L26- Immune System in Action

what is innate immunity

first line of defence, non-specific e.g. PRR (TLRs, NODs)

what mechanisms are used in innate immunity

• barriers

• cells (macrophages, neutrophils, NK, DC)

• molecules (enzymes, peptides, C-)

what is adaptive/ acquired/specific immunity

• develops later

• highly specific

• BCR/TCR

• memory (stage 2)

what mechanisms are used in adaptive/acquired/specific immunity

B cells: release antibodies

what is interactive immunity

antibodies: mechanisms 1-7

what mechanisms are used in interactive immunity

T cells: activation of nearly all other cells via cytokine secretion

• e.g. macrophages, B cells

what process occurs during local infection- penetration of the epithelium

DC is activated by the PRR

what process occurs during lymphatic spread

• DC presents captured Ag on MHC class II to CD4+ T cells

• activated T cell subsets exit lymph node

what process occurs during adaptive immunity

pathogen specific T cell subunits return to original site of pathogen

how does protection against infection occur as an innate immune response to local infection- penetration of the epithelium

wound healing induced antimicrobial proteins and peptides, phagocytes and complement destroy invading microorganisms

how does protection against infection occur as an innate immune response to local infection of tissues

• complement activation

• dendritic cells migrate to lymph nodes

• phagocyte action

• NK cells activated

• cytokines and chemokines produced

how does protection against infection occur as an adaptive immune response to lymphatic spread

• pathogens are trapped and phagocytosed in lymphatic tissue

• adaptive immunity initiated by migrating dendritic cells

how does protection against infection occur as an adaptive immune response to adaptive immunity

infection is cleared by:

• a specific antibody

• T-cell-dependent macrophage activation and cytotoxic T cells

what are the extracellular sites of infection

• interstitial spaces, blood, lymph

• epithelial surfaces

what are the organisms involved in extracellular sites of immune response involving interstitial spaces, blood and lymph

• viruses

• bacteria

• protozoa

• fungi

• worms

what are the organisms involved in extracellular sites of immune response involving epithelial surfaces

• neisseria gonorrhoeae

• streptococcus pneumoniae

• vibrio cholerae

• helicobacter pylori

• candida albicans

• worms

describe the protective immunity of extracellular sites such as interstitial spaces, blood and lymph

• complement

• phagocytosis

• antibodies

describe the protective immunity of extracellular sites such as epithelial surfaces

• antimicrobial peptides

• antibodies especially IgA

what are the intracellular sites of infection

• cytoplasmic

• vesicular

what are the organisms involved in intracellular sites of immune response involving cytoplasmic sites

viruses

• chlamydia spp.

• rickettsia spp

  protozoa

what are the organisms involved in intracellular sites of immune response involving vesicular sites

• mycobacterium spp.

• yersinia pestis

• legionella pneumophila

• cryptococcus neoformans

• leishmania spp.

describe the protective immunity of intercellular cytoplasmic sites

• NK cells

• cytotoxic T cells

describe the protective immunity of intercellular vesicular sites

T-cell and NK-cell dependent macrophage activation

what can symptoms of infectious disease be caused by (pathogenicity)

• direct effects of pathogens

• indirectly, by immune responses

what are the direct mechanisms of tissue damage

infectious agent damages host

• endotoxin production (cholera)

• endotoxin (gram-ve sepsis)

• direct cytopathic effect (smallpox)

what are the indirect mechanisms of tissue damage

immune system damages host

• immune complexes (kidney disease)

• anti-host antibody (rheumatic fever)

• cell-mediated immunity (tuberculosis)

give examples of the immune response

• infectious agent

• immunodeficiency

• immunopathology

• hypersensitivity (allergy, autoimmunity)

describe leprosy as an example of an infectious agent

• 2016 had 173,358 cases

• Mycobacterium leprae

• intracellular bacteria

• granulomatous lesions

• nasal droplets? armadillos?

