Pathology - Chapter 3
innate immune system
(nonspecific) response is fast and broad and targeted at ANY invader
Adpative immune system
(specific) slower programmable system that interact with invading non-self material. Responses are highly specific to fight that specific invader. Response is then memorized for use again in the future
Type 4 hypersensitivity (catch phrase) (mediated by)
Delayed Hypersensitivity (mediated by T cells)
Thymic Hypoplasia (DiGeorge Syndrome)
Deletion of q arm of chromosome 22 leads to underdevelopment of the thymus so T cell function is deficient. Since Helper T cells help activate B cells this is SCID
CD4+ cells are CD8+ cells are
CD4+ - helper T cells CD8+ - Cytotoxic T cells
definitive with confirming lab data (AIDs diagnosis)
CD4+ 200 cells/ml (normal range is 500-1,000)
MHC class II present to
CD4+ helper T cells
MHC class I presents to
CD8+ (cytotoxic T cells)
Type 2 hypersensitivity (catch phrase) (mediated by)
Cytotoxic Hypersensitivity (mediated by B cells)
Antibodies of type 2 hypersensitivity can cause
1. death of target cell (host cell) 2. antibody can block a receptor altering its function
mortality rate of lupus
30% mortality in first 10 years
Describe Type A blood
A antigens, anti-B antibodies
Autoimmine disease
A condition in the body's immune system attacks the body's own cells
What is the hygiene hypothesis?
A lack of early childhood exposure to infectious agents, symbiotic microorganisms, and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system - this is seen in westernized countries which have high rates of allergies In developing countries they are exposed to more things and have a lower prevalence of allergies
Type AB blood can receive
A, B, AB, O
Type A blood can receive
A,O
MHC class II are present on what type of cells
APC
what country has the highest burden of AIDS
Africa
hay fever
Allergic rhinitis, running noses and eyes
Antigen vs Hapten
Antigen: any substance capable of inciting an adaptive immune response (usually non-self-proteins) Hapten: small molecule which itself cannot incite and immune response, but can act as an antigen If combined with a carrier
rheumatoid arthritis (RA) - what is it and what tissues does it effect
Autoimmune disease affecting the lining membrane (synovium) of joints and may also affect the extra-articular tissue in heart, lung, skin, blood vessels
Describe Type B blood
B antigens, anti-A antibodies
Type B blood can receive
B,O
AIDs vs HIV
HIV is the virus that causes AIDs
examples of allergic disease
Hay fever Urticaria Atopic dermatitis Systemic anaphylaxis asthma
what type of cells does HIV infect
Helper T cells
Types of Anitbodies
IgA IgE IgM IgG IgD
Type 1 hypersensitivity is mediated by what types of antibodies
IgE
What class of antibodies are produced against Rh postive antigens in hemolytic disease of the newborn
IgG
Type 2 Hypersensitivity is mediated by what type of antibodies
IgG and IgM
Type 3 Hypersensitivity is mediated by what type of antibodies
IgG and IgM
Which antibodies are formed first and then what type takes over
IgM antibodies are produced fast following initial exposure (quick rise and then fall) IgM numbers fall after cleared IgG antibodies begin to be produced following the initial exposure but very slowly increase Upon a second exposure levels of IgG are very high
Explain Type 1 hypersensitivity
Immediate hypersensitivity (occurs quickly) due to preformed antibodies (IgE) formed during the 1st exposure 1st exposure = sensitization, B cells secrete IgE antibodies and attach to mast cells On subsequent exposures, the antigen combines with the IgE antibody already present on the surface of mast cells and triggers the mast cell degranulate
Type 3 hypersensitivity (catch phrase) (mediated by)
Immune complex hypersensitivity (mediated by B cells)
Organ Specific Autoimmune Diseases
MS Hashimoto Thyroiditis Myasthenia Gravis Type 1 Diabetes
how do antibodies work?
