Immune System PDF

Immune System -​ Evolution is linked to endosymbiosis -​ Eukaryotes, multi-celled organisms, animals -​ A vital system -​ Highly complex -​ Understanding of this system has led to real benefits for mankind e.g. vaccines Intro -​ We have external defenses e.g. skin -...

Immune System -​ Evolution is linked to endosymbiosis -​ Eukaryotes, multi-celled organisms, animals -​ A vital system -​ Highly complex -​ Understanding of this system has led to real benefits for mankind e.g. vaccines Intro -​ We have external defenses e.g. skin -​ Innate immune system, i.e. what we are born with, antibodies from mother’s breatmilk etc -​ The Adaptive/ Acquired Immune Response, acquired through contact with pathogens -​ The Inflammatory Response -​ Cells and soluble factors e.g. secreted by cells -​ The primary function of the immune response is to find and destroy invading infectious agents e.g. viruses, bacteria, protistans (protista/protozoa) worms etc and reduce to a minimum the damage they cause -​ Immune system involves recognising the invader and mounting a reaction against it to eliminate it Infectious Agents -​ Mostly microbes such as viruses and bacteria but also worms fleas live and ticks which vector many microparasites -​ All can cause damage to the host and some can and do kill -​ Viruses include influenza, HIV, COVID-19 measles and mumps -​ Bacteria include typhoid, cholera, MRSA, E. coli, bubonic plague, lyme disease -​ Protozoa include malaria, sleeping sickness, red water fever -​ Worms include liver fluke, tapeworm and roundworms -​ All viruses and many bacteria and protozoa only replicate inside cells i.e. are intracellular parasites or pathogens. The “cell is a safe place to be, if you are a pathogen”- plasma membrane is impenetrable to soluble factors (antibodies) -​ For the immune system to confront and eliminate these infectious agents, it must recognise and destroy these infected cells (collateral damage) -​ But other bacteria, some protozoa and larger parasites like worms live in extracellular spaces, body fluids and tissues so a different type of immune response is necessary to deal with these -​ Intracellular pathogens have to leave cell to infer another and have to move through blood and tissue fluid so is confronted by the same immune response as just stated External Defences -​ Most important -​ The skin is impenetrable barrier to pathogens -​ Very tight gap junctions between cells -​ Inflammatory response -​ Pathogens cause inflammation -​ Three components ➔​ Increased blood supply to the infected area ➔​ Increased permeability of capillaries allowing escape of larger molecules and cells ➔​ Migration of leukocytes (i.e. white blood cells) out of venules into surrounding tissues ➔​ Leukocytes are mostly neutrophils but later monocytes and lymphocytes Innate Immunity -​ Natural or native immunityÍn place before infection occurs -​ Its poised and ready for rapid response -​ Physical barriers, cellular and soluble factors -​ Reacts to infectious agents (e.g. microbes) -​ Non-specific and without a memory -​ Myeloid line (lineage including monocytes/platelets) -​ Cells are phagocytes -​ Polymorphonuclear granulocytes are white blood cells which include ➔​ Neutrophils, Eosinophils ➔​ Mast cells and Basophils (allergic responses) ➔​ Monocytes, macrophages, dendritic cells (all antigen presenting cells (APC)) breakdown and present the infectious agent to Adaptive response ➔​ APC are involved in both the innate and adaptive immune responses ➔​ Macrophages have a key role for APC -​ Pluripotent hematopoietic stem cells differentiate into bone marrow as myeloid or lymphoid stem cells Innate Immunity: Soluble Factors -​ Proteins and peptides -​ Complement 30 proteins -​ Lytic, opsonins, chemotactic -​ Interferons -​ Protect cells against invasion by viruses -​ Other proteins include cytokines and chemokines -​ Complement proteins attack bacteria through lysis which is the disintegration of bacteria -​ They activate phagocytes through chemotaxis -​ They use opsonisation on bacteria which tags them and draws phagocytes on them to be engulfed Opsonisation -​ An opsonin is a macromolecule that becomes attached to the surface of a microbe and can be recognised by surface receptors of neutrophils and macrophages and increases the efficiency of phagocytosis -​ Opsonisation is the process of attaching opsonins such as igg or complement fragments to microbial surfaces to target the microbes for phagocytes -​ Adaptive Immune Response -​ Very specific response with memory -​ Triggered into action by antigen presentation (APC) -​ Antigen + epitope (part of antigen recognised by immune system) i.e. active part -​ Antibody -​ MHC 1 and MCH 2 -​ Vaccine -​ Herd immunity -​ Novel (emerging) pathogen + zoonosis (diseases which can pass from human to animal or vice versa) Myeloid Cells -​ Give rise to red blood cells, granulocytes, monocytes and platelets whereas lymphoid cells give rise to lymphocytes and natural killer cells -​ The pluripotent stem cell in bone marrow called the lymphoid line which creates T cells and B cells -​ T cells mature in the thymus gland and organises adaptive response and cellular response -​ B cells mature in the bone marrow are a re a humoral