lecture 13, immune system I

functions of the immune system

1. recognition and elimination of abnormal self-cells (have to know who is who

   • cancer cells, virally infected cells (develop all the time but the immune system is always watching)

2. removal of dead/ damaged cells (lots of turn over)

   • worn red blood cells

3. protection against disease causing pathogens (something capable of causing disease)

   • bacteria, parasites, viruses

problems encountered by the immune system include

1. autoimmunity (target something that was good)

   • failure to discriminate between self and non-self

   • MS, rheumatic fever (MS, attribute of autoimmunity, destroy myelin of axon)

2. allergy

   • hyper-responsiveness

   • peanuts, pollen

3. immunodeficiency (if don’t have immune system increase risk of infection)

pathogens

• can cause infection and disease when they invade surfaces/internal environment of the body

pathogens can be

1. bacteria

2. eukaryotes

3. viruses

bacetria

• prokaryotic cell structure

• cell wall made from peptidoglycan → thick sugar layer (thick in gram neg, thin in gram pos)

  • important target for penicillin, lysozyme

• capsule (sticky) may or may not be present external to cell wall

  • contributes to disease

• temperature, pH, nutrient requirements

• mainly free living

• unicellular

eukaryotes

• parasites, fungi

• similar cell structure to human cells

• bigger

viruses

• obligate intracellular parasites (you have what they love)

• require host cell machinery for replication

• create abnormal cells that must carefully destroyed (because are killing you)

• can occasionally be treated with antivirals (can never completely get rid off, not curing just limits replication)

  • HIV, herpes, influenza

• may also be oncogenic (DNA affecting, cancer)

• last for long

• don’t live independently

pathogens - bacteria vs viruses

branches of the immune system

1. the innate immune system

2. the adaptive immune system

the innate immune system

• present at birth

• non-specific(doesn’t change, doesn’t learn, doesn’t develop)

  • activated in response to pathogen associated molecular patterns (PAMPS) ex. recognize a human via hair

• NO MEMORY COMPONENT

• activates almost immediately in response to foreign organisms (even if not infected yet)

• includes physical, chemical, cellular, and molecular components

• needs to get one guy but causes destruction to everything in the background

the adaptive immune system

• highly specific (only time you accidentally target a wrong one is if they‘re identical)

• memory component → activates quickly

• develops over time based on exposure to antigens

  • naturally or via vaccination (not born with it, no memory, if they have to develop it)

• includes

  i. humoral immunity

  ii. cell mediated immunity

the immune system must be able to

1. detect/identify foreign substances

2. communicate with other immune cells (you call and let them know what you found so they can send the right team)

   • recruit other immune cells

3. coordinate all players of the immune response with one another

4. destroys/suppress the invader

• immune cells signal via cytokines (find cells on a target cell)

  • proteins released from an immune cell

  • go on to act on other immune cells that carry the necessary receptor

immunogens

• are materials that stimulate an immune response (can be you sometimes, sometimes target something good because it looks bad)

  • antigens are the segments of the immunogen that specifically interact with elements of the immune system (have many antigens as foreign material → some things are better)

    • epitopes specifically bind to antibodies

      • immune system proteins

      • what your actually binding to an antigen of foreign body

anatomy of the immune system

• consists of

  • lymphoid tissues

  • leukocytes (key players)

lymhpoid tissue

• a. primary tissues

  • thymus (T lymphocyte maturation) and bone marrow (make all blood cells, B lymphocyte maturation)

  • site of leukocyte production and maturation

• b. secondary tissue

  • location of immune cell interaction with pathogens

  • triggers a response

    • spleen (filters blood)

      • monitors blood for pathogens

      • destroys worn red blood cells

    • lymph nodes

      • form a component of the lymphatic system (blind ended, one way away from tissue)

      • large amount of filtered fluid enters each day

lymph nodes

• filters fluid enters into lymphatic capillaries

• passes though lymph nodes en route to the heart

• lymphocytes are aggregated in the lymph node (a lot in there)

  • activate in response to antigens in lymphatic fluid

    • eliminate spread to other parts of the body (contain the spread, try to keep local)

• tonsil and gut associated lymphoid tissue (GALT) forms aggregates of lymphatic tissue

  • function in immune system surveillance

leukocytes

• form important components of both the innate and adaptive immune response

• 700 MBC/uL of blood

• very large cells

• two classes

  1. granulocytes

  2. agranulocytes

granulocytes

• prominent of cytoplasmic granules (easy to see)

• include

  • basophils

    • mast cells when in tissues (histamine containing)

  • eosinophils (parasitic defense)

  • neutrophils

    • most numerous leukocytes

  • **all three types are capable of degranulation (comes out and is functional)

arganulocytes

• monocytes (like a baby, stay at home no job)

  • marcophages once mature in tissue (move out and have profession

• lymphocytes

  • T lymphocytes (bone marrow and mature in thymus)

  • B lymphocytes (bone marrow and mature in bone marrow)

  • natural killer cells (kill cancer cells etc.)

