Direct vs. Indirect transmission

Direct:

• Direct contact between reservoir and new host
• Physical, fecal contamination, airborne droplets

Indirect:

• Reservoir deposits organism on fomite (inanimate object), which transmits pathogen to new host.

Principles of Infection Control

• Requires breaking chain of transmission
• Use antimicrobials
• Destroy nonhuman reservoirs/vectors
• Block portal exit
• Improve immune system

Epithelial Barriers: How is Invasion Prevented?

Skin Characteristics

• Block foreign material entering body
• Provide multilayer protection (“Onion”)
• Dry surface does not promote organism growth
• Sloughing of skin/mucosal cells aids in microorganism removal
• Skin has higher fat content to inhibit growth of bacteria and fungi
• Epithelium difficult to penetrate

Epithelial Barriers: Mucous Membrane Linings

-          Barrier separating sterile internal body

-          GI/GU tracts, lungs

Epithelial Barriers: Chemical

• Acidic environment of skin (low pH), ruinge vagina, inhibit bacterial growth
• Saliva mucus, tears, sweat contain bacterial-killing enzyme
• Sebaceous gland secretions are antifungal

Principle of Herd Immunity

Decrease the number of susceptible hosts in the population, thereby limiting the possibility of transmission of the disease.

Host-microbial balance: When does imbalance occur?

What facilitates microbial adherence?

Adherence: Ability of a microorganism to latch onto and gain entrance into its host

-          Direct penetration

-          Sticks to tissue surface

-          Slime layer (glycocalyx) facilitates adherence also

-          Adhesion molecules

Principles of antimicrobial resistance

• Caued by:
• Individuals treated with antibiotics taking only part of the prescribed dose
• Over-prescribing of antibiotics
• Allows low-dose resistance
• Resistant form may be transmitted to other indiviuals
• Major threat to successful mgmt of bact infections

Microorganism Characteristics:

Bacterial enzymes

Encapsultation

• Bacterial enzymes:
• Help microorganism to spread or invade tissues
• Encapsultation:
• Prevents opsonization (recognizing and binding) by antibodies
• Prevents phagocytosis (by immune cells)

Microorganism Characteristics:
Virulence

• Ability to cause disease
• Microorganism consistently causes diseasein all infected hosts
• Interaction between host/pathogen harms host

Microorgansm Characteristics:

Antimicrobial Resistance

• Microorganism's ablity to mutate in response to environmental changes in host
• Mutation allows successful host infection

Microorganism Characteristics:

Endospre formation

• Allows microorgansim to survive under harsh environmental conditions
• like laying an egg
• Resting cell released when organism dies
• protects DNA & cytoplasm
• Gram(+) bacteria
• Example: Clostridium bacteria
• Reactivation of the spore occurs when conditions are again favorable
• Resistant to nearly all household cleaning agents

Exotoxin vs. endotoxin – what kind of bacteria have endotoxins?

Exotoxins: Polypeptides released by organisms

• Antigenic, toxic, unstable when exposed to heat
• Bind to receptors in target organs and interfere with metabolic processes
• Examples: Tetanus, cholera

Endotoxins:

• Strictly related to gram (-) bacteria
• Part of lipopolysaccharide bacterial cell wall
• Triggers massive immune response when bacterium lyses
• Leads to cell shock and multiple organ failure
• Example: Enterobacteria

Physical Characteristics of bacteria

• Single-celled
• Peptidogycan cell wall prevents osmotic lysis
• Degrade/break down dead tissue
• Classified into four major groups
• Gliding
• Spirochetes
• Mycoplasmas
• Rigid bacterias

Bacteria: morphologies

Classified by morphology and response to Gram Staining

• Cocci
• Round, nonmotile, may clump together like bunches of grapes, in pairs, or long strands
• Bacilli
• Rod shaped, about 1/2 are motile
• Spiral

