IMMUNOLOGY I Flashcards

(49 cards)

1
Q

Define Antigen

A

Antigens are anything that causes an immune response.
Eg. bacteria, viruses, fungi, parasites, or smaller proteins that they express (aka “pathogens”).
Antigens are like a name tag for each pathogen that announce the pathogens’ presence to your immune system.
Some antigens are general, whereas others are very specific.
A general antigen signals “danger!”
A specific antigen signals “I’m a bacteria that will cause an infection in your lungs!” or “I’m HIV”

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2
Q

Define Antibody

A
An antibody (immunoglobulin or Ig) is a protein molecule created by our immune system to target an antigen for destruction. 
These proteins bind to the foreign antigen, thereby disabling the antigen and “tagging” it for destruction by other immune defenses.
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3
Q

Define Cytokines

A

CYTOKINES are cell-to-cell communication proteins that control cell development, differentiation, and movement to a specific part of the body. They are produced by a variety of leukocytes.

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4
Q

Define Interleukins

A

Interleukins (ILs) are 13 cytokines that are regulators (in part) of immune responses, inflammatory reactions, and hematopoiesis

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5
Q

interleukin 1 and 6 are responsible for what?

A

fever

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6
Q

Interleukin 6 causes what?

A

acute-phase response

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7
Q

Tumor Necrosis Factor (TNF)

A

Tumor Necrosis Factor (TNF) activates neutrophils, mediates septic shock, causes tumor necrosis.

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8
Q

Chemokines

A

Chemokines are a type of cytokine released by infected/injured cells. They initiate an immune response (signal circulating neutrophils and macrophages), and warn neighboring cells of the threat.

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9
Q

Interferons (IFN)

A

Block virus replication. Alpha, beta and gamma subtypes (IFN-α, IFN-β, IFN-γ)
IFN-γ is the strongest IFN, is produced by T cells, and activates macrophages, natural killer cells, and neutrophils

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10
Q

Type I Interferon

A

Type I includes the (α) & (β) forms
Function is to induce viral resistance in cells
Type I IFNs can be produced by almost any cell type in the body

Type I IFNs- friend or foe?
Has been shown under some circumstances to suppress T-cell responses and memory T-cells; this is important, especially in HIV
May interfere with bactericidal mechanisms
In influenza, it limits viral replication but creates pathologic inflammation in the lung

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11
Q

Type II Interferon

A

Type II is the (γ) form.
Type II interferon is secreted only by natural killer cells and T lymphocytes;
Its main purpose is to signal the immune system to respond to infectious agents or cancerous growth.

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12
Q

Explain divisions of immune system

A

Innate
aka ‘natural’, ‘non-specific’
FAST

Adaptive
aka ‘specific’, ‘humoral’ or ‘cell-mediated’
SLOW

HOWEVER, there is some crossover between the functions of the two branches!!

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13
Q

Hematopoiesis

A

The formation and development of the cells that make up “blood”
Embryo and fetus : occurs primarily in liver, spleen, thymus;
Birth –adult: occurs primarily in bone marrow small amount in lymphatic tissues

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14
Q

Innate Immunity

A
Components:
Physical barriers
Granulocytes (aka PMNs)
Monocytes
Macrophages
Dendritic Cells
Natural Killer Cells
Complement Cascade
Characteristics
IMMEDIATE
Non-Specific Response…no memory
Response does NOT increase
     with repeat exposure
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15
Q

First level of protection: Physical Barriers

A
Skin
Protects against invasion
Acidic pH of sweat
Fatty acids and enzymes from pores/follicles
Mucous Membranes
Tears
Saliva
Mucus
All contain  lysozyme….which protects against gram (+) bacteria
Gastric secretions…external? Yes!
Acidic pH
Commensal bacteria- “normal bacterial flora”
Microbial Antagonism
Both external and  internal
Compete with potential pathogens
Upset by antibiotic use
Example: vaginal candidiasis resulting from change in lactobacillus and/or G. vaginalis concentrations
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16
Q

When the barrier (first level of protection) isn’t sufficient protection: the inflammatory response

A

Damaged tissue and/or cell mediated histamine, prostaglandin and leukotriene release causes vasodilation and leaky capillaries
Cell mediated heparin release causes decreased clotting
RESULT: Increased blood flow to area, immunologic factors leak out of capillaries into interstitial space to do their jobs……

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17
Q

Adhesion molecules

A

Membrane proteins that connect cells to other cells or the extracellular matrix (ECM)
Play a major role in the recruitment of neutrophils to the site of inflammation…. neutrophils “roll” along the luminal surface of blood vessel towards the site of injury, then squeeze out between cells of capillary wall.

