Module 3: Topic 2: Inflammation / Immune Flashcards
Name three types of “first line” defense
- Physical 2. Mechanical 3. Biochemical
Describe characteristics of “first line” PHYSICAL and MECHANICAL defense
- Anatomical and NON-SPECIFIC - Tightly associated epithelial cells: skin, lining of GI, GU and resp. tracts. - Tight cell junctions prevent microbes from entering -“washing” = normal turnover of the cells i.e. skin cells sloughing off or -mechanical cleansing = vomiting / urinating -Goblet cells producing mucous –> cilia –> coughing -low temp of skin prevents bacteria from growing (prefer 37 C) -skin pH 3-5
Describe characteristics of “first line” BIOCHEMICAL defense
-biochemical barriers synthesized and secreted by epithelial cells to trap and destroy micro-organisms. -mucus -perspiration/sweat -saliva -tears -earwax -Sebaceous glands –> antibacterial/anti-fungal fatty acids -lysozyme- attacks gram + cell walls (sweat, tears and saliva)
Biochemical Barriers
-Epithelial derived chemicals -Bacteria derived chemicals
Epithelial Derived Chemicals (Biochemical Barrier)
Antimicrobial peptides (small molecular weight): -generally positively charged polypeptides (15-95 AAs) -disrupt bacterial cell wall (no cholesterol) Two classes: 1. CATHELICIDINS - linear alpha-helical shape (1 in humans) 2.DEFENSIN- type alpha (need activation) and beta (active) (beta may help defend from HIV) (50 types in humans) Lung produces: COLLECTINS Includes surfactant proteins. Other epithelial antimicrobials: -RESISTIN-LIKE MOLECULE BETA -BACTERICIDAL/PERMEABILITY INDUCING PROTEIN (BPI) -stored in neutrophils and GI epithelium -ANTIMICROBIAL LECTINS - GI carbs work against gram + bac.
Bacterial Derived Chemicals (Biochemical Barrier)
-normal microbiome: GI tract/ vaginal tract -aid in multiple ways (digestion, keeping pathogens out)
Commensal organism
(to the benefit of one organism without affecting the other)
Mutualistic organism
to the benefit of both organisms
Describe “second line” of defense
-The inflammatory process -physiologic, internal, NON SPECIFIC -Purpose: isolate, destroy, remove
Describe “third line” of defesne
SPECIFIC LONG-TERM CAN BE INDUCED BY VACCINATION EFFECTED ONLY BY
SERUM PROTEINS (IMMUNOGLOBULINS)
ANTIBODIES)
Review this chart
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ANTIGEN vs. IMMUNOGEN
An immunogen refers to a molecule that is capable of eliciting an immune response by an organism’s immune system, whereas an antigen refers to a molecule that is capable of binding to the product of that immune response.
So, an immunogen is necessarily an antigen, but an antigen may not necessarily be an immunogen.
WHAT IS A HAPTEN?
Antigens that are too small to be immunogens by themselves but become immunogenic in combination with larger molecules that function as carriers for the hapten.
For example, the antigens of penicillin and poison ivy are haptens, but they initiate allergic responses only after binding to large-molecular-weight proteins in the allergic individual’s blood or skin.
McCance, Kathryn L.; Huether, Sue E. (2015-06-08). Pathophysiology: The Biologic Basis for Disease in Adults and Children (Pathophysiology the Biologic Basis) (Page 229). Elsevier Health Sciences. Kindle Edition.
TYPES OF IMMUNE MODULATORS THAT INCREASE/DECREASE IMMUNE RESPONSE
EXTERNAL(EXOGENOUS) AND INTERNAL (ENDOGENOUS)
EXTERNAL/EXOGENOUS IMMUNE MODULATORS
Trauma
Disease
Pollution
Radiation
Drugs
UV light
INTERNAL/ENDOGENOUS IMMUNE MODULATORS
Age
Sex
Nutritional status
Genetic background
Reproductive status
When is there a need for immunosuppression?
- Organ/Tissue Transplant
- Allergic Reaction
- Autoimmune Disease
What is natural immunity?
- Not produced by antigen
- Present at birth
- Host-dependent
- The natural epithelial barrier and inflammation confer innate resistance and protection.
What is acquired (adaptive) immunity?
- Results from the immune response
- Slower than innate system
- SPECIFIC
- has “memory”
What is Active Immunity?
- Immune components produced host (antibodies / T-lymphocytes)
- Either after natural exposure to an antigen or after immunization.
- Typically “long lived”
What is passive immunity?
- Occurs when preformed antibodies or T lymphocytes are transferred from a donor to the recipient.
- Immune components produced by donor
- Temporary immunity b/c donor’s components eventually destroyed by recipient’s system
- Example: maternal transfer, immune serum transfer (Hep A, Rabies, Sanke bites)
Primary and Secondary Immune Response Graph
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Primary Immune Response
- Initial antigen exposure → latent/lag phase b/c of B-cell differentiation/proliferation
- 5-7 days = IgM ab specific to antigen
- IgM 1st, IgG 2nd
- IgG will be equal or less than IgM production
If no further exposure to antigen happens - ab are catabolized and quantities fall.
Describe Secondary Immune Response
- Second challenge by same the antigen
- Rapid response (b/c memory cells are already present and don’t need differentiation)
- Larger amounts of ab produced
- IgM in small quantities
- IgG in GREAT QUANTITIES
What are lymphocytes?