Gram Stain Reaction

• Gram-positive appear dark purple under microscope
• thick, multi-layer cell walls with teichoic acids
• Gram-negative appear pink
• Don't retain crystal violet dye
• Lipid walls (lipoproteins, lipopolysaccharides)
• Acid-fast resist staining altogether (but once stained resist decoloration)

Characteristics of Retroviruses

• Contains coding info for reverse transcriptase to create mRNA and DNA from its own genome
• DNA replicates when host cell replicates
• Example HIV

Fomite

Inanimate object upon which the reservoir deposits organism

Transmits pathogen to new host

Example: door knobs, faucet handles, light switches

Lactoferrin

Colonization

(Step in transmission of infection)

Microorganism does not cause disease in host, but can be transmitted to others

Balance between host and organism

Reverse Transcriptase

enzyme that enables virus to create mRNA and DNA from its own genome, using the host's "machinery"

HIV

Innate Immunity

Require no previous exposure to effectively respond to antigen

• NK cells
• Phagocytic cells
• neutrophils
• macrophages

Adaptive Immunity

(general)

Specific Defenses

• Respond more effectively to 2nd exposure
• Highly restricted in ability to recognize antigens
• B and T lymphocytes

Components of the Immune System:

Skin & Mucous membranes

• Defensins
• Cryptocidins
• Positively charged to bind to negatively charged pathogens

Components of the Immune System:

Lymphoid System

• Spleen
• Thymus Gland
• Lymph nodes

Where do T-cells mature?

Where do B-cells mature?

What occurs in the lymph nodes?

Lymph fluid flows through for immune cells to filter, detect, and react to foreign material

Antigen presentation by macrophages

Leukocytes: agranulocytes vs. granulocytes

Granulocytes - Polymorphonuclear

- Neutrophils: macrophage

- Eosinophils: macrophage

- Basophils ~ Mast cells

Agranulocytes - Mononuclear

- Lymphocytes: B and T Cells, NK cells

- Moncytes: immature, become macrophages in tissues

- Dendridic cells

Which leukocytes are macrophages?

Neutrophils

Eosinophils

Dendridic cells

Which leukocytes are lymphocytes:

B cells

T cells

NK cells

What is required for a macrophage to engulf an offender?

What are the primary effectors of the immune system?

Leukocytes

What do neutrophils primarily respond to?

What do eosinophils primarily respond to?

Allergic reactions

Intestinal parasite infections

Basophils: Which become mast cells?

• Granulocytes
• Basophils circulate in vascular system
• If they migrate to connective tissue, they don't reenter blood stream.
• Mast cells are basophils that stay in connective tissue.  Live for weeks to months.

**Degranultaion begins inflammatory response associated with allergic reactions!**

What is the role of cytokines secreted by macrophages?

Induce inflammation and chemotaxis

Histamine in granules

Mast cell degranulation

(C3a-triggered)

NK Cells as lymphocytes:

• Assoc. with innate immunity
• Can respond without previous exposure
• No B- or T-cell markers; not dependent on thymus for development
• Effectively kill tumor and virally infected cells without previous exposure
• Not specific for a particular antigen
• Use Fc receptors to recognize Ab-coated cells
• Fc receptors are the constant "handle" on an antibody that allows binding

CD4+ T Cells (Th cells) - What do they do?

Directors of immune response

Stimulate B-cells to make Ab

Stimulate CTL (CD8+) to seek & destroy

CD8+ T Cellls (CTL cells - don't worry about supressor-Ts)

• Cytoxic KILLER Ts -
• Administer a lethal hit to offenders by activating rapid DNA defragmentation and nuclear collapse
• --> Apoptosis

Epitope + Ag and fitting together

• Epitope is the specific shape of the antigen
• The Ag epitope must 'fit' the B-cell receptor for activiation
• The more specific the fit, the more receptors connected, the better the response

Complement: Classical pathway

Complement: Alternative Pathway

MAC: how does it induce cell death?