Chronic inflammation chronic cytokine release & leukocyte infiltrationrelease of lysozyme & free radicals tissue damage

 Mutations in genes encoding cell adhesion molecules cause (we think) a variety of disorders
vascular system (atherosclerosis?), skin, kidney and muscle, and the immune and nervous systems (Alzheimer’s disease? Autism?)
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18
Q

Basophils

A
Least common 
Mature in bone marrow
Circulate in bloodstream
Allergic & helminth responses
Release histamine & heparin
Reduction of clotting & increased blood flow resulting from vasodilation
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19
Q

Eosinophils

A

Derived from the bone marrow…usually 1-6% of circulating WBCs
Both circulating in bloodstream & present within organs… particularly the GI tract and respiratory tract
Release H2O2 and other oxygen radicals to kill microbes:
Viruses, parasites (esp. helminths)
Release leukotrienes- lipid signaling molecules that causes airway smooth mm contraction
Active in allergic reactions, asthma

Stimulate T-lymphocytes
Act as “antigen presenting cells” (APCs)
Weakly phagocytic

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20
Q

Neutrophils

A

Most abundant of the granulocytes
Circulate in the bloodstream
One L of blood contains about five billion neutrophils!
“First Responders”
particularly active against bacteria & fungi
Arrive within minutes of injury
Chemotaxis- neutrophils respond to chemokines
In turn release other cytokines to recruit monocytes & macrophages
Strongly Phagocytic
Neutrophil Extracellular Traps (NETs)
‘throw out’ extracellular fibers that bind bacteria

21
Q

Mast Cells

A

Release histamine and heparin causing inflammatory cascade
Leave the bone marrow as immature cells, mature in tissues
Present in tissues that are boundaries b/t “inside” and “outside” (esp. mucosa)
Will degranulate if:
Injured
Encounters antigen or allergen
Exposed to complement proteins
Massive release of histamine results in anaphylaxis
Body-wide vasodilation leads to edema, decreased BP etc.

22
Q

Monocytes

A

“agranular”
Give rise to dendritic cells & macrophages
Develop in bone marrow; half are stored in the spleen, half migrate to tissues and differentiate into dendritic cells and macrophages
Monos, Macros and Dendros have 3 primary functions:
Phagocytosis
Antigen presentation (APCs)
Cytokine production

23
Q

Dendritic Cells

A

The ‘strongest’ of the APCs- best at activating helper-T lymphocytes
Antigens are captured by dendritic cells
The dendritic cell then migrates to the nearest lymph node & presents the antigen to T Cells and B Cells
Specialized dendritic cells in skin
Langerhans cells*

24
Q

Macrophages

A

Large phagocytes
release TNF and Interleukins (ILs)
Also act as APCs
Present under the skin, lungs, GI tract and most other tissues
Macrophages have 3 stages of readiness
a) resting = cleaning up cellular debris (scavengers)
b) primed = more active engulfing of bacteria, display fragments of bacteria for T cells (act as APCs)
c) hyper-activated = inflammatory cytokines cause macrophages to enlarge and start rapidly destroying pathogens and/or cancerous cells
After digesting a pathogen, a macrophage will present the antigen to a helper T cell.
Antigen is integrated it into the cell membrane and displayed attached to an MHC class II molecule (MHCII)
The MHCII indicates to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface

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Specialized Macrophages: Kupffer cells
Specialized macrophages within the liver Destroy bacteria & old RBCs Chronic activation of Kupffer cells (toxins, EtOH) leads to overproduction of inflammatory cytokines & chronic inflammation Result: liver cell damage, CA As phagocytes, macrophages may become hosts for pathogens! Eg. TB (bacterium), Leishmanisasis (parasite), Cikingunya (virus)
26
Natural Killer Cells
NK cells are cytotoxic lymphocytes, but don’t need to “recognize” or remember a pathogen to kill it! Particularly active against viruses and cancerous cells NK cells also have granules that contain destructive enzymes Mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus Killing activity is enhanced by cytokines secreted by macrophages NK cells kill their target by releasing perforins and proteases that cause cell membrane lysis or trigger apoptosis in the target cell can also cause apoptosis in their target by surface contact on-call” hang out in the bloodstream, liver and spleen Operate on a “kill” or “don’t kill” system will kill cells that have unusual surface receptors NK cells can “kill” even during their resting phase, but are better killers when activated (by cytokines) They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection.
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Major Histocompatibility Complex (MHC) Proteins
The human MHC is aka the Human Leukocyte Antigen (HLA) Cell surface molecules which help the immune system to determine if a protein is “self” or “not-self” Bind antigen to cell surface and display for recognition by T cells 3 sub-groups: MHC I,II & III Key points: Determines organ donation compatibility Autoimmune disease is a malfunction in this recognition system (ex. ankylosing spondylitis is HLA-B27 positive) Participates in T & B cell activation Displayed in combo with a piece of antigen by APCs
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Acute phase proteins
Produced by LIVER in response to inflammation induced release (by macrophages & T cells) of IL-1,IL-6 & TNF (remember, ILs are cytokines that help regulate immune responses, inflammatory reactions, and hematopoiesis; IL’s 1 & 6 are responsible for fever) C-reactive protein (CRP) Mannose-binding lectin (MBL) Lipopolysaccharide-binding protein All acute phase proteins identify or “mark” pathogens or injured cells for destruction in some way Ex. MBL binds to mannose-rich glycans on microbial cell walls, then activates complement Ex. CRP binds to bacterial and fungal cell walls and damaged or dead human cells, then activates complement
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Complement system (aka the Complement Cascade):
enhances the ability of phagocytic cells to destroy pathogens Composed of ~ 30 different proteins that work together to signal the other immune cells that the attack is ON! 3 possible complement activation pathways Classical (requires triggering) Alternative (continuously activated at low level) Lectin Pathway (requires very specific type of triggering) BOTTOM LINE: Complement is activated by antigens Complement proteins are made by the liver C3 is the most abundant complement protein in humans
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Functions of Complement
Opsonization - enhancing phagocytosis of antigens by ‘marking’ them for destruction Chemotaxis - attracting and activating macrophages and neutrophils; inducing mast cells & basophils to degranulate Lysis - rupturing pathogen cell-membranes by forming the Membrane Attack Complex (MAC) Complement Functions (video FYI only) Complement “Fixation”: antigen combines with an antibody and its complement, causing the complement factor to become inactive or fixed. The complement-fixation reaction can be tested in the laboratory by exposing the patient's serum to antigen, complement, and specially sensitized red blood cells. Complement-fixation tests can be used to detect antibodies for infectious diseases, especially syphilis and viral illnesses. They are rarely used in clinical practice today.
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Opsonization
enhancing phagocytosis of antigens by ‘marking’ them for destruction
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Chemotaxis
attracting and activating macrophages and neutrophils; inducing mast cells & basophils to degranulate
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Lysis
rupturing pathogen cell-membranes by forming the Membrane Attack Complex (MAC)
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Complement “Fixation”:
antigen combines with an antibody and its complement, causing the complement factor to become inactive or fixed. The complement-fixation reaction can be tested in the laboratory by exposing the patient's serum to antigen, complement, and specially sensitized red blood cells. Complement-fixation tests can be used to detect antibodies for infectious diseases, especially syphilis and viral illnesses. They are rarely used in clinical practice today.
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Membrane Attack Complex
C5b forms a complex with C6, C7, C8, and C9 to form the MAC This causes lysis of the cell by disrupting osmotic balance Microbe will swell and burst
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INNATE IMMUNITY KEY POINTS
Response is IMMEDIATE Response in NON-SPECIFIC; it is the same each time, regardless of the pathogen Response DOES NOT INCREASE with repeat exposure to pathogen
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Adaptive Immunity: Antibodies
Each recognizes only ONE antigen Bind to a specific site on the invader Function in several ways Directly block binding of the invader to cells Inactivate viruses and neutralize toxins “Mark” the pathogen for destruction by phagocytes = opsonization
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Antibodies Structure
``` 2 light chains 2 heavy chains Antigen binding sites Fab (variable) region antigen-specific Fc region (constant) class effect ```
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Antibodies Classes
``` IgM IgG IgA IgE IgD “GAMED ```
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IgM
BIG….pentamer of 5 units First class produced Half-life of about 10 days Increased IgM = RECENT exposure to antigen Large molecule- usually confined to intravascular space, however Inflammation -> increased capillary permeability Allows various plasma proteins, like IgM, to enter the interstitial space Formed early in the Primary Immune Response
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IgG
4 subclasses…IgG 1-4 Predominantly found in Blood Lymph CSF Peritoneal fluid Evenly distributed in intra/extravascular space Functions: Only class that crosses the placenta Good- confers mom’s immunity Bad – Mom may form IgG against fetal RBC antigens (ie. the Rh antigen)  destruction of fetal RBCs ……more on this later Bad- Difficult to use IgG as indicator of infection in baby (ex. HIV) Longest half-life of the Ig’s ~ 23 days Used for passive immunization against rabies and hepatitis Helps Natural Killer cells find their targets- opsonization Immobilizes bacteria by binding to their cilia or flagella Activates complement Neutralizes toxins and some viruses by binding IgG is formed late in the primary immune response
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Polyclonal & Monoclonal antibodies (Ab)
``` Polyclonal Ab: Prepared from immunized animals Each Ab can interact/bind with multiple sites on an antigen Monoclonal Ab: Produced in the lab Bind only to one site on an antigen ```
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IgA
``` Primarily found in External Secretions Mucus Tears Saliva Gastric fluids Colostrum Sweat ``` Function Protection of infant- present in breast milk Prevents viruses from entering cells Prevents pathogens from attaching to and penetrating epithelial surfaces Respiratory and GI tracts
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IgE
``` Present in LOW amounts in serum Short half-life….2 days Binds to mast cells and basophils when it encounters its antigen, triggers degranulation releasing histamine, leukotrienes & heparin from the granulocytes Increased in atopic individuals Increased in presence of parasites ```
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IgD
Present on surface of naïve B-cells Present in low amts in serum Function is unknown
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The Adaptive Immune System
Action requires days to develop Response is specific to an antigen Response is enhanced through repeated exposure to antigen Develops “memory”….subsequent exposures result in a more rapid and intense immune response
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Adaptive Immunity: Primary & Secondary Lymphoid Organs
Primary Lymphoid Organs: Where immature lymphocytes (Bs & Ts) grow up and proliferate Thymus (T-cells) in children Bone marrow Secondary Lymphoid Organs ``` Where antigens are presented to mature (but naïve) B & T lymphocytes to initiate the adaptive immune response Spleen Lymph nodes Tonsils & adenoids Appendix ```
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B-Cells (B-lymphocytes)
Eliminate EXTRACELLULAR PATHOGENS Is an APC! Presents a piece of the antigen in combination w/ a MHC molecule on its surface Produce ANTIBODIES (immunoglobulins, Ig) Has membrane-bound antibodies (functions as the B-cell receptor) Recognition of antigen by the B-cell receptor (which is an antibody), coupled with a signal from “Helper” T-cells (CD-4), prompts the B-cell to divide into “clones” These “clones” or effector cells (Plasma Cells) produce antibodies Produces memory B cells
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T-Cells (T-lymphocytes)
Destroy INTRACELLULAR pathogens: viruses and intracellular bacteria Subtypes: “Killer” T-cells (CD-8): cytotoxic- specialize in identifying and killing cells infected w/ viruses Attack cells that have been infected “Helper” T-cells (CD-4) Does not directly kill pathogens- raises the “alarm” via cytokines Assists in the activation of “killer” T-cells Signal B cells to begin secreting antibodies (Ig) Activated cell differentiates into effector cells & memory cells