed of gp120 and gp41. It contains reverse transcriptase, integrase and protease within the capsid.

State how HIV would replicate

HIV is a retrovirus so it will replicate the same way a retrovirus does. HIV > negative DNA using reverse transcriptase > integrates with host DNA > mRNA. It then assembles to create new virion that can leave the cell

What is HIV

human immunodeficiency virus

What blood tests are used to test for HIV

Viral load and CD4. Viral load measure the quantity of viral particles. CD4 levels should be higher in order to fight infections. Normal viral load level 200 copies/ml, in HIV patients it is >1mil copies/ml. Normal CD4 count is 400-1600 per mm3, in an individual with HIV it is <200 per mm3. In HIV when viral load is high the CD4 is low.

What role does CD4 play in HIV

HIV binds to the CD4 receptors, it can then destroy the white blood cell by apoptosis, can kill uninfected wbc, signal CD8 antibodies to kill the wbc

How is HIV transmitted

Broken skin, blood, anal/vaginal intercourse, mucus membranes, shared equipment, from mother to child.

Outline the two treatments for HIV for those who are high risk

PrEP - pre exposure prophylaxis

PEP - post exposure prophylaxis

Pre is used for those who are at an increased risk of contracting HIV, and post is for those who have been in contact with HIV but will minimise their chance of acquiring HIV, they are not diagnosed and must take within 72 hours for 28 days

How can individuals be treated for having HIV

ART - anti retrovirus treatment. This stops symptoms and will also prevent the individual from spreading HIV. The aim of ART is a viral load suppression and if it stays below 200 for 6 months they will be classified as undetectable. Made up of 2 nucleoside reverse transcriptase inhibitors and 1 drug from another class.

HIV prevention

condoms, treatment as prevention, PrEP, PEP, harm reduction measures such as needle exchange and safer injecting facilities.

How does HIV cause harm

HIV infects cells such as CD4 cells so T helper cells, macrophages and dendritic cells. All of these cells carry CD4 receptors which allow entry of HIV. HIV causes the depletion of T helper cells by direct killing through apoptosis, apoptosis of unaffected bystander cells and can cause CD8 cells to kill the CD4 cells. The abnormal activation of B cells can cause inappropriate immunoglobulin production. If CD4 levels become so low this makes individuals at greater risk of AIDS

Outline the important of latency in HIV infection

This term is used to describe the long asymptomatic period between initial infection and advanced HIV which is typically known as AIDS. HIV replicates actively throughout the course of infection even during the asymptomatic period, once the HIV DNA is integrated into the host DNA it cannot be removed.

What can happen when HIV mutates

The virus mutates and produces variations of itself, variations of HIV strains when a person is taking medication can result in drug resistant strains of HIV. HIV medication cannot precede the drug-resistant HIV from multiplying causing treatment to fail.

What is the importance of monitoring antiviral resistance

Drug resistant testing identifies which, if any, HIV medications won’t be effective against a persons HIV, the results help us to determine which HIV medications to include in the HIV treatment regions. Taking the drugs as their supposed to be taken minimises the risk of drug resistance.

As a clinician what is it important to remember when treating a HIV patient

Don’t stigmatise

Don’t assume things such as sexuality

Don’t inappropriately focus on how they acquired the infections

What mental implications may there be with HIV

Low mood

Suicidal

Afraid to speak out

Experience of stigmatisation

Isolation

this often prevents individuals from getting treatment

What are some initial symptoms of HIV

a rash

a fever

run down

nausea

oral thrush

Which co-receptors are present in the binding of HIV to the cell

CCR5 in monocytes

CXCR4 in lymphocytes

What is the role of hemagglutinin

Binds to and allows influenza virus into the cell by binding to and recognising saliac acid receptors

What is the role of neuraminidase

These cleave the sialic acid receptors and this is essential in letting the new influenza particles out of the cell

What viruses infect the body through the resp system

Measles, mumps, rubella, covid, influenza

What virus enters the body through blood

Hep B/C or ebola

How does HIV enter the body

through sexual intercourse, mucus membranes, contamination of needles

What is the target and receptor of HIV

T cells, monocytes and dendritic cells

CD4 receptor and CXCR4 and CCR5 co receptors

what is the target and receptors for influenza

Respiratory epithelium

Sialic acid residues (help from hemagluttinin as this attaches the virus to these receptors)

Target and receptor of rhinovirus

Nasal epithelium

ICAM-1

Target and receptor of Epstein-Barr virus

b cells

Complement receptor 2

What type of virus is influenza

myxovirus

What is CD40L

A protein found on T helper cells which binds to CD40 on the B cell to tell them to produce antibodies

List the viruses that are transmitted via oral transmission

Hep A and norovirus

How do mutations go unseen

RNA polymerase cannot detect mutations

How does chronic granulomatous disease affect the body

There is a defect in NADPH, NADPH causes the superoxide burst which causes phagocytosis, without the NADPH being functional the phagocytosis cannot occur so the dead, faulty cells cannot be killed or removed. This can be treated with antibodies and cytokines.

What antibodies are involved in allergy and what are involved in autoimmunity

Allergy - IgE

Auto-immunity - primarily IgG but sometimes IgM

Mechanism of hypersensitivity

the body creates antibodies which attach to the body’s own cells marking them as dangerous and they will be killed

What virus is transmitted via direct inoculation

Zika

Role of gp120 and gp41

gp120 - binds to the CD4 and engages a coreceptor to initiate viral entry

gp41 - triggers fusion of the viral and host cell membranes after the coreceptor binds.

How is it difficult to create antiviral drugs

Viruses use the host cells own components to replicate which leaves few targets for drugs to not damage own cells

What is the cause of type 2 hypersensitivity

The body labels its own cells with antibodies which marks them as harmful, triggered by IgG and IgM

What is the cause of type 3 hypersensitivity

Antigen-antibody complex deposits into tissue cause complement activation, inflammation and results in tissue damage

What is the cause of type 4 hypersensitivity

cell mediated caused by CD4 and CD8

What are the symptoms of measles

Rash in mouth

Fever

Flu like

Conjunctivitis

What are the symptoms of mumps

Viral meningitis

Headache

fever

swelling

What are the symptoms of rubella

Rash

Fever

aching joints

What is the condition called that is caused by Zika virus transmission from mother to foetus

Microcephaly

What are the symptoms of ebola

Nausea

Blood in faeces

Bleeding from nose, mouth, ears, eyes

What is hormone is responsible for thyroid

TSH

Name a non-specific autoimmune disease

Systemic lupus erythrematosis

What does systemic lupus erythrematosis cause

Damage to blood vessels, small capillary networks, joints

What can be released by mast cells

Histamine

Leukotrienes

Cytokines

Prostaglandins

Proteases

PAF