Membrane-attack complex

Causes Na+ and water to flood the offender, causing it to burst

Purpose of inflammation (there are 3)

1. Neutralize and destroy invading and harmful agents
2. Limit spread of harmful agents to other tissue
3. Prepare damaged tissue for repair

*Chemical signs of inflammation

3 players in healing

Fibroblasts

Endothelial cells

Myofibroblasts

4 kinds of exudates

• Serous exudate
• serosanguineous drainage
• Fibrinous exudate
• Sticky, thick
• Purulent exudate
• Pus (dead neutrophils)
• Hemorrhagic exudate
• RBC's mixed in with serous fluid; can be sign of severe inflammation

What is MHC and why is it important?

• Major Histocompatibility Complex
• also known as human leukocyte antigen (HLA)
• Allows immune system to know which of its cells are "self" (vs. foreign, thus needing destruction).

Cytotoxic T-cells and Memory T-cells

What is their role in specific immunity?

• Cytotoxic T-cells: (CD8+) recognize Ag displayed in association with MHC-I.
• receptor specifically recognizes antigen (presented by Ag-presenting cell)
• Activated Cytotoxic T-cells:
• Proliferate into Memory T-cells & effector cells
• Trigger apoptosis

B cells/memory B cells; role in specific immunity

Memory B Cells

• Contain antigen receptors
• Memory of exposure to Ag is stored in memory B cell clones

Antibodies: What do they do?

Precipitation, agglutination, neutralization, oopsonization, complement activation

• Each arm of Ig Y structure can bind to an Ag epitope
• Allows Ab and Ag to bind together into large, insoluble complexes that precipitate out of body fluids
• Can function as antitoxins (to neutralize bacterial toxin)
• Antibodies bound to foreign Ag on cell membranes
• Can activate complement cascade

5 Ab classes and their general association

• IgG - most common type, smallest, neutralizes toxins, binds & facilitates destruction of bacteria
• IgM - large pentameters, in vessels, B-cell surfaces
• IgD - W. IgM B-cell membranes, Ag-receptor that stimulates B-cell
• IgE - Type I Hypersensitivity reactions; histamine
• IgA - secretions

Neutrophilia

Antigen

Macromolecule that provokes an immune system response

Defensins

• Antimicrobial peptides
• Immune component found on skin & mucous membranes

Cryptocidins

• bacteriocidal agent
• found in intestines

Kupffer cells

Monocytes, become macrophages

Located in the liver

Langerhans cells

• Type of epithelial cell
• Thought to have a role in immune reactions that affect the skin
• May serve as a defense mechanism for the body

Dendridic cells

• Leukocytewhose function is to EAT
• Derived in bone marrow
• Structurally and functionally similar to macrophages
• Throughout body - mononuclear phagocyte system
• Summoned by cytokines/chemokines, inflammation
• Innate response
• Engulf Ag
• Bring it back to lymph node -> "show" Ag to B- and T-cells *Antigen presentation*

Macrophages

Cell surface is covered with variety of receptor proteins

* Antigen Presentation

Secrete cytokines

Induce inflammation and chemotaxis

Surface receptors include:

• antibodies
• cytokines
• selectin/integrin (adhesion molecules)
• complement
• toll-like receptors detect foreign patterns

Shift to the left

• An increase in immature neutrophils,which indicates an infection in progress.
• The term "shift to the left" is a holdover from when lab results were written by hand - the less mature neutrophils were listed first on the left-hand side of the report card.

Selectin

Adhesion molecule on cell surface of macrophages

For "stick and role" phenomenon

Arachidonic acid (not whole pathway)

• Begins with arachidonic acid
• Generates PGs, thromboxane, leukotrienes

Integrin

Adhesion molecule located on cell surface of macrophages

Epitope

Specific part of Ag that fits receptors.

Recognized by immune cells, initiates immune response

Plasma Cells

B-cells that produce Ab at very high rate of speed

Die off shortly after

Kinins

Induces powerful vasodilation

Diapedesis

• The process of passing through the blood vessel walls and migrating to the inflamed tissue
• Result of increased vascular permeability.
• When WBC has a chance to get through and get into the area of infection.

