Infection & Immune response 🧫

How do lymphocytes develop

Development begins in the haematopoietic stem cells > lymphoid progenitor cells > lymphocytes > T & B lymphocytes. T lymphocytes mature in the thymus into fully functioning cells and then once matured they will return to the blood. B cells mature in the bone marrow which is also where development begins for both.

Summarise the role of T cells in activating B cells

This is done using CD4 T cells, these cells don’t kill cells directly instead the T cells activate as conductors of the immune system by activating B cells by signalling to them to promote antibody infection to help fight and aid clearance.

Explain the role of the lymphatic system

The lymphatic system is made up of lymphatic vessels, lymph and lymph organs. It is responsible for the removal of interstitial fluid from tissues and it is then known as lymph. It absorbs and transports fat from the digestive system and is involved in the immune system and production of mature lymphocytes and detecting foreign antigens.

What is lymph & how is it formed

Higher blood pressure in capillaries cause water to leak from them into the interstitial space (the space between the cells). Osmosis draws some of the fluid back into the capillary however there is some excess fluid and found in the interstitial space, this must be re absorbed and put back into the blood circulation and this is done using lymphatic vessels. These vessels can absorb interstitial fluid and small proteins which have been leaked, the vessels are lined with endothelial cells which allows fluid to enter lymphatic capillary, this fluid is now known as lymph.

What are lacteals & their role

Lacteals are lymphatic vessels within the villi of the small intestine, they absorb large dietary fats and vitamins that can’t enter the bloodstream. The fats are transported in the lymphatic system to the circulatory system first adsorption.

How does lymph flow

From the lymphatic capillaries, larger lymphatic vessels carry and return lymph back to the circulatory system.

Give examples of how lymph is transported

Pulsation from close by arteries and compression helping to move lymph along the vessels and from surrounding muscles can help move lymph towards trunk by doing things like walking.

What prevents the backflow of lymph

Valves in the lymphatic system

What is the structure of lymphatic trunks

Lymphatic trunks are made when lymphatic vessels come together.

Outline the process of lymphatic drainage

Lymphatic trunks (in the right side); side of the neck, head, upper limb, thorax, upper abdominal wall which all drains fluids into the right subclavian vein in the root of the neck via the right lymphatic duct. Lymph from all other regions drains into the thoracic ducts then to the left subclavian vein

Summarise lymph drainage in the body

Lymphatic vessels > lymphatic trunks > lymphatic ducts > blood circulatory system > subclavatory veins.

What are the primary and secondary lymphoid organs

Primary; bone marrow and thymus which are responsible for production of mature lymphocytes.

Secondary; lymph nodes, tonsils, spleen, MALT/GALT/BALT which are responsible for filtering where antigens are detected and antigen-driven proliferation and differentiation occurs.

What is the structure of lymph nodes

Small structures which interrupt the lymphatic vessels, they are dense areas of lymphoid tissue which allows fluid are surrounded by a dense fibrous capsule.

What are afferent lymphatic vessels

enter the lymph node

What are efferent lymphatic vessels

exit the lymph node

What is the role of lymph nodes

Filter lymph to detect any foreign antigens and mount an immune response

How do lymph nodes react to infection

they can become swollen or painful, this suggests that the immune systems are active and there is underlying infection eg cold, dental decay, ear infection or when there’s cancer present because cells can break away from the primary tissue and move to the lymph node to create a secondary tumour.

What is the definition of microbiology

The study of microorganisms and their relationship with humans

What is the structure of antibodies

They are Y shaped macromolecules consisting of 4 polypeptide chains (quaternary structure) called immunoglobulins, these 4 chains are 2 heavy and 2 light chains which are joined together by a disulphide bond. They have a variable region, this is the region which is different for different antibodies as this is where the antigen binds. There is also a constant region on the antibodies found at the bottom of the light chain.