Neutralization- they neutralize antigens so they can no longer attack Mobilize other component of immune system - red flag, making invader easier to be seen by other cells
Type of Polymorphonuclear Granulocytes (PMNs) + what they do generally
Neutrophils: mediate acute inflammation by phagocytosis of bacteria Basophils: mediate allergic reactions Eosinophils: parasitic infections
Describe hemolytic disease of the newborn
Occurs if mother is Rh- and the fetus is Rh+ During labor fetal-maternal blood transfer causes mother is be exposed to Rh D antigens so mother makes antibodies against Rh D antigens Now during the mothers second pregnancy (fetus Rh+) maternal Rh D antibodies will attack the Rh D on the fetus
chronic organ rejection
Occurs months to years after transplant T cell mediated Ischemia and hypoperfusion of organ There is always some risk of organ rejection occurring at anytime after transplant
acute organ rejection
Occurs within a few weeks of the transplant T cell mediated - T cells attack mismatch MHCs
Rh positive mean
RBC have RhD antigens and will have no anti Rh D antibodies
Rh negative means
RBC have no RhD antigens and will have anti-RhD antibodies only following exposure to RhD antigens
what type of virus is HIV? (explain it)
Retrovirus - this means the viruses RNA gets synthesized into abnormal DNA and this gets inserted into the host cell's genome and stays and gets produced and thats how new viral particles are produced
Rh positive can receive
Rh negative or postive
What can mother take to prevent 2nd baby from experiencing symptoms
Rhogham
SCID disease are most likely to lead to persistant ________ infections while NON-SCID diseases are most likely to lead to perisstant ________ infections
SCID - viral infections NON-scid - bacterial infections
Examples of physical and chemical barriers:
Skin Sclera- the white of the eye, is covered with chemical barriers (antibacterial properties) Body Membranes: o Respiratory tract - lined with cilia that beat to remove invaders o Gi Tract - due to acidic environment o Urinary Tract - urine flushes bacterial from urethra
types of lymphocytes
T cells, B cells, NK cells
Types of T cells
T-Helper cells cytotoxic T cell regulatory T cells
Functions of the lymphatic system
To house and support immune cells To filter tissue fluid for non-self content In the intestines only, to absorb dietary fat and deliver it into the blood
What type of hypersensitivity is Lupus
Type 3
what type of hypersensitivity is RA
Type III
X-linked agammaglobulinemia (XLA)(Bruton's disease
X-linked recessive defect of B cell development, so patients lack the ability to produce normal immunoglobins (T cells are unaffected) - NOT SCID
xenograft
a transplant from animal species
Stages of HIV infection
acute- levels of virus increasing sharply and then decline, high levels of T cells and then declines - acute flu syndrome (fever,rash, sore throat, muscle soreness) latent- low levels of virus and VERY slow decline in T cell number - few clinical symptoms crisis- occurs when T cell levels decline dramatically, this causes levels of the virus to skyrocket - considered full blown AIDS - opportunistic infections and cancers occur
All atopy is _______ but not all allergy is _______
all atopy is allergic but not all allergy in atopic
MHC class I is present on what cells
all nucleated cells
Atopic dermatitis
an unusual inflammation of the skin, eczema
Explain Myasthenia Gravis
antibodies form that bind and block Ach receptors which prevents stimulation of skeletal muscles and leads to weakness
Explain Type 2 Hypersensitivity
antibodies produced by B cells that react with antigens on the surface of host cells and these get recognized as non-self and get targeted for attack
what is an immune complex
antigen and antibody combine
Inaccessible self-antigens (autoimmune disease cause)
antigens may have been hidden from contact with immune cells since conception and have becomes revealed in some way or another (trauma). Since the immune system has never seen these antigens before the immune system will attack them.
