BM108 - Block C

Pathogen

Organism that can produce a disease, and cause pathogenic effects

CAR-T cells

Genetically engineered T cells that target a specific tumour antigen

Virion size

10-400 nm

Virus core

Genome, either DNA or RNA

Virus caspid

A coat that protects the genome

Virus envelope

Present on some viruses, outermost layer. Contains proteins, carbohydrate, and lipids

Virus life cycle

6 steps: attach, enter by endocytosis, uncoats, replicates, assembles new virions, progeny leaves

Measles

Highly contagious respiratory virus. Starts with cold-like symptoms (after 10 days), rash (14-16), immunity develops (19-23)

Measles viraemia

primary; lymph nodes, secondary (day 4-7); general infection of liver epithelium, monocytes, dendritic cells, lymphocytes, etc.

Measles structure

Paramyxovirus, negative single-stranded RNA virus. ~100nm in diameter

Measles casualties

9/10 protected will not be infected if exposed. Complications affect hearing, throat, pneumonia, diarrhea, seizures, swelling of brain. Can cause coma and death

Bacteria structure

Prokaryotes, unicellular, have no nucleus, large DNA molecule in cytoplasm, size range between 500nm-2uM. Rigid cell wall to define shape (rod, spherical, spiral). Capsule around the cell wall

Pilli

Present on some bacteria and archaea. Hair-like cell-surface appendage required for bacterial conjugation

Flagellum

Long whip-like tail structure that helps tiny cells move. Used for locomotion, sensing changes, and attachment

Extracellular bacteria

Multiply in the host but on surfaces and in cavities. Use virulence mechanisms to evade the immune system. e.g.; staphylococcus aureus

Intracellular bacteria

Invade host cells to multiply. e.g.; salmonella enterica

Mycobacterium tuberculosis

Attacks lung firs pulmonary TB (~2 weeks post infection), intra-macrophage therefore can spread to kidney spine and brain.

M. tuberculosis treatment

antibiotics (rifampicin/isoniazid), 6-9 months treatments, but pb with resistant bacteria, long and expensive

M. tuberculosis prevention

BCG vaccine (~70-80% effective against the most severe TB (meningitis) not pulmonary TB)

Fungi structure

Eukaryotic, 3-15um length, 2-8um diameter. 3 basic cell types; spore, hyphae, yeast.

Fungal infection

Opportunistic environmental, infects endothelial or epithelial cells intracelullarly (induced endocytosis or active).

Mycelium

Spores germinate to produce this - branched hyphae. Produce fruiting bodies that then produce spores

Candidiasis

Candida albicans enters any mucosal surface (gut, lungs). Opportunistic, abundant on skin, part of normal mucosal surfaces — infection occurs in immunosuppressed people

Candida albicans

Exists mainly as yeast as part of a biofilm but can switch between yeast and filamentous forms.

Systemic candidiasis

Life threatening fungal infection of blood stream. Fungus can enter via mucosal surface, untreated has 30-50% mortality.

System candidiasis symptoms

Macronodular skin lesions (10%), candidal endophthalmitis (inflammation of eye, 10-28%), occasionally septic shock (hypotension, tachycardia)

Systemic candidiasis treatment

Antifungal (topical, intravenous, if needed immune system treatment)

Systemic candidiasis prevention

immunity support/lifestyle

Protozoa structure

Eukaryotic organisms between 1um (plasmodium spp) to 30um long (trypanosoma brucei)

Protazoa infection site

Varies; via insects, contaminated food or water, sexually.

Protozoa overview

Intra/extracellylar; can invade (plasmodium) or reside on surface (typanosome). Infection caused when immune system cannot control parasite

Malaria

Intitiated by feeding mosquito. Plasmodium sporozoites migrate to liver replicating merozoites which are released in blood and invade RBCs

Malaria - merozoites stages

Ring, trophozoite, schizont, replicating more merozoites. Small proportion develop into gametocytes

Malaria treatment

Antimalarial medication varies on type of plasmodium infecting

Malaria affected

Major cause of death in tropical and subtropical regions; particularly in sub-Saharan Africa. Most vulnerable; children under 5, pregnant, individuals with HIV/AIDS, travellers

Malaria reduction

due to better prevention; insecticide-treated bed nets, spraying, better diagnostics and treatment

Extracellular parasites

Live outside of host cells, in the body fluids, tissues, and organs. e.g. blood, lymph, reproductive tracts

Extracellular parasite structure

Too big for cells to kill, e.g. tapeworms up to 15m.

Extracellular parasites infection methods

ingestion of larvae (meat-tapeworm), eggs (soil/food - ascaris), skin contact (hookworm), or mosquito bite (filarial worm)

Ascaris affected

576-740 million people, causes anaemia in 10% of cases. Impair the physical and intellectual development of children

Ascaris infection cycle

Ingest eggs from contaminated faeces or food, eggs hatch in intestine, larvae get through intestinal wall and travel via blood to lungs, mature, get coughed and swallowed, returns to growth

Ascariasis symptoms

Diarrhea, blood in poo, passing a worm poo, abdominal pain, nausea, vomiting, weight loss

Ascariasis treatment

Antiparasitic medications (albendazole, mebendazole). Surgical extraction in severe cases

Ascariasis prevention

sanitation

Bacteria generation time

minutes-hours

Two arms of immune response

Innate, and adaptive

innate immunity

first responders, no lasting immunity, not specific

Adaptive immunity

Developed during a lifetime, immunological memory, very specific

Body surface

Initial line of defense, few microorganisms can penetrate an intact barrier.

