Immunology Flashcards
What is the innate immune system?
First line of defense against bacteria, viruses, and parasites RAPID response (min to hours) NON-SPECIFIC defense (attacks all foreign antigens in the same way) NO memory defense
Physical barriers are part of the ________ immune system
Innate (Natural)
Examples: Lysozyme in tears/other secretions Skin surface, fatty acids, and normal flora Rapid pH change between stomach/intestines Cilia in nasopharynx Mucus lining in trachea Stomach pH of 2 Normal gut flora Flushing of urinary tract
The complement system is a group of 30+ ________________ that activate in a cascade-like manner in response to _________.
30+ plasma proteins, in response to an antigen (anything foreign to body)
It enhances (“compliments”) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism
Promotes inflammation to help clear infection
Attacks the pathogen’s cell membrane —> lysis
Sequence of events in the complement pathway
- Activation through either the classical, let in, or alternative pathways (most common)
- Formation of the enzyme C3 convertase (cleaves C3)
- Opsonization and phagocytosis
- Inflammation
- Membrane Attack Complext (MAC) formation and lysis
The three pathways of the complement system:
- Classical Pathway - triggered by antibodies (such as IgM and IgG) binding to an antigen; most responses use this pathway
- Lectin Pathway: lectin proteins bind to mannose residues on the microbial surface
- Alternative Pathway: complement proteins act directly on cell surfaces (unusual)
The most abundant complement protein is _______.
C3
C3 convertase cleaves C3 to activate the classical pathway
The coating of a microbe by an antibody (or complement protein) to “tag” it for phagocytosis is called:
Opsonization
Marks the cell for destruction
Phagocytosis is the mechanism by which host cells:
Engulf and destroy an organism (some phagocytes are better than others)
The final step in the classical pathway of the complement system is the formation of the _________________
Membrane Attack Complex (MAC) —> Lysis
MAC is a complex of complement proteins that form to cause the lysis of a microbe
C5b, C6, C7, C8, and C9 are the proteins that bind to form MAC
Once these proteins combine on the surface of an antigen, the cell wall disintegrates and cell rupture ensues
________________ is an autoimmune disease that is also a huge player in complement deficiencies
SLE
*Same deficiencies seen in pyogenic infections
C1,C2,C4 deficiency —> deficiency in cleanup of IC and activation of classical pathway
C3 deficiency —> inability of cleanup of IC, complement activation
Factor H deficiency —> loss of control in the activation of alternative pathway, low C3 concentrations
Stages of an inflammatory response
- Tissue Damage
- Chemical signals alert endothelial cells along the capillary wall
- Neutrophils become “sticky” and stop rolling along the capillary wall
- Mast cells release histamine
- Histamine causes vasodilation and openings in between endothelial cells
- Fluid and leukocytes enter the affect tissu
- Neutrophils “squeeze” through endothelium (“extravasation”)
- Neutrophils are attracted to the damaged site and ingest/destroy bacteria
*Neutrophils = professional phagocytes (monocytes = 2nd line)
Neutrophils, eosinophils, and basophils are _______________
Monocytes and Lymphocytes are _________________
Granulocytes; Agranulocytes
Granulocytes have granules (packets of histamine, lysosymes, etc to help breakdown things)
Monocytes are the most important agranulocytes
Never Let Monkeys Eat Bananas
The distribution of WBCs in descending order:
Neutrophils (62%) Lymphocytes (30%) Monocytes (5%) Eosinophils (2.5%) Basophils (0.5%)
All about the Neutrophils!
The most abundant WBC - the body’s first responders
Particularly active against bacteria
Adhere to the vascular endothelium using adhesion molecules
“Squeeze” out into the tissue to attack bacteria
Undergo phagocytosis very efficiently to kill antigens
Promote inflammation
Increased neutrophils on the WBC diff is suggestive of…..
