Immunology Chapter 1

Pathogens

Disease causing microorganisms

Antibody (Ab)

Proteins that bind to toxins and neutralize activity (bind antigens)

Antigen (Ag)

Substances that cause antibody generation (by immune cells)

Innate Immunity

Immediate, but nonspecific response with no memory

First line of defense against microbes

Macrophages & Neutrophils

Short duration and response time

Adaptive Immunity

Delayed but specific response, has memory

Long-lasting defense

Lymphocytes: B-cells and T-cells

Long duration and response time

Avoidance

Prevent exposure (anatomic and chemical barriers) and behavioral modifications

Resistance

Reduce or eliminate pathogens through effector mechanisms (innate and adaptive immune system)

Tolerance

Ability to resist damage

Immune System Function

Recognition, effector functions, regulation, and memory

Monocytes

Circulates in blood, baby version of macrophage

Macrophage

In the tissues, highly phagocytic, long life span, antigen presenter, and scavenger cells (cleans up dead cells and cell debris)

Granulocytes

Phagocytes, oddly shaped nuclei, short life span (a few days)

Eosinophils/Basophils

Small %, promote allergic responses and anti-parasitic activity. Have phagocytosis and bactericidal mechanism activation

Neutrophils

Most abundant granulocytes

Dendritic Cells

#1 antigen presenter, made in bone marrow and live in tissues, uptake through phagocytosis and degrade pathogens, T-lymphocyte activators

Mast Cells

Quick response; release histamine (cause inflammation), found in places where an allergic reaction can occur (airways, intestines, and skin)

Natural Killer (NK) Cells

Lymphoid lineage (innate immune system response), no specificity (no memory), ability to kill virus-infected cells and certain tumor cells

Pattern recognition receptors (PRRs)

Present on dendritic cells, macrophages, and neutrophils. Have toll like receptors (on surface) and NOD-like receptors (inside the cell). Interact w/ PAMPs to initiate response

Pathogen-associated molecular patterns (PAMPs)

On most pathogen, but not on host cells (i.e., LPS, peptidoglycans, mannose rich oligosacharides)

Cytokines

Proteins that cause inflammation (interferons, interleukins, tumor necrosis factor)

Chemokines

Subfamily of cytokines. Chemically attract to bind and bring monocytes and neutrophils to infected tissue (CCL, CCR, CXC)

Main inflammatory cells

Macrophages and neutrophils

Naive lymphocytes

Never encountered an antigen

Effector lymphocytes

Met an antigen, activated, differentiated, and fully functional

B lymphocytes (B-cells)

Production of antibodies

T lymphocytes (T-cells)

Cytotoxic and helper

B-cell Receptor (BCR)

Y shaped, 2 identical heavy chains & 2 identical light chains, variable and constant region, have secreted and membrane-bound form, recognizes the epitope of antigen (part of the whole antigen)

T-cell Receptor (TCR)

Has two chains; alpha & beta and are connected to “T” cell, variable and constant region, TCR binds fragmented antigen (epitope as its own piece), fragment presented on MHC molecule, TCR binds antigen presented on MHC

Clonal Selection Theory

The process by which specific B-cell and T-cell lymphocyte are specifically determined and activated. Specificity determined during maturation stage in bone marrow (for B cells) and thymus (for T cells)

Clonal Expansion

Activated lymphocytes will multiply with the identical specific receptor, to increase the immune response to a specific antigen

Clonal deletion

Any receptors that will bind self molecules are deleted

Primary lymphoid organ

Bone marrow (B-cells)

Thymus (T-cells)

Secondary lymphoid organ

Spleen, lymph nodes, tonsil, appendix, mucosal lymphoid tissue of the gut, nasal tract, respiratory tract, urogenital tract

Antigen presenting cells (APC)

Antigen presentation starts the adaptive immune response. B-cells, Dendritic cells, and Macrophages are the main cells that present to t-cells (dendritic are most potent)

Adaptive Immunity

1. Starts w/ the presentation of antigens by APCs

2. APCs breakdown bacterial antigen, travel to lymph nodes and present to T-cells

3. Along w/ co-stimulatory molecules and MHC (w/ antigen), T-cells clone

4. T-cells are activated

5. If any T-cells recognize self-antigens (those present on our cells), the T-cells will die via apoptosis

Lymphatic Circuit

W/ Infection

1. Pathogen and dendritic cell travel via afferent lymphatic vessels to the lymph node (afferent = towards)

2. Lymph recirculates via efferent lymphatic vessels to the thoracic duct and back into the bloodstream. Blood circulation also brings B and T cells to the lymph nodes (efferent = away)

Lymphoid Tissue

Afferent lymphatic vessels bring in APC & Ag

High endothelial venules

B cells: found in bone marrow

T cell: found in thymus

Splenic lymphoid tissue

Highly specialized secondary lymphoid tissue

Anything that interacts w/ the spleen comes in through the blood and leaves through the blood

Red pulp: RBC destruction

White pulp: T cells found in the periarteriolar lymphoid sheath (PALS); B cells found in the follicles and also marginal zone B-cells

Peyer’s Patches

Covered by an epithelial layer containing specialized cells called M cells. M cells bring Ag into Peyer’s patch. Only efferent venules take lymph away in Peyer’s patch

Lymphocyte activation

1. Antigen (Ag) binds to the receptor

2. Co-stimulatory signal (T cell from dendritic cell and B cell from T cell)

   1. One signal will not activate the process; a secondary signal is needed to activate this process

First Exposure

Primary immunization

Second Exposure

Secondary immunization or booster immunization

Affinity maturation

Only B cells. Every time a B cell encounters an Ag, the BCR becomes better and better in recognizing the Ag.

Lag Phase (antibody response)

1st time is longer. 2nd time is shorter

Ab titer (antibody response)

Amount of antibody cloning. 1st time is low. 2nd time is high

Ab affinity (antibody response)

Ab maturation. 1st time is low. 2nd time is high

Ab plateau

Length of time Abs fight. 1st time is short. 2nd time is long

Effector cells

1. High cytoplasm/nucleus ratio

2. Presence of RER (for protein synthesis) is needed for antibody production

3. Abundant mitochondria

Neutralization (B cell humoral immunity)

Ab bind on pathogen to prevent toxin from entering the cell.

Opsonization (B cell humoral immunity)

A way to signal for something else to help destroy. Surrounds a pathogen for a phagocyte to come eat it.

Complement activation (B cell humoral immunity)

Activates complement system

Cytotoxic T-cells (cell mediated immunity)

CD8 cells on protein surface

Recognizes MHC class I presenting an Ag that is attached to an APC

Helper T-cells (cell mediated immunity)

CD4 cells

Th1, Th2, Th17

Recognizes MHC class II presenting to an Ag that is attached to an APC

MHC molecules

Major histocompatibility complex (an antigen on our cells)

T cells only recognize antigens as peptide fragments presented by MHC molecules

Intracellular antigens

Presented on MHC I. Recognized by CD8 Cytotoxic T cells. Your cell made these Ag, and it’s on MHC I

Extracellular antigens

Presented on MHC II. Recognized by CD4 Helper T cells. Inside the cell but your cell did not make the Ag.

T cells and MHC I

Cytotoxic CD8 T-cells recognize the antigen peptide on MHC I

Cytotoxic T-cell kills the infected cell

T cells and MHC II

Helper CD4 T cell recognize antigen peptide on MHC II

Helper CD4 T cell will activate the macrophages or B-cells