response -​ Humoral response (HR): An antibody-mediated response that occurs when foreign material (antigens) are detected in the body Definitions Antigen -​ A molecule that reacts with preformed antibodies at the specific receptors on T and B cells. Most are proteins. They are intrinsic and extrinsic Epitope -​ That portion of the antigen which combines with the antibody Antibody -​ A soluble molecule produced by animals in response to antigens -​ It has the particular property of combining specifically with the antigen that induced its formation (known as the antibody-antigen complex) -​ Humoral response -​ Proteins -​ Immunogammaglobulin (Ig) -​ 5 classes MHC -​ Major Histocompatibility Complex -​ Term arose in relation to the ability to accept tissue grafts from an unrelated donor aka tissue typing -​ Same haplotype (at least 100 genes involved) if tissue to be accepted -​ MHC 1 expressed with intrinsic antigens whereas MHC 2 is expressed with extrinsic antigen -​ MHC 1 is associated with cellular response -​ MHC 2 is associated with humoral (soluble factor) response -​ Antigens presented with MHC 1 or 2 Adaptive Response: Cells -​ Lymphocytes derived from lymphoid line (the myeloid line is for the innate immune) -​ T and B cells -​ T receives “identity” in thymus -​ B receives “identity” in bone marrow -​ T helper cell organises both cellular (cytotoxic lymphocytes) and humoral response, the latter via B cells T- Cells -​ Thymus derived -​ Two basic types -​ T helper cells (Th) cells CD4+ marker -​ T cytolytic or T cytotoxic cells (Tc) CTL’s CD8+ marker -​ T helper cell master of adaptive response (but attacked by Human Immunodeficiency Virus (HIV)) B-cells -​ Produce in the bone marrow where they mature -​ Produce humoral response -​ Plasma cells (effector cells) and memory cells -​ Plasma cells produce antibodies -​ Short life span apoptosis (programmed cell death) -​ Memory cells survive for a long time as part of clone Soluble-Factors: Antibody -​ Flexible adaptor -​ Y shaped -​ Two inner heavy chains and two outer light chains -​ Hypervariable “hot spots” VH (heavy chain) and VL (light chain) -​ FAB receptor binds to antigen -​ Constant regions -​ FC receptor recognised by and phagocytosed neutrophils and macrophages -​ Types of antibodies ➔​ IgG monomer (1) classical Y shape; main antibody in secondary immune response ➔​ IgM pentamer (5); primary immune response against blood inhabiting extrinsic microbes ➔​ IgA dimer (2); secondary immune response opsoniser ➔​ IgD monomer (1); function poorly understood ➔​ IgE monomer (1); associated with the allergic response Snake Anti-Venoms -​ Venom 95% protein- polypeptide -​ Antivenom is antibodies (immunoglobulins raised in horses against antigenic venom) -​ Passive immunity (serum containing the raised antibodies inoculated into snake bite victim -​ Some antivenoms are polyvalent and will neutralise toxic venoms of several species -​ Others are monovalent and only neutralise venom of one species -​ However body has no memory following recovery Other aspects of immunity -​ Vaccine -​ Herd immunity -​ Epidemiology -​ SIR models -​ “Chain reaction-type transmission” -​ Novel pathogen -​ R zero -​ Allergy Vaccine -​ First developed by edward jenner- published 1798 -​ Cowpox recovery protected against smallpox -​ Gave cowpox and showed protected against smallpox -​ Latin vaccinus “from the cows” -​ Vaccines are a preparation of microbial antigen (dead or alive or avirulent) -​ Administered to patient to give protection against that microbe -​ Louis Pastuer: rabies, cholera -​ Jonas Salk: 1950/60s polio Epidemics -​ Prevalence -​ Burden Intensity -​ Epidemic ➔​ Sudden increase in prevalence (% of population infected) ➔​ Severity related to Lethality, herd immunity, numbers and density of susceptible hosts -​ Pandemic ➔​ Epidemic occurring over a very wide area, crossing international boundaries i.e. on a continental, hemispheric or global scale  -​ Endemic ➔​ The constant presence of a disease within a specified geographical area (low prevalence) -​ Hyperendemic ➔​ Constant disease presence but at very high prevalence and in all age groups -​ Susceptible host Transmission -​ R zero (reproductive rate) -​ Herd immunity -​ Lethality -​ Bio-warfare -​ Vector borne (very high R zero) -​ Sylvatic cycles -​ Rural, domestic and urban cycles Novel Pathogen -​ Pathogen entering a population-community which has no herd immunity i.e. adaptive immunity to that specific pathogen (huge concern) -​ May arise through accidental importation -​ Mutation producing new strain e.g. influenza ➔​ Spanish flu 1918 ➔​ Wuhan COVID-19 ➔​ West Nile Fever virus USA 1999 R zero of pathogen -​ Measles 5 to 18 -​ Influenza 2 to 4 -​ Covid-19 4 to 8 -​ Chicken pox 7 to 11 -​ Mumps 11 to 14 -​ Polio 5 to 7 -​ HIV 2 to 5 homosexual -​ HIV 10 to 11 heterosexual Lethality -​ Mortality not morbidity -​ % of death Zoonoses -​ Emerging infectious diseases EIDs e.g. COVID-19 -​ Sylvatic/ Silent foci -​ Animal diseases which can transfer to humans or vice versa -​ Micro or macro parasites transmissible between a vertebrate animal to man -​ Micro e.g. influenza, rabies, HIV, Bubonic Plague, Sars 1 and 2, Lymes, COVID -​ Macro e.g. liver fluke, trichinosis, anisakiasis, beef tapeworm