Opsonization

• Recognition and binding by antibodies
• A pathogen is essentially ID'd and "marked" by an Ab for future destruction. 
• Some bacteria have capsules that prevent opsonization

Margination/pavementing

• WBC's line up against the edges of the vessel in preparation for migration out of the vessel.
• Next step is diapedesis (emigration of WBCs to site of injury).

Chemotaxis

• Migration/movement of cells based on chemical changes.
• Macrophages secrete cytokines (chemical cell messengers) that induce chemotaxis. 

4 theories of autoimmunity

1. Antigenic mimicry
• Self/foreign antigens made of same materials, so small alterations in self tissue lead to attack
2. Release of sequestered antigens
• Self antigens not in direct contact with lymphocytes during fetal development
• Antigens “hid” in places lymphatics couldn’t reach.  When illness hits, Ag’s released
3. T-cell theories
• Thymus gland defects
• Decreased supressor T-cell function
• Altered T helper cell function
4. B-Cell theories
• B cells lose their responsiveness to supressor
• T-cell signals increase on B-cell function and autoAb production

IgG

• Most common type (75-90%)
• Smallest
• Easily escapes bloodstream to enter interstitial fluid
• Neutralizes toxins, binds and facilitates destruction of bacteria

IgM

• Largest
• Mostly found in intravascular pool; cannot penetrate capillary wall
• First to be produced on exposure to Ag or after immunization
• Major Ab found on B-cell surfaces
• Works best to activate complement cascade

IgA

• Produced by plasma cellslocated in tissue/under skin/mucous membranes
• Primarily found in saliva, tears, tracheobronchia SECRETIONS,
• Secretory IgA
• complex made by binding to secretory component produced by epithelial cells;
• prevents proteolysis
• Allows transport of IgA into secretions

IgD

• Found in tiny amounts in serum
• Located primarly on B-cell membranes (with IgM)
• Thought to be cellular Ag receptor that acts to stimulate B-cell to:
• multiply
• differentiate
• secrete other specific immunoglobulins

IgE

• Associated with inflammatory and allergic reactions
• Immunity against helminthic parasites
• Causes mast cell degranulation when Ag detected at mast cell surface
• Type I hypersensitivity reactions

Types of Inflammation

• Acute
• Short in duration (<2 weeks)
• Involves discrete set of events
• Chronic
• More diffuse
• extends over longer period
• May result in scar tissue formation or deformity
• granuloma
• Fact: inflammation has now been linked to many pathologic processes, including CVD, diabetes, and insulin resistance.  It remains to be demonstrated if inflammation is causitive to these and other pathologies

Five cardinal signs of inflammation

1. Redness
2. Swelling
3. Heat
4. Pain
5. Loss of function

Type I hypersensitivity

• Etiology: Allergic
• IgE response to antigens
• IgE binds to Fc receptors on mast cells
• AKA "immediate hypersensitivity" (15-30 min postexposure)
• Atopic, anaphalylacic

Primary Ab involved in Type I Hypersensitivity and role of intracellular Ca++

• IgE (primary Ab)
• Increased intracellular Ca++ leads to granulation and inflammation

Type I hypersensitivity: How long does it take?

"Immediate hypersensitivity"

Rxn occurs 15-30 min after exposure to Ag

Type I hypersensitivity: Principal chemical mediator

Histamine

(If you answered "IgE": IgE is principal mediating antibody, not chemical)

Steps of WBC reaction in Type I Hypersenitivity

1. Ag exposed to B-cells
2. B-cells crank out IgE
3. IgE binds to mast cells
4. Exposure of mast cell to Ag --> Cross-linking of IgE and Ag's
5. Increased intracellular Ca++
6. Degranulation
7. Inflammation

Clinical manifestations of Type I Hypersensitivity

• Mild:
• Hives
• Seasonal allergic rhinitis
• Eczema
• More problematic:
• Throat constriction
• Localized edema
• Wheezing
• Tachycardia
• Anaphylaxis
• most severe, occurs in very small # of highly allergic inividuals

Type II hypersensitivity

• Tissue-specific, cytotoxic, or cytolytic hypersensitivity
• Ab's attack Ag's on surface of specific cells or tissues

Primary Ab's involved in Type II hypersensitivity

• IgG
• IgM

How is tissue damaged accomplished in type II hypersensitivity?

