Introduction to the Immune System Flashcards
Define the roles of the Immune System
- Defense against infection
- Defense against tumors
- Injure cells and induce pathologic inflammation
- Recognizes and responds to tissue grafts and newly introduced proteins
Define Adaptive Immunity
Response of Ag-specific lymphocytes to Ag includes MEMORY
Define Innate Immunity
Protection against Ag that relies on mechanisms that exist before exposure
What is CD?
Cluster of Differentiation
Cell surface molecules expressed on various cell types are designated by a CD number
CDs to memorize
CD21 = CR2 = C3dR CD25 = IL-2Ra CD152 = CTLA4 CD95 = Fas
Define Cytokines
Molecules that tell other cells what to do, mediate the immune response
They act through autocrine, paracrine, and exocrine actions.
Pleiotropic and redundant
They include: IL, TNF, IFN-a/B/y, TGF-B, CSF
Define Chemokines
They tell other cells to come here. Chemotatic cytokine (IL-8)
Define Immunogen
Ag that evokes a specific immune response
Define Tolerogen
Ag that induces immunologic tolerance
Define Endogenous Ags
Body’s own cellular components or intracellular pathogens
What are the different classifications of endogenous Age?
Autoantigens: SELF-Ag
Alloantigens: Tissue specific Ag, which is present in one individual but not another
Intracellular pathogens: Viruses, parasites, intracellular bacteria
Define Exogenous Ags
Ags that enter body or system, freely circulate in body fluids and are trapped by APCs
Uptake of Exo Ags by APCs mediated by phagocytosis
What structures make up Innate Immunity?
Epithelial Barriers, Mast Cells, Phagocytes, Dendritic Cells, Complement, NK cells and ILCs
What structures make up Adaptive Immunity?
B-lymphocytes (which may become Plasma cells)
T-lymphocytes (T-helpers, Cytotoxic T, Tregs, NK cells)
What are the Characteristics of Innate Immunity?
Respond rapidly Normally inactive in absence of infection Found in ANY vascular tissue Limited diversity NO Memory Stimulates Adaptive Immunity
What cell types are Phagocytes?
Neutrophils
Monocytes/Macrophages
Dendritic Cells
What are some characteristics of Neutrophils?
AKA: polymononuclear Circulate, short-lived First at Site of Infection Make up 54-62% of WBCs Component of pus (pyogenic)
CD marker for Neutrophil
CD15, CD16b
_1__ is present in the bloodstream and turns into _2__ in tissues. What phagocytes fill in the blanks?
- Monocytes
2. Macrophages
What are some characteristics of Monocytes/Macrophages (MO)?
Respond to site of inflammation in 1-2 days
Survive longer than neutrophils
Levels increased in chronic inflammation, immune-mediated diseases, stress, and necrosis
2 Major functions by:
M1 classical MO
M2 alternative MO
Define M1 classical macrophages.
They are induced by innate immunity to play a role in INFLAMMATION.
Define M2 alternative macrophages.
They are induced by IL-4 and IL-13 to play a role in TISSUE REPAIR and CONTROL of INFLAMMATION.
Other functions of MOs at various stages include?
Garbage collectors ("resting" state) Ag presenting cells ("activated" state) Vicious killers ("Hyperactivated" state)
CD marker for MOs
CD14 (TLR4)
Recognizes and binds to LPS
What are some characteristics of Dendritic Cells?
Include surface expression and CD marker
Professional APCs
Capture Ag, migrate to lymphoid tissue and present Ag to mature, naive T cells
Express: High levels of Class II HLA/MHC and CD80 (B7)
*May also present Ag with Class I HLA/MHC
What is significant about dendritic cells expressing high levels of Class II HLA/MHC + CD80?
It makes Dendritic cells better APCs than Macrophages and B-cells.
What is the major function of APCs?
They are the bridge b/w innate and adaptive immunity.
Define Specific Immunity.
Distinguish b/w different, closely related, microbes and molecules
Define Acquired Immunity.
Potent protective responses are “acquired” by experience
Characteristics of Adaptive Immunity
Specific for Ag
Diverse - receptors are produced by somatic recombination of gene segments
Has Memory
What are some characteristics of Eosinophils?
Differentiate in response to IL-5
Responsible for combating multi-cellular parasites
Major role in atopic diseases
What are some characteristics of Basophils?
Bi-lobed nucleus
Release pharmacologically active substances contained within granules
Role in Atopic diseases
Combat parasitic diseases
What are some characteristics of Mast Cells?
2 types: tissue and mucosal
Can be stimulated to degranulate by direst injury, chemicals, alcohols, and certain Abs, cross linking of IgE receptors, or activated C’ proteins
Key role in inflammatory process
Atopic responses
CD marker for Mast cells
CD23
Mature, Naive vs. Effector vs. Memory lymphocytes
Naive is when It has not been activated by Ag yet.
Effectors have been activated by Ag
Memory lymphocytes remember that you have immunity to a pathogen.
Humoral vs. Cell-mediated Immunity
Humoral - Antibodies neutralize and eradicate exogenous Ags (B-cells, produce immunoglobulins)
Cell-mediated - Activation of cell to eradicated endogenous antigens (T-cells)
Function of Effector B-cells
CD marker?