What is the Fab and Fc domains

Fab domain; binds to antigen

Fc domain; binds to complement (the heavy chains)

What is IgM antigen

This is a pentamer and is the first antigen produced, strong binding to antigen

What is IgG antigen

It is a monomer, most abundant antibody and crosses the placenta for immunoprotection for developing foetus

What is IgA antigen

It is a dimer, secreted so found in tears, saliva, mucus membranes of resp & GI systems and in breast milk too

What is IgE antigen

It is a monomer, produces allergic response and parasitic immune response

What is IgD antigen

It is a monomer found on the surface of B cells

What are the 3 processes that occur during adaptive immune response

Neutralisation, Opsonisation, Complete activation

What is the process of neutralisation

antibody will coat toxin/virus and will neutralise the activity that it wants to do

What is the process of opsonisation

pathogen is coated in antibody making it more recognisable for macrophages to phagocytose it.

What is complete activation

triggers response to eliminate pathogens, clear damaged cells.

List the primary lymphoid organs

bone marrow and the thymus

What is the function of the primary lymphoid organs

These organs are responsible for the production and maturation of lymphocytes.

State the secondary lymphoid organs

Lymph nodes, spleen, throat, intestine

What is the function of secondary lymphoid organs

Structures where the T&B lymphocytes go to understand what is going on in the body and can then fight/respond accordingly eg producing antibodies. These are the organs where the cells of the immune system can go and fight off infection and foreign substance.

Explain how T Lymphocytes develop

The process is initiated with haematopoiesis where a haematopoietic stem cell differentiates into a lymphoid progenitor cell and furthermore into a lymphocyte then T lymphocyte. They then leave the blood and go to the thymus, the thymus is where the T lymphocytes develop into fully functioning cells, they are then released back into the bloodstream.

Summarise the role of T helper lymphocytes

T helper cells act as a conductor of the adaptive immune system by activating B lymphocytes by signalling to them to produce antibodies to help fight antigens.

List the symptoms of inflammation & why they occur

Redness; vasodilation

Heat; vasodilation and fever

Swelling; fluid in the extracellular matrix

Pain; pain mediators such as serotonin and bradykinin

Loss of function; caused by swelling and pain

Describe inflammation as a protective response

Localises the immune systems attention to the area if infection bringing cells/molecules to the areas to repair damage that may have been caused due to the infection.

What are the benefits of inflammation

Isolates the damaged area so prevents metastasis of infection

Mobilises effector cells and molecules to the site so that immune cells and molecules can be distributed throughout the body. Promotes healing and tissue repair so creates environment conductive to repair. Overall it protects the body

Outline the problems with too much inflammation

If inflammatory responses become out of proportion or outlive the threat they are dealing with, they can cause more damage to the body than the infection/trauma itself would have produced. Thus resulting in organ/tissue damage so a loss of function or allergies, autoimmune disease, chronic inflammatory conditions, cardiovascular disease.

Classify microorganisms in broad terms

cellular; bacteria, fungi, protozoa

acellular; virus’s and prions

describe the structure of bacteria

it does not have a membrane bound nucleus, genetic information is stored within the plasmids. It has a cell wall which has a thick capsule surrounding it, membrane, ribosomes, cytoplasm. They also have flagellum and phili to allow them to be motile.

The role of gram staining in bacteria identification

Gram positive - the gram stain goes purple, this is due to a greater abundance of peptidoglycans in the cell wall.

Gram negative - the gram stain dyes the bacteria pink due to less peptidoglycans in the cell wall.

The process of gram staining is as follows, dye with crystal violet, iodine. The crystal violet forms complexes with the peptidoglycans so when there is less then the purple colour will not be bright.

Sites of the body which are sterile and some which are not

Sterile sites; blood, tissues, organ systems, CNS, lower resp tract, sinuses, inner and middle ear, renal system down to the posterior urethra, female reproduction, tract down do the cervix, eye.

Non-sterile sites; nose, vagina, mouth, skin, throat and large intestine.

Define infection

Micro-organisms invade host tissues and actively multiple in a way that cause harm or damage the host.

