Innate and Acquired Immunity

exam 1

what is innate immunity?

-natural or inherent immunity
-recognize pathogen and prevent against infection
-basis for inflammatory response

what does innate immunity include?

-structural barriers
-cell activation and recruitment
-chemical mediator
-vascular changes

what are the structural barriers that prevent infection?

-epithelial cells
-mucus

epithelial cells provide what type of barriers?

-physical barrier
-skin
-respiratory tract
-GI tract

What structures and cells are included in the innate immune response?

dendritic cells and natural killer cells

dendritic cells

-antigen presenter
-produce type 1 interferons
-anti viral activity (inhibits viral infection and replication)

natural killer cells

-anti viral activity
-anti bacterial (intracellular)

selective plasma proteins

-complement system
-C reactive proteins
-mannose binding lectin

complement system activation has how many proteins?

20

what are the three pathways for activation?

-classical pathway
-alternate pathway
-lectin pathway

Alternate pathway

-innate
-direct activation
-some microorganisms
-No Ag-Ab binding required

Classical pathway

-acquired
-Ag bind to Ab
-Ab bind to C1
-multiplicative effect

What cell type is infected with HIV?

destruction of CD4 T cells

what is systemic lupus erythematosus?

-multisystem disease
-acute or insidious onset
-autoantiboides and antinuclear antibodies

Toll like receptors

pattern recognition molecules/receptors
-epithelial cells and phagocytes

where are toll like receptors?

cell surface and endosomes

how are toll like receptors recognized?

-extracellular
-ingested microbes; cytosolic microbes

activation of nuclear factor kappa b (NF-Kb)

potent inflammatory transcription factor

interferon regulatory factors (IRFs)

stimulate anti viral cytokines

acquired immunity

specific immune response against a specific antigen

B cells produced

antibodies that attack invaders

Memory B cells are for

the next encounter

where are B cells made

-fetal liver
-bone marrow

where are T cells made?

-thymus (divide, diversity, selection)

what are the type of T cells?

-Helper
-Cytotoxic
-suppressor
-Memory

where does B cells mature and select?

bone marrow

where do T cells mature and select?

Thymus

what is the main site of the human lymphoid tissue

lymph nodes

what are the lymphoid tissues?

-bone marrow
-GI tract
-spleen
-tonsils
-adenoids

what do the human lymphoid tissues do?

-concentrate antigen
-antigen presentation to lymphocytes
-optimize acquired immune response

what are the 5 antibodies?

-IgM
-IgG
-IgE
-IgA
-IgD

IgM

-primary response to Ag
-10 binding sites

IgG

-75% of antibodies
-2 binding site

IgE

-small percentage
-involved in allergies

IgA

saliva, tears, milk

IgD

functions as receptor on B cells

what is the structure of antibodies?

-2 light chains
-2 heavy chains
-form H-L pair
-2 binding sites
-variable portion at the ends
-constant portion 3/4 molecule

antigen- antibody binding

-non covalent
-specific
-puzzle pieces

what are the two primary actions of antibodies?

-direct attack of invader
-activation of complement

what are the ways of a direct attack?

-agglutination
-precipitation
-neutralization
-lysis

agglutination

-Ab bind to Ag causing clumping
-bacteria

precipitation

-Ab binds to soluble Ag causing precipitation
-tetanus toxin

neutralization

Ab binds to toxic site

what are autoimmune diseases?

humoral or cellular immune response mounted against ones own tissues
-any cell or tissue
-effects 1-2% of population

genetic predisposition

-triggering mechanism needed
-virus
-hidden self antigen
-trauma

examples of predisposition

-lupus
-rheumatoid arthritis
-MS
-MG
-graves disease

prevalence of autoimmune disease

women > men

what are the three criteria for a diagnosis of an autoimmune disease?

-evidence of an autoimmune reaction
-clinical findings are not secondary to another condition
-lack of other identifiable causes

what are the three mechanisms to maintain self tolerance?

-clonal deletion
-clonal anergy
-peripheral suppression by T cells

what are the mechanisms for loss of self tolerance?

-bypass of helper T cell tolerance
-molecular mimicry
-polyclonal lymphocyte activation
-imbalance of suppressor helper T cell function
-emergence of sequestered antigens

bypass of helper T cell tolerance

-modification of T cell antigens
-expression of co-stimulatory molecules

modification of T cell antigens

-induced by drugs or micoorganisms
-autoimmune hemolytic anemia

expression of co-stimulatory molecules

infections induce expression of co-stimulatory molecules on macrophages

molecular mimicry

-rheumatic heart disease
-antibodies against Strep cross react with hearth valves

polyclonal lymphocyte activation

-anergic clones are activated by Ag-independent mechanism
-endotoxin = polyclonal stimulant
-Epstein Barr virus = all B cells

imbalance of suppressor helper T cell function

-too little suppressor or too many helper
-mechanism for lupus

Emergence of sequestered antigens

-exposed after trauma
-sympathetic ophthalmitis
-ocular antigens

what is the primary defect of systemic lupus erythematosus?

failure to maintain self tolerance

what are the clinical manifestations of systemic lupus erythematosus?

