Patho Exam 4-2 Flashcards
What mediators are released when a mast cell degranulates ?
- Cytokines (IL4 and TNF-a)
- Histamine
- Netrophil chemotactic factor (phagocytosis)
- Eosinophil chemotactic factor (phagocytosis)
Common causes of mast cell degranulation
- Physical injury
- chemical agents (bee stings, venom, etc.)
- Immunologic (anapalytoxins such as IgE)
- Activation of TLR’s
What attracts a neutrophil to the injury site?
- Bacterial proteins
- C3a and C5a
- neutrophil chemotactic factor
Roll of neutrophils in inflamation
- Ist phagocyte to arrive (6-12 hrs)
- ingest bacteria, cellular debris and dead cells
What is the main function of NK cells
To eliminate cells infected by viruses and cancer
Two functions of eosinophils
- Primary against parasites
- main regulator mast cell of the products released by mast cells (keep it isolated to the intended area) by enzymatic degradation of chemical mediators
What are the rolls of interleukins?
- alteration of adhesion molecule expression
- induction of leukocyte chemotaxis
- proliferation and maturation of leukocytes in bone marrow
- enhancement or suppression of inflamation
Rolls of interferons?
Protection against viruses: INF-a and INF-b are released by macrophages. INF-y is released by T Lymphocytes
Roll of TNF-a
Locally it stimulates endothelial adhesion molecule expression and chemokine production by endothelial cells and macrophages.
Systemically 1. Fever, 2. proinflamatory liver proteins, 3. Muscle wasting and thrombosis (prolonged infection CA), 4. Death by shock of Gram -
What releases TNF-a
- Macrophagres primary
- Mast cells
Roll of chemokines
- Chemotaxis of leukocytes
What releases chemokines?
- macrophages
- fibroblasts
- endothelial cells
What are the types of chemokines?
- CC (monocytes, lymphocytes, eosinophils)
- CXC (IL8)
Which complement fragments are chemotactic for neutrophils?
- C3a and C5a
Which complement fragment is responsible for opsinization. (binds to receptors of phagocytes)
C3b
Which complement fragments are anaphalytoxins?
C3a, C5a and C4a
complement fragment vasodilates and capillary permeability?
C2b
In the alternative pathway C3b is protected by what?
Factor H and Factor I
In the alternative pathway C3b binds to what
Factor B which is activated by factor D. This forms C3bBb AKA C5 convertase
The main purpose of the 3 complement pathways is?
- opsonization (C3b)
- mast cell degranulation (C3a, C5a and C4a)
- Leukocyte Chemotaxis (C3a les arg, C5a les arg)
- Cell lysis (C9)
Flow of the plasma kinin cascade
- Hageman Factor (XII) is activated producing XIIa
- XIIa converts prekallikrein into Kallikrein
- Kallikrein converts Kinogen into Bradykinin
Tissue factor (extrinsic) pathway is activated when
There is damage to the epithelial cells of blood vessels and thromboplastin (Tissue Factor) interacts with XIIa
Contact factor (intrinsic) pathway is activated when
There is damage to the vessel wall and Hageman factor (XII) CONTACTS the subendothelial cells
What does plasmin do?
- Degrades fibrin and fibrinogen (clots)
- Activates the Hageman factor
- Activate C1. C3 and C5
Activation of the Hageman factor has what 4 effects?
- Clotting cascade by activating X1
- control of clotting by indirectly activating plasmin
- Activation of the kinin system Hageman is (XIIa)
- Activation of C1
Where are TLR’s found
On cells which encounter pathogens.
- Mast cells
- Macrophages
- Epitheliall cells
- Neutrophills
- Dendritic cells
- Lymphocytes
Function of PAF
Similar to Leukotrienes
Types of cytokines
- chemokines
- interleukins
- lymphokines
- tumour necrosis factor
- interferons
Functions of lymphokines
- Promote maturation of monocytes into macrophages.
- Enhance macrophage migration.
- Cause chemotaxis.
- Induce production of lymphokines.
- Produce lymphotoxins. (TNF-b)
What are RANTES (b-chemokine)
- Produced by T cells, endothelial cells, platelets during chronic inflammation.
- Affects monocytes, NK cells, T cells, basophils, eosinophils
Define Epitope
The antigenic determinant, the portion of the antigen which is configured for recognition and binding by an antibody
Define Paratrope
The section of the antibody or lymphocyte which matches to an antige’s epitope. AKA the antigen binding site
What are the membrane associated immunoglobulins on the surface of B Cells in the BCR?
- mIgM
- mIgD
What is the function of Iga and Igb on a BCR
Intracellular signaling which communicates information to the nucleus
What is the function of the CD3 proteins on the TCR
Intracellular communication to the nucleus of the T cell which stimulates differentiation and proliferation.
Antigen presentation is the primary roll of what molecules?
MHC
What type of molecule is an MHC
Glycoprotein
Function of IgG
- 80% of the antibodies in the blood
- is the most protective against infections
- can cross the placenta
- four subclasses of IgG numbered 1-4.