Mucus - innate immunity

Sticky to trap invaders, but also has microbial properties

Skin glands - innate immunity

Secrete antimicrobial molecules such as mild acids and enzymes

stomach acid - innate immunity

destroys invaders

Subtypes of innate immune cells

Granulocytes, and monocytes

Phagocytic

Majority of innate immune cells

Phagocytosis

Process of engulfing and destroying pathogens by endocytosis

Neutrophil

Phagocytose and kill bacteria; mediate inflammation. Normally the first cell to arrive. Granulocyte

Monocyte

Develops into macrophages and some cases dendritic cells. Monocyte

Macrophage

Phagocytose microbies; mediate inflammation; present antigens to adaptive immune cells (T cells). monocyte

Dendritic cells

Properties like macrophages. Main antigen presenting cell

Basophil

enters tissue at site of injury and secretes heparin and histamine. granulocyte

Eosinophil

Phagocytose and release chemicals that will kill parasites. Participate in allergic responses. granulocytes

Mast cells

Secretes histamine in inflammatory response; participate in allergic response

NK Cells

attack general features cancerous and virus infected cells. also part of specific immunity

Inflammation

Innate local response to infection or injury. Allows the elimination of foreign invaders, clears the area of dead cells and prepares for tissue repair.

key cells in inflammation

Phagocytes including; neutrophils, macrophages, dendritic cells, and mast cells. Induced and regulation by cytokines

Pathogen Associated Molecular Patterns PAMPs

Recognition of features common to many types of pathogens

Toll Like Receptors TLRs

Accomplish recognition of PAMPs, on membranes of immune cells e.g. macrophages and dendritic cells

CD4 T cells

Assist in activating cells, part of cell-mediated immunity

Cytotoxic CD8 T cells

Directly kill infected cells, part of cell-mediated immunity

B cells

Mature into plasma cells, part of humoral immunity

Plasma cells

Matured B cells. Secrete antibodies, part of humoral immunity

NK Cells (Adaptive)

Similar to T cells but also perform non-specific actions

Lymphocytes

CD4 T cells, Cytotoxic CD8 T cells, B cell, Plasma cell, NK cells

Lymphatic system

Network of lymphatic vessels and lymphoid organs with circulating lymphocytes

Primary lymphatic organs

Where B and T cells mature

where B cells mature

Bone marrow

where T cells mature

Thymus

Secondary lymphatic organs

Where lymphocytes activate and replicate

MHC - Major Histocompatibility Complex

Cellular “identify tags”, genetic markers of self

MHC II

Found only on antigen presenting cells (APCs) such as macrophages, B cells, and dendritic cells. CD4 on helper T cells bind here

MHC I

Found on all cells in the body except erythrocytes. CD8 on cytotoxic T cells bind here.

Th activation

Microbes phagocytosed are digested into fragments. MHC complex is transported to cell surface to bind to Th cells with CD4 protein helping link

Following Th activation

Binds to macrophage that has engulfed the same type of virus, then binds to cytotoxic T cells. can then secrete cytokines that stimulate other Th cells

Tc cells (cytotoxic T cells)

Bind to virus infected cells and release proteases and perforin which forms channels within the infected cell. This causes the cell to take in water and burst

B cells

Activated by antigens and Th cells, they proliferate into plasma cells that make antibodies. Major defense against bacteria and toxins

Antibody structure

Composed of two heavy chains and two light chains with a variable region that differs, and a constant region that remains the same for each class

Clonal selection

Antigen binds to B cells displaying a type of Ig. This binding stimulates only this specific B cell to divide, resulting in the clones to express the same receptor

Antibody function

Opsonisation (marks pathogen for phagocytosis), forms complexes destroyed by phagocytes, blocks binding sites so viruses cannot invade

memory cells

T and B cells that persist awaiting future infection by the same pathogen

Bacterial pathogens (examples)

legionella, salmonella, yersinia pestis (black plague), clostridium (tetanus), streptococcus, m. tuberculosis

Viral pathogens (example)

Coronavirus, ebola virus, influenza, norovirus, zika virus, HIV

Fungal pathogens

1.5. million fungi species, but only about 300 cause human illness. Rarely fatal, often opportunistic

Parasitic pathogens

Different sizes, can be unicellular or multicellular. Have different life cycles/stages

Parasitic pathogens - multicellular examples

Toxoplasma - causes cysts in the brain, malaria - causes schizonts in the liver

Parasitic pathogens - multicellular organism examples

hookworm, tapeworm

Complement system

innate immunity, can be brought into action during adaptive. Kills microbes without phagocytosis. Attacks the membrane by creating pores in the pathogen (MAC). Cells swell and burst

Cytokine signalling

Different types of small proteins produced by a variety of cells. acts on cells which have a specific receptor. Produced by most immune cells controlling growth. Can act on more than one cell

Interferon signalling

Secreted by (mainly) host cells that inhibit viral replication inside host cells. Not specific. There are three types (alpha, beta, gamma)

Apoptosis

programmed cell death (no inflammation)

Antibodies role

Prevents virus from uncoating, transcribing it’s genome. Stops pathogen from attaching to it’s specific receptor to enter host cells. Stops essential function of pathogen