Neutralization of microbe
Phagocytosis
Complement activation
CD19, CD21
Function of Helper T-cells
CD marker?
Activation of macrophages
Inflammation
Activation (proliferation and differentiation) of T and B lymphocytes
CD3, CD4
Th1: IL-2, IFN-y
Th2: IL-4, IL-5, IL-13
Th17: IL-17, IL-22
Function of Cytotoxic T-cells
CD marker?
Killing of infected cells
CD3, CD8
Function of Regulatory T-cells
CD marker?
Suppression of Immune Response
CD3, CD4, CD25, IL-10, TGF-B
How does the Lymphatic system work?
It drains the tissues and transports lymphocytes and antigens to secondary lymphoid tissue, where the lymphocytes can interact with the antigens.
As blood is circulating, some fluid leaks out of the capillaries. This fluid is lymph. Most of the fluid will return back to the circulatory system through one way valves into the lymphatic vessels.
Lymph moves via muscle movement.
What occurs in the lymphoid tissue?
Dendrites or APCs will enter the lymphoid tissue through the Afferent lymphatic vessels. Lymphocytes will enter through the high endothelial venues. They follow lymphocyte specific chemokine to different regions of tissue (different zones for B and T cells). There they are activated by an APC and leave through the circulatory system.
If they are not activated they leave through the Efferent lymphatic vessels and go to the next lymphoid tissue. They will eventually end up at the thoracic duct and go back into circulation.
Function of Natural Killer Cells in Innate Immunity
CD marker?
Recognize infected, stressed, or malignant cells and kill them by releasing granzymes and perforins leading to apoptosis of target cell
Activated by IL-12, IL-15, and Type 1 IFNs
Activated NKs secrete IFN-y (activates macrophages)
CD16, CD56
What is the difference b/w NK cells and Cytotoxic T cells?
NK cell don’t recognize specific antigens like cytotoxic T cells do.
What is the relationship b/w NK cell and macrophages?
NK cells are activated by IL-12, which are release by macrophages. NK cells will then release IFN-y, which hyperactivates macrophages. Macrophages will then produce more IL-12, activating more NKs… and so on.
What is a primary immune response?
It is the first time an Ag is encountered.
Activation of naive cells to perform effector functions
Generation of memory cells
What is a secondary immune response?
It is the second time an Ag is encountered.
Memory cells are activated
There is a stronger, faster effector response
Describe the Mucosal Immune System.
Largest SA as barrier against outside world
More bacterial DNA than human
Microbiome - part of innate immune system
Contains very specialized cells and responses for protection
IgA - Ab abundantly produced in mucosal tissue, bind/neutralizes microbes
Define the Cutaneous Immune System.
SKIN - second largest barrier
Has specialized innate and adaptive cells and responses
Langerhans - primary APC in epidermis
Phases of Adaptive Immune Response
Antigen Recognition (T cells activated by APCs, B cells by Antigens)
Lymphocyte Activation (Clonal expansion and differentiation of lymphocytes - Ab producing cells and effector cells)
Antigen Elimination (by Abs and effector Ts)
Homeostasis (Apoptosis of infected cells)
Memory (surviving memory cells)
Describe Systemic Immunity.
Lymphocytes travel to secondary (peripheral) lymphoid organ where they will come into contact with antigens that traveled from site of infection via lymph.
Antigens also travel to the spleen via blood. Activation of lymphocytes and initiation of adaptive immune responses. Effector Ts and Abs migrate to site of infection.
Define Active Immunity.
Introduction of an Ag that provokes an adaptive immune response. Has memory!
Artificial = vaccine Natural = infection
Define Passive Immunity.
Introduction of Ab or antiserum into naive recipient
No memory!
Artificial = IVIG (intravenous immunoglobulin) Natural = maternal
What are the Primary lymphoid organs? Secondary?
Primary = Bone marrow and Thymus Secondary = Spleen, Lymph node, mucosal immune tissue
Describe the time line for Innate and Adaptive Immunity.
Phase 1 (0-4 hrs) = Non-induced Innate - skin, pH, saliva
Phase 2 (4-96 hrs) = Induced Innate, broadly specific - phagocytosis, C’ system, inflammation, cytokines
Phase 3 (>96 hrs) = Induced Adaptive, highly specific - B cells (Ab), helper Ts, CytT
Circulatory immune cells vs. Tissue immune cells
Circulatory = Neutrophils, Eosinophils, Basophils, Monocytes, T/B/NK cells, platelets, RBCs
Tissue = Tissue eosinophil, Mast cell, Macrophage, T-lymphocyte, Plasma cell, NK cell
Describe the migration of T and B lymphocytes in secondary lymphoid tissue.
Naive T-cells enter through high endothelial venules
Adhesion molecules used by Ts to bind to endothelium constitutively expressed
Chemokines produced in T-cell zones bind to chemokine receptor CCR7 on naive T-cells
Chemokine interaction with CCR7 causes T-cells to bind tightly to HEVs
Naive Ts migrate to T-cell zone
Naive B = similar
Migrate to LN follicles being guided by chemokines that bind to CXCR5 receptor on B cells