Function of IgM
- large pentamer molecule
- produced first in response to antigen to provide the most rapid antibody response to infection
Function of IgA
can be divided into two subclasses bound by a J chain
- IgA1 is found in the blood
- IgA1 is a monomer
- IgA2 is found in body secretions.
- IgA2 is called secretory IgA and is a dimer; it protects against penetration of organisms through mucous membranes
Function if IgE
- important in the defense against parasites
- unfortunately is most often elevated in allergic disorders
- least common of all the Ig’s
Function of IgD
- molecule found on the surface of immature B cells where it functions as an antigen receptor.
Which cells are the professional APC’s
- Dendritic cells
- Macrophages
- B lymphocytes
(Dave Mathews Band)
Which cells express MHC II cells.
- Dendritic
- Macrophages
- B lymphocytes
What are the 4 Th cell subsets and their functions
- Th-1 cell - stimulates Tc cells (cellular immunity)
- Th-2 cells- stimulates B cells (Humoral immunity)
- Th-17 cells - stimulates inflammation
- Treg cells - release immunosuppressive cytokines
Where do superantigens bind?
To the MHC II and TCR’s outside of theire normal binding site.
What effects can a SAG have?
Over production of inflammatory cytokines as a result of excess activation of T cells leading to
- Fever
- Low BP
- Shock
Examples of SAG’s
- toxins of Staph A
- toxins of Strep Pyrogenes
A naive B cell expresses which antibody?
IgM
A mature B cell expresses which antibodies?
IgM and IgD
How do antibodies directly prevent infection
By binding to the virus or bacterial toxin and inhibiting it from binding to its intended target receptor on the host cell.
How do antibodies indirectly prevent infection
By activating the complement system or by stimulating phagocytosis
What are the 3 signals for T cell maturation
- Antigen binding to CD4 and TCR
- Costimulation of CD80 and CD28
- Activation of IL 1 receptors
Th 1 secretes what? Which does what?
- Secretes INF-y
- Inhibits Th2
Th2 secretes what? Which does what?
- Secretes IL 4 and IL 10
- Inhibits Th1 and Th17
Define allergy
The deleterious (harmful) effects of hypersensitivity to an environmental allergen.
Define autoimmunity
A disturbance in the immunologic tolerance of self antigens.
Define alloimmunuty
In immunologic response by an individual to the tissues of another
Characteristics of Type I Hypersensitivity reaction
- Mediated by IgE and the products of mast cells
- Most occur due environmental factors (pollen)
- Attracts Eosinophils (parasite eaters)
- Develops immediately
Characteristics of a Type II Hypersensitivity reaction
- Tissue specific
- Symptoms depend on which tissue is targeted
- Some drugs target specific cells and cause a Type II
- Can damage healthy tissue
- Immediate
- IgG and IgM
5 Mechanisms of Type II Hypersensitivity reactions
- IgG or IgM activation of the complement system
- IgG and C3b are opsonis and promote phagocytosis
- Neutrophil mediated damage. Atibodies bind, start the complement system, chemotaxis for neutrophils, neutrophils bind to membrane and destroy healthy tissue
- ADCC- Antibodies bind to Fc receptors on NK cells
- Antibodies bind and block receptors (Graves and Myasthenia Gravis)
What does ADCC stand for
Antibody Dependent Cellular Cytotoicity
Characteristics of Type III Hypersensitivity reactions
- Similar to neutrophil mediated damage in type II
- Formed by antigen/antibody complexes formed in the blood and deposited later in the tissue or vessel.
- Activates complement cascade
- May lead to hypocomplementism
- Serum Sickness, Raynauds, SLE
- Immediate
Characteristics of Type IV Hypersensitivity Reactions
- Mediated by T lymphocytes (Tc, Th1 and Th17)
- Th1 and Th17 produce cytokines which recruit macrophages
- Graft rejections
- Contact with poison ivy and metals
- Hashimotos, Arthritis, DM1
- Tb skin test
4 types of Hypersensitivity Reaction
I - IgE Mediated
II - Tissue Specific
III - Immune Complex Mediated
IV - Cell Mediated
Causes of autoimmune diseases
- Breakdown of the barriers to immunologically privileged sites (Blood/brain, blood/ocular). Damage to one eye can spread may spread self antigens to the other
- Molecular mimicry - Antigen closely resembles a host cell. Ex. Rheumatic fever after Group A Staph sore throat
- Neoantigen (Haptens)
- Forbidden clone - A lymphocyte with self recognition is accidently not deleted
- Defective peripheral tolerance (deficient T reg cells)
Define SLE
Systemic Lupus Erythematous. An autoimmune disease in which a large amount of autoantibodies are produced.
Autoantibodies produced by SLE target what?
- Nucleic acids (Most common)
- Erythrocytes
- coagulation proteins
- phospholipids
- lymphocytes
- platelets
2 Examples of Alloimmunity
- Transient Neonatal diseases
- Transplant rejection
- Transfusion reactions
What is the difference between Primary and Secondary Immune deficiency?
- Primary is congenital
- Secondary is acquired
What are the 5 primary immune deficiencies ?