- Primary immunocyte
- Small, round, WBC
- Comes from pluripotent stem cell
- Found in liver, spleen, bone marrow (fetus, child, adult)
- Need to mature through lymphatic vascular journey
- Journey through lymph → antibodies; humoral immunity
- Journey through thymus → sensitized, attack antigens; cell mediated immunity
Immune Response Pictograph
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Antigen
Reacts with preformed components of the immune system
Antigenicity
The capacity of a chemical structure (either an antigen or Hapten) to bind specifically with a group of certain products that have adaptive immunity: T cell receptors or antibodies (a.k.a. B cell receptors)
Immunogen
An antigen that can induce the formation of immune system components.
Is an antigen or any substance that may be specifically bound by components of the immune system (antibody, lymphocytes).
Immunogenic
Is the ability to initiate the immune response.
Will induce an immune response resulting in the production of antibodies or functional T cells.
Characteristics for antigen to be immunogenic:
(1) being foreign to the host,
(3) having an adequate chemical
complexity,
(4) being present in a sufficient quantity.
(2) being appropriate in size (large)
Describe antigen criteria: foreignness
- Foremost criteria for immunogenicity
- Tolerance is an active process – distinguishes self from foreign by
–suppressor T cells (T-regulatory cells)
–Ts and anti-idiotypic antibody
McCance, Kathryn L.; Huether, Sue E. (2015-06-08). Pathophysiology: The Biologic Basis for Disease in Adults and Children (Pathophysiology the Biologic Basis) (Page 229). Elsevier Health Sciences. Kindle Edition.
Immunogenic Antigen
Antigens that are foreign, fat, complex & abundant are immunogenic.
Tolerogenic Antigen
Self antigens that are fat, complex, and abundant but not foreign are tolerogenic.
Factors Affecting Immunogenicity
- Route of antigen administration:
- IV, SQ, Intraperitoneal, Intranasal, Oral
- Each route stimulates different set of lymphocyte-containing tissue → different immune responses (cell mediated vs. humoral)
- Host’s genetic make up also affects response (genes are on Chromosome 6)
Describe features of the Human Leukocyte Antigen (HLA)
- Identical twins have identical HLA
- (expect the same immune response)
- Knows the code for recognizing foreigners
- Proteins found on nearly every cell surface
- Defend the body against infection
- Distinguish foreigners from self
- Produced by genes on the major histocompatibility complex (MHC)
- Four loci on chromosome 6 (A,B,C,D)
Describe Class I Antigens
Class I antigens (A, B, & C loci) are on all cells except RBCs
MHC I: graft rejection (guide cytotoxic T cells)
Describe Class II Antigens
Class II antigens have 3 separate loci (DR, DP, & DQ)
Confined to B cells, macrophages, epithelial cells, and some Ts
MHC II: antigen presentation, graft rejection (Th cells), autoimmune disease
What is the location of a gene on a chromosome called?
Locus (The location of a gene is stable)
How many alleles can each loci have?
50-100s
What is an allele?
A variation of a gene and what it controls.
How are MHC genes inherited?
As a block.
What is a haplotype?
All the MHC genes inherited from one parent.
There is 1/4 chance of matching a sibling’s haplotype.
Are HLA antigens found in RBCs?
No
Approximately, how many red cell antigens are on the surface of RBCs?
80
ABO System Summary
Two major antigens A & B
IgM isohemagglutinin : is natural occurring ab
A - A antigen → anti-B antibodies
B - B antigen → anti-A antibodies
AB- A& B antigens → no antibodies = universal recipient
O - no antigens → anti A & anti B antibodies = universal donor
What type of antigen and antibodies does type A blood have?
A Antigen
anti-B Antibodies
What type of antigen and antibodies does type B blood have?
B Antigen
anti-A antibodies
What type of antigen and antibodies does type AB blood have?
A and B Antigens
No Antibodies
UNIVERSAL RECIPIENT
What blood type is the universal recipient?
AB
What type of antigen and antibodies does type O blood have?
No Antigen
anti-A and anti-B Antibodies
UNIVERSAL DONOR
Which blood type is a universal donor?
O
B Lymphocytes
Mature in tissues (human bursal equivalent)
B cell precursors cannot react with antigens
Post bursal B cells produce plasma membrane bound antibodies (IgM) to the 8th power antigenic determinants
Clonal Selection
–Most accepted theory on antigen recognition
–All generic to begin with
–Plasma cells exposed for first time then become memory cells
Clonal Diversity Pictograph
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Immunoglobulins
Antibodies produced in response to immunogen
immunoglobulins - generic term
antibodies - specific for a certain antigen
Five Classes of Ig (GAMED)
Ig G
IgA
IgM
IgE
IgD
Cytokines
Lymphokines -produced by lymphocytes
Monokines - produced by immonocytes/macrophages
Functions of Cytokines:
- Necessary in immunity
- Growth & proliferation of cells
- Growth & development of placenta
Interleukin
B cell antibody response is controlled by IL-2
IL-2 is secreted by activated (ie. Those having recognized agMHC) Th cell.
Fetal & Neonatal Immune Function
Deficient
- antibody production
- phagocytic activity
- complement activity
Last trimester can produce primary response (IgM) to CMV, rubella, Toxoplasma gondii
Little IgA or IgG
Active transport passes maternal ab into fetal circulation
At birth maternal ab are catabolized as neonate IgG begins to rise
Protective level 5-6 months
Aging
- Thymus decreases in size to only 15% by 45-50 years of age
- Numbers of T cell do not decrease
- Function of T cells & macrophages deteriorates
- May see delayed or decreased hypersensitivity response.
- Diminished immunity conferred by immunization.