• On specific cells:
• Cell lysis: mediated by Activated Complement Fragments (MAC)

Transfusion reaction:

What is it?

What antibody (immunoglobulin) is involved?

• It occurs when an individual recieves blood from someone with a different/incompatible blood type. 
• IgM

Erythroblastosis fetalis: describe mechanism

• Mediating antibody: IgG
• Rh(-) mother is exposed to fetus's Rh(+) blood (which contains Rh antigens).
• Becomes an issue after the first pregnancy/exposure with a Rh(+) baby.
• Mother's IgG crosses placenta and attacks fetal blood cells.

Type III hypersensitivity

• AKA "Immune complex reaction"
• Immune and phagocytic systems fail to effectively remove Ag-Ab complexes.
• Not tissue specific

Primary Ab's involved in Type III hypersensitivity

• IgG

Mechanism of Type III hypersensitivity

• Ag-Ab complexes activate complement cascade, which attracts phagocytic cells to tissue
• Persistent low-grade infections, inhalation of Ag's into alveoli
• autoimmune production of antibodies
• may result in chronic production of Ag-Ab complexes

Which branch of the immune response is involved in Type IV hypersensitivity?

How is Tuberculosis a Type IV hypersensitivity reaction?  What happens?

"Granulomatous hypersensitivity"

Chronic Type-IV hypersensitivity reaction

Process:

• Ag engulfed by unsuspecting macrophages, which fail to kill it off.
• --> A "core" of inflammatory cells is produced (eosonophils, macrophages, etc)
• --> Forms a ball/mass granuloma
• --> Epitheliod cells fuse into giant multinucleated cells
• --> Core surrounded by lymphocytes
• --> granulmoa becomes fibrotic
• --> central necrosis (caseous)

Chronic mucocutaneous candiasis

• Autosomal recessive disorder
• Selective deficiency of cell-mediated immunity against C. albicans.

IgA deficiency

• Most common B-cell primary immunodeficiency disorder
• IgA-bearing lymphocytes fail to become plasma cells
• resulting in lack of serum and secretory IgA

What does it mean to have a secondary vs. primary immunodeficiency disorder?

• Primary:
• May be from congenital, genetic, or acquired defects that directly affect immune cell function.
• Secondary:
• Immune function is impaired as a result of other non-immune system disorders that secondarily suppress immune function
• problems in neuroendocrine and immune sys interaction

Autoimmunity

 Immune system attacks own tissues

• immune system recognizes its own cells as foreign and mounts an immune response that injures "self" tissues
• Cause of abnormal excessive immune responses toward own tissues
• Breakdown of self tolerance
• self tolerance = recognitoin
• Rememger MHC/HLA roles
• Possible theories:
• Polygenic
• Multifactorial

Hypersensitivity

• Describes mechanism of injury
• May or may not invoke autoimmunity

*Self-tolerance

• = recognition of own cells
• MHC: Allows immune system to know what "self" is

Rh(+) vs. Rh(-)

• Rh(+) cells have Rh Ag's, no anti-Rh Ab's.
• Rh(-): have no Rh Ag's or Ab's,
• but will develop Ab's upon exposure to Rh Ag's (Rh+ blood).
• subsequently incompatible with Rh+ blood groups.