Lupus is associated with what type of antibodies in the blood
antinuclear antibodies (ANA)
secondary immune response
any exposure following the initial encounter
Allergen
any substance that induces an allergic reaction
primary lymphoid organs
associated with lymphocyte development
Sjogren syndrome (SS)
autoimmune disease of the lacrimal and salivary glands
treatment for Type 1 Hypersensitivity
avoidance Pharmacologic management: - antihistamines - Cortiosteriods - Anti IgE Therapy - Beta Adrenergic desensitization
Treatment of Sjogren syndrome (SS)
based on symptoms: - eye drops - drinking fluid
Chemokine receptor antagonists
bind to co receptor preventing the virus from binding by physically blocking it
How does HIV enter cells
binds to CD4 receptor AND CCR5 cor-eceptor
what do antihistamines do
block histamine receptors, preventing it from binding
How is lupus diagnosed?
blood test - presence of ANA - ESR and CRP
what location do these immune complex tend to end up and cause damage
blood vessels, kidneys and joints
the primary lymphoid organs are
bone marrow(B cells) and thymus (T cells)
Describe type AB blood
both A and B antigens and no antibodies
What type of MHC will APC have
both MCH I and II
What do beta adrenergics do
bronchodilation
Clinical findings and Symptoms of Lupus
butterfly shaped rash fever photosensitivity (sensitivity to sun) arthritis kidney dysfunction (glomerunephritis) cytopenia (reduction in blood cell count) vasculitis myocarditis Brain - microinfarct, psychosis, dementia
how are immune complexes normally cleared out
by RBCs
How do people with AIDS usually end up dying
by an opportunistic infection
RF test can indicate
can indicate RA but may also occur in other diseases as well
What type of opportunistic infections tend to occur in people with AIDS
candidiasis tuberculosis salmonella herpes
Primary Immunodeficiency Disease
caused by inherited genetic defects
immunity
cellular and molecular mechanism to defend the body against non-self-threats
The T cell system is also termed ______
cellular immune system
Goals of AIDs treatment
control virus control other infections
Neurological symptoms of AIDS
dementia seizures mood swings
Local effects of Type 1 hypersensitivity
depend on the site of entry, could include rash, swelling, diarrheas, gas, bloating, tears, running nose
Symptoms of Sjogren syndrome (SS) (glandular and extraglandular)
dry irritated red eyes dry mouth difficulty swallowing extra-glandular: vasculitis, neuropathy, lymphoma
How do immunodeficiency diseases tend to become apparent?
due to unusual or persistent infections
what is the most common allergen
dust mites
the late phase of IgE mediated allergic reactions is mediated by what type of cells
eosinophils
Minor transfusion reactions include:
fever, chills this is not due to ABO mismatch but some other antibody in the blood reacting not life threatening
primary immune response
first encounter (exposure) to the antigen
Rheumatoid Factor (RF)
found in the blood, proteins produced by your immune system that can attack healthy tissue in your body
IgA antibodies
found in tracts where MALT is abundant (respiratory and GI tract)
Atopy
genetic tendency to develop allergic diseases
MHC
glycoprotein complex on the surface of cells, present antigens to responding cells of the immune system
Amyloidosis
group of disease in which amyloid proteins are abnormally deposited
Severe Combined Immunodeficiency (SCID)
group of disorders affecting both T cel and B cell function - due to deficiency of T cells *makes the patient prone to infections(viral) and cancers*
explain how type 4 hypersensitivity works
hapten combines with protein in the epidermal cells forming an antigen that can be recognized by APC APC presents antigen to T helper cells (in lymph nodes) T cells get activated and release cytokines leading to the proliferation of T cells and macrophages T cells and macrophages migrate to the area where hapten was introduced. Macrophages cause damage by releasing ROS and enzymes which leads to tissue damage. T cells can directly induce cell damage
Major transfusion reactions include:
hemolysis thrombosis (be life threatening)
HAART
highly active antiretroviral therapy, suppresses virus replication by acting on different stages of life cycle of HIV, increase latency period- maybe indefinitely
urticaria
hives
the B cell system is also termed
humoral immunity
phases of IgE-mediated allergic reaction
immediate - wheel and flare late - occur hours later is swollen
Type 1 hypersensitivity (catch phrase) (mediated by)
immediate hypersensitivity - mediated by B cells
Explain what Type 3 hypersensitivity is
immune complexes do not get cleared out and they deposit on tissues and lead to an inflammatory response that leads to tissue destruction
How does lupus work
immune complexes form and get deposited and initiate inflammation
local deposition of immune complexes
immune complexes form and remain at the site of antigen introduction
Why does the body attack itself in autoimmune diseases
imperfect T and B cell programing inaccessible self antigens altered self antigens molecular mimicry infection and inflammation decreased supressor T cell function genetic susceptibility
IgE
important in allergic reactions
Entry inhibitors
inhibits endocytosis of virus into cell
what do cortiocosteriods do
inhibits the enzyme that converts phospholipids in membranes into arachidonic acid. During this in turn prevents the formation of prostaglandin and leukotrienes which lead to inflammation *so corticosteriods reduce inflammation*
where do amyloids deposit in amyloidosis
intercellular spaces of various organs (can affect one organ or be systemic)
Allergy
is an exaggerated but otherwise normal immune response to a foreign antigen
What type of neoplasms occur in AIDS
kaposi sarcoma lymphoma (brain)
definitive without confirming lab data (AIDs diagnosis)
kaposis sarcoma in someone less than 60 year of age
what do NK cells do?