-fever
-urinary findings
-neuropsychiatric manifestations

fever

with no obvious cause

urinary findings

-hematuria
-proteinuria
-classic nephritic syndrome
-renal failure

neuropsychiatric manifestations

psychosis

what are common symptoms of systemic lupus erythematosus?

-fatigue
-fever
-butterfly shaped rash on face
-skin lesions that worsen with sun
-fingers and toes turn white or blue when exposed to cold or during stress
-shortness of breath
-chest pain
-dry eyes
-headaches
-confusion
-memory loss

mortality of systemic lupus erythematosus

-acute: within months
-chronic: flare ups and remissions
-Tx: adrenocortical steroids, immunosuppressive drugs
-ten year survival: 70%

what are the causes of death for systemic lupus erythematosus?

-recurrent infection
-diffuse CNS involvement
-renal failure

what cells are destructed with HIV infection?

CD4 T cells

what are the four classifications of hypersensitivity reactions?

-Type I
-Type II
-Type III
-Type IV

Type I hypersensitivity reaction

1. RAPID reaction to Ag (allergen).
2. stimulates TH2 cells & IgE production
3. IgE binds to mast cells

Subsequent exposure - Ag binds to IgE, mast cells activated, mediators released to trigger inflammation/vasodilation (running nose)

what are examples of type I hypersensitivity?

-hay fever
-bronchial asthma

What are the phases of Type I response?

-initial phase
-second phase

initial phase

-vasodilation
-vascular leakage
-smooth muscle spasm
-evident: 5-30 min after exposure
-subsides: 60 mins

second phase

-2 to 8 hours later without preexposure
-lasts several days
-50% of individuals
-mucosal epithelial damage
-intense infiltration of eosinophils, PMNs, basophils, monocytes

mediator release in Type I hypersensitivity

-mast cell mediators
-arachidonic acid metabolites
-cytokines

Mast cell mediators

-histamine
-proteases
-chemotactic factors

arachidonic acid metabolites

-prostaglandins
-leukotrienes
-platelet activating factor

cytokines

-TNF
-IL-1 and IL-4
-chemokines

Manifestations of Type I

-hay fever
-urticaria
-asthma

hay fever characteristics

-runny nose
-swollen nasal passages
-sneezing
-histamine
-antihistamines

urticaria

-Ag enter specific skin areas
-Hives
-histamine
-antihistamines

Asthma

-Ag-Ab reaction in bronchioles
-spasm
-slow reacting substance of anaphylaxis
-antihistamines: not therapeutic

Type II hypersensitivity reaction

antibodies formed against target antigens that are either normal or altered cell membrane components

injures cells --> phagocytosis --> tissue inflammation

what are the three different categories of type II hypersensitivity?

-complement mediated reactions
-antibody dependent cell mediated cytotoxicity
-antibody mediated cellular dysfunction

Myasthenia gravis (Type II)

antibody reacts with acetylcholine receptor on motor end plate of skeletal muscle

What are the consequences of myasthenia gravis?

impaired neuromuscular transmission

what is the clinical manifestations of myasthenia gravis?

muscle weakness

what is the treatment for myasthenia gravis?

-acetylcholinesterase inhibitor
-plasmaphoresis

type III hypersensitivity reactions

-Ag-Ab immune complexes initiate acute inflammatory reactions in tissues
-activation of complement
-accumulation of PMNs

antigen that initials response for type III may be

-exogenous antigens
-endogenous antigens

exogenous antigens

-bacteria
-viruses

endogenous antigens

DNA mount an autoimmune response

what are the sites of occurrence for Type III?

-circulation
-extravascular

circulation

-deposited in tissue
-acute serum sickness

extravascular site

-in situ
-Kidney
-heart
-joints
-skin
-serosal surface
-small vessels

what are the clinical manifestations of Type III?

-fever
-urticaria
-arthralgias (joint pain)
-lymph node enlargement
-proteinuria
-tissue damage
-microthrombi

Type III diseases

1. lupus - nuclear Ag - nephritis, skin lesions, arthritis
2. reactive arthritis - bacterial Ag - acute arthritis
3. polyarteritis nodosa - hep B Ag sometimes involved - systemic vasculitis
4. Serum sickness - various proteins - arthritis, vasculitis, nephritis
5. glomerulonephritis secondary to strep infection - nephritis

Type IV hypersensitivity reaction

hypersensitivity mediated by T cells

what are the two classifications of Type IV?

-delayed type hypersensitivity
-cellular toxicity

delayed type hypersensitivity

-initiated by T cells (Th1 and Th7)
-recruit macrophages

cellular toxicity

-mediated by cytotoxic T cell
-graft rejection
-resistance to viruses

TB test

= delayed type hypersensitivity to previous infection
-second exposure results in T-helper response

8-12 hrs = erythema & induration
2-7 days = peak response = 1-2 cm.
Will subside slowly