Define colonisation

Micro-organisms are present and growing at the site but not causing any symptoms

What factors can make someone more susceptible to infection

age, gender, ethnicity, hygiene, nutrition, medical conditions and drugs, immunosuppressed individuals, presence of foreign objects such as central line, artificial heart line etc

State some common colonisers

***

Outline the specimen journey

The sample is processed in an appropriate part of the lab, processing may involve microscopy, culture, sensitivity techniques or referral techniques for genome sequencing.

Explain the importance of samples

Samples must get to labs on time, in appropriate containers and with sufficient clinical detail. In emergencies we don’t have to wait for sampling to come back and it’s important that treatment is just started immediately eg sepsis, outbreak, meningitis.

What is the meaning of sepsis

A physiological response to severe infection causing cytokine cascade, free radical production and vasoductive mediators.

What is used to manage sepsis

sepsis packs are used to guide the early identification and management of septic patients, ideally within the first hour including; blood cultures and samples, IV antibiotic administration, oxygen, measure lactate, start IV fluid, monitor hourly urine output.

Explain the chain of infection

Infectious agent such as virus/bacteria/fungi

Reservoirs so things such as people, water, equipment

Portals of exit such as skin, droplets, secretion/excretion

Means of transmission such as airborne, direct contact

Portals of entry such as resp or GI tract, broken skin, mucous membrane

Susceptible host such as a surgery, immunosuppression

How could infection be controlled

Hygiene, sanitation, disinfection, isolation, air flow, wound care, aseptic technique, rapid identification of the organisms.

What cells and molecules are involved in the innate immune response

Macrophages, Neutrophils, Eosinophils, Basophils, NK cells, dendritic cells & complement

Generalise how neutrophils and macrophages kill pathogens

They do this through receptors, pathogens can bind to the receptors known as FC receptors as they recognise the FC region of the antigen.

What is complement

Complement is a series of solvable proteins that can be directly involved in the killing of pathogens

How is complement activated and what does this cause

complement is activated by the antigen-antibody complex or molecules from pathogens. complement activation causes recreuitment of inflammatory cells, opsonisation of pathogens and the killing of pathogens

What do neutrophils do in the innate immune system

They are the first line of defence and most abundant wbc, they are phagocytic and have lots of bacteriostatic and toxic factors to destroy pathogens. They release soluble mediators which talk to other cells to tell them what to do next. They are granulocytes meaning they contain granules, the granules contain cytotoxic enzymes which will kill bacteria, these granules will fuse with phagosome to destroy bacteria.

What do macrophages do in the innate immune system

Macrophages are phagocytes, they reorganise their actin cytoskeleton to engulf and destroy pathogens. they initiate inflammation by secreting molecules eg cytokines and repair tissue and homeostasis. they develop in tissues as when they are in the blood they are monocytes. Macrophages are activated by inflammation and are long lived

Outline how the adaptive immune response is activated & how it works

Pathogens enter the body and activate the adaptive immune response, activated dendritic cells move to the lymphoid organs carrying the pathogen. Activated Dc’s activate the antigen specific CD4 and CD8 T cells. T cells migrate out of the lymph nodes and they migrate to the infected tissue where they help innate cells to kill the pathogen and antibodies aid clearance.

What is the humoral adaptive immune system

antibody mediated attack using B cells. B cells activate the B cell receptors which are also known as ANTIBODIES

What is the cell-mediated adaptive immune system

cellular attack carried out by T cells. T cells activate the T cell receptor

What is the role of MHC in the adaptive immune response & how do they do it

MHC are used to present antigens to T cells, this happens by the T cell receptors recognising the MHC complex.

What is the responsibility of CD4

Helps B cells to make an antibody response

What is the responsibility of CD8

This is a cytotoxic T cell so is responsible for recognising antigen presented cells on MHC I and they can then kill the pathogen

How are T cells activated

• antigen presentation in the context of MHC

• Surfaces molecules costimulation; the essential secondary signals which are behind the T cell receptors which are required for entire activation of T cells

• soluble molecules; release of cytokines as these provide the third signal necessary as it causes cell proliferation.