SCID

• Severe combined immunodeficiency disorders
• Result from embryonic defects
• Severe immune sys. dysfunction
• Reticular dysgenesis
• Rx: bone marrow transplant (limited success)

Types of HIV transmission

• Sexual
• via semen or vagina/cervical secretions through homosexua, bisexual, or heterosexual intercourse
• Parenteral
• via blood, blood products, or blood-contaminated needles or syringes
• Perinatal
• transmission in utero, during delivery, or in breast milk

How HIV is NOT transmitted

• Urine, saliva, tears, CSF, feces
• Saliva particulates or aerosol routes
• HIV is NOT transmitted via dried blood
• virus cannot live outside the body
• Note that HBV (hep B) can survive in dried blood

Time frame for post-exposure intervention

• 72 hours
• admin of 2 reverse transcriptase inhibitors, and as needed for 4 wks after exposure.
• If advanced disease, also take protease inhibitor.

HIV as a retrovirus

• RNA Retrovirus
• Causes defect in cell-mediated immunity
• Viral DNA must be converted to DNA before viral genes can be copied to make copies of RNA virus.

Describe the 9 steps to how HIV infection occurs

• 1. Virus enters body --> adheres to lectin on DC (dendridic cell) - uses DC as a "trojan horse" to sneak into the lymph node.
• Why? Th Cells congregate in lymph nodes!
• 2. Virus binds by gp120 envelope to the CD4 molecule on Th cell
• 3. Binding to the Th cell via gp120 allows binding to coreceptors CCCR₅ and CXCR₄ 
• Binding of the co-receptors causes the Th cell membrane to melt away, so virus + cell fuse.
• 4. Virus injects core into cell, activates reverse transcriptase and copying begins.
• RNA --> DNA --> protein
• Virus's DNA incorporates (permanently) into host DNA
• all new copies of cell now infected (kind of a dick move)
• 5. Virus buds from infected cell, tearing holes in the membranes
• 6. As new copies are made, gp120 protein is replicated, allows fusion into more Th cells
• 7. When Th cells fuse, a huge SYNCYTIUM forms
• this is how virus infects multiple Th cells at once
• 8. Syncytium prevents receptor availability for immune Ab binding
• so Ab's are useless (another dick move)
• 9. At first, CD4 cells are replenished as virus is cleared, but over time, CD4 cells are lost.
• Seen as a falling CD4/CD8 ratio.
• Accelerating fall in rato = poor prognostic sign

Why are Ab's useless against HIV syncytiums

• Syncytium prevents receptor availability for Ab binding

Why do people with HIV only respond to old infections, and not new ones?

• Because naive T-cells (that would be able to respond to new infections) persist in low numbers.
• This is indicative of deterioration of immune function

Describe the effect of HIV on T-cells, B-cells, and macrophages

• T cells
• Th cells are targeted by HIV virus
• Reduction in Th lymphocytes
• B cells
• decreased responsiveness because they depend on the T-helper cells, which are declining in #
• Macrophages
• Become more functionally impaired as infection progresses
• Contributes to T-cell decline by increasing CD4+ cell death...

CD4/CD8 ratio

If low (<1), poor prognostic sign

In worsening HIV, CD4+ cound down while CD8+ count up.

Opportunistic infections

Latent period

• Period afterseroconversion.
• Ranges from 3-12 years
• Ongoing antiviral immune activity
• Virus production maintained/stabilized at set level
• Person feels well; may have chronic lymphadenopathy or mild general symptoms
• CD4+ count greater than 400/microliter

Testing for HIV

• Dx of infection requires confirmation by Western blot test.
• ELISA (Enzyme-linked immunosorbent assay) done first. 
• Western blot - used if ELISA is positive
• OraQuick Rapid HIV-1
• New, rapid fingerstick-based assay
• 20 min
• positive result must still be confirmed by Western blot
• False-negatives can occur
• Best method to test neonates:
• culture virus from blood and peripheral tissue