- B-lymphocyte deficiencies
- T-lymphocyte deficiencies
- Combined T- and B- lymphocyte deficiencies
- Complement deficiencies
- Phagocytic deficiencies
Define hypogammaglobulinemia and agammaglobulinemia
- Hypo is less than normal B Lymphocytes
- Agamma is none or almost no B lymphocytes
Burton’s agammaglobulinemia
- Burton’s agammaglobulinamia (X linked)
- mutation on the gene for Burton’s tyrosine kinase
- No nuclear communication in B Cells
- B cells do not mature
- T cells function normally
Types of primary B cell deficiencies
- Burton’s agammaglobiulinemia
- autosomal agammaglobulinemia
- X linked hyper- IgM syndrome
Types of primary T cell deficiency
- DiGeorge Syndrome
- Chronic mucocutaneous candidiasis
Types of complement deficiencies
- C3 deficiency most severe
- MBL deficiency
- Properdin deficiency
Types of Phagocyte deficiency
- Congenital neutropenias - caused by chronic bacterial infections
- Leukocyte Adhesion deficiencies - results from mutations
- C3 receptor deficiencies - recurrent bacterial infections
- Chediak Higashi syndrome - defect in cytoplasmic granules
- Chronic granulomatous disease
Types of secondary immune deficiencies
- Normal physiological conditions
- Stress
- Dietary insufficiencies
- Malignancies
- Metabolic or genetic disorders
- Environmental
- Physical trauma
- Medical treatments
- Infections
Severe deficits in protein or calorie intake lead to
- Deficiencies in T cell function and numbers.
- Complement activity, neutrophil chemotaxis, bacterial killing depressed
Effects of Zinc deficiency
- Profoundly depresses both T and B cell function.
- Zinc required as cofactor
Deficiencies in pyridoxine, pantothenic acid, folic acid, vitamin A and E lead to
Severe depression in both B and T cell function.
Acute Phase of HIV infection
- Symptoms of acute viral infection
- CD-4 T cell count normal.
- Serologically negative.
- Infectious to others in 2 weeks.
Window phase of HIV infection
May not have antibody, but virus growing.
If Infected by blood:
- Antibody appears within 4-7 weeks.
If Infected by sexual exposure:
- May be seronegative for many months.
- May be infectious to others within 2 weeks
Subclinical Phase of HIV infection
- Seropositive for multiple antibodies against HIV-1.
- Slight, chronic lymphadenopathy.
- Virus replicating: Viral products released sporadically.
- CD-4 T cell count decreasing.
Intermittent stage of HIV infection
- Early stages of HIV-1.
- Acute viral infections without opportunistic infections.
- CD-4 T cell count continues to drop.
- Viral products released sporadically.
- May last 10 years.
AIDS phase of HIV infection
- CD4/CD8 ratio
Symptoms during the asymptomatic phase of HIV/AIDS
- Mild symptoms
- Night sweats
- swollen lymph glands
- diarrhea
- fatigue
Symptoms for seropositive stage of HIV/ AIDS
- Opportunistic infections (Pneumocytis carinii pneumonia).
- Atypical malignancies (Kaposi sarcoma).
- Persistent lymphadenopathy.
- Weight loss.
- Recurrent fevers.
- AIDS dementia complex.
Definition of transformation
The process by which a normal cell becomes a cancer cell
Define Anchorage- independence
Normal cells must be firmly attached to a surface in order to grow however CA cells can grow while suspended in a soft gel
Define Anaplasia
Cancer cells do not differentiate into specialized functions. Anaplasia is recognized by a loss of organization and marked increase in nuclear size
Define Plemorphic
Cancer cells are varying in size and shape compared to normal cells. Benign tumors will retain the ability to produce normal cells. A malignant tumor will rarely produce a normal cell.
Define clonal proliferation (expansion)
A cancer cell can proliferate faster than its neighboring normal cells due to anchorage independence and lack of contact inhibition
What are proto- oncogenes
Normal genes that participate in growth regulation such as
- Growth factors receptors.
- Transcription factors.
- Nuclear protein receptors.
- Cell signaling molecules.
What are oncogenes
Mutant gene whose altered function or expression results in :
- Abnormal stimulation of cell division.
- Proliferation in absence of growth signals.
What are tumor suppressor genes
- Facilitate neoplastic transformation via a cellular recessive model:
- Loss of function of both alleles.
- Function opposite proto-oncogenes. - Gate-keeper genes:
- Directly regulate cell cycle or growth inhibition. - Caretaker genes:
- Indirectly repair DNA and maintain genomic integrity.
Characteristics of Benign tumors
- Grow slowly
- Well defined capsule
- not invasive
- well differentiated (look like the tissue they arose from)
- low mitotic index (cell division is rare)
- Do not metastasize
Characteristics of malignant tumors
- Grow rapidly
- Not encapsulated
- Invade local structure and tissue
- poorly differentiated (may not be able to determine tissue of origin)
- Highly mitotic (many dividing cells
- Can spread distantly (through blood and lymph vessels)