• 2 main clinical forms- tuberculoid and lepromatous

describe tuberculoid leprosy

• organisms present at low to undetectable levels

• low infectivity

• granulomas and local inflammation (peripheral nerve damage)

• normal serum immunoglobulin levels

• normal T-cell responsiveness

• specific response to M.leprae antigens

describe lepromatous leprosy

• organisms show florid growth in macrophages

• high infectivity

• disseminated infection, bone, cartilage and diffuse nerve damage

• hypergammaglobulinemia

• low or absent T-cell responsiveness, no response to M.leprae antigens

what cytokines are more active in lepromatous leprosy than tuberculoid

TH2 cytokines

what cytokines are more active in tuberculoid leprosy than lepromatous

TH1 cytokines

describe immunodeficiency

• decreased ability to fight infection

• primary or secondary

• mechanism affected determines susceptibility

• certain cancers are also linked with immunodeficiencies

• HHV8 in HIV patients

describe primary immunodeficiency

• intrinsic defect in the immune system

• genetic

• most conditions are rare

• can be dominant or recessive, autosomal or X-linked

  • gene defect may or may not be identified

describe secondary immunodeficiency

• immune system is initially intact

• a consequence of another condition

what are the causes of secondary immunodeficiency

• malnutrition

• lymphoproliferative disease

• immunosuppressive or cytotoxic drugs

• infection (e.g. measles, HIV)

• stress

what is the functional consequence of severe combined immunodeficiency

no T or B cell

what is the functional consequence of X-linked agamma-globulinaemia

no B cells or antibodies

what is the functional consequence of NK cell defect

no functional NK cells

what is the functional consequence of IgA deficiency

no IgA synthesis

what is the functional consequence of MHC class I deficiency

no CD8 T cells

what is the susceptibility of severe combined immunodeficiency

general

what is the susceptibility of X-linked agamma-globulinaemia

extracellular bacteria, viruses

what is the susceptibility of NK cell defect

herpes viruses

what is the susceptibility of IgA deficiency

respiratory infection

what is the susceptibility of MHC class I deficiency

viruses

describe immunopathology

• immune responses can cause problems for the host (excessive, inappropriate or ineffective

  • different immune mechanisms involved

what does immunopathology occur in

• infection

• allergy

• autoimmune disease

describe hypersensitivity reactions

type I-IV responses

what are type I-III hypersensitivity reaction

antibody mediated

what are type IV hypersensitivity reactions

cell mediated (delayed type)

what is type I hypersensitivity

IgE, Allergy

• mast-cell activation and granule release

• anaphylaxis - IgE, Fc receptors on mast cells and basophils

what is type II sensitivity

IgG and IgM mediated destruction

give an example of type II sensitivity

erythroblastosis fetalis (RBC destruction)

give examples of autoimmunity

• SLE

• diabetes

give an example of type III sensitivity : autoantibodies

systemic lupus erythematosus (SLE)

• immune complexes deposited at susceptible sites

what are symptoms of systemic lupus erythematosis

• glomerulonephritis

• rash

• arthritis

give an example of type IV sensitivity

type I diabetes

• immune attack on insulin- producing beta cells in the pancreas

• over reactive effector T cells

descrive type IV sensitivity in type I diabetes

• an effector T cell recognises peptides from a beta-cell specific protein and kills the beta cell

• glucagon and somatostatin are still produced by the alpha and theta cells, but no insulin can be made

what causes autoimmune diseases

• loss of self tolerance

• increasing frequencies in western cultures

• more common in females (sex hormones)

• e.g. type I diabetes, SLE, rheumatoid arthritis

what is the disease mechanism for rheumatoid arthritis

autoreactive T cells and autoantibodies against antigens localised to joint synovium

what is the disease mechanism for systemic lupus erythematosus

autoantibodies and autoreactive T cells against DNA, chromatin proteins and ubiquitous ribonucleoprotein antigens

what is the disease mechanism for crohn’s disease

autoreactive T cells against intestinal flora antigens

what is the disease mechanism for multiple sclerosis

autoreactive T cells against brain and spinal chord antigens

what is the disease mechanism for type 1 diabetes

autoreactive T cells against pancreatic islet cell antigens

what is the consequence of multiple sclerosis

formation of sclerotic plaques in the brain and spinal chord with destruction of myelin sheaths surrounding nerve cell axons, leading to muscle weakness and ataxia

describe the use of vaccines as a way to activate the immune system

• tumour specific antigens may provide targets for vaccination (melanoma, breast cancer)

• vaccines against papilloma virus for prevention of cervical cancer

• injection of BCG vaccine (TB) into bladder tumours can lead to immune killing of tumour cells

describe immunotherapy as a way to activate the immune system

• antibodies used to bind to tumours or cytokines and induce specific killing

• antibodies/drugs that can release the immune system blocks that cancer cells can produce

• inhibits the negative immune regulation (immune response remains ‘on’)

describe monoclonal antibody therapy

anti-TNF alpha therapy in rheumatoid arthritis