Common early signs of HIV infection

• Flu-like or mononucleosis-like symptoms
• CD4+ T-cell count greater than 400cells/μL
• Decreased # of WBC's including lymphocytes
• EXCEPT: increase in CD8+ T cells
• Decreased platelets
• Elevated ESR
• HIV count in genital fluids very high

Seroconversion

• Point where enough Ab's are detected in the blood
• Between 3 weeks and 6 months after exposure (rarely after 14 months)
• Signs and symptoms of acute retroviral syndrome or primary HIV infection
• flulike symptoms that can mimic other viral illnesses

Erythrocyte sedimentation rate

• ESR
• measurement of the rate with which RBCs setlle in saline or plasma over a specified time period.
• Not specific for any particular disease.
• Indicator of course of disease, useful in monitoring disease thearpy
• Increases as disease worsens.

HIV ELISA

• Enzyme-linked immunosorbent assay
• Detects antibodies if sample (blood or oral mucosal transudate) of an infected person reacts with the surface antigen of a killed HIV virus.
• Does not detect antigens
• therefore can't detect infection in earliest stage (before seroconversion)
• Positive results must be confirmed with Western Blot Ab test to dx pt with HIV

HIV Western Blot

• Immunoflorescence assay (IFA) used to validate positive serologic (ELISA) tests. 
• Expensive and time-consuming
• Uses electrophoresis
• ID's specific Ab's against HIV protein Ag
• Specificity (in combination w/ ELISA) >99%
• Takes 1-2 weeks

Complete blood count

• Detects Anemia
• neutropenia
• thrombocytopenia (in advanced disease)

Viral load

• Plasma viral load
• Indicates the amount of viral replication and the effectiveness of therapy
• Helps predict disease pogression
• Level of HIV RNA in plasma strongest indicator of outcome over time

True or false:  An adaptive immune response can be initiated in the periphery

Antibodies - mnenomic

My Delightful Gamma Eats Ants

Process: Type I hypersensitivity

1. Ag exposed to B cells
2. B-cells crank out IgE
3. IgE binds to mast cells (covered with IgE receptors/vesicles filled with vasoactive substances)
4. Exposure of mast cell to Ag -> IgE & Ag's crosslink
5. Increased intracellular Ca²⁺
   
6. Degranulation
7. Inflammation
   

Blood Groups

Rh-factor (positive vs. negative)

• Rh-positive: contain Rh antigen on blood cells
• Rh-negative: do not have Rh antigen.
• Anti-Rh antibodies develop only after exposure to the Rh antigen.

Erythroblastosis fetalis is what type of hypersensitivity reaction?

Type II hypersensitivity examples

• Myasthenia Gravis
• Graves disease
• Lymphocytic thyroidosis
• Hyperacute graft rejection

What are the effects of histamine?

• Increased vascular permeability
• Vasodilation
• Urticaria
• Smooth muscle constriction
• Increased mucus secretion
• Pruritus

Blood types: Group A

Which Ab's?
Which Ag's?

• Has A-antigens present
• Contains Anti-B Ab's

Group A blood type - Transfusion Reactions:

Type B donor blood

Type O donor blood

• Donor is B:
• Recipient's circulating Anti-B Ab's attack donor's B Ag's.
• Donor is O (has no Ag's):
• Donor's Anti-A Ab's attack recipient's A Ag's. 
• Reaction may be less severe because of small(er) amount of Ab's in donor's plasma   

Group B Blood type: Antibodies and Antigens present

• Antigen: B
• Antibodies: Anti-A

Group B recipient: Transfusion reactions if

Donor is A

Donor is AB

Donor is O

• Donor is A
• Recipient's circulating (anti-A) Ab's attack donor's A Ag's. 
• Donor is AB
• Same rxn as A
• Donor is O (has both anti-A and anti-B Ab's but no Ag's)
• Donor's anti-B Ab's attack recipient's B-Ag's. 
• Not as severe because of small amt of Ab's in donor plasma.  