kill virus infected cells and tumor cells part of innate immune system
Lab data alone can confirm _____ but not ______
lab date can confirm HIV infection but cannot prove AIDs because AIDS is a clinical diagnosis proved by the presence of certain AIDS-related diseases
Thymic Hypoplasia (DiGeorge Syndrome) can cause
lack of parathyroid glands hypoparathyroidism anomalies of the neck, face, ears, heart, and aorta
Tonsils
largest mass of MALT tissue
spleen function
largest secondary organ screen blood for blood borne bacterial infections and destroys RBCs
IgM
largest, 1st type made, providing initial protection while IgG production is getting underway
Characteristics of AIDS
lower helper T cell count recurrent infection that are not normally observed certain kinds of neoplasms (cancer) Cachexia (wasting away)
Systemic effects of RA
lungs bones cartilage pericardium
systemic autoimmune diseases
lupus, rheumatoid arthritis
the secondary lymphoid organs are
lymph nodes spleen tonsils adenoids linings of tracts (respiratory tract and GI tract) in the form of MALT
Antigen presenting cells include
macrophages, B cells, dendritic cells
An X-linked recessive disease is more likely to be seen in females or males
males
Type 1 hypersensitivity involves what type of cells
mast cells and basophils
macrophages
mature from monocytes phagocytosis
infection and inflammation (autoimmune disease casue)
may alter self antigens in a way that makes them appear to be non-self
treatment for lupus
mild cases - NSAIDS Severe cases - steroids and antineoplastic drugs
amyloid proteins
misfolded proteins; aggregate & stick together
major cross match
mix of donor RBC with recipient serum checking for preformed antibodies in recipients serum against the donors RBC
minor cross match
mix of donor serum with recipients RBCs checking for performed antibodies in donor serum that could hemolysis recipients RBC
Lymph nodes
monitor lymph fluid for microbes and tumor cells
How does HIV resistant occur
mutation in CCR5 - affects ability of HIV to enter cells can be homozygous or heterozygous
How is damage actually caused by the immune complexes
neutrophils bind to them and release enzymes and free radicals and this can damage tissue
are symptoms experienced during sensitization
no
Describe type O blood
no antigens, both A and B antibodies
Does testing for ANA in the blood always indicate lupus
no this test is highly sensitive but has low specificity so it may just sell us there is an autoimmune
What is the first line of defense?
non-immune defense- consists of physical and chemical barriers
IgD
not found in blood, Receptors of B cells
Secondary Immunodeficiency Disease
occur secondary to another disease, radiation, malnutrition, infection, age (most common)
Systemic effects of Type 1 hypersensitivity
occurs due to mass activation of mast cell all over the body, can lead to anaphylactic shock, and decrease in BP
Hyperacute organ rejection
occurs very fast after transplant due to preformed antibodies (Due to a previous transplant or pregnancy) that react with graft endothelial cells usually happens during the transplant surgery
a non SCID disorder mean
only B cells are affected = lack of antibodies
Type O blood can receive
only O
Rh negative can receive
only Rh negative
death due to lupus is usually due to
organ failure of the kidney or brain
dendritic cells function
phagocytosis
activated b cells become __________ and their function is
plasma cells that secrete anti bodies
examples of type 4 hypersensitivity
poison ivy metal reaction (jewelry) tuberculosis test
how to minimize GVH?