What is the morphology of a neutrophil

Purple nucleus (basophilic)

Pink and purple granules (neutral)

Multilobed nucleus

What is the morphology of an eosinophil

Purple nucleus (basophilic)

Pink granules (acidophilic)

Bilobed nucleus

What is the morphology of a basophil

Purple Nucleus (basophilic)

Purple granules (basophilic)

Bilobed nucleus

What is the morphology of lymphocytes

Nucleus that takes up majority of the cell

What is the morphology of a monocyte

Kidney bean shaped nucleus

List the symptoms of inflammation and why they may be caused

redness; vasodilation

head; vasodilation and fever

swelling; fluid in the extracellular matrix

loss of function; pain and swelling

State the purpose of the inflammatory response

localise the immune systems attention to the area of infection bringing molecules/cells to repair damage.

What are the benefits of the inflammatory response

It isolates the area so prevents metastasis of the infection

allows molecules and cells which are patrolling the body to know to accumulate at the one place

promotes healing and tissue repair

What is a problem with the inflammatory response

Sometimes the inflammatory response can be too intense and end up causing more harm than good the infection would have resulting in the loss of organ or tissue function

Outline how neutrophils and macrophages detect a pathogen

Both neutrophils and macrophages detect a pathogen using FC receptors, these receptors recognise the Fc region of the antigen which is on the pathogen.

List how neutrophils and macrophages kill pathogens

Acidic conditions in Lysosomes

Toxic oxygen derived products

Toxic nitrogen oxides

Antimicrobial peptides

Enzymes

Competitors

How do T lymphocytes detect pathogen

T lymphocytes detect pathogens using T lymphocyte receptors (TLR). These receptors recognise different pathogen associated molecular structures, and detect a fundamental structure of the pathogen which allows them to process which pathogen has been detected.

How do T lymphocytes kill pathogens

They send a signal to specific cells to tell them to kill the pathogen

Outline the function of basophils

They cause the inflammatory response so an allergic response

Outline the function of neutrophils

To phagocytose bacteria, fungi and foreign debris

What is the function of eosinophils

They destroy parasites

What is the function of monocytes

To clear up damaged cells and faulty cells

What is the function of lymphocytes

These are enhanced when there’s a virus, can produce antibodies, help antibodies or signal to cells to kill others

Where are endotoxins found

They are a part of the cell wall in gram negative bacteria

what do endotoxins do

They cause a strong immune response which can cause a toxic effect such as sepsis

What are superantigens

They defend against the immune system through the non specific activation of T cells, they trick the immune system into causing an immune response.

Outline the mechanism of bacteria

They invade the body through things such as cuts, food, mouth. They then colonise so establish their presence in organs/tissues. They then evade the immune system so hide or evolve to prevent being destroyed. Bacteria release toxins which cause diseases like symptoms in an individual, this causes the inflammatory response in the body to kill the bacteria

What are the structures of bacteria

Spherical - cocci

Rods - Bacilli

Spirals

How can cocci appear

Singular, doublets, chains or clusters

How do bacilli appear

Singular, doublets or chains

How do spirals appear

Singular

List the 3 functions of useful bacteria

They can break down food, absorb nutrients and prevents the growth of harmful bacteria

Outline the steps to the chain of infection

Infectious agent; virus, bacteria, fungi

Reservoirs; water, person, equipment

Portal of exit; excretion, secretion

Transmission; airborne, contact, digestion

Portal of entry; open wound, resp or GI tract

Susceptible host; someone will a immunosuppressant disorder or someone who has undergone surgery

Function of PAMPs and DAMPs

Interact with pattern recognition receptors (PRR) to alert the immune system of danger

Function of chemokines

attract neutrophils

Function of cytokines in general

vascular permeability

Function of complement

Opsonisation of bacteria making them more identifiable for phagocytosis

Attract more phagocytic cells

Directly kill bacteria

Give examples of bacteria and their shape

Methicillin-resistant and staph aureus - gram pos coccus

Clostridium difficile - gram pos bacilli

Pseudomonas aeruginosa - gram neg bacillus

Nisseria meningitidis - gram neg cocci

What is a granzyme

It is a serine protease released by CD8 cells