An acute bacterial infection, particular if bands (immature neutrophils) are high
An increase in BAND neutrophils means that the bone marrow has been signaled to release more WBCs and can be described in lab values as LEUKOCYTOSIS WITH A LEFT SHIFT
______ signifies a “left shift”
> 8% bands (immature neutrophils)
Indicative of an acute bacterial infection
Typically, bands only make up 3-6%
Elevated neutrophil count is called …
Neutrophilia
Causes:
• Acute bacterial infection (also fungal, viral, parasitic, spirochete)
• Noninfectious inflammation (hypersensitivity rxn, postop state, acute gout
• Metabolic: DKA, uremia, preeclampsia
• Other: exogenous corticosteroids
Low neutrophil count is called …
Neutropenia
Defined by the absolute neutrophil count (ANC)
Causes: • Infection (esp VIRAL) • Bone Marrow disease • Radiation therapy • Chemotherapy drugs • Toxins • Hereditary
_____________ are WBCs that play a role in allergic and antigen response
Basophils
Release granules that contain:
- HISTAMINE (increases blood flow to area)
- Heparin (reduces clotting)
____________ target larger parasites (ie Helminths) that are too large for one WBC to phagocytize
Eosinophils
Modulate allergic inflammatory response (help the basophils)
Rare in blood but numerous in the mucous membranes of the respiratory, digestive and lower urinary tracts
__________ are early responders in Type I allergies
Mast Cells
Release histamine and heparin
Present in barrier tissues (mucosa)
Play important roles in allergy and ANAPHYLAXIS reactions (think Type I hypersensitivity)
Largest WBC
Monocytes
Found in the blood and SPLEEN
Monocytes migrate into the tissues to become:
• Macrophages
• Dendritic Cells
Why you get splenomegaly with a MONONUCLEOSIS infection
Monocytes are themselves agranulocytes but can differentiate into macrophages, which are granulocytes
The three different types of Lymphocytes
B-cells
T-cells
Natural Killer Cells
The two primary lymphatic organs are ________ and _________
Bone Marrow - formation of B and T cells and site of B cell maturation
Thymus - site of T cell maturation
Secondary lymphatic organs are where lymphocytes __________
Encounter antigens (shouldn’t occur in primary lymphatic organs because they are sterile)
Spleen - removes old blood cells, synthesizes antibodies, removes antigens by way of blood and lymph circulation, stores extra RBCs
Lymph Nodes - filter foreign molecules and cancer cells (why we see LAD in cancer)
Tonsils/Adenoids - filter bacteria and viruses
Mucosa-Associated Lymphoid Tissue (MALT) - regulates mucosal immunity
What’s so special about bone marrow?
Located in the spongy inner portion of bone
Location of hematopoiesis
Primarily located in the pelvis, ribs, vertebrae, and sternum
Hosts B CELL maturation
Ok, so what about the Thymus?
Located in the mediastinum, behind the sternum
Larger as a child, shrinks with age (by age 4, it’s 2% of original size)
Hosts T CELL maturation
Thymus sail sign
Sail like shadow in right upper chest on X-ray of a child
Benign - it’s just the thymus (which you don’t see on adults)
So spleens are cool too. What do they do?
Largest lymphoid organ
Removes old blood cells, holds storage of RBCs, recycles iron
Synthesizes antibodies, specifically IgM memory cells (made after first exposure to an antigen)
So what happens when you don’t have a spleen
Asplenia
Modest increase in circulating WBCs/platelets
Diminished response to some vaccines
Increased susceptibility to infection by ENCAPSULATED BACTERIA:
1. Streptococcus pneumoniae
2. Haemophilus influenzae
3. Neisseria meningitides
(B/c complement not effective at labeling these for phagocytosis due to outer capsule)
***Immunize before surgical removal if possible
What’s the point of all these damn lymph nodes?
Small 1mm to 1-2 cm in size
Encapsulated by connective tissue
Filter foreign molecules and cancer cells
Become enlarged with certain diseases
Yay Tonsils!
First line of defense against ingested or inhaled pathogens
Combat common respiratory illnesses such as the common cold
Pharyngeal tonsils = adenoids
Palatine tonsils
Lingual tonsils
Mmmmm MALT
Mucosa-Associated Lymph Tissue
System of small concentrations of lymphoid tissue found in various submucosal sites
Populated by B cells and T cells, plasma cells and macrophages
Specializes in antigens passing through the mucosal epithelium
Acts by sampling antigen and delivering it to the lymphoid tissue
NALT (nasal), BALT (bronchial), and GALT (gut)
How is adaptive immunity different from innate immunity?
Second line of defense
Highly specific
Memory defense
The ability to distinguish _______ vs _________ is important because of the destructive nature of the adaptive immune system
Self vs Non-self (foreign antigens)
Autoimmune diseases arise from the loss of this ability
The innate immune system only activates the adaptive immune system if needed (if foreign cells present)
Define humoral immunity
Mechanisms: Antibody-mediated
Cell type: B-lymphocytes
Mode of Action: Antibodies in circulating serum
Purpose: Primary defense against extracellular pathogens (circulating viruses/bacteria)
Define cell-mediated immunity
Mechanism: Cell-mediated
Cell type: T-lymphocytes
Mode of action: Direct cell to cell contact or secreted soluble products
Purpose: Primary defense against INTRACELLULAR pathogens (viruses, fungi, intracellular bacteria, TUMOR ANTIGENS)
So let’s talk about this B-lymphocytes some more…
B cells are made in the Bone marrow, mature in the Bone marrow
Once mature, these mature naive B-cells enter blood circulation and migrate to the secondary lymphatic organs (spleen, lymph nodes, MALT)
B-cells will produce specific antibodies to fight against particular antigens ONCE THEY’VE BEEN ACTIVATED
Steps to activating B-lymphocytes
- Recognition: Antigen binds to the mature, naive B-lymphocyte surface receptor
- Proliferation: B-lymphocytes proliferate and make clones
- Differentiation: Clones will either become a plasma cell or a memory cell (plasma cells die quickly, memory cells stick around for months/years) —> years later, memory B cells can activate a secondary immune response
So what exactly ARE antibodies?