Group AB blood type: Antigens and Antibodies present

• Antigens: A and B
• Antibodies: none

Group AB blood - Transfusion reactions

Donor is A

Donor is B

Donor is O

AB is the universal recipient (*to a degree).  It has no circulating Ab's, so it won't mount an immune response against donor RBC's. 

*Donor's plasma may contain Anti-A and/or Anti-B antibodies, which may attack the A or B antigens on the recipient's RBC's, but this is a minor problem. 

Blood types: Group O - Antigens and Antibodies present

• Antigens: none
• Antibodies: Anti-A and Anti-B

Recipient is blood group O - Transfusion reactions:

Donor is A

Donor is B

Donor is AB

• Group O recipient is incompatible with all three (A, B, and AB group) donors
• The donor's circulating anti-A and anti-B antibodies will mount an immune response from the recipient. Can be systemic and severe.

Type O blood: why is type O the universal donor?

Type III hypersensitivity: how does tissue damage occur?

Ag-Ab complexes aren't removed effectively, so they deposit into tissues. This results in:

• Activation of complement (C_3a and C_5a):
• histamine from mast cells
• Subsequent tissue inflammation:
• chemotaxis from neutrophils release enzymes and free radicals
• DESTRUCTION...

Type III hypersensitivity: Where do complexes collect?

• Ag-Ab complexes deposit in tissues, but not tissue-specific. 

Type IV hypersensitivity & Principal Ab's involved

• Delayed Hypersensitivity
• Tissue damage resulting from delayed cellular reaction to an Ag
• No primary Ab involvement

Type IV hypersensitivity: Describe the mechanism

1. Hapten binds with another 'carrier' protein to make a complete antigen
2. Ag taken up by Ag-presenting cell
3. Taken to lymph node
4. Presented to Th cells
5. Lymphokines released
6. Inflammation --> destruction

**Adaptive - takes time**

Type IV hypersensitivity: Which branch of the immune response?

Type IV hypersensitivity: Principal mediators and principal effector cells

• Principal mediators:
• Lymphocytes: lymphokine-producing T-cells
• CD8+ Killer T cells
• Principal Effectors:
• Lymphocytes
• Macrophages/mast cells

Helper-T cells (Th) in specific immunity

• CD4+
• Recognize Ag in association with MHC-II.
• Bind to MHCII, recognizing specific antigen (presented by Ag-presenting cell)
• Generate signaling cascade in Th cell cytoplasm
• Linked to cascade through CD₃

Role of T-Cells (generally) in specific immunity

HIV Retrovirus/Reverse transcription video. 

(Copy/paste link into your browser)

http://www.youtube.com/watch?v=HhhRQ4t95OI

How does the HIV virus enter the lymph nodes?

It adheres to a dendridic cell, which the virus uses a "trojan horse" to sneak into the lymph node.

Why does the HIV virus go to the lymph nodes?

What immune cell does the HIV virus bind to (once inside the lymph nodes)?

What protein allows viruses to attach to the CD4+ cell? 

What is a syncytium?

• A multinucleated mass of cytoplasm, created by fusion of many cells

What enables the HIV virus to infect multiple cells at once?

• the formation of a syncytium (by fusing to the Th cell membrane)

Describe the overall action/process of reverse transcriptase

• RNA strand is injected into the CD4+ (Th) cell
• Once inside, reverse transcriptase works to create a single strand of viral DNA (using it's own RNA strand as a backwards template - reverse transcribing)
• Reverse transcriptase then synthesizes a complementary strand to create a double-helix of viral DNA
• Then the viral DNA is inserted into the host's own DNA. 
• Now, the cell will use its own machinery to synthesize viral proteins
• That qualifies the virus as a sneaky, lazy jerk...

What is significant about the CD4/CD8 ratio in terms of HIV infection?

• It signifies the decrease in CD4+ (T-helper) lymphocytes.
• without Th cells, macrophages become more functionally impaired.
• B-cells don't respond as well because they depend on Th cells to release cytokines.