pretransplant treatment -such as chemotherapy or radiation to suppress the recipient's immune system and the original bone marrow
Nucleotide reverse transcriptase inhibitors
prevents production of viral DNA from RNA
Protease Inhibitors
prevents proteolytic processing so they virus particle released from the cell is not infectious
Types of amyloidosis (2)
primary - no known causes, antibodies form amyloids (light chains break down and collect) secondary - secondary to some other condition
timeline of primary and secondary immune response
primary immune response is slow and takes about a few secondary immune response is fast due to preformed memory cells
what do helper T cells do?
produce cytokines
presumptive with confirming lab data (AIDs diagnosis)
recurrent pneumonia
RA tends to be episodic which means what?
relapse and remission (go back and forth
mast cell degranulation results in
release of histamine (and others) that cause vasodilation, increased capillary permeability, and accumulation of edema Arachidonic acid derivatives (leukotrienes and prostaglandins) lead to vasodilation and increased permeability as well
Treatment for primary Amyloidosis
replace abnormal antibodies vis bone marrow transplant (get new B cells)
molecular mimicry (autoimmune disease cause)
resemblance of pathogen and host antigen, immune response that is initiated by a microbe gets directed at self cells instead
Symptoms of hemolytic disease of the newborn
serve cases: increased bilirubin, CNA damage, death mild cases: mild anemia, jaundice
what tissues are most affected in lupus by immune complexes
skin, serosal membranes, kidney, joints, and brain
smaller or larger immune complexes circulate longer
smaller ones
IgG
smallest and most abundant in blood neutralizes microorganisms, produced slowly but persists a long time, can cross placenta
graft vs host reaction (GVH)
specific to bone marrow transplants, when Immune cells in the graft tissue recognize the host as foreign and attempt to reject host tissue
what do regulatory T cells do?
suppress the immune system keeping it from getting out of hand
crossmatch test
test to see if donor blood is compatible with recipient blood
lymphatic system
the network of lymph vessels and lymph nodes
what do cytotoxic t cells do?
they target and destroy cells that the immune system has identified as containing alien antigen, either a cancer cell or a cell infected by a virus.
How is AIDS transmitted?
through blood and bodily fluids
Examples of type 2 hypersensitives
transfusion reactions hemolytic disease of the newborn autoimmune reactions
homograft (isograft)
transplant between identical twins
allograft
transplant for genetically dissimilar people of the same species
what is the most common autoimmune disease
type 1 diabetes
Kaposi sarcoma (KS)
type of skin cancer often seen in patients with AIDS; consists of brownish/red/purple papules on the skin
X-linked agammaglobulinemia is due to a deficiency in _____________ what is its normal function?
tyrosine kinase - important for B cell development, without it B cells do not complete development
What are antineoplastic drugs? and what do they do
used with cancer to reduce cell division, to reduce the number of WBC
altered self antigens (autoimmune disease cause)
viral infections can alter self proteins
Imperfect T and B cell programing (autoimmune disease cause)
when T and B cells are being programmed in the thymus and bone marrow some nontolerant T and B cells survive (in other words the process of programming our lymphocytes is not a perfect process and some error can occur). This wrongly programmed T and B cells if they persist can attack self-cells
What is drug induced lupus?
when a drug causes autoimmune like lupus, once you stop taking the drug the symptoms stop 10% of cases are this
secondary lymphoid organs
where lymphocytes reside and are activated
Risk factors of lupus
women 20-40
autograft
your own tissue transplanted
Groups of people at risk for infection by HIV
· Homosexual or bisexual males · Iv drug users · Patient with hemophilia (have a lot of blood transfusions) · Recipients of transfusion of human blood · Heterosexual contact with some of the above are also at risk
distant deposition of immune complexes
· occur when complex forms in blood and is deposited to distant tissues