  • dendritic (vaccinate you, bring foreign material to lymphocyte and tell them to develop memory)

three functional classifications of leukocytes

1. phagocytes (and vomit out destroyed fragments)

   • neutrophils

   • monocytes and macrophages

   • **engulf foreign material

2. cytotoxic cells

   • eosinophils (destroy parasites)

   • cytotoxic T cells (adaptive, release enzymes that poke holes)

   • destroy foreign and abnormal self cells

3. antigens presenting cells (APCs)

   • B cells (phagocytose but save destroyed fragments and put on display)

   • dendritic cells

   • macrophages and monocytes

   • present antigehns to other immune cells

basophils

• contain histamine, heparin, cytokines

• mast cells are their tissue counterpart

esoinophils

• allergy and parasitic infections

• attach to large parasites

  • secrete extracellular enzymes

neutrophils

• short lived

• highly phagocytic

• most abundant

• increase dramatically

• produce many chemical mediators → important to talk to each other)

• able to migrate into tissues during infection (because if changes that happen)

• multiply quickly

• always the highest → get higher when find something

macrophages

• phagocytic

• man the tissues → in alveoli

• able to destroy larger materials than neutrophils

• antigen presenting cells

lymphocytes

• mainly concentrated in lymphoid tissues

• important mediators of the adaptive immune response

• include: T lymphocyte, B lymphocyte and NK

dendritic cells

• located in skin and organs

• contain long fingerlike projections

• capture antigen and migrate to secondary lymphoid tissues to present antigen to lymphocytes

the innate immune system takes over when

• takes over when physical and chemical defenses fail

  • able to either clear or contain the infection (keep it local, blood clotting)

  • non-specifically recognizes a broad range of materials as foreign

physical barriers

1. skin

2. mucos membrane

3. fluid flow

skin

• the outer surface consists of dead cells and protective protein called keratin

• the layers of the skin are frequent shed which removed microbes

• skin is very dry which inhibits microbial growth

  • skin infections are more common on moist areas of the skin or in moist environments

  • the outer layer of the skin is an excellent defense and is rarely penetrated by microbes (difficult to break)

  • most infections occur under the skin once the skin has been broken although fungi can sometimes grown on the skin’s surface: eating dead skin cells (treat with topical cream)

  • some microbes are able to eat dead skin cells and oils that are secreted by the skin

  • if this happens body odor occurs

• connected via tight junctions

mucous membranes

• these membranes are involved in fluid exchange

• they offer less protection than the skin

• mucous membranes line ‘tracts’ such as the digestive, reproductive and respiratory tracts

• they secrete mucous which is a glycoprotein that keeps the membrane from dying and cracking

  • the mucous traps microbes

  • cilia than moves the mucous containing microbes away

  • mucociliary escalator (bring up and stimulate cough to try and remove)

• open to outside

• always dirty

fluid flow

• saliva, tears, urine, and vaginal secretions move microbes away/out of the body

• purge

chemical barriers

1. acidity of body fluids and the skin

2. lysozyme

3. the normal microflora

acidity of fluids and skin

• stomach: hydrochloric acid (parietal cells) creates a pH of 2

  • this low pH destroys many bacteria and toxins

• skin: fatty acids and lactic acid create a pH of 3-5

  • these conditions prevent the growth of many microbes

lysozyme

• an enzyme that degrades peptidoglycan (found in bacterial cell walls)

• lysozyme is found in sweat, tears, salvia and nasal secretions

the normal microflora

• this is acquired shortly after birth

• it functions to prevent the growth of pathogens

  • this occurs because of competitive exclusion and microbial antagonism (meant to poison competitors)

• compete for seats

phagocytosis

• during infection monocytes and granulocytes migrate to the infected area through capillary pores

  • recruits more immune cells by producing cytokines

• there are four main phases

  1. chemotaxis

     • phagocytes are attracted to foreign particles, damaged cells etc.

     • have to be aware

     • get rid of foreign invaders

  2. adherence

     • phagocyte attached to a foreign pathogen associated molecular pattern

       • attaches with pattern recognition receptor

         • needs to be recognized

         • needs to be on receptor on cell

  3. ingestion

     • pseudopods extend and engulf the particle (forms endosome → phagosome)

       • encapsulated bacteria, cell fragments, foreign debris

     • the particle is trapped in the phagosome

  4. digestion

     • digestive enzyme, oxidizing agents enter the phagosome due to fusion with lysosome

some pathogens/viral particles can be

• opsonized increasing the efficiency of phagocytosis

  • easier to find

  • attach something to outside of foreign particle so immune cells can find it and destroy it

• encapsulated bacteria cannot be phagocytosed by traditional means

  • requires antibodies from the adaptive immune response

  • lower chance, can’t actually grab it, sugar block binding sites

inflammation

• sign and symptoms include:

  • pain, erythema (redness and vasodilation), heat, edema (increase vascular permeability), and loss of function

• inflammation functions to destroy an bacteria/foreign material

• it also acts to prevent the spreading of an injurious agents (maintain localization)

• it repairs and replaces damage tissue (heal and put back epidermal layer, scar tissue)

• proteins produced during the acute phase shortly after the injury occurs

  • increases plasma protein from the liver (liver responsible for protein synthesis of the liver)

    • C-reactive protein

      • opsonization (once of your own proteins coat the structure, easier for immune)

    • anti-proteases

      • protect tissue

      • minimize harm to innocent tissues in the background

      • levels of inflammatory protein should decrease as infection goes on

chronic inflammation

• diseases such as rheumatoid arthritis see chronically elevated levels (increase inflammatory proteins but WBC count is normal because there is no infection)

stages of inflammation

1. tissue damage

2. vasodilation

   • the blood vessel dilates

   • more blood reaches the affected area

   • this allows white blood cells to access the area

   • brings nutrients for faster healing

   • this is causes redness, swelling (edema), increased temperature and pain

   • the pain is also due to tissue damage

   • this allows fibrinogen clot formation (soluble proteins present in plasma now)

     • this segregates the affected area

     • prevents the spread of infection → blood clotting)

     • fibrin → insoluble mesh to plug the leakage, start clot formation

3. phagocytosis

   • phagocytes destroy invading microbes

4. tissue repair

   • new cells are produced

fever

• an increase in body temperature

• fever is controlled by the hypothalamus (homeostasis) in the brain (muscle contractions produce heat)

• it is triggered by toxins, LPS, and chemical produced by the immune system

  • all of these things reset the bodies thermostat

• fever results in

  • muscle contraction (shivering)

  • faster phagocytosis (due to increased temperature)

  • slows the growth of heat limited microbes (off set their sweet spot)

    • ex. E. coli prefers to grow at 37°C, growth slows at 40°C

  • up to certain temperature, fever is a defense against disease

    • but a fever is defense above 43°C can cause death (we are plasma membrane)

NK cells

• recognize virally infected cells

  • activate way faster than adaptive immune cells (turn on quickly)

    • cytotoxic T lymphocytes (counter-part)

  • force the infected cell to complete apoptosis (force to die)

  • able to attack cells displaying tumor antigens (hopefully squash it early)

  • produce interferons (antiviral chemical)

    • promote antiviral activity (cause healthy cells to up their antiviral defenses, hear first alarms)

    • IFNa and INFb: work on host cells to up their antiviral response

    • IFNy activated macrophages (phagocytic cells) and other immune cells

molecular defenses

• histamine

• interleukin I (IL-I)

• bradykinin

• the complement system

• transferins

histamine

• produced by mast cells and basophils

• degranulation helps to initiate the inflammatory response (release or spit out histamine to ecf)

• recruits more leukocytes

  • clean up mess

• causes vasodilation (Increase flow, decrease P) and increased vascular permeability (systemic, decrease MAP - hard to keep organs)

  • promotes the escape of plasma proteins into the tissue

    • leads to edema and other symptoms of inflammation

• involved in the anaphylactic response

• mast cells stationed in mucosal membranes can degranulate in response to respiratory/digestive irritants (local entry points)

• antihistamines block the effect of histamine

interleukin I (IL-I)

• affects endothelium of capillary (increase gap size, becomes leakier, WBC can leave faster)

  • more hospitable to movement of WBCs and proteins

• stimulates the production of acute phase protein production in the liver

• works on the hypothalamus to induce fever

  • pyrogen

bradykinin

• produced via a cascade reaction → have one thing lead to another to get this

• increased vasodilation

• increased pain

the complement system

• composed of ∼30 proteins that circulate in the blood

• they work together as a cascade

  • the action of one protein triggers the action of the next

• complement can be triggered by surface molecules of invading microbes

  • ex. lipopolysaccharide (LPS)

    • factor on certain bacterial cells

the result of the complement cascade

1. opsonization → coating

   • C proteins attach to microbes and act as a flag to attract phagocyte

     • this increases phagocytosis by 1000x

   • activated compliment protein stuck on bacteria → light on your head

2. enhance inflammation

   • increases blood vessel permeability

   • attracts phagocytes to the infection site

   • all of this is better when under c-system because it is trusted

3. cytolysis

   • formation of the membrane attack complex (MAC) form a pore and inset into wall, enter and exit

   • this pokes holes in the bacterial cell membrane ‘

     • split the cell because of this

     • cell is done

transferins

• iron binding proteins in blood, milk, saliva, and tears (bacteria is unicellular and doesn’t have Hb for iron to bind to but it needs iron for ETC, they compete for iron)

• binds and sequesters iron so that it cannot be used by bacteria

• slows bacterial growth