Plasma cells produce antibodies (aka immunoglobulins (Ig), aka gammaglobulins)
Antibodies “tag” antigens to mark them for destruction (opsonization)
Destruction is via phagocytosis or chemotaxis
The five different classes of antibodies, in the order they appear when encountering antigens
IgM IgG IgA IgE IgD
(Methinks Great Americans Eat Donuts)
IgM antibodies
The first responder - first antibody produced by the plasma cells
Indicates acute/recent infection
LARGE - 5 Y-shaped molecules connected in star shape
IgM is very good at activating the complement system
5-10% of antibodies in blood
5-10 day half-life
IgG
Second responder - second antibody produced by the plasma cells
IgM levels fall as IgG levels rise
IgG is good at opsonization
IgG can also activate the complement system
75% of antibodies in the blood (MOST ABUNDANT)
21 day half-life - indicate acute/subacute infections
IgA
(2 linked Y-shaped molecules)
IgA is found primarily in the mucosal membranes and secretions (as secretory IgA)
Present in the GI tract, respiratory tract, saliva, sweat, and tears
Good at eliminating pathogens through mucosa
IgA is a weak opsonizer and is not effective in activating the complement system
IgA disorders
IgA Nephropathy: deposition of IgA in the kidneys
Henoch-Schonlein Purpura: IgA vasculitis caused by deposition of IgA in small vessels
Celiac Disease: presence of IgA anti-endomysial antibodies
IgA Pemphigus: IgA antibodies that target proteins in the skin, causing autoimmune blistering disorder
IgE
Produced in response to allergens
Defends against helminths (roundworms) and parasites
IgE bind to mast cells
IgE causes the release of histamine
Plays a large role in Type I Hypersensitivity Reactions
Hang with eosinophils and mast cells
IgD
Involved primarily in the activation of B-cells
Not very well understood and is thought to play a small role in several different immune processes
So how do vaccines work anyway?
Vaccines are a form of acquired immunity that allows us to target specific diseases
Vaccines introduce an antigen that stimulates the body to produce antibodies
Memory cells are there if the antigen tries to reattack in the future
What is Cell-Mediated Immunity
Cell-mediated immunity deals with INTRACELLULAR bacteria, viruses, and any bacteria that are out of reach of antibodies
T-lymphocytes are made in the bone marrow but mature in the Thymus
Once mature, T-cells express surface receptors, known as T-cell receptors (TCRs)
Mature naive T-cells must undergo a 2-signal activation
Steps to activating T-lymphocytes
1st signal: TCR binds to the MCH-antigen complex of antigen-presenting cell (APC)
2nd signal: T-cell surface receptor CD28 must bind with B7, located on the APC
Activated T-cell functions
Once T-cells are activated, they divide (proliferate)
They then differentiate into Helper T-cells, Cytotoxic T-cells, Suppressor T-cells, and Memory T-cells
Helper T-cells produce cytokines that stimulate macrophages for phagocytosis
Cytotoxic T-cells kill virus-infected and tumor cells
Types of T-cells: Helper T-cells
Stimulate B-cells, stimulate T-cells to proliferate, activate macrophages, activate NK cells
Surface receptors: CD4+
Binds to MHC II
Types of T-cells: Cytotoxic T-cells
Aka Natural Killer Cells
Kill virus-infected cells, kill tumor cells
Surface receptor = CD8+
Binds to MHC I
Types of T-cells: Suppressor T-cells
“The regulator”
Prevent immune system over activity by helping recognize self from non-self
No surface receptors
Does not bind to MHC complex
Types of T-cells: Memory T-cells
“The Veteran”
Recognizes antigens from previous exposure
No Surface receptors
Does not bind to MHC complex
Antigen Presenting Cells
Essential for adaptive immunity
Can be any nucleated cell in the body except for T-cells
Their function is to prepare an antigen and present it to the T-cells
Antigen Presenting Cells (APCs) have Major Histocompatibility Complexes (MHCs) on their surfaces that display the antigen to the T-cell receptors on cytotoxic and helper T-cells
MHC I binds to _______ on ____________ T cells
CD8+
Cytotoxic T cells (Natural Killer Cells)
MHC I are found on the surface of all nucleated cells
MHC II binds to _______ on ____________ T cells
CD4+
Helper T-cells
MHC II are only found on the surface of B-cells, dendritic cells, and macrophages (